OBJECTIVE: To investigate the effectiveness of the suture anchor technique without knots for reconstruction of the anterior talofibular ligament (ATFL) combined with the reinforcement of the inferior extensor retinaculum in treating chronic lateral ankle instability (CLAI). METHODS: The clinical data of 31 patients with CLAI who were admitted between August 2017 and December 2023 and met the selection criteria were retrospectively analyzed. There were 18 males and 13 females, with an age range from 20 to 48 years (mean, 34.6 years). All patients had a history of repeated ankle sprain, with a disease duration of 6-18 months (mean, 9.65 months). The anterior drawer test and inversion stress test were positive, and tenderness was present in the ligament area. Stress X-ray films of the ankle joint showed a talar tilt angle of (10.00±2.78)° and an anterior talar displacement of (9.48±1.96) mm on the affected side. MRI revealed discontinuity, tortuosity, or disappearance of the ATFL structure. Preoperatively, the visual analogue scale (VAS) score was 5.2±2.1, and the American Orthopaedic Foot and Ankle Society (AOFAS) score was 62.9±7.1. All patients underwent arthroscopic debridement of the ankle joint followed by reconstruction of the ATFL using the suture anchor technique without knots combined with reinforcement of the inferior extensor retinaculum. Postoperatively, pain and function were assessed using the VAS and AOFAS scores. Stress X-ray films were taken to measure the talar tilt angle and anterior talar displacement to evaluate changes in ankle joint stability. Patient satisfaction was assessed according to the Insall criteria. RESULTS: All 31 surgeries were successfully completed. One case had wound exudation, while the remaining surgical incisions healed by first intention. Two cases experienced numbness on the lateral aspect of the foot, which disappeared within 1 month after operation. All patients were followed up 15-84 months (mean, 47.2 months). No complication such as anchor loosening, recurrent lateral ankle instability, superficial peroneal nerve injury, rejection reaction, or wound infection occurred postoperatively. The anterior drawer test and inversion stress test were negative at 3 months after operation. Stress X-ray films taken at 3 months after operation showed the talar tilt angle of (2.86±1.72)° and the anterior talar displacement of (2.97±1.32) mm, both of which were significantly different from the preoperative values ( t=12.218, P<0.001; t=15.367, P<0.001). At last follow-up, 2 patients had ankle swelling after exercise, which resolved spontaneously with rest; all 31 patients returned to their pre-injury level of sports or had no significant discomfort in daily activities. At last follow-up, 25 patients were pain-free, 4 had mild pain after exercise, and 2 had mild pain after walking more than 2 000 meters. The VAS score was 0.8±0.9 and the AOFAS score was 91.6±4.1, both of which were significantly different from the preoperative scores ( t=10.851, P<0.001; t=-19.514, P<0.001). According to the Insall criteria, 24 patients were rated as excellent, 4 as good, and 3 as fair, with a satisfaction rate of 90.3%. CONCLUSION The suture anchor technique without knots for reconstruction of the ATFL combined with reinforcement of the inferior extensor retinaculum provides satisfactory short- and mid-term effectiveness in treating CLAI.
Humans ; Male ; Adult ; Female ; Joint Instability/surgery* ; Lateral Ligament, Ankle/surgery* ; Retrospective Studies ; Middle Aged ; Ankle Joint/diagnostic imaging* ; Young Adult ; Suture Anchors ; Treatment Outcome ; Suture Techniques ; Plastic Surgery Procedures/methods* ; Chronic Disease ; Ankle Injuries/surgery*

