BACKGROUND:Titanium implants are widely used in clinical practice because of their high strength and good biocompatibility.However,during implantation,bacterial infection and tissue damage environment produce a large number of reactive oxygen species,which can easily lead to delayed tissue healing and surgical failure.Consequently,the development of titanium implants with antimicrobial and antioxidant properties becomes paramount. OBJECTIVE:Considering the potent antimicrobial attributes of copper ions and the remarkable antioxidant qualities of polyphenols,we proposed the fabrication of polyphenol-mediated copper ion coatings on titanium surfaces.These coatings were subsequently assessed for their in vitro antimicrobial and antioxidant properties. METHODS:Nanostructures were generated on the titanium surface using the alkali thermal method.The titanium was immersed in a solution containing tannic acid and copper ions to achieve polyphenol-mediated copper ion coatings.The surface morphology and water contact angle were detected.The loading and release of copper ions were examined using atomic absorption spectroscopy.Staphylococcus aureus was inoculated on the surface of pure titanium sheet(blank group),alkali heat treated titanium sheet(control group),and polyphenol mediated copper ion modified titanium sheet(experimental group)to observe the bacterial survival status.Osteoblast precursor cells MC3T3-E1 were co-cultivated on the surface of three groups of titanium sheets to assess their antioxidant properties and bioactivity. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the polyphenol-mediated copper ion modified titanium sheet had rod-like nanostructures and no cracks on the surface.The surface hydrophilicity of copper ion modified titanium sheet mediated by polyphenol was close to that of pure titanium sheet.Atomic absorption spectrometry results showed a 51%increase in the loading capacity of copper ions after polyphenol mediation,with a uniform release of copper ions.(2)The antibacterial rates of titanium sheets in the blank group,control group,and experimental group were 0%,21.65%,and 93.75%,respectively.The live/dead staining and CTC staining showed that the live bacteria on the surface of titanium plates in the blank group were the most,and the live bacteria on the surface of titanium plates in the experimental group were the least.(3)The results of live/dead staining and CCK-8 assay showed that the three groups of titanium sheets had good cytocompatibility,and the titanium sheets in the experimental group were more conducive to the proliferation of MC3T3-E1 cells.Active oxygen fluorescence probe detection exhibited that compared with the other two groups,the fluorescence intensity of active oxygen on the surface of the experimental group was significantly reduced.The results of alkaline phosphatase and alizarin red S staining showed that the osteogenic differentiation and extracellular matrix mineralization of MC3T3-E1 cells on the surface of titanium sheets in the experimental group were stronger than those in the other two groups.(4)These results show that the polyphenol-mediated copper ion coating has strong antibacterial and antioxidant properties and promotes osteogenic differentiation.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

Objective:To investigate the effects and mechanism of metformin on the proliferation and expression of fibrotic proteins of human hypertrophic scar (HS) fibroblasts (Fbs).Methods:The study was an experimental study. From June 2021 to June 2022, 5 patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 3 males and 2 females, aged from 21 to 36 years. HS tissue was collected, Fbs were isolated and cultured, and Fbs of passage 5 to 7 were used for experiment. Fbs were taken and cultured in their respective media supplemented with phosphate buffered solution (PBS) or metformin at final molarities of 5, 10, 20, and 40 mmol/L for 48 hours. The cell proliferation activity was detected using the cell counting kit-8 (CCK-8), and the proliferation inhibition rate of cells was calculated. The content of hydroxyproline in the cell culture supernatant was measured using a hydroxyproline assay kit. The phosphorylation levels of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in the cells were detected by Western blotting, and the ratios of phosphorylated Akt (p-Akt) to Akt and phosphorylated mTOR (p-mTOR) to mTOR were calculated. After 24 hours of culture, the mRNA expressions of type Ⅰ collagen, type Ⅲ collagen, and α-smooth muscle actin (α-SMA) in the cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Another batch of Fbs were divided into control group (with conventional culture), LY294002 group, metformin group, and LY294002+metformin group. LY294002, metformin, and LY294002+metformin were added to the culture media of the last three groups, respectively, with the final molarities of LY294002 and metformin being 20 μmol/L and 10 mmol/L, respectively. CCK-8 was used to detect the cell proliferation activity at 0 (immediately), 24, and 48 hours of culture. After 48 hours of culture, Western blotting was used to detect the phosphorylation levels of Akt and mTOR in the cells, and the ratios of p-Akt to Akt and p-mTOR to mTOR were calculated. The sample size for the cell proliferation inhibition rate experiment was 4, and the sample size for the other experiments was 3.Results:After 48 hours of culture, compared with the cells treated with PBS, the proliferation inhibition rates of the cells treated with 5, 10, 20, and 40 mmol/L metformin were significantly increased (with t values of 10.69, 14.20, 19.73, and 52.54, respectively, P<0.05), the content of hydroxyproline in the culture supernatants of the cells treated with 10, 20, and 40 mmol/L metformin was significantly decreased (with t values of 8.06, 7.86, and 10.25, respectively, P<0.05), and the ratios of p-Akt to Akt in the cells treated with 10, 20, and 40 mmol/L metformin and the ratios of p-mTOR to mTOR in the cells treated with 20 and 40 mmol/L metformin were significantly decreased (with t values of 2.82, 4.28, 9.88, 5.66, and 9.08, respectively, P<0.05). After 24 hours of culture, compared with those treated with PBS, the mRNA expressions of type Ⅰ collagen and α-SMA in the cells treated with 5, 10, 20, and 40 mmol/L metformin and the mRNA expressions of type Ⅲ collagen in the cells treated with 10, 20, and 40 mmol/L metformin were significantly decreased (with t values of 4.35, 8.53, 9.57, 14.77, 4.14, 5.58, 7.89, 9.37, 5.18, 6.85, and 9.15, respectively, P<0.05). At 24 and 48 hours of culture, the proliferation activities of the cells in LY294002 group (with t values of 6.30 and 13.60, respectively) and metformin group (with t values of 6.47 and 10.69, respectively) were significantly lower than those in control group ( P<0.05). After 48 hours of culture, the ratios of p-Akt to Akt in the cells of LY294002 group and metformin group were 0.554±0.027 and 0.681±0.029, respectively, which were significantly lower than 1.053±0.193 in control group (with t values of 4.45 and 3.31, respectively, P<0.05). The ratio of p-Akt to Akt in the cells of LY294002+metformin group was 0.387±0.023, which was significantly lower than that in metformin group ( t=5.95, P<0.05). After 48 hours of culture, the ratio of p-mTOR to mTOR in the cells of LY294002 group was significantly lower than that in control group ( t=4.01, P<0.05), and the ratio of p-mTOR to mTOR in the cells of LY294002+metformin group was significantly lower than that in metformin group ( t=6.05, P<0.05). Conclusions:Metformin can inhibit the proliferation and expression of fibrotic proteins type Ⅰ collagen, type Ⅲ collagen, and α-SMA of human HS Fbs through phosphatidylinositol 3-kinase/Akt/mTOR signaling pathway.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To explore the relationship between systemic immune inflammatory index and ferritin(SF)and the clinicopathologic features and prognosis of gastric cancer(GC).Methods A retrospective analysis was conducted on 152 gastric cancer patients who underwent D2 gastrectomy at the Radiation Oncology Department of Qingbaijiang District People's Hospital in Chengdu from January 2017 to December 2020.Neutrophil count was divided by lymphocyte count to calculate Neutrophil to lymphocyte ratio(NLR).The SF level in plasma was evaluated by ELISA kit.According to the results of multivariate analysis,a new prognosis prediction system including NLR-SF score(NSS)was established.Results Multivariate Cox regression analysis showed that NLR(HR=1.053,95%CI=1.014～1.094,P=0.007),tumor grade(HR=1.944,95%CI=1.279～2.955,P=0.002)and SF(HR=1.005,95%CI=1.002～1.008,P=0.002)were independent factors affecting the prognosis of GC patients.ROC analysis showed that when the cutoff value of SF was 215.5,the AUC of predicting the death of GC patients was 0.800(95%CI=0.731～0.869),the sensitivity was 68.5%,and the specificity was 86.7%.When the cutoff value of NLR was 3.36,the AUC of predicting the death of GC patients was 0.869(95%CI=0.810～0.928),the sensitivity was 81.5%,and the specificity was 91.7%.Higher NSS was significantly correlated with the number of lymph node metastasis>3 cases,the number of deaths,the increase of neutrophil,platelet,SF,NLR and PLR levels(P<0.05),and the decrease of lymphocytes(P<0.05).Kaplan-Meier survival curve analysis showed that the higher the NSS,the shorter the survival time(χ2=75.168,P<0.001).ROC analysis showed that the AUC of NSS in predicting the death of GC patients was 0.902(95%CI=0.852～0.952),the sensitivity was 90.2%,and the specificity was 80.0%.Conclusions This study confirms that NLR and SF are independent prognostic factors of GC patients,and the NSS constructed by combining them is of great value in predicting the overall postoperative survival.

Chronic thromboembolic pulmonary hypertension(CTEPH)is a severe form of pulmonary hypertension(PH),and is classified as the fourth major category of pulmonary arterial hypertension.CTEPH is primarily caused by chronic thrombosis,leading to the obstruction of blood flow in the pulmonary arteries and result ing in a sustained increase in pulmonary artery pressure.The unclear pathogenesis of CTEPH,however,means that its early diagnosis is challenging,treatment options are limited,and prognosis assessment is often inaccurate.In-depth research into these mechanisms will thus improve our understanding of the pathophysiological processes of CTEPH,and also provide a theoretical basis for developing new therapeutic strategies.This review focuses on the current method of establishing CTEPH rat models and their advantages and disadvantages,offering researchers a reference for selecting and constructing CTEPH rat models.

