To observe the clinical efficacy and safety of denosumab injection combined with teriparatide injection in patients with osteoporotic fractures after percutaneous kyphoplasty (PKP).

Patients with osteoporotic fractures treated with PKP in our hospital were divided into treatment group and control group according to different medication regimens. On the basis of conventional treatment, the control group was subcutaneously injected with teriparatide injection at a dose of 20 μg once daily for consecutive 12 months. The treatment group was additionally subcutaneously injected with denosumab injection on the basis of the control group’s regimen, at a dose of 60 mg once every 6 months, with a total of 2 administrations. The clinical efficacy, bone mineral density (BMD), bone metabolism indicators, pain relief and functional recovery status and incidence of refracture, and safety evaluation were compared between the two groups.

A total of 108 patients were enrolled, including 53 in control group and 55 in treatment group. After treatment, the total effective rate was 90.91% (50 cases/55 cases) in treatment group and 75.47% (40 cases /53 cases) in control group; lumbar vertebrae L_2-4 BMD levels were (0.88±0.13) and (0.82±0.11) g·cm^-2, respectively; femoral neck BMD levels were (0.81±0.14) and (0.75±0.13) g·cm^-2, respectively; greater trochanter BMD levels were (0.69±0.08) and (0.65±0.08) g·cm^-2, respectively; total hip BMD levels were (0.85±0.16) and (0.78±0.16) g·cm^-2, respectively; the receptor activator of nuclear factor-κB ligand (RANKL) levels were (4.82±1.24) and (5.53±1.29) pg·mL^-1, respectively; total procollagen type Ⅰ N-terminal propeptide (T-P1NP) levels were (44.93±9.12) and (40.58±8.95) ng·mL^-1, respectively; β-cross-linked C-telopeptide of type 1 collagen (β-CTX) levels were (0.38±0.08) and (0.43±0.07) ng·mL^-1, respectively; N-terminal midfragment of osteocalcin (N-MID) levels were (19.32±2.97) and (17.93±2.59) ng·mL^-1, respectively; the visual analog scale (VAS) scores were (1.88±0.66) and (2.16±0.55) points, respectively; the oswestry disability index (ODI) scores were (10.83±1.73) and (12.12±2.89) points, respectively; the incidence of refracture within 1 year of treatment was 0% (0 cases/55 cases) and 9.43% (5 cases /53 cases). The aforementioned indicators showed statistically significant differences between the two groups (P<0.05, P<0.01). The main adverse drug reactions in treatment group include nausea, muscle pain and injection site reactions; the control group included nausea, muscle pain, palpitations and injection site reactions, and both groups had mild adverse drug reactions. The total incidence of adverse drug reactions in treatment group and control group were 12.73% (7 cases/55 cases) and 9.43% (5 cases/53 cases), respectively, with no statistically significant difference (P>0.05).

Denosumab injection combined with teriparatide injection in the treatment of patients with osteoporotic fractures after PKP surgery can significantly improve clinical efficacy and bone density, promote bone formation, reduce the recurrence of fractures, and has favorable safety.

To observe the clinical efficacy and safety of folic acid tablets combined with vitamin B₆ tablets as an adjuvant therapy for obese patients with polycystic ovary syndrome (PCOS).

Obese PCOS patients admitted to our hospital were divided into treatment group and control group according to the medication plan. The control group was treated with ethinylestradiol and cyproterone acetate tablets (taken orally before bedtime every night), metformin hydrochloride tablets (0.25 g, taken orally before breakfast and dinner), and orlistat capsules (60 mg, twice a day). The treatment group was treated with folic acid tablets (5 mg, once a day) and vitamin B₆ tablets (10 mg, once a day) in addition to control group. Compare clinical efficacy, glucose metabolism indicators, reproductive endocrine hormones, mean ovarian volume (MOV), mean number of follicles (MFN), inflammatory factors, serum homocysteine (Hcy), triglyceride (TG) levels and body measurement parameters between two groups, and evaluate their safety.

