To observe the effects and safety of vericiguat tablets combined with roxadustat capsules in hemodialysis patients with heart failure after myocardial infarction.

Hemodialysis patients with chronic heart failure after myocardial infarction were randomly assigned into the treatment group and the control group based on the random number table method. Patients in the control group orally took roxadustat capsules, beta-blockers, angiotensin Ⅱ receptor antagonists, statins, nitrates and lifestyle guidance as appropriate. Roxadustat capsules: for those weighing less than 60 kg, 100 mg per time; for those weighing more than 60 kg, take 120 mg each time; 3 times a week. Patients in the treatment group were given oral administration of vericiguat tablets on this basis, 2.5 mg each time, once a day. The treatment duration lasted six months. The clinical efficacy, heart function-related indicators, apoptosis-related factors, inflammatory factors, endothelial function indicators, anemia, iron metabolism conditions and safety evaluation were compared between the two groups.

A total of 125 cases were enrolled in this study. The treatment group included 63 cases, and the control group included 62 cases. After the treatment, the total effective rates of the treatment group and the control group were 90.48% (57 cases /63 cases) and 77.42% (48 cases /62 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the left ventricular ejection fraction in the treatment and the control groups were (55.87±7.05)% and (50.02±6.13)%, respectively; the left ventricular end systolic volumes were (75.08±14.29) and (80.45±13.88) mL, respectively; the left ventricular end diastolic volumes were (109.61±21.25) and (117.91±24.73) mL, respectively; the 6-minute walking tests were (454.69±38.68) and (409.59±39.68) m, respectively; the B-type natriuretic peptide levels were (530.54± 36.68) and (578.73±43.62) ng·L^-1, respectively; the high-sensitivity troponin Ⅰ levels were (24.62±4.17) and (32.59±4.83) ng·L^-1, respectively; the soluble apoptosis factor levels were (3.15±0.79) and (5.70±0.99) μg·L^-1, respectively; the soluble apoptosis factor ligand levels were (2.30±0.57) and (9.06±1.40) μg·L^-1, respectively; the interleukin-1β levels were (5.47±0.72) and (7.96±0.66) pg·mL^-1, respectively; the interleukin-6 levels were (14.36±2.95) and (18.77±3.11) pg·mL^-1, respectively; the nitric oxide synthase levels were (55.00±5.25) and (50.40±5.83) U·mL^-1, respectively; the nitric oxide levels were (128.86±28.04) and (117.62±23.15)μmol·L^-1, respectively. The above indicators in the treatment group were statistically significantly different from those in the control group (all P<0.05). The main adverse drug reactions in the treatment group were symptomatic hypotension, hyperkalemia and nausea and vomiting, while those in the control group were mainly nausea and vomiting, upper abdominal discomfort and fatigue. The total incidence of adverse drug reactions in the two groups was 9.52% (6 cases /63 cases) and 9.68% (6 cases/62 cases), respectively. There was no statistically significant difference (P>0.05).

Vericiguat tablets combined with roxadusta capsules has improved the cardiac function and ventricular remodeling of hemodialysis patients with chronic heart failure after myocardial infarction, reduced inflammatory factors and apoptosis-related factors, protected vascular endothelia, and achieved remarkable clinical efficacy, which is superior to that of roxadustat capsules alone with basic drugs for chronic heart failure, and has fewer adverse reactions.

To observe the clinical efficacy and safety of Shuxuetong injection combined with sacubitril/valsartan tablets in the treatment of patients with cerebral infarction complicated with hypertension.

Patients with cerebral infarction complicated with hypertension admitted to our hospital were randomly divided into the treatment group and the control group according to the random number table method. The control group was given sacubitril/valsartan sodium tablets 100 mg each time, twice a day, orally. On the basis of the control group, the treatment group was given Shuxuetong injection 6 mL each time, once a day, intravenously. Both groups were treated for 2 weeks. The clinical efficacy, 24-hour average diastolic and systolic blood pressure, National Institutes of Health Stroke Scale (NIHSS) score, activities of daily living (ADL) score, hemorheology (whole blood viscosity, fibrinogen and hematocrit), blood lipids [total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) levels], serum von Willebrand factor (vWF) and homocysteine (Hcy) levels of the patients in the two groups were compared, and the safety was evaluated.

This study ultimately included 92 patients, with 46 in the treatment group and 46 in the control group. After treatment, the total effective rates of the treatment group and the control group were 93.48% (43 cases/46 cases) and 78.26% (36 cases/46 cases), respectively. The treatment group was significantly higher than the control group (P<0.05). The NIHSS scores of the treatment group and the control group were (7.93±1.44) and (10.24±1.86) respectively; the ADL scores were (79.02±8.05) and (71.66±7.36) respectively. The NIHSS score of the treatment group was significantly lower than that of the control group (P<0.05), and the ADL score was significantly higher than that of the control group (P<0.05). The systolic blood pressure of the treatment group and the control group was (120.51±12.77) and (136.48±14.29) mmHg, respectively; the diastolic blood pressure was (80.36±9.66) and (89.74±11.02) mmHg, respectively; the whole blood viscosity was (4.69±0.59) and (7.16±0.84) mPa·s, respectively; the fibrinogen level was (3.17±0.65) and (4.41±1.02) g·L^-1, respectively; the hematocrit was 0.30±0.04 and 0.41±0.05, respectively; the total cholesterol level was (4.22±0.54) and (5.86±1.01) mmol·L^-1, respectively; the triglyceride level was (1.35±0.32) and (1.79±0.44) mmol·L^-1, respectively; the LDL-C level was (2.03±0.25) and (2.48±0.38) mmol·L^-1, respectively; the vWF level was (131.57±14.36)% and (144.74±14.61)%, respectively; the Hcy level was (12.32±1.48) and (18.62±2.09) μmol·L^-1, respectively. All the above indicators in the treatment group were significantly lower than those in the control group (all P< 0.05). The adverse reactions in the treatment group mainly included hypotension, hyperkalemia and bleeding. The adverse reactions in the control group mainly included hypotension, hyperkalemia and renal dysfunction. The total incidence of drug adverse reactions in the treatment group and the control group was 10.87% (5 cases/46 cases) and 8.70% (4 cases/46 cases) respectively. There was no statistically significant difference in the two group (P> 0.05).