BACKGROUND:Previous studies found that Semen Ziziphi Spinosae extract prolongs slow-wave sleep and promotes growth hormone secretion in mice by increasing the expression of brain tissue serotonin 1A receptor (5-HT1AR),which binds to serotonin,thus leading to bone growth. Serotonin 1A receptor acts as a protein,and its expression abundance is regulated by miRNAs. The authors hypothesized that Semen Ziziphi Spinosae extract may regulate the expression of 5-HT1AR through miRNAs and thus exert drug effects. OBJECTIVE:To observe the effect of Semen Ziziphi Spinosae extract on bone growth by regulating the miR-7b-3p/5-HT1AR pathway in mouse brain tissue. METHODS:(1) Kunming mice were divided into a normal control group,a drug administration group (gavage administration of Semen Ziziphi Spinosae extract 0.320 mg/g),a positive control group (gavage administration of jujuboside 0.013 mg/g),a Semen Ziziphi Spinosae extract+5-HT1AR selective inhibitor group (8 μg of P-MPPF,a 5-HTIAR selective inhibitor,was injected into the lateral ventricle every day for the last 3 days during the gavage administration of Semen Ziziphi Spinosae extract). After 25 days,the effects of Semen Ziziphi Spinosae extract on bone growth,serum growth hormone level and brain 5-HT1AR expression were observed. (2) Then the chip method was used to observe differentially expressed miRNAs in the brain tissues of growing mice and ordinary mice. PCR validation and dual luciferase reporter gene assay confirmed the regulatory relationship between the screened Mir-7B-3p and 5-HT1AR. (3) Mouse cerebral cortical cells were cultured and identified in vitro,and the effect of Semen Ziziphi Spinosae extract on 5-HT1AR expression in cerebral cortical cells was observed using western blot. (4) Kunming mice were divided into a normal control group,a medication group,a miR-7b-3p inhibitor group,a medication+5-HT1AR inhibitor group,and a positive control group. The expression of 5-HT1AR in brain tissues of mice and the binding activity of 5-HT and 5-HT1AR were observed. (5) Sprague-Dawley rats were divided into a normal control group,a medication group,a miR-7b-3p inhibitor group,a medication+miR-7b-3p mimics group and a positive control group. Changes in slow wave sleep in mice were observed.RESULTS AND CONCLUSION:(1) Semen Ziziphi Spinosae extract could promote the growth of body length and tibia,growth hormone secretion,and brain tissue 5-HT1AR level in mice. (2) The number of differentially expressed miRNAs screened by GeneChip was 16,of which 13 were up-regulated and 3 were down-regulated. Bioinformatics results predicted that down-regulation of miR-7b-3p could regulate 5-HT1AR expression,and dual-luciferase reporter gene experiments confirmed a direct regulatory relationship between the two. (3) Semen Ziziphi Spinosae extract and silencing of miR-7b-3p expression in cerebral cortical cells could cause high expression of 5-HT1AR. After silencing of miR-7b-3p,5-HT1AR expression,binding activity of serotonin and 5-HT1AR and growth hormone secretion in mouse brain tissue were all elevated. After overexpression of miR-7b-3p,5-HT1AR expression,binding activity of serotonin and 5-HT1AR and growth hormone secretion were all reduced. Accordingly,the slow-wave sleep period in mice was also prolonged or shortened. To conclude,Semen Ziziphi Spinosae extract can reduce the level of miR-7b-3p and increase the expression of 5-HT1AR in brain tissue to prolong slow wave sleep and promote the secretion of growth hormone,thereby playing a postive effect on bone growth. These findings provide a scientific basis for the use of Semen Ziziphi Spinosae extract as a potential measure to promote bone growth.

Objective This study aims to establish a transnational evaluation framework for academic competitiveness in obstetrics and gynecology,precisely positioning West China Second Hospital(WCSH)globally,identifying development bottle-necks and proposing strategic improvements.Methods Based on Elsevier's SciVal platform,bibliometric data from 12 top global institutions(7 Chinese,5 international)during 2020-2024 were analyzed.A three-dimensional indicator system was construc-ted:research output(publication volume,Q1 publications),academic impact(citations,citations per paper,FWCI),and col-laboration(international collaboration rate).Entropy weight method was employed to assign objective weights to calculate com-posite competitiveness scores.Results WCSH led in total publications(n=541)but underperformed in Q1 publication rate(34.57％vs domestic average 43.01％)and FWCI(0.67＜global baseline 1.0).Its international collaboration rate(2.8％)lagged significantly behind global peers(e.g.,NUH Singapore:53.5％).Entropy weighting identified Q1 publications(31.8％)and FWCI(28.5％)as core drivers.WCSH ranked 9th among 12 global institutions(4th domestically).Conclusion WCSH exhibits"scale advantage with quality gaps and collaboration deficit".Strategic recommendations include quality-fo-cused incentive reform,enhanced international networks,and dynamic monitoring.The study provides a data-driven transnational evaluation paradigm for the disciplinary development of obstetrics and gynecology.