Objective: To investigate the chemical compositions of Maxing Shigan Decoction (麻杏石甘汤, MXSGD) and elucidate its anti-influenza A virus (IAV) mechanism from prediction to validation. Methods: Ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the chemical compositions of MXSGD. Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV. A protein-protein interaction (PPI) network was then constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations. A total of 24 BALB/c mice were infected with IAV to build IAV mouse models. After successful modelling, the mouse models were randomly divided into model, MXSGD high-dose (2.8 g/kg), MXSGD low-dose (1.4 g/kg), and oseltamivir (20.14 mg/kg) groups, with an additional normal mice as control group (n = 6 per group). The treatments were administered by gavage daily between 8:00 a.m. and 10:00 a.m. for five consecutive days. Upon completion of the administration, the body weight ratio, lung index, protein content in the bronchoalveolar lavage fluid (BALF), and the levels of inflammatory factors including interleukin (IL)-6 and tumor necrosis factor (TNF)-α in mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection. Furthermore, the expression levels of mechanistic target of rapamycin (mTOR), hypoxia inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF) proteins in the HIF-1 signaling pathway, which was enriched by network pharmacology, were detected by Western blot. Results: A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method. These chemical components can be classified into 9 primary categories and 31 secondary categories. After intersecting the chemical component targets with IAV-related targets, a total of 567 potential MXSGD components targeting IAV were identified. The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways, including apoptosis, TNF, HIF-1, and IL-17 signaling pathways. The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α, mTOR, and VEGF were all lower than – 5.0 kcal/mol. Furthermore, molecular dynamics simulations confirmed the structural stability of the resulting complexes. Animal experiments showed that compared with the normal controls, IAV-infected mice showed significantly reduced body weight ratio, markedly increased lung index, protein content in BALF, and the levels of inflammatory factors such as IL-6 and TNF-α (P < 0.01), thereby causing damage to the lung tissue; consequently, the expression levels of mTOR, HIF-1α, and VEGF proteins in the lung tissues of these mice were significantly elevated (P < 0.01). However, after MXSGD treatment, the mouse models presented a significant increase in body weight ratio, as well as marked decreases in lung index, protein content in BALF, and the levels of inflammatory factors including IL-6 and TNF-α (P < 0.01). Furthermore, the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR, HIF-1α, and VEGF proteins in lung tissues (P < 0.01 or P < 0.05). Conclusion MXSGD exerts anti-IAV effects through multi-component, multi-target, and multi-pathway synergism. Among them, 1-methoxyphaseollin is identified as a potential key component, which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway, providing experimental evidence for the clinical application of MXSGD.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder.The prev-alence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand.The vascular EDS(vEDS)are rare among the subtypes but are the worst in prognosis.The article reports a case of vEDS admitted to the hospital.The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons.The diagnosis was made after the genetic testing.The patient suffered from vEDS.Then,the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient.The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging.This article hopes to report this case and to share the experiences to the bet-ter understanding of this disease.

Objective To evaluate the effect of medial meniscal posterior root tear(MMPRT)on tibi-al external rotation through the dial test and assess the effect of pull-out repair for MMPRT on patho-logical tibial rotation.Methods Totally 40 patients undergoing MMPRT repair using pull-out way be-tween January 2022 and January 2023 were studied retrospectively.The dial test at 30°/90° knee flex-ion was performed on the affected and healthy sides of the patients before and after surgery to assess the tibial external rotation.Results The mean age of the 40 patients was 56.4±7.5 years,with a mean body mass index(BMI)of 24.1±3.0.Among them,6 were male(34%)and 34 were female(85%).The median time from injury to surgery was 3.8±2.9 months.The preoperative tibial external rotation angles measured by the dial test at 30°and 90°knee flexion were 31.34±5.38°and 36.75°±6.62°respectively.Postoperatively,these angles decreased significantly to 24.24°±5.88°and 24.76°±5.47°,respectively(P=0.00).Moreover,significant differences were observed in the changes in tibial external rotation angles of the affected knee before and after surgery,7.10°(95%CI[6.01°,8.19°])at 30°flexion and 11.99°(95%CI[10.68°,13.29°])at 90°flexion.The gap in the tibial external rotation angle between the affected and unaffected sides were significant before surgery at 30°(8.33°,95%CI[7.32°,9.33°])and 90°(13.03°,95%CI[11.82°,14.23°])flexion but not after surgery at 30°(0.48°,95%CI[-0.25°,0.98°])and 90°(0.34°,95%CI[-0.02°,0.70°])flexion.Conclusion The dial test finds increased tibial external rotation in patients with MMPRT,and pull-out repair can correct this pathological tibial external rotation.Moreover,an increased tibial external rotation angle measured by the dial test at 30°and 90°can indicate MMPRT.Therefore,special attention should be given to inter-preting the results of the dial test in cases of MMPRT.