For patients with cerebral infarction and hypertension, the treatment with Shuxuetong injection combined with sacubitril/valsartan sodium tablets shows better therapeutic effects initially. It can improve neurological function, enhance self-care ability, lower blood pressure and lipid levels, and improve hemorheology.

To observe the clinical efficacy and safety of autologous platelet-rich gel (APG) combined with timolol eye drops in postoperative patients with diabetic foot ulcer.

Patients with diabetic foot ulcers who were admitted to the department of endocrinology of our hospital and underwent surgical treatment were divided into control group and treatment group based on postoperative intervention protocols. In control group, wounds were cleaned and disinfected, then evenly covered with 0.5-1.0 cm thick APG, dressed with petrolatum gauze and sterile gauze once weekly for 4 weeks. The treatment group received the same APG treatment combined with timolol maleate eye drops (one drop per square centimeter of wound surface dripped on the inner gauze over APG); dressing was applied after absorption, administered once every two days for 4 weeks. Compare the clinical efficacy, wound progress, serum inflammatory markers, angiogenesis indicators, wound collagen, blood flow in the dorsalis pedis artery and safety between the two groups.

This research included 80 participants, among whom 42 were allocated to control group and 38 to treatment group. After treatment, the treatment group achieved a total clinical efficacy rate of 86.84% (33 cases/38 cases), this outcome was markedly superior to the control group’s 66.67% (28 cases /42 cases), and the inter-group difference was statistical significance (P<0.05). After treatment, the wound area in treatment group and control group were (5.96±1.56) and (6.86±1.84) cm², respectively; wound depth were (0.56±0.08) and (0.62±0.13) cm, respectively; wound symptom scores (TIME) were (3.84±0.79) and (4.26±0.96) points, respectively; wound healing time was (57.18±9.52) and (64.26±11.37) days, respectively; the serum omentin-1 levels were (899.04±86.77) and (853.56±80.25) ng·L^-1, respectively; the intercellular adhesion molecule-1 (ICAM-1) levels were (211.03±31.73) and (230.25±36.92) μg·L^-1, respectively; the endostatin levels were (38.84±4.73) and (42.05±5.29) ng·L^-1, respectively; the vascular endothelial growth factor (VEGF) levels were (100.60±12.11) and (93.93±9.92) ng·mL^-1, respectively; the platelet-derived growth factor (PDGF) levels were (85.58±9.15) and (80.50±8.13) ng·mL^-1, respectively; the basic fibroblast growth factor (bFGF) levels were (84.33±12.26) and (78.16±10.64) ng·mL^-1, respectively; the type Ⅰ collagen levels were (2.77±0.70) and (2.36±0.63) mg·mL^-1, respectively; the type Ⅲ collagen levels were (2.52±0.75) and (2.09±0.62) mg·mL^-1, respectively; dorsalis pedis artery inner diameter were (2.03±0.33) and (1.85±0.29) mm, respectively; peak flow velocity were (0.79±0.17) and (0.68±0.15) m·s^-1, respectively; blood flow were (21.55±4.30) and (19.38±3.89) mL·min^-1, respectively. The differences of the above indicators between the two groups were all statistically significant (P<0.05, P<0.01). Regarding adverse drug reactions, the treatment group had local pruritus, local dryness and mild stinging; the control group had mild local irritation, and mild redness and swelling. The total incidence of adverse drug reactions in treatment group and control group were 7.89% (3 cases/38 cases) and 7.14% (3 cases/42 cases), respectively, with no statistically significant difference between the two groups (P>0.05).

For patients with diabetic foot ulcers following surgery, the combination therapy of APG and timolol eye drops demonstrates definite clinical efficacy. It effectively promotes wound healing, shortens healing time, alleviates inflammatory responses, enhances angiogenesis and collagen deposition in the wound, and contributes to the improvement of pedal blood supply, all with a favorable safety profile.

To explore the effects of Wilms tumor 1-associating protein (WTAP) rs7766006 polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors.

Pediatric patients with brain tumors who received chemotherapy at our hospital were included as study subjects. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was used for WTAP rs7766006 genotyping. Clinical data collected included chemotherapy toxicities and tumor progression. The associations of WTAP rs7766006 G>T polymorphisms with chemotherapy toxicities and progression-free survival (PFS) were analyzed. The expression of WTAP in brain tumors and its prognostic significance, and the potential mechanism of rs7766006 G>T polymorphisms in WTAP expression were explored based on bioinformatics methods.

Among the 107 children with brain tumors included, the rs7766006 GG homozygous, GT heterozygous, and TT homozygous genotypes accounted for 40.19% (43 cases/107 cases), 44.86% (48 cases/107 cases) and 14.95% (16 cases/107 cases), respectively. The frequencies of G and T alleles were 62.62% (134 cases/214 cases) and 37.38% (80 cases/214 cases) respectively. The incidence rates of mucositis in the GG, GT, and TT genotype groups were 53.49% (23cases/43 cases), 27.08% (13 cases/48 cases) and 43.75% (7 caes/16 cases), respectively. The incidence rates of coagulation disorders in three groups were 18.61% (8 cases/43cases), 2.08% (1 case/48 cases) and 6.25% (1 case/16 cases), respectively. The difference in the incidence rates of the two chemotherapy toxicities mentioned above between the GG and GT genotypes was statistically significant (all P<0.05). However, there were no significant differences in the incidence of other chemotherapy toxicities among the three groups (all P>0.05). The disease progression rates for the GG, GT, and TT genotype groups were 65.12% (28 cases/43 cases), 43.75% (21 cases/48 cases), and 62.50% (10 cases/16 cases), respectively. The risk of disease progression in children with the GG genotype was significantly higher than in those with the GT genotype (P<0.05). Bioinformatics analysis showed that the WTAP expression in brain tumors 6.00±0.66 was significantly higher than that in normal tissues 4.63±1.34 (P<0.001). The median overall survivals for the WTAP high-expression group and the low-expression group were 537 and 2 835 days, respectively (P<0.001). The rs7766006 polymorphism was located in the exonic splicing enhancer site and possibly regulated WTAP expression by affecting alternative splicing.