A total of 150 patients were included, with 73 in treatment group and 77 in control group. The total effective rates of treatment and control group were 90.41% (66 cases/73 cases) and 77.92% (60 cases/77 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, the fasting plasma glucose (FPG) levels of treatment group and control group were (4.42±0.58) and (4.66±0.53) mmol·L^-1, respectively; the fasting insulin (FINS) levels were (9.16±1.77) and (10.03±2.06) mIU·L^-1, respectively; the homeostatic model assessment of insulin resistance (HOMA-IR) levels were 1.80±0.46 and 2.08±0.65, respectively; the anti-Müllerian hormone (AMH) levels were (4.03±1.19) and (4.63±1.32) ng·mL^-1, respectively; the inhibin B (INHB) levels were (102.33±14.54) and (108.81±17.63) pg·mL^-1, respectively; the MOV levels were (7.36±1.88) and (6.77±1.24) cm³, respectively; the numbers of MFN were (8.89±1.86) and (8.24±1.45) cell, respectively; the interleukin-6 (IL-6) levels were (16.87±3.22) and (18.34±3.67) pg·mL^-1, respectively; the tumor necrosis factor-alpha (TNF-α) levels were (10.19±3.06) and (11.83±3.22) pg·mL^-1, respectively; the Hcy levels were (14.78±3.52) and (16.16±3.64) μmol·L^-1, respectively; the TG levels were (3.49±0.61) and (4.15±0.66) mmol·L^-1, respectively; the body mass index (BMI) levels were (31.09±3.06) and (32.16±3.17) kg·m^-2, respectively; the body fat percentages were (31.42±3.24)% and (32.89±3.38)%, respectively; and the waist-to-hip ratio (WHR) levels were 0.92±0.21 and 1.01±0.26, respectively. There were statistically significant differences in the above indicators between treatment group and control group (P<0.05, P<0.01). The adverse drug reactions in treatment group were gastrointestinal discomfort, while those in control group were headache. The overall incidence rates of adverse drug reactions in treatment and control groups were 1.37% (1 case/73 cases) and 2.60% (2 cases/77 cases), respectively, with no statistically significant difference (P>0.05).

The adjuvant treatment of PCOS with folic acid combined with vitamin B₆ tablets has good clinical efficacy and safety. It can significantly reduce the levels of serum Hcy in patients and improve the insulin resistance status and lipid metabolism of patients.

To observe the clinical efficacy and safety of local infiltration of levobupivacaine injection combined with tranexamic acid injection in patients undergoing posterior lumbar interbody fusion.

Patients undergoing posterior lumbar interbody fusion surgery in our hospital were divided into treatment group and control group based on the local infiltration medication regimen postoperatively. The control group received 20 mL of normal saline for local infiltration, and the treatment group received 20 mL of a mixed solution containing levobupivacaine injection (concentration 0.25%, 37.5 mg diluted to 15 mL) and tranexamic acid injection (concentration 10%, 0.2 g diluted to 5 mL). The two groups were compared in terms of visual analogue scale (VAS) scores at rest and during activity at 2, 6, 12, 24 and 48 hours postoperatively, postoperative rescue analgesia rate, serum inflammatory markers, stress indicators at 24 hours postoperatively, postoperative recovery indicators, and safety evaluation was conducted.

