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 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.

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.

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 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 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 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.