WTAP rs7766006 GG genotype might be a risk factor for oral mucositis, coagulation disorders, and progression in children with brain tumors.

To evaluate the predictive value of different risk models for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB)-related cirrhosis receiving antiviral therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF), and to clarify the effects of pharmacological differences among various nucleos(t)ide analogs (NAs) on HCC risk, so as to provide a reference for clinical diagnosis and treatment.

A total of 252 treatment-naive patients with CHB-related cirrhosis without a history of HCC who received NA antiviral therapy from May 2015 to May 2020 were retrospectively enrolled. They were divided into the ETV group (n=108), TDF group (n=96), and TAF group (n=48) according to the NA used. Cox proportional hazards model was used to construct an HCC risk prediction model. Patients were classified into low-risk group (0-3 points), intermediate-risk group (4-7 points), and high-risk group (8-13 points) based on the Asia-Pacific Association for the Study of the Liver (APASL) REALB score. All patients continued to receive corresponding NA therapy and were followed up until the study endpoint. The predictive performance of each risk score was compared using time-dependent area under the receiver operating characteristic curve (AUROC), and the differences in HCC incidence among different NA groups were analyzed. The main outcome measures included HCC incidence, international normalized ratio (INR), alpha-fetoprotein (AFP), diabetes mellitus, drinking history, predictive performance of the REALB score, and prognosis-related effects of different NAs.

A total of 252 patients were screened, and finally 108 patients were assigned to the ETV group, 96 to the TDF group, and 48 to the TAF group. The median follow-up duration was 56.96 months, and hepatocellular carcinoma (HCC) was diagnosed in 19.00% (48 cases/252 cases) of patients. The 1year incidence rates of HCC in the ETV, TDF, and TAF groups were 4.63% (5 cases/108 cases), 5.21% (5 cases/96 cases), and 4.17% (2 cases/48 cases), respectively; the 3 year rates were 12.96% (14 cases/108 cases), 13.54% (13 cases/96 cases), and 12.50% (6 cases/48 cases), respectively; and the 5 year rates were 17.59% (19 cases/108 cases), 18.75% (18 cases/96 cases), and 16.67% (8 cases/48 cases), respectively. No statistically significant differences were observed among the three groups (all P>0.05). Multivariate stepwise regression analysis revealed that INR (HR=2.77, 95% CI: 1.46-5.25, P<0.01), AFP (HR=1.00, 95% CI: 1.00-1.00, P<0.05), diabetes mellitus (HR=3.06, 95% CI: 1.54-6.08, P<0.01), and history of alcohol consumption (HR=2.25, 95% CI: 1.04-4.86, P<0.05) were independent risk factors for HCC development. The predictive performance of the REALB score at 3 years (AUROC=0.74) and 5 years (AUROC=0.70) remained higher than that of other models except the RWSHCC model, while its 1year AUROC was similar to those of other models. Statistically significant differences in the 1, 3, and 5 year HCC incidence rates were found between the intermediaterisk group and the highrisk group (all P<0.001).

Different NAs (ETV, TDF, TAF) have comparable efficacy in controlling HCC risk in patients with CHB-related cirrhosis, and differences in their pharmacological properties do not significantly affect HCC risk. The REALB score shows stable and excellent predictive ability for HCC in patients receiving NA antiviral therapy and can be used as a preferred tool for clinical prognosis evaluation.

To observe the clinical efficacy and safety of porcine pulmonary surfactant injection combined with budesonide suspension in premature infants with respiratory distress syndrome (RDS).

Infants with RDS were divided into control group and treatment group based on treatment methods. The control group received endotracheal administration of poractant alfa injection at 200 mg·kg^-1, with a supplemental dose of 100 mg·kg^-1 after 12 h. The treatment group additionally received inhaled budesonide suspension at 0.25 mg·kg^-1, twice daily. Both groups continued treatment for 3 d. The clinical symptoms and respiratory support parameters, blood gas analysis parameters, serum inflammatory and stress markers, clinical efficacy and safety evaluation were compared between the two groups.

A total of 136 were enrolled, with 59 cases in treatment group and 65 cases in control group. After treatment, the total efficacy rates in treatment group and control group were 89.83% (53 cases /59 cases) and 78.46% (49 cases /65 cases), respectively; time to disappearance of tachypnea were (36.85±5.62) and (39.52±7.15) h, respectively; time to disappearance of retractions were (40.58±7.93) and (43.88±8.61) h, respectively; time to disappearance of lung rales were (49.34±7.96) and (54.18±9.63) h, respectively; duration of mechanical ventilation were (4.15±0.78) and (4.45±0.87) d, respectively; total duration of oxygen therapy were (7.56±1.32) and (8.12±1.13) d, respectively; duration of neonatal intensive care unit (NICU) stay were (17.42±2.55) and (18.66±3.28) d, respectively; partial pressure of oxygen (PaO₂) levels were (65.24±9.24) and (61.58±9.85) mmHg, respectively; partial pressure of carbon dioxide (PaCO₂) levels were (41.85±6.61) and (44.92±7.13) mmHg, respectively; oxygenation indexes (OI) were 8.44±0.95 and 8.92±1.16, respectively; interleukin-6 (IL-6) levels were (45.78±5.42) and (48.74±7.25) pg·mL^-1, respectively; C-reactive protein (CRP) levels were (11.63±1.56) and (12.65±3.04) mg·L^-1, respectively; cortisol (Cor) levels were (296.54±36.87) and (315.16±45.32) nmol·L^-1, respectively; adrenocorticotropic hormone (ACTH) levels were (61.23±7.65) and (65.20±9.48) pg·mL^-1, respectively. There were statistically significant differences in the above indexes between treatment group and control group (all P<0.05). During treatment, the main adverse drug reactions in treatment group included air leak syndrome, pulmonary hemorrhage, decreased blood oxygen saturation, hyperglycemia and bradycardia; the control group included pulmonary hemorrhage, decreased oxygen saturation, hyperglycemia and bradycardia. The total incidence of adverse drug reactions in treatment group and control group were 13.56% (8 cases/59 cases) and 13.85% (9 cases/65 cases), respectively, with no statistically significant difference (P>0.05).