A total of 92 patients were finally enrolled, with 48 in control group and 44 in treatment group. After treatment, the resting VAS scores at 48 hours postoperatively in control group and treatment group were (1.75±0.44) and (1.55±0.50) points, respectively; the activity VAS scores were (2.54±0.50) and (2.32±0.47) points, respectively; the interleukin-6 (IL-6) levels at 24 hours postoperatively were (57.02±5.15) and (54.23±4.52) pg·mL^-1, respectively; the tumor necrosis factor-α (TNF-α) levels were (34.12±5.40) and (30.88±5.13) pg·mL^-1, respectively; the S100 calcium-binding protein B (S100β) levels were (110.78±9.66) and (104.13±10.54) pg·mL^-1, respectively; the serum cortisol (Cor) levels were (95.87±14.69) and (89.43±13.73) ng·mL^-1, respectively; the norepinephrine (NE) levels were (369.43±51.81) and (342.86±48.13) ng·mL^-1, respectively; the advanced oxidation protein products (AOPP) levels were (66.19±12.36) and (58.97±11.74) μmol·L^-1, respectively; the rescue analgesia rates at 0-11 h postoperatively were 33.33% (16 cases/48 cases) and 13.64% (6 cases /44 cases), respectively; and at 12-24 h were 22.92% (11 cases /48 cases) and 6.82% (3 cases /44 cases), respectively; the first ambulation time were (2.79±0.62) and (2.48±0.55) days, the first flatus time were (30.79±5.35) and (28.02±5.20) hours, the hospital stay were (7.38±1.44) and (6.66±1.29) days, respectively; and the quality of recovery-15 (QoR-15) score at postoperative day 3 were (116.69±7.42) and (121.66±8.72) points, respectively; statistically significant differences were observed in all the above indicators between the two groups (all P<0.05). The adverse drug reactions in treatment group included nausea and vomiting, fever and urinary retention, while those in control group included fever, nausea and vomiting, urinary retention and pruritus. The overall incidence of adverse drug reactions in treatment group and control group were 9.09% (4 cases/44 cases) and 14.58% (7 cases/48 cases), respectively; complications included poor wound healing, with incidence rates of 2.27% (1 case/44 cases) and 2.08% (1 case/48 cases), respectively, with no statistically significant differences between the groups (P>0.05, P>0.01).

In posterior lumbar interbody fusion, local infiltration of levobupivacaine injection combined with tranexamic acid injection around the incision provides more effective and sustained postoperative analgesia, significantly reduces systemic inflammation and stress response, promotes early postoperative rehabilitation, shortens hospital stay, and does not increase the risk of complications.

To investigate the clinical efficacy and safety of general anesthesia induced by benzenesulfonate remimazolam for injection combined with esketamine hydrochloride injection in elderly patients with severe knee osteoarthritis undergoing total knee arthroplasty.

The elderly patients with severe knee osteoarthritis undergoing total knee arthroplasty were divided into control group and treatment group according to the method of anesthesia induction. The treatment group received intravenous injection of 0.1 mg·kg^-1 benzenesulfonate remimazolam for injection combined with 0.5 mg·kg^-1 esketamine hydrochloride injection for anesthesia induction. The control group received 0.05 mg·kg^-1 midazolam injection combined with 1 mg·kg^-1 propofol emulsion injection for anesthesia induction. The other anesthesia methods were consistent between the two groups. The recovery time, hemodynamics, postoperative pain score (VAS), postoperative sedation score (Ramsay sedation scale), anxiety and depression score (HAD), mini-mental state examination score (MMSE), incidence of delirium (POD) and adverse anesthetic events were compared between the two groups.

A total of 232 patients were enrolled, with 115 cases in control group and 117 cases in treatment group. The recovery time of the control group and the treatment group were (26.30±4.84) and (24.52±4.66) min, respectively; heart rate after induction were (71.84±4.17) and (73.58±4.36) beats·min^-1, respectively; heart rate at the end of operation were (74.59±4.46) and (76.13±4.32) beats·min^-1, respectively; mean arterial pressure after induction were (81.90±5.69) and (84.11±5.72) mmHg, respectively; mean arterial pressure at the end of operation were (86.73±5.57) and (88.51±6.42) mmHg, respectively; VAS scores at 6 h after operation were (3.77±0.54) and (3.53±0.69) points, respectively; VAS scores at 12 h after operation were (3.21±0.64) and (3.00±0.66) points, respectively; the postoperative 1-hour Ramsay sedation scores were (3.82±0.66) and (3.21±0.57) points, respectively, and the postoperative 6-hour Ramsay scores were (2.65±0.48) and (2.31±0.46) points, respectively; at 3 d after operation, HAD-A scores were (10.53±1.86) and (9.94±1.73) points, respectively; HAD-D scores were (10.56±2.10) and (9.86±2.05) points, respectively; MMSE scores were (21.34±1.82) and (22.22±1.93) points, respectively; within 7 d after operation, the incidences of POD were 15.65% (18 cases/115 cases) and 6.84% (8 cases/117 cases), respectively; during anesthesia induction, the incidence of adverse drug reactions were 20.87% (24 cases/115 cases) and 9.40% (11 cases/117 cases), respectively. The differences of above indicators were all statistically significant comparing between the two group (P<0.05,P<0.01). The main adverse drug reactions during the anesthesia induction period in treatment group and control group included hypotension, hypertension, bradycardia and tachycardia.

