Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

OBJECTIVE:The optimal non-surgical therapy for chronic ankle instability remains unclear due to the continuous introduction of novel treatment methods despite the availability of several non-surgical options for improving foot and ankle function and dynamic balance in chronic ankle instability patients.This study aims to investigate the most effective non-surgical therapy options to improve foot and ankle function and dynamic balance for patients with chronic ankle instability using a network meta-analysis. METHODS:Using"CAI,exercise,and randomized controlled trial"as search terms,a literature search of PubMed,Embase,Cochrane Library,and Web of Science databases was conducted through a computer network to collect information from the databases from their inception to March 2024 on non-surgical therapies for the treatment of chronic ankle instability randomized controlled trials on foot and ankle function or dynamic balance in patients.EndNote software was utilized for literature management.RevMan 5.4 software and Cochrane Risk of Bias Assessment Tool were used to evaluate the risk of bias of the included literature.Paired meta-analysis and network meta-analysis of the outcomes such as the Foot and Ankle Ability Measure in daily living subscale score,Foot and Ankle Ability Measure in sports activities subscale score,Star Excursion Balance Test-Anterior score,Star Excursion Balance Test-Posteromedial score,Star Excursion Balance Test-Posterolateral score and Cumberland ankle instability tool score were performed using the network commands of Stata 14.0 software.The strength of evidence rating of the outcome metrics was evaluated according to the GRADE Level of Evidence and Strength of Recommendation Grading Criteria. RESULTS:Of the 22 randomized controlled trials that met the inclusion criteria,1 study was rated as low risk,8 studies were rated as medium risk,and 13 studies were rated as high risk,enrolling a total of 952 patients and 25 treatments.(1)Network meta-analysis showed that compared with the control group,Isokinetic Strength Training,Balance Training,Balance+Stroboscopic Glasses Training,Strength Training,Joint Mobilizations Training,CrossFit Training,CrossFit Training+Self-Mobilization,Wobble Board Training,National Academy of Sport Medicine corrective exercise program,Trigger Point Dry Needling,and Neuromuscular Training had different significant enhancement effects on improving foot and ankle function and dynamic balance in patients with chronic ankle instability(P<0.05).(2)Cumulative probability ranking results showed that the three treatments with the highest ranked Cumberland ankle instability tool score were Joint Mobilizations Training(88.6%)>Visual Feedback Balance Training(83.1%)>CrossFit Training+Self-Mobilization(74.8%);the three treatments with the highest ranked Star Excursion Balance Test-Anterior score were Joint Mobilizations Training(88.4%)>Isokinetic Strength Training(86.9%)>National Academy of Sport Medicine corrective exercise program(65.0%);the three treatments with the highest ranked Star Excursion Balance Test-Posteromedial score were Balance+Stroboscopic Glasses Training(87.4%)>Neuromuscular Training(74.6%)>Strength Training(68.9%);the three treatments with the highest ranked Star Excursion Balance Test-Posterolateral score were CrossFit Training+Self-Mobilization(74.6%)>Balance+Stroboscopic Glasses Training(70.0%)>Neuromuscular Training(63.7%);the three treatments with the highest ranked Foot and Ankle Ability Measure in daily living subscale score were National Academy of Sport Medicine corrective exercise program(91.9%)>Balance+Stroboscopic Glasses Training(85.6%)>Wobble Board Training(82.2%);the three treatments with the highest ranked Foot and Ankle Ability Measure in sports activities subscale score were Balance+Stroboscopic Glasses Training(93.5%)>Balance Training(86.7%)>National Academy of Sport Medicine corrective exercise program(86.4%). CONCLUSION:Non-surgical therapies can significantly improve foot and ankle function and dynamic balance in patients with chronic ankle instability.National Academy of Sport Medicine corrective exercise program had the best efficacy in improving foot and ankle daily activity function in chronic ankle instability patients;Balance+Stroboscopic Glasses Training had the best efficacy in improving foot and ankle sports function and posterior medial dynamic balance;Joint Mobilizations Training had the best efficacy in improving anterolateral dynamic balance and ankle instability condition;and CrossFit Training+Self-Mobilization had the best efficacy in improving posterior lateral dynamic balance.The strength of evidence for each outcome was low,influenced by the risk of methodological bias and risk of publication bias of the included studies.Therefore,the above conclusions need to be validated by more high-quality pilot studies.

Abstract Childhood hypertension is becoming a substantial public health challenge with profound implications for children s quality of life and long term health. The study analyzes the global prevalence of childhood hypertension and the relationship between macroecological factors, meso environmental factors, and micro individual factors based on the perspective of life course and childhood hypertension. And it further summarizes existing prevention and control strategies: systematic prevention and control based on policy and social support, health promotion based on behavioral science theory, and dynamic monitoring and management based on individualized prevention and control, to provide a reference for promoting the advancement of childhood hypertension prevention and control strategies.