Poractant alfa injection combined with budesonide suspension can improve the total effective rate of treatment for RDS in preterm infants, accelerate symptom relief, inhibit inflammatory response and oxidative stress, without increasing the risk of additional adverse drug reactions.

To explore the effect and safety of rituximab injection in the treatment of patients with primary membranous nephropathy (PMN).

PMN patients were selected as the study subjects and divided into control group and treatment group according to envelope method. Patients in control group received valsartan capsules, 80 mg·d^-1, and the patients in treatment group was treated with 375 mg·m^-2 rituximab injection, (once a week, and adjusted to once per month after one month of therapy) on the basis of control group. Both groups received continuous treatment for six months. The clinical efficacy, renal function indexes (24-hour urine protein, creatinine, blood urea nitrogen), immune cells (Th1 cells, Th2 cells, Th17 cells), immune-related factors [immunoglobulin G subtype 4 (IgG4), interleukin-4 (IL-4)], vascular endothelial cell function [plasminogen activator inhibitor-1 (PAI-1), endothelin-1 (ET-1)], soluble suppression of tumorigenicity 2 (sST2) and Toll-like receptor 4 (TLR4) levels were compared and analyzed and the safety were evaluated.

The clinical effective rates of the treatment group and the control group were 86.49% (64 cases/74cases) and 63.51% (47 cases/74 cases), respectively, and the difference was statistically significant (P<0.01). After treatment, the 24 h urine protein in the control group and the experimental group were (2.03±0.39) and (1.49±0.32) g·24 h^-1, respectively; the serum creatinine were (98.11±12.29) and (76.69±10.12) μmoL·L^-1, respectively; blood urea nitrogen was (7.39±0.89) and (6.08±1.27) mmoL·L^-1, respectively; the proportion of Th2 cells were (0.92±0.11) % and (0.76±0.13) %, respectively; the levels of sST2 were (1.59±0.38) and (1.19±0.31) ng·mL^-1, respectively; the levels of TLR4 were (125.09±13.91) and (91.58±10.67) ng·mL^-1; the levels of ET-1 were (53.58±5.34) and (41.77±4.35) pg·mL^-1. The differences of the above indicators between two groups were all statistically significant (all P<0.01). The drug adverse effects of treatment group and the control group were 16.22% (12 cases/74 cases) and 13.51% (10 cases/74 cases) (P>0.05).

Rituximab injection is beneficial for primary membranous nephropathy to improve renal function and vascular endothelial cell function, reduce the release of sST2 and TLR4, reduce the expression of immune-related factors, improve clinical efficacy, and have a good safety profile.

To investigation the effect of arbutin on hypoxia/reoxygenation (H/R)-induced injury of cardiomyocytes (H9C2) through the neurogenic locus notch homolog protein 1(Notch1)/hairy and enhancer of split 1 (Hes1) signaling pathway.

An H/R-induced H9C2 cell injury model was established. The optimal intervention concentration of arbutin was screened by pretreating cells with various concentrations (12.50-200.00 μmol·L^-1). H9C2 cells were divided into a normal group, a model group, experimental-L, M, H groups (25.00, 50.00, and 100.00 μmol·L^-1 arbutin, respectively), and an inhibitor group {100.00 μmol·L^-1 arbutin+10.00 μmol·L^-1 N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT)}. Cells in the normal group were cultured under normal conditions, while H/R models were established in the remaining groups. All treatment groups received arbutin pretreatment at concentrations ranging from 12.50 to 200.00 μmol·L^-1 for 24 hours before modeling. Cell proliferation was detected by the CCK-8 assay, and apoptosis was assessed by TUNEL assay; mitochondrial membrane potential was measured by JC-1; reactive oxygen species (ROS), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) levels were detected using kits. Expression of Notch1, Hes1, Bcl-2, Bax, and caspase-3 was detected by Western blot.

Arbutin at concentrations of 25.00–200.00 μmol·L^-1 significantly increased the survival rate of H/R-induced H9C2 cells (P<0.05). Arbutin at 25.00, 50.00, and 100.00 μmol·L^-1 was selected as the low, medium, and high doses for subsequent experiments. The creatine kinase isoenzyme MB (CK-MB) levels in the normal group, model group, experimental-H group, and inhibitor group were (2.45±0.39), (8.72±0.82), (3.56±0.42), and (5.48±0.57) U·mL^-1, respectively; the cTnI levels were (22.58±2.23), (68.34±5.96), (30.12±3.26), and (49.62±5.15) ng·L^-1, respectively; the LDH levels were (53.42±5.44), (163.72±13.41), (65.45±6.57), and (98.33±9.85) U·L^-1, respectively; the relative ROS levels were 1.01±0.12, 3.34±0.35, 1.46±0.18, and 2.24±0.23, respectively; the SOD levels were (96.23±8.12), (24.31±2.24), (78.39±7.93), and (43.78±4.49) U·mg^-1, respectively; the GSH-Px levels were (74.82±7.55), (16.42±1.83), (61.32±6.29), and (35.72±3.38) U·mg^-1, respectively; the MDA levels were (15.45±2.03), (58.33±5.57), (21.56±2.24), and (42.47±4.13) μmol·L^-1, respectively; the apoptosis rates were (2.45±0.39)%, (29.86±3.25)%, (9.86±0.91)%, and (21.34±2.25)%, respectively; the red/green fluorescence intensity ratios were (5.78±0.65)%, (1.42±0.20)%, (4.89±0.54)%, and (2.85±0.33)%, respectively; the Notch1 protein expression levels were 1.27±0.12, 0.34±0.03, 1.05±0.08, and 0.54±0.05, respectively; the Hes1 protein expression levels were 0.95±0.10, 0.25±0.03, 0.81±0.08, and 0.57±0.05, respectively; the Bcl-2 protein expression levels were 1.01±0.11, 0.31±0.03, 0.89±0.08, and 0.61±0.06, respectively; the Bax protein expression levels were 0.45±0.04, 1.34±0.12, 0.61±0.06, and 0.93±0.09, respectively; and the caspase-3 protein expression levels were 0.23±0.03, 0.91±0.09, 0.37±0.04, and 0.64±0.06, respectively. Comparisons between the normal group and the model group, between the model group and the experimental-L, M, H groups, and between the experimental-H group and the inhibitor group all showed statistically significant differences for the above indicators (all P<0.05).

Arbutin alleviates H/R-induced H9C2 cell injury by activating the Notch1/Hes1 pathway and inhibiting oxidative stress.

To explore the effects of woginostatin (WOG) on the biological behaviors of gastric cancer cells through long non-coding RNA small nucleolar RNA host gene 16 (LncRNA SNHG16)/microRNA (miR)-302a-3p/E2F transcription factor 1 (E2F1).

In cell experiment, human gastric cancer cells (MGC-803) were divided into cell control group (normal culture), cell experimental-H group (100 μmol·L^-1 WOG treated cells), oe-NC group (transfected oe-NC), oe-LncSNHG16 group (transfected oe-LncSNHG16), mimic-NC group (transfected mimic-NC), miR-302a-3p mimic group (transfected miR-302a-3p mimic), WOG + oe-NC group (transfected oe-NC based on 100 μmol·L^-1 WOG treated cells), WOG + oe-LncSNHG16 group (transfected oe-LncSNHG16 based on 100 μmol·L^-1 WOG treated cells), WOG +oe-LncSNHG16+miR-302a-3p mimic group (transfection of oe-LncSNHG16 and miR-302a-3p mimic on the basis of 100 μmol·L^-1WOG treatment group). In animal experiment, the subcutaneous transplanted tumor model of gastric cancer was established in BALB/C male nude mice. The nude mice were randomly divided into animal experimental-L, -M and -H dose groups (15, 30 and 60 mg·kg^-1 WOG gavage), and the animal control group was gavaged with equal volume of physiological saline, with 10 mice in each group. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of LncRNA SNHG16, miR-302a-3p and E2F1. The cell viability was detected using the cell counting kit 8 (CCK-8). The cell proliferation, invasion and apoptosis were detected using 5-ethynyl-2′-deoxyuridine (Edu), Transwell and in situ terminal transferase labeling technique (TUNEL).

In cell experiment, the relative expression levels of LncRNASNHG16 in cell control group, cell experimental-H group, mimic-NC group, miR-302a-3p mimic group, oe-NC group and oe- LncSNHG16 group were 1.00±0.13, 0.47±0.05, 1.00±0.10, 0.81±0.12, 1.02±0.09 and 3.76±0.41, respectively; the relative expression levels of miR-302a-3p were 1.00±0.11, 3.60±0.39, 1.00±0.09, 3.74±0.32, 0.97±0.10 and 0.27±0.03, respectively; the relative expression levels of E2F1 mRNA were 1.00±0.14, 0.23±0.02, 1.00±0.10, 0.33±0.03, 0.95±0.08 and 2.18±0.25, respectively. Compared the cell experimental-H group with cell control group, compared miR-302a-3p mimic group with mimic-NC group and compared oe-LncSNHG16 group with oe-NC group, the above indicators were all statistically significantly different (P<0.01, P<0.001). The proliferation rates of cell control group, cell experimental-H group, WOG + oe-LncSNHG16 group and WOG + oe-LncSNHG16 + miR-302a-3p mimic group were (95.04±10.14)%, (36.36±4.75)%, (97.64±11.04)% and (31.87±3.56)%, respectively; the number of invasive cells were (147.36±15.01), (43.31±6.25), (153.45±15.22) and (37.35±5.04), respectively; the apoptosis rates were (7.83±0.83)%, (35.77±4.38)%, (8.44±0.88)% and (29.35±3.09)%, respectively. There were statistically significant differences in the above indexes between the cell experimental-H group and the cell control group, between the WOG + oe-LncSNHG16 group and the cell experimental-H group, and between the WOG + oe-LncSNHG16 group and the WOG + oe-LncSNHG16 + miR-302a-3p mimic group (all P<0.001). In animal experiment, the tumor volume of animal control group and animal experimental-L,-M,-H groups were (2 554.50±280.41), (2 194.10±234.22), (1 512.40±166.75) and (1 146.20±124.32) mm³, respectively; the tumor mass was (2.13±0.28), (1.84±0.23), (1.65±0.21) and (1.32±0.14) g, respectively. There were statistically significant differences in the above indicators between experimental-L, -M, -H groups and animal control group (P<0.05, P<0.01, P<0.001).

WOG can inhibit the proliferation and invasion of gastric cancer cells and promote their apoptosis. This may be related to the regulation of the LncRNA SNHG16/miR-302a-3p/E2F1 axis, which blocks the cell cycle.

To explore the mechanism of the inhibitory effects of plumbagin on the malignant biological behaviors and glycolysis of tongue squamous cell carcinoma cells through fibronectin type Ⅲ domain-containing protein 3B (FNDC3B).

Human tongue squamous cell carcinoma cells (TCA8113) in the logarithmic growth phase were obtained. TCA8113 cells were divided into blank group (normal cultured), experimental-L, M, and H group (TCA8113 cells were treated with 1, 2 and 4 μmol·L^-1 plumbagin), oe-NC group (TCA8113 cells were transfected with the negative control plasmid oe-NC), oe-FNDC3B group (TCA8113 cells were transfected with oe-FNDC3B), experimental-H+oe-NC group (based on experimental-H group, transfected with the oe-NC plasmid) and experimental-H+oe-FNDC3B group (based on experimental-H group, transfected with the oe-FNDC3B plasmid). Real-time quantitative polymerase chain reaction was used to detect FNDC3B mRNA relative expression levels. Cell viability was assessed using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Cell invasion was evaluated using the Transwell assay. Immunofluorescence staining was performed to detect the protein relative expression levels of FNDC3B, hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Cell apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.

The numbers of invasive cells in blank group, experimental-H group, experimental-H+oe-NC group and experimental-H+oe-FNDC3B group were (89.71±13.59), (69.67±14.78), (62.33±10.11) and (158.23±20.95), respectively; the apoptosis rates were (10.07±2.41)%, (23.38±4.75)%, (20.65±5.43)% and (8.44±1.18)%, respectively; the relative expression levels of HK2 were 1.00±0.15, 0.58±0.09, 0.55±0.07 and 0.71±0.10, respectively; the relative expression levels of LDHA were 1.00±0.12, 0.63±0.11, 0.61±0.09 and 0.89±0.15, respectively; the relative expression levels of P53 were 1.00±0.15, 1.59±0.31, 1.64±0.28 and 1.25±0.22, respectively; the relative expression levels of P21 were 1.00±0.13, 1.51±0.26, 1.48±0.19 and 1.19±0.17, respectively; the relative expression levels of CDK6 were 1.00±0.13, 0.28±0.04, 0.33±0.06 and 0.79±0.12, respectively. There were statistically significant differences in the above indicators between experimental-H group and blank group, and between experimental-H+oe-FNDC3B group and experimental-H+oe-NC group (all P<0.05).

Plumbagin may promote the apoptosis of tongue squamous cell carcinoma cells, and inhibit the invasion and glycolysis of cancer cells by regulating the P53/P21/CDK6 signaling pathway through FNDC3B.

To investigate the protective effect and underlying mechanism of kaempferol (Kae) on flap ischemia-reperfusion injury (FIRI) in rats by regulating glutathione peroxidase 4 (GPX4)-mediated ferroptosis and gasdermin D (GSDMD)-mediated pyroptosis.

McFarlane method was used to establish the ischemia-reperfusion model of rat dorsal flap. A total of 91 SPF SD rats were randomly divided into sham group, model group, experimental group, agonist group, inhibitor group, Kae+agonist group and Kae+inhibitor group, with 13 rats in each group. After successful modeling, the experimental group was given kaempferol 50 mg·kg^-1 by gavage; the agonist group was intraperitoneally injected with 2 mg·kg^-1 NOD like receptor thermoprotein domain associated protein 3 (NLRP3) activator once a week; the inhibitor group was intraperitoneally injected with 30 mg·kg^-1 disulfiram once a week; the Kae+agonist group received intraperitoneal injection of 2 mg·kg^-1 NLRP3 activator+50 mg·kg^-1 kaempferol; the Kae+inhibitor group received intraperitoneal injection of 30 mg·kg^-1 disulfiram+50 mg·kg^-1 kaempferol for 2 weeks. The iron content in tissues was detected by iron content detection kit; the levels of serum interleukin-1 β (IL-1 β) and IL-18 were detected by enzyme linked immunosorbent assay (ELISA); the expressions of proliferating cell nuclear antigen (Ki67) and platelet endothelial cell adhesion molecule-1 (CD31) were detected by immunohistochemistry; the protein expressions of GPX4, Caspase-1 and GSDMD-NT were detected by Western blot.

The flap survival rates of the sham group, model group, experimental group, agonist group, inhibitor group, Kae+agonist group and Kae+inhibitor group were (96.73±1.10)%, (67.04±1.60)%, (85.39±1.22)%, (57.96±1.52)%, (75.80±1.72)%, (80.28±0.95)% and (90.49±0.76)%, respectively; the tissue iron content levels were (11.57±4.89), (68.04±7.64), (43.87±9.13), (85.97±8.41), (47.78±11.11), (69.68±6.17) and (29.36±7.66) μmol·L^-1; the levels of IL-1 β were (43.83±13.96), (246.02±37.60), (172.19±29.46), (354.39±36.05), (153.56±26.89), (271.13±39.54) and (97.53±24.67) pg·mL^-1, respectively; the relative expression levels of CD31 were 6 694.96±711.29, 2 126.32±277.21, 3 592.33±317.33, 484.36±56.24, 3 568.83±316.65, 1 901.66±383.85 and 4 804.18±360.03, respectively; the relative expression levels of Ki67 were 75.56±6.57, 24.11±4.02, 37.94±4.08, 12.17±2.28, 38.01±3.80, 24.32±2.76 and 54.65±7.01, respectively; the relative expression levels of GPX4 were 0.92±0.02, 0.30±0.07, 0.47±0.08, 0.12±0.04, 0.47±0.08, 0.27±0.07 and 0.62±0.13, respectively; the relative expression levels of Caspase-1 were 0.08±0.03, 0.40±0.07, 0.29±0.04, 0.68±0.07, 0.28±0.03, 0.40±0.06 and 0.18±0.06, respectively; the relative expression levels of GSDMD were 0.06±0.04, 0.57±0.05, 0.30±0.04, 0.93±0.09, 0.30±0.03, 0.56±0.07 and 0.16±0.02 respectively. There were statistically significant differences in the above indexes between model group and sham group, between experimental group and model group, and between Kae+agonist group, Kae+inhibitor group and experimental group (all P<0.05).

Kaempferol can alleviate flap ischemia-reperfusion injury in rats, and its protective effect may be related to upregulating GPX4 expression, inhibiting ferroptosis, and regulating the NLRP3/Caspase-1/GSDMD pyroptosis signaling pathway.

To investigate the role of the phosphatidyqinositol-3 kinase / protein kinase B / nuclear factor-erythroid 2 related factor 2 (PI3K/Akt/Nrf2) pathway in remifentanil postconditioning-induced protection against myocardial ischemia-reperfusion (IR) injury in rats.

Establishing a rat model of myocardial ischemia-reperfusion injury (MIRI) by left anterior descending coronary artery ligation. Subsequently, the rats were randomly assigned to the following groups: control (only threading was performed without ligation), model (ischemia was induced for 30 minutes followed by 30 minutes of reperfusion), experimental (remifentanil was continuously infused by at a dose of 10 μg·kg^-1·min^-1 from 25 minutes of ischemia to 5 minutes before reperfusion), LY294002 (while receiving remifentanil intervention, 0.3 mg·kg^-1 LY294002 was administered), and ML385 (while receiving remifentanil intervention, 30 mg·kg^-1 ML385 was administered). Serum levels of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Apoptosis index (AI) of myocardial cells in each group was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) were measured using real-time quantitative polymerase chain reaction.

The measured parameters for the control, model, experimental, LY294002, and ML385 groups were as follows. Serum interleukin-6 (IL-6) were 0.76±0.15, 3.44±0.35, 1.46±0.37, 3.17±0.28 and 3.07±0.18. IL-1β were 0.34±0.08, 1.18±0.21, 0.66±0.28, 0.94±0.13 and 0.81±0.25, respectively. Serum tumor necrosis factor-α (TNF-α) were 0.98±0.17, 2.38±0.27, 1.17±0.21, 2.27±0.26 and 2.66±0.16, respectively. Apoptosis index (AI) were 0.95±0.67, 20.73±1.63, 10.20±2.48, 15.69±2.41 and 16.31±1.55, respectively. PI3K mRNA relative expression level were 1.00±0.08, 1.69±0.15, 1.90±0.12, 0.98±0.14 and 1.78±0.13, respectively. Akt mRNA relative expression level were 1.00±0.09, 1.56±0.22, 1.85±0.13, 0.87±0.21 and 1.69±0.31, respectively. Nrf2 mRNA relative expression level were 1.00±0.08, 2.62±0.16, 3.11±0.28, 1.37±0.25 and 1.03±0.14, respectively. Statistically significant differences were observed for all the above parameters when comparing the experimental group with the model group, and when comparing the LY294002 and ML385 groups with the experimental group (P<0.05, P<0.01, P<0.001, P<0.0001).

Remifentanil postconditioning exerts a protective effect on myocardial IR injury by reducing IR-induced cardiomyocyte apoptosis and inflammatory response in rats, and may be related to the PI3K / Akt / Nrf2 signaling pathway.

To establish an ultra-high performance liquid chromatography-tandem mass spectrometry method for the determination of 14 sedative hypnotics and their metabolites in serum and urine.

Serum or urine samples were treated with acetonitrile to precipitate proteins. Separated on an Agilent EclipsePlus C18 RRHD column, the liquid was eluted with 0.1% formic acid in water and methanol, at a flow rate of 0.30 mL·min^-1 and column temperature of 35 ℃. Quantified by the internal standard method, and multiple reaction monitoring (MRM) was performed by electrospray ionization (ESI⁺). The method was evaluated for specificity, standard curves and limits of quantification, precision and recovery, matrix effects, and stability. This method was applied to test the proficiency testing samples from the 2023 National Medical Emergency Toxicant Detection Laboratory Comparison Program, including qualitative and quantitative test samples for emergency poisoning assessment of sedative-hypnotic drugs in serum.

The method demonstrated good specificity, with no cross-interference between the various sedative hypnotics and their metabolites. The linear range of 14 sedative hypnotics and metabolites were 1.00-45.00 μg·L^-1, with a correlation coefficient greater than 0.998 2, the detection limit in serum and urine was 0.30 μg·L^-1, and the quantification limit was 1.00 μg·L^-1. In serum, recovery rates at three spiked levels (10.00, 50.00 and 200.00 μg·L^-1) ranged from 85.60% to 105.20%, with relative standard deviations (RSD) between 0.73% and 4.45%. In urine, recovery rates ranged from 88.93% to 108.12%, with relative standard deviations between 0.50% and 6.92%. Fluphenazine hydrochloride and clozapine were identified by this method. The two determined quantitative concentrations of fluphenazine hydrochloride were 339.00 μg·L^-1 and 349.00 μg·L^-1 , with an average value of 344.00 μg·L^-1 and a deviation of 2.90%. The two determined quantitative concentrations of clozapine were 1 668.00 μg·L^-1 and 1 707.00 μg·L^-1 , with an average value of 1 688.00 μg·L^-1 and a deviation of 2.30%. The final feedback result was satisfactory.

This method is rapid and accurate, making it suitable for emergency poisoning detection of sedative hypnotics. Its application to the blind sample detection of emergency poisoning cases is satisfactory.

To conduct data mining on tepotinib-associated adverse drug events (ADEs) using the US FDA Adverse Event Reporting System (FAERS) database, providing evidence for its clinical safety.

ADE reports for tepotinib from FAERS (Q1 2021 to Q4 2024) were analyzed. Signal detection methods included the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Multi-item Gamma Poisson Shrinker (MGPS). Sex-based differences in ADE signals were assessed using Fisher’s exact test with Bonferroni correction.

A total of 523 ADE reports identified tepotinib as the primary suspect drug, revealing 37 positive Preferred Terms (PT) across 14 System Organ Classes (SOCs). Notably, ADEs involving the ear and labyrinth disorders, infections and infestations, and nervous system disorders were not documented in the drug label. Several PTs—including malignant pleural effusion, infectious pleural effusion, central nervous system metastasis, pneumothorax, deafness, pericardial effusion, and dysgeusia—were newly identified as potential risks. Sex-stratified analysis showed higher diarrhea risk in women and a stronger appetite loss association in men. Importantly, interstitial lung disease (ILD) exhibited a significant signal in men (ROR=16.28, ROR025=8.71) but not in women, suggesting sex may be a key risk factor for tepotinib-induced ILD.