Compared with the regimen of midazolam injection combined with propofol emulsion injection, the regimen of benzenesulfonate remimazolam for injection combined with esketamine hydrochloride injection for anesthesia induction can shorten recovery time, maintain stable hemodynamics, improve analgesic effect, relieve anxiety and depression, improve cognitive function, and have good safety.

To observe the clinical efficacy and safety of capecitabine tablets combined with oxaliplatin for injection (XELOX) in the treatment of gastric cancer.

Patients with stage Ⅱ gastric cancer who underwent D2 radical surgery in the hospital were divided into control group and treatment group by the random number table method. Starting at 4 weeks postoperatively, the control group was administered tegifur capsules with dosage adjusted based on body surface area of 40 or 60 mg, taken twice daily for 14 consecutive days, followed by a 1-week break, with each 21-day cycle repeated for 8 consecutive cycles. The treatment group received 130 mg·m^-2 of intravenous oxaliplatin on the first postoperative day, followed by capecitabine tablets at 1 000 mg·m^-2 per dose, twice daily from days 1 to 14, followed by a 1-week break, with each 21-day cycle repeated for 8 consecutive cycles. The carcinoembryonic antigen (CEA), carbohydrate antigen 72-4 (CA72-4), carbohydrate antigen 19-9 (CA19-9), microRNA-34a (miR-34a), disease-free survival (DFS) and overall survival (OS) were compared between the two groups, and the safety evaluation was performed.

A total of 150 patients were screened, and 130 cases were enrolled in the trial, including 65 cases in control group (with 5 dropouts) and 65 cases in treatment group (with 5 dropouts). Ultimately, 60 patients from each group were included in the statistical analysis. After 8 cycles of treatment, CEA levels in treatment group and control group were (4.83±1.22) and (6.33±1.14) ng·mL^-1, CA19-9 levels were (24.33±3.58) and (28.86±4.18) U·mL^-1, CA72-4 levels were (5.48±1.22) and (7.27±1.55) μg·L^-1, the relative expression levels of miR-34a were 2.57±0.45 and 2.13±0.42, respectively. Compared with control group, the aforementioned indicators in treatment group showed statistically significant differences (all P<0.05). The median DFS values in treatment group and control group were 56 and 48 months, respectively, and the difference in DFS survival curve between the two groups was statistically significant (P<0.05); the median OS values were 62 and 60 months, respectively, and there was no statistically significant difference between the two groups (P>0.05). Adverse drug reactions in treatment group included leukopenia, thrombocytopenia and peripheral neurotoxicity, while those in control group included leukopenia and thrombocytopenia. The incidence rates of peripheral neurotoxicity in treatment group and control group were 6.67% (4 cases/60 cases) and 0% (0 cases /60 cases), the incidence rates of hand-foot syndrome were 21.67% (13 cases/60 cases) and 0% (0 cases/60 cases), the incidence rates of grade ≥ Ⅲ leukopenia were 16.67% (10 cases /60 cases) and 5.00% (3 cases /60 cases), the incidence rates of grade ≥ Ⅲ thrombocytopenia were 8.33% (5 cases /60 cases) and 0% (0 cases /60 cases), respectively. The incidence rates of the aforementioned adverse drug reactions in treatment group were statistically significantly different from those in control group (all P<0.05).

The application of XELOX regimen as postoperative adjuvant chemotherapy for stage Ⅱ gastric cancer can effectively improve the levels of tumor markers and prolong the DFS, and has more obvious advantages compared to tegafur capsule gimeracil oteracil potassium single-drug regimen, but the adverse drug reactions are also more obvious.

To observe clinical features of programmed cell death protein-1 (PD-1) inhibitor-induced liver injury in tumor patients and analyze its influencing factors.

Tumor patients treated with PD-1 inhibitors were enrolled. The clinical data were analyzed. The occurrence of liver injury during treatment was assessed according to CTCAE V5.0 criteria. Clinicopathological features of patients with liver injury were summarized. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for liver injury in tumor patients, and a nomogram prediction model was constructed receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were employed to evaluate validity of the model.

The incidence of PD-1 inhibitor-induced liver injury among the 310 patients enrolled was 11.94% (37 cases/310 cases). Grade 1, grade 2, grade 3 and grade 4 liver injuries were observed in 12 cases (32.43%), 15 cases (40.54%), 8 cases (21.62%) and 2 cases (5.41%), respectively. Clinical types included cholestatic type in 23 cases (62.16%), abnormal liver biochemistry type in 12 cases (32.43%), and hepatocellular injury type in 2 cases (5.41%). The median time to the occurrence of liver injury was 28.50 (5.00-217.00) d. After drug withdrawal or symptomatic treatment, liver function recovered, and the mean recovery time was (21.45±6.94) d. Multivariate logistic regression analysis found female gender [odds rotio (OR)=2.36, 95% confidence interval (CI)=1.11-4.99], history of comorbid liver disease (OR=2.62, 95%CI=1.10-6.24), and liver metastasis (OR=3.10, 95%CI=1.28-7.49) as independent risk factors influencing the occurrence of liver injury in tumor patients (all P<0.05). ROC analysis showed that the area under curve (AUC) (95%CI) of the nomogram prediction model for predicting liver injury was 0.86 (0.82-0.90), with sensitivity of 78.38% and specificity of 83.52%. Hosmer-Lemeshow test showed good goodness-of-fit (χ²=12.58, P>0.05). Validation with Bootstrap revealed good agreement between the calibration curve and the actual curve (Brier score=0.09). DCA demonstrated that the nomogram prediction model provided clinical benefit when the threshold was between 0.05 and 0.99.

PD-1 inhibitor-induced liver injury is relatively common in tumor patients. Female gender, history of liver disease and liver metastasis are associated with its occurrence. The nomogram prediction model constructed based on these factors exhibits good predictive performance and can provide reference for early identification of high-risk patients.

To investigate the effect and mechanism of liraglutide on cisplatin-induced acute kidney injury in renal tubular epithelial (HK-2) cells.

HK-2 cells were randomly divided into control group, model group and experimental group. The control group was cultured conventionally, the model group was treated with 20 μmol·L^-1 cisplatin reagent for 48 hours, and the experimental group was treated with 100 nM liraglutide reagent in addition to the model group for 48 hours. Cell proliferation activity was detected by cell counting kit-8 (CCK-8) method. Western blot was used to detect cysteine-aspartic acid protease 3 (Caspase 3), cleaved cysteine-aspartic acid protease 3(C-Caspase3), B cell lymphoma-2 (Bcl-2) associated X protein (BAX), nuclear factor E2 related factor 2 (Nrf-2), superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1) and reference β-actin protein relative expression levels; the relative expression levels of kidney injury molecule-1 (Kim-1), BAX and Bcl-2 related messenger ribonucleic acid (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction, and cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dutP nick end labeling (TUNEL). Reactive oxygen species (ROS) levels were measured by superoxide anion fluorescent probe (DHE).

CCK-8 assay showed that 100 nmol·L^-1 was the optimal intervention concentration of liraglutide. After 48 hours of intervention, the relative expression levels of K1M-1 mRNA in control group, model group and experimental group were 0.98±0.25, 56.23±23.25 and 2.61±0.79, respectively; BAX /Bcl-2 mRNA relative expression levels were 1.01±0.08, 15.47±3.01 and 5.41±0.54, respectively; the apoptosis rates were (5.60±0.40)%, (40.00±4.79)% and (6.40±0.87)%, respectively; the fluores cence value of positive rates of DHE were 1.95±0.03, 3.01±0.28 and 1.51±0.13, respectively; the relative expression levels of Nrf-2 protein were 0.80±0.01, 0.47±0.01 and 0.68±0.02, respectively; the relative expression levels of SOD2 protein were 0.96±0.04, 0.57±0.28 and 0.91±0.04, respectively; the relative expression levels of HO-1 were 1.01±0.08, 0.47±0.05 and 1.56±0.18, respectively. There were statistically significant differences in the above indicators between model group and control group, and between experimental group and model group (P<0.05, P<0.01, P<0.001, P<0.000 1).

Liraglutide can reduce the apoptosis rate and oxidative stress level of renal tubular epithelial cells in cisplatin-induced acute kidney injury, and increase the level of superoxide.

To investigate the effects and mechanism of naringenin inhibiting the non-receptor tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway on the proliferation and apoptosis of esophageal cancer cells.

The effects of different doses of naringenin on KYSE150 cell viability was screened using cell counting kit-8 (CCK-8), and naringenin concentration was selected. KYSE150 cells were sequentially divided into control group (conventional culture), low-dose experimental group (10 μmol·L^-1 naringenin), high-dose experimental group (40 μmol·L^-1 naringenin), JAK2/STAT3 pathway inhibitor group (20 μmol·L^-1 AG490) and JAK2/STAT3 pathway activator group (40 μmol·L^-1 naringenin and 10 μmol·L^-1 coumermycin A1). The 5-bromo-2 ’- deoxyuridine (Brdu) positive cell rate was detected using the Brdu staining method, the number of cell clones formed was detected using the clone formation assay, the expression of proliferation and apoptosis related genes was detected using reverse transcription real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), the apoptosis rate was detected using flow cytometry, the terminal deoxynucleotide transferase mediated 2’-deoxyuridine-5’- triphosphate notch end labeling (TUNEL) positive rate was detected using the TUNEL staining method, the expression of JAK2/STAT3 pathway related proteins was detected using Western blot, and the effect of naringenin on the growth of KYSE150 xenograft tumors Ki-67 nuclear antigen (Ki67) and tumor tissues growth in nude mice was detected using immunohistochemistry.

The half maximal inhibitory concentration of naringenin on KYSE150 cell viability is close to 40 μmol·L^-1. The Brdu positivity rates of KYSE150 cells in control group, low-dose experimental group, high-dose experimental group, JAK2/STAT3 pathway inhibitor group and JAK2/STAT3 pathway activator group were (58.64±5.23)%, (46.23±4.05)%, (21.05±3.04)%, (23.62±3.15)% and (35.98±3.21)%, respectively; the clone formation numbers were (102.36±10.25), (78.64±7.21), (50.05±4.32), (52.39±5.03) and (61.55±5.12) cells, respectively; the relative expression levels of CyclinB1 messenger ribonucleic aeid (mRNA) were 1.02±0.11, 0.74±0.05, 0.45±0.04, 0.48±0.05 and 0.62±0.06, respectively; the relative expression levels of cyclin dependent kinase 1 (CDK1) mRNA were 1.03±0.07, 0.62±0.05, 0.27±0.03, 0.30±0.04 and 0.51±0.04, respectively; the apoptosis rates were (4.15±0.42)%, (15.62±1.02)%, (29.65±2.03)%, (27.84±1.98)% and (19.66±1.20)%, respectively; the positive rates of TUNEL were (8.65±0.82)%, (20.64±2.03)%, (37.68±3.05)%, (35.62±2.16)% and (28.14±2.01)%, respectively; the relative expression levels of Bcl-xl mRNA were 1.02±0.07, 0.72±0.06, 0.41±0.04, 0.44±0.05 and 0.59±0.05, respectively; the relative expression levels of Bcl-2 mRNA were 1.01±0.05, 0.59±0.04, 0.36±0.03, 0.39±0.04 and 0.50±0.03, respectively. Compared control group with low-dose experimental group, high-dose experimental group and JAK2/STAT3 pathway inhibitor group, compared low-dose experimental group with high-dose experimental group and JAK2/STAT3 pathway inhibitor group, compared high-dose experimental group with JAK2/STAT3 pathway activator group, the above indicators all showed statistically significant differences (all P<0.05). In nude mouse experiments, the tumor volumes of animal control group, animal low-dose experimental group and animal high-dose experimental group were (1 287.65±98.54), (821.22±71.65) and (425.39±37.69) mm³, respectively; the tumor masses were (1.85±0.12), (1.20±0.09) and (0.73±0.05) g, respectively; the Ki67 positivity rates in tumor tissues were (69.52±5.36)%, (44.35±3.12)% and (20.06±2.85)%, respectively. The above indicators of the animal low and high-dose experimental groups were statistically significantly different from those of animal control group, and the above indicators of the animal high-dose experimental group were statistically significantly different from those of animal low-dose experimental group (all P<0.05).

Naringenin clearly inhibits the proliferation and promotes apoptosis of esophageal cancer KYSE150 cells by suppressing the JAK2/STAT3 signaling pathway.

To investigate the mechanism of esketamine (Esk) ameliorating postpartum depression (PPD)-like behaviors in mice by regulating the two pore domain potassium channel (TWIK)-related K⁺ channel 1(TREK-1) to activate the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, and to provide experimental evidence for clarifying the pathogenesis of PPD and developing novel targeted therapeutic strategies.

A total of 50 C57BL/6J pregnant mice were randomly divided into five groups (n=10 per group): control group, model group, experimental group, oe-NC group and oe-TREK-1 group. A PPD model was established in pregnant mice using the chronic unpredictable mild stress (CUMS) method. The control group was given an equal volume of normal saline; the model group was given normal saline after CUMS modeling; the experimental group was intraperitoneally injected with Esk (5 mg·kg^-1) once daily for 3 weeks after modeling; the oe-NC group was injected with lentivirus-encapsulated oe-NC by the tail vein before modeling and subsequent Esk administration; the oe-TREK-1 group was injected with lentivirus-encapsulated oe-TREK-1 by the tail vein before modeling and subsequent Esk administration. Depressive-like behaviors were evaluated using the sucrose preference test (SPT) and tail suspension test (TST). Hematoxylin-eosin (HE) staining and Nissl staining were used to observe the pathological morphology of hippocampal tissue; real-time fluorescent quantitative polymerase chain reaction and Western blotting were employed to detect the relative expression levels of TREK-1 in hippocampal tissue; enzyme-linked immunosorbent assay was utilized to measure the expression levels of serum sex hormones; immunohistochemistry was adopted to detect the expression of microglial marker proteins; Western blotting was used to determine the relative expression levels of endoplasmic reticulum stress-related proteins; immunofluorescence was applied to detect the relative expression levels of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB).

The sucrose preference rates in the control, model, experimental, oe-NC and oe-TREK-1 groups were (84.74±14.46)%, (19.08±2.86)%, (79.62±12.54)%, (80.15±11.38)% and (52.44±8.15)%, respectively; the immobility time ratios in the tail suspension test were (31.16±4.63)%, (75.38±14.62)%, (49.26±8.59)%, (48.97±7.82)% and (62.53±9.24)%, respectively; the relative expression levels of TREK-1 mRNA in the hippocampal tissues were 1.00±0.15, 2.87±0.45, 1.55±0.21, 1.56±0.19 and 2.18±0.36, respectively; the relative expression levels of TREK-1 protein were 1.00±0.16, 2.75±0.38, 1.86±0.27, 1.84±0.19 and 2.44±0.34, respectively; serum estradiol (E2) levels were (1 263.55±152.77), (638.16±78.32), (985.24±107.48), (981.67±106.34) and (752.33±116.45) pg·mL^-1, respectively; progesterone (P) levels were (9.53±1.06), (3.48±0.59), (8.54±1.07), (8.47±1.04) and (5.62±1.02) ng·mL^-1, respectively; prolactin (PRL) levels were (15.98±2.19), (29.31±4.62), (19.25±2.58), (19.88±2.67) and (23.47±3.46) ng·mL^-1, respectively; the relative expression levels of Iba-1 protein in the hippocampus were 1.00±0.16, 0.35±0.05, 0.87±0.14, 0.85±0.13 and 0.61±0.11, respectively; the relative expression levels of GRP78 protein were 1.00±0.17, 1.58±0.16, 1.17±0.14, 1.09±0.18 and 1.35±0.17, respectively; the relative expression levels of CHOP protein were 1.00±0.14, 1.71±0.23, 1.13±0.16, 1.11±0.12 and 1.34±0.18, respectively; the relative expression levels of Cleaved caspase-12 protein were 1.00±0.16, 1.45±0.19, 1.19±0.13, 1.16±0.12 and 1.38±0.16, respectively; the relative fluorescence intensities of BDNF were 1.00±0.16, 0.38±0.06, 0.84±0.09, 0.83±0.11 and 0.64±0.08, respectively; the relative fluorescence intensities of TrkB were 1.00±0.17, 0.57±0.09, 0.92±0.14, 0.91±0.12 and 0.75±0.11, respectively. Statistically significant differences were observed in the above indicators between the model group and the control group, between the experimental group and the model group, and between the oe-TREK-1 group and the oe-NC group (P<0.05, P<0.01, P<0.001).

Esketamine can alleviate PPD-like behaviors in mice by inhibiting TREK-1 expression, regulating sex hormone balance, improving microglial function and endoplasmic reticulum stress, and thereby activating the BDNF/TrkB pathway.

To investigate the potential targets and pathways of eupalinolide B (EB) in doxorubicin (DOX)-induced dilated cardiomyopathy (DCM), and to verify EB inhibits cardiomyocyte apoptosis and inflammatory response by regulating the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway.

Database screening was used to identify the intersecting targets of EB and DCM, followed by functional and pathway enrichment analyses and molecular docking validation. A DCM mouse model was established. The successfully modeled mice were randomly divided into model group, experimental-L group (5 mg·kg^-1 EB), experimental-H group (20 mg·kg^-1 EB), positive control group (5 mg·kg^-1 positive drug captopril), inhibitor group (1 mg·kg^-1 p38 MAPK inhibitor SB203580) and activator group (20 mg·kg^-1 EB+0.10 mg·kg^-1 p38 MAPK activator anisomycin). In addition, normal and healthy mice were selected as the blank group. Each group had 10 mice. After the intervention, cardiac function was detected by echocardiography; serum and myocardial tissues were collected, serum inflammatory factors and myocardial injury markers were measured by enzyme-linked immunosorbent assay (ELISA); pathological damage, fibrosis and cell apoptosis of myocardial tissue were detected by hematoxylin and eosin (HE) staining, Masson staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; the expression of apoptosis-related proteins, inflammatory factors, phosphorylation (p-)p38 MAPK and p38 MAPK in myocardial tissue was detected by immunohistochemistry and Western blot.

A total of 34 potential targets of EB and 1 018 DCM-specific targets were screened, and 5 potential targets of EB for DCM treatment were identified, involving the MAPK signaling pathway. The left ventricular fractional shortening (LVFS) values in blank group, model group, experimental-L group, experimental-H group, inhibitor group and activator group were (41.26±0.07)%, (26.60±0.72)%, (30.90±0.29)%, (44.26±1.73)%, (42.62±1.82)% and (33.66±2.74)%, respectively; the N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were (734.85±90.24), (1 509.28±163.17), (1 240.62±157.95), (841.57±88.06), (862.91±87.92) and (1 159.76±125.71) pg·mL^-1, respectively; the B-cell lymphoma-2 (Bcl-2) positive rates were (16.81±1.82)%, (3.02±0.54)%, (6.97±0.86)%, (14.29±1.43)%, (13.51±1.46)% and (8.14±0.95)%, respectively; the Bcl-2-associated X protein (Bax) positive rates were (1.59±0.18)%, (18.37±2.51)%, (12.42±1.63)%, (3.84±0.45)%, (4.09±0.41)% and (11.53±1.28)%, respectively; the relative expression levels of p-p38 MAPK/p38 MAPK were 0.23±0.03, 0.86±0.09, 0.64±0.08, 0.35±0.04, 0.38±0.05 and 0.61±0.08, respectively. Comparisons between model group and blank group, between experimental-L/-H groups or inhibitor group and model group, and between activator groups and experimental-H group, the above indicators all showed statistically significant differences (all P<0.05).

EB may alleviate the myocardial inflammatory response and cardiomyocyte apoptosis in DOX-induced cardiomyopathy mice and improve myocardial damage by inhibiting the phosphorylation of p38 MAPK.