AIM: To evaluate the diagnostic value of serum Th1-type cytokine levels and extraocular muscle-related parameters in thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective study was conducted on 45 patients diagnosed with TAO in our hospital from January 2023 to December 2024, and 20 normal volunteers during the same period as controls. Venous blood samples of the patients were collected to detect the concentrations of Th1-type cytokines [interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), and interleukin-12(IL-12)] in the serum. Additionally, the end diastolic velocity(Ved), velocity maximum(Vmax), resistance index(RI)of the central retinal artery, as well as the thickness and left-right diameter of the medial rectus muscle were measured. Logistic regression model was used to analyze the risk factors of TAO, and receiver operating characteristic curve(ROC)was adopted to evaluate the diagnostic efficacy of each index for the occurrence of TAO.RESULTS: The general information of the two groups was comparable. Compared with the normal control group, the serum concentrations of IFN-γ and TNF-α in TAO patients were significantly increased, Ved and Vmax were lower than those in the control group, and RI and the thickness of the medial rectus muscle were higher than those in the control group(all P<0.05). Logistic regression analysis showed that serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle were all risk factors for TAO. ROC curve analysis indicated that the AUCs of serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle for the diagnostic efficacy of TAO were 0.756, 0.769, 0.732, and 0.642, respectively. The combined detection of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle had an AUC of 0.840 and a Youden index of 0.59, which was superior to the detection of a single indicator.CONCLUSION: The levels of serum Th1-type cytokines and extraocular muscle-related ultrasound indicators have certain value in the diagnosis of TAO. The combination of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle has better diagnosis efficiency in TAO, which can provide a certain reference for the early diagnosis of TAO.

Objective:To explore the application of short video situational teaching based on clinical pathway management cases in cardiology internship teaching.Methods:30 medical students who were interned in the Department of Cardiology of Xiangya Hospital of Central Souty University from June 2020 to May 2021 were selected as the control group, using traditional clinical teaching mode, and another 30 medical students from June 2021 to May 2022 were selected as the observation group. Short video situational teaching based on clinical pathway management cases was used to compare the performance evaluation results, satisfaction evaluation results, teaching effectiveness, improvement of critical thinking ability, and teaching method evaluation results of the two groups of students. Perform chi square test and t-test using SPSS 20.0. Results:The results showed that the performance of the observation group students in the entrance examination [theoretical: (88.25±5.14) vs. (80.23±5.34); operational: (90.36±5.23) vs. (86.58 ± 5.12)] was better than that of the control group, and the difference was statistically significant; The observation group showed statistically significant differences in teaching effectiveness compared to the control group ( P<0.05); The critical thinking ability score of the observation group students was better than that of the control group ( P<0.05); The observation group students rated the teaching methods higher ( P<0.05). Conclusions:The use of situational teaching in cardiology internships can enhance the critical thinking ability of medical students, meet clinical needs, and is worth promoting in diagnostic teaching.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

Aim To investigate the effect of Tripterygi-um wilfordii polyglycosides(TWP)on renal protection and the expression of cannabinoid 2 receptor/NADPH oxidase4/NOD like receptor protoin3(CB2R/NOX4/NLRP3)in renal tissue of IgA nephropathy(IgAN)rats.Methods The IgAN rat model was replicated u-sing the"BSA+CCl4+LPS"combined method,and intervention with TWP was administered.A fully auto-mated biochemical analyzer was used to detect 24-hour urine protein quantification(24h-UTP),urine red blood cell count(URBC),serum albumin(ALB),ala-nine aminotransferase(ALT),serum creatinine(Scr),and blood urea nitrogen(BUN).The pathological changes in renal tissue were observed under light mi-croscopy,and IgA deposition in the mesangial area was observed using immunofluorescence.The protein ex-pressions of CB2R,NOX4 and NLRP3 in renal tissue were detected by Western blot.Results Compared with the model group,the pathological damage to the kidneys of rats in the TWP group was significantly re-duced,and the deposition of IgA electron dense materi-al was significantly reduced.The levels of ALB in rats treated with TWP increased,while the levels of 24h-UTP,URBC,ALT,Scr,and BUN all decreased.The expression of CB2R protein in renal tissue of rats trea-ted with TWP increased,while the expression of NOX4 and NLRP3 proteins was reduced.Conclusion TWP can effectively improve renal injury in IgAN rats,and its mechanism may be related to the regulation of the CB2R/NOX4/NLRP3 signaling pathway.

Objective To explore the clinical efficacy of antibiotic bone cement covered reconstruction steel plate in the treatment of infected anterior pelvic ring fracture.Methods From January 2017 to March 2022,11 patients with infected ante-rior pelvic ring fracture were treated with antibiotic bone cement covered reconstruction steel plate including 7 males and 4 fe-males and the age ranged from 27 to 49 years old.The pelvic fractures were classified according to the Tile typology:4 cases of Cl type,4 cases of C2 type,and 3 cases of C3 type.Among them,2 cases of infected anterior ring were infected after internal fixation of anterior ring,and 9 patients were infected with infected anterior ring due to incomplete early debridement,which was classified as infected according to the injury severity score(ISS)for 24 to 38 scores.The anterior ring was internally fixed by extended debridement,irrigation,and antibiotic bone cement covered reconstruction plate,and the posterior ring fractures were all closed reduction and internally fixed with sacroiliac screws.Results All 11 cases obtained follow-up from 13 to 20 months.A-mong them,2 patients had recurrence of postoperative infection,1 case was re-dissected and replaced with antibiotic bone cement-coated internal fixation,and 1 case had a milder infection without accumulation of the medullary cavity,and the infection was controlled by retaining the plate and replacing the antibiotic bone cement only after dissecting.Two cases developed incisional oozing,which healed after removal of the internal fixation three months postoperatively.All patients did not show pelvic fracture redisplacement or reinfection during the follow-up period.All 11 cases eventually healed bony.At the final follow-up,according to the Matta score,the fracture reduction was excellent in 6 cases,good in 4,and possible in 1.According to the Majeed functional score,it was excellent in 6,good in 3,and possible in 2.Conclusion Antibiotic bone cement covered reconstruction plate is ef-fective in the treatment of infected anterior pelvic ring fracture,with high intraoperative safety and low recurrence rate of infec-tion,which is conducive to the early postoperative rehabilitation and significantly shortens the course of the disease.

Objective To retrospectively analyze the ultra-fast track anesthesia(UFTA)methods and perioperative anesthesia management experiences of transcatheter mitral valve edge-to-edge repair(TEER)in the treatment of functional mitral regurgitant.Methods In this retrospective study,patients underwent the TEER procedure and received UFTA in Fuwai Yunnan Hospital,from May 2022 to September 2022 for heart failure combined with moderate to severe or severe functional mitral regurgitant were included.Baseline,preoperative complications,cardial function and anesthesia classification,amino-terminal probrain natriuretic peptide(NT-proBNP),ultrasound examination results,surgery time,extubation time,intraoperative anesthetic and vasoactive drug,complications related to TEER and UFTA,perioperative,and postoperative 30-day and one-year follow-up data were collected.All perioperative clinical data were recorded and analyzed.Results A total of 30 patients were enrolled,11 patients(36.7％)were female,mean age was(63.6±6.1)years,NYHA classification IV 14 patients(46.7％),left ventricular ejection fraction(LVEF)(36.0±8.1)％,the end-diastolic volume of the left ventricle(66.0±8.2)mm,mitral regurgitation 4+14 patients(56.7％),3+17 patients(43.3％),NT-proBNP(1 934.1±1 973.5)pg/ml,1 patient(3.3％)used high-dose vasoactive drugs during surgery.All patients did not experience nausea,vomiting,delirium,respiratory depression,perioperative transesophageal echocardiography-related gastrointestinal bleeding,pericardial effusion,cerebrovascular accidents,emergency surgery or secondary intervention,or other serious adverse events within 24 hours after surgery.No 30-day all-cause death occurred;the mean postoperative hospital stay was(7.4±2.8)days.All patients completed one-year follow-up,LVEF(37.6±11.1)％,the end-diastolic volume of the left ventricle(63.2±8.6)mm,mitral regurgitation 2+7 patients(23.3％),1+23 patients(76.7％),NT-proBNP(1 949.2±2 576.6)pg/ml.Conclusions Ultra-fast track anesthesia can be safely applied to TEER in treating functional mitral regurgitant patients.

Objective To analyze the incidence of major adverse cardiovascular events(MACE)in 45 patients who unexpectedly interrupted dual antiplatelet therapy(DAPT)within one month after percutaneous coronary intervention(PCI).Methods A total of 4 876 patients who successfully underwent PCI and implanted one or more stents(excluding acute ST segment elevation myocardial infarction,drug coated balloon or non-drug coated ballooon only,and oral anticoagulants)between January 1,2017 and December 31,2022 were selected as the study subjects.A total of 45 patients with unexpected interruption of DAPT within one month after PCI were analyzed,and their clinical outcomes were followed up.Results Among the 45 patients,there were 29 males and 16 females,aged 48-80(61.7+15.3)years.The reasons for interrupting DAPT include:35 cases of bleeding;3 cases of malignant tumor surgery(including 2 bleeding patients);5 cases of trauma;2 cases of hematological diseases;2 cases of self-interruption of DAPT.6 patients who received low-molecular-weight heparin replacement therapy during the discontinuation period did not experience stent thrombosis or other MACE.Among the 39 patients without antithrombotic replacement therapy,5 developed stent thrombosis and acute myocardial infarction(5/45,11.1％).Except for 1 patient who voluntarily stopped DAPT 2 weeks after PCI,the remaining 4 cases were those who with concurrent bleeding within 2 weeks after PCI.DAPT was stopped for more than 10 days,and stent thrombosis occurred on the 10th,11th,11th,and 13th days after DAPT was stopped.Among the 4 patients,2 patients developed acute left heart failure and 1 patient died.Another case died due to brainstem hemorrhage.Conclusions Premature interruption of DAPT after PCI has a high potential risk.Patients who stop taking medication earlier,for a longer duration,and without replacement therapy have a higher risk.