Clinicians should prioritize monitoring high-frequency, high-signal, and newly detected ADEs during tepotinib therapy. The drug label should be updated to include sex-specific ILD risk warnings.

Based on the adverse event reporting system (FAERS) database of the US Food and Drug Administration (FDA), drugs related to pseudomembranous colitis (PMC) were identified to provide a reference for clinical safe medication.

Extract the reports of drug-related adverse events (AEs) of PMC from the FAERS database for the period from the first quarter of 2004 to the fourth quarter of 2024. Risk signal detection was performed using the reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods. Analysis was conducted on the top 20 drugs in terms of the number of reports and the top 20 drugs in terms of signal values.

A total of 18 356 cases of drug induced PMC were retrieved, and 485 drugs with positive risk signals were identified. The proportion of females was the highest, accounting for 52.09% (9 562 cases/18 356 cases). The number of patients over 60 years old was the largest, accounting for 36.88% (6 769 cases/18 356 cases). Among drug-related diagnoses, Crohn’s disease accounted for 5.67% (1 040 cases/18 356 cases) and ulcerative colitis for 5.53% (1 016 cases/18 356 cases), with a larger number of cases. Among the patient outcomes, the hospitalization-initial or prolonged rate was the highest, accounting for 50.43% (9 257 cases/18 356 cases). Among the top 20 drugs by number of reports, infliximab ranked first. According to the ATC classification, antineoplastic and immunomodulating agents and anti-infectives for systemic use were the most numerous, each accounting for 30% (6 varieties/20 varieties), among which vedolizumab was not mentioned PMC in the label. In the top 20 drugs ranked by ROR signal intensity, anti-infective drugs accounted for the highest proportion of 60% (12 varieties/20 varieties), and belladonna was not mentioned in relation to PMC in the label.

A variety of drugs can cause PMC. Clinicians should remain vigilant, promptly perform diagnostic evaluations, discontinue the offending drugs, and initiate appropriate treatment to ensure medication safety.

To explore the efficacy of eravacycline combined with colistimethate sodium in treating sepsis caused by carbapenem-resistant Escherichia coli producing New Delhi metallo-β-lactamase (NDM) secondary to complex intra-abdominal infection.

The anti-infection regimen was dynamically adjusted according to abdominal-pelvic enhanced MRI, laboratory tests, changes in main inflammatory indicators (peripheral blood white blood cell count and procalcitonin), and drug sensitivity test results.

After 13 days of treatment with eravacycline (50 mg, q12h) and colistimethate sodium (150 mg, q12h), the patient's condition and inflammatory indicators improved significantly, with no drug-related adverse reactions during hospitalization.

The combination is safe and effective for the above-mentioned sepsis, providing crucial technical support for clinical treatment of NDM-producing carbapenem-resistant Escherichia coli infections.

To analyze the strengths and weaknesses of China’s R&D in obesity/overweight drug clinical trials by comparing domestic and international trial characteristics, and put forward suggestions based on national conditions.

Clinical trial data of drugs for overweight/obesity were retrieved from ClinicalTrials.gov (CT.gov) and the China Drug Clinical Trial Registration and Information Disclosure Platform (Registration Platform), and divided into a domestic trial group and an international trial group. A bibliometric method was used for comparative analysis from the dimensions of drug type, dosage form, trial design, number of trials, age, gender, and sample size.

Domestically, chemical drugs dominated (77.57%, 211 cases/271 cases), while international trail chemical drugs (51.30%, 256 cases/499 cases) and biological products (48.30%, 241 cases/499 cases) developed balancedly. Domestic trials focused on tablets (46.32%, 126 cases/271 cases) and injections (47.06%, 128 cases/271 cases), whereas international trials were dominated by injections (57.52%, 287 cases/499 cases) (P<0.001). Domestic randomization rate (92.25%, 250 cases/271 cases) was much higher than overseas (79.56%, 397 cases/499 cases), but blinding application was lower (44.65%, 121 cases/271 cases vs. 65.33%, 326 cases/499 cases). Few domestic trials included children (1.11%, 3 cases/271 cases), with only 3 female-specific studies.

Global obesity/overweight drug trials are mainly in China and the US, but China lags behind with unbalanced structure and insufficient population representativeness. China should improve R&D level through policy incentives and international cooperation based on clinical needs.

Investigator initiated trial (IIT) contracts serve as critical legal documents defining the rights and responsibilities of all parties involved in clinical research. This study systematically analyzed issues identified during the review of IIT contracts at a medical institution, explored the underlying causes, and proposed targeted risk prevention and control measures.

A retrospective analysis was conducted on IIT contracts reviewed at a medical institution from January and December 2025. Common issues identified during contract review were summarized and categorized. Distribution patterns and contributing factors were systematically examined.

A total of 96 IIT contracts were reviewed and 917 issue instances were identified. These issues were primarily categorized as follows: legal rights and responsibilities (36.86%, 338 cases/917 cases), protection of research participants’ rights and ethics (6.22%, 57 cases/917 cases), resources and funding management (17.78%, 163 cases/917 cases), data and intellectual property (20.72%, 190 cases/917 cases) and risks associated with human genetic resources (18.43%, 169 cases/917 cases). These issues posed potential risks for medical disputes, commercial bribery, and administrative penalties. Consequently, this study proposed core risk prevention strategies including defining key stakeholder responsibilities, strengthening participant protection, optimizing the management of research funding and conflicts of interest, establishing robust frameworks for intellectual property protection and data privacy, and enforcing strict oversight of human genetic resources.

IIT contracts management requires strengthened review of key elements and establishment of a comprehensive contract management system. The findings provide a practical reference for medical institutions to optimize IIT contract management, thereby supporting the high quality development of clinical research.