Objective:To improve the understanding of primary pulmonary lymphoepithelioma-like carcinoma (PPLELC).Methods:A retrospective case series study was conducted. The clinical data of 31 patients with PPLELC who were admitted to the First Affiliated Hospital of Guangxi Medical University from January 2012 to June 2023 were retrospectively analyzed, and their clinical features were summarized. The correlations of organ metastasis, tumor stage, serum tumor markers, lactate dehydrogenase, and albumin with survival time were analyzed.Results:Among the 31 patients, 13 (41.9%) were male and 18 (58.1%) were female, aged (50±9) years old, with no smoking history in 24 cases (77.4%). The common clinical manifestations were cough(24 cases, 77.4%) and sputum (19 cases, 61.3%), and 7 patients (22.6%) were detected by physical examination; 24 cases (77.4%) had elevated levels of serum tumor markers, and the rest of the 7 cases (22.6%) had normal levels of various tumor markers. All of the patients had a single lesion, with a predominance of the right middle lung (8 cases, 25.8%), and 23 cases (74.2%) had lymph node metastasis. Immunohistochemical detection showed that the positive rate of CK was 67.7% (21/31), and the positive rates of squamous cell carcinoma markers CK5/6, p63 and p40 were 90.3% (28/31), 80.6% (25/31) and 77.4% (24/31), respectively. The positive rate of EBER in situ hybridization detection was 85.2% (23/27). Genetic testing showed 6 cases had epidermal growth factor receptor (EGFR) mutation. The median survival time [ M ( Q1, Q3)] of the groups without lymph node metastasis and with lymph node metastasis was 33.0 months (7.3 months, 9.3 months) and 19.0 months (7.0 months, 27.0 months), and the difference was statistically significant ( P < 0.001). The median survival time of patients with stage Ⅰ-Ⅱ and with stage Ⅲ-Ⅳ was 20.0 months (12.5 months, 42.0 months) and 18.5 months (6.5 months, 38.5 months), and the difference was statistically significant ( P = 0.002). One stage Ⅰ A patient was treated with surgery alone and survived at 92 months of follow-up. Ten cases were treated with immunotherapy and had a good outcome. Conclusions:PPLELC is prevalent in non-smokers, the lesions are mostly in the right middle lung, and it is easily misdiagnosed as squamous cell carcinoma. The positive EBER in situ hybridization detection can help the diagnosis; lymph node metastasis is common. Tumor stage, lymph node metastasis and CYFRA21-1 level may be correlated with the survival of patients. The patients can benefit from immunotherapy, and anti-angiogenic therapy combined with chemotherapy is an optional treatment regimen.

Objective To evaluate the efficacy of MOOC combined with flipped classroom teaching in clinical train-ing of urology.Methods A total of 100 clinical medical students from Peking Union Medical College were randomly assigned to either an experimental group or a control group.The experimental group adopted the teaching mode of MOOC combined with flipped classroom,while the control group adopted classic teaching method.The two groups were compared in terms of their theoretical exam scores,case analysis skills and teaching satisfaction level.Results There were no significant difference in theoretical examination scores between experimental group and con-trol group(the mean value of scores are 45.12 and 44.50,respectively).However,the interview scores from ex-perimental group was significant higher than that of control group(the mean value of scores are 42.28 and 40.10,respectively,P＜0.001).The MOOC combined with flipped classroom mode significantly improved students'capacity building of clinical reasoning for diagnosis and communication skills.Students were more willing to continue receiving this teaching mode.Conclusions The integration of MOOC with the flipped classroom model sig-nificantly enhances the quality and efficacy of urology teaching.

Objective:To investigate the efficacy of tibiofibular-based reconstruction technique with single femoral tunnel for Fanelli type C posterolateral complex (PLC) injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 16 patients with Fanelli type C PLC injury admitted to Tianjin Hospital from July 2016 to July 2019, including 10 males and 6 females, aged 20-61 years [(36.5±13.9)years]. PLC reconstruction was performed by tibiofibular-based technique with single femoral tunnel using gracilis tendon and semi-tendinosus autografts. If the posterior and anterior cruciate ligaments (PCL/ACL) rupture were combined, arthroscopic single bundle reconstruction was performed simultaneously. If the posteromedial corner (PMC) injury was combined, PMC repair or reconstruction surgery was performed simultaneously. Operation time and intraoperative blood loss were recorded. When the bone needle and tunnel for PLC were drilled during the operation, the interference of the femoral tunnel through the cruciate ligament was observed under the arthroscope. Before and at 6 and 12 months after operation, the varus stability of the knee joint was evaluated with the difference of lateral joint space width of both knees and the International Knee Documentation Committee (IKDC) objective classification of varus stability of the knee joint; the external rotation stability was evaluated with the difference of external rotation angle of both knees and the IKDC objective classification of external rotation stability of the knee joint. Before, at 6 and 12 months after operation and at the last follow-up, IKDC 2000 subjective score and Lysholm score were compared. The occurrence of complications was observed.Results:All the patients were followed up for 12-36 months [24(15, 33)months]. The operation time was 100-220 minutes [175.0(111.3, 200.0)minutes], with intraoperative blood loss of 30-150 ml [(84.3±36.5)ml]. Intraoperative arthroscopy showed no interference of perforation between PLC and cruciate ligament femoral tunnel. The differences of lateral joint space width of both knees at 6 and 12 months after operation were 0.5(0.2, 1.4)mm and 0.6(0.2, 1.5)mm respectively, which were both significantly improved compared with 12.1(10.8, 12.6)mm before operation ( P<0.05), while there was no significant difference at 6 and 12 months after operation ( P>0.05). The IKDC objective classification of varus stability of the knee joint was grade A in 13 patients, grade B in two and grade C in one at 6 or 12 months after operation, and showed statistical difference from grade D in all the patients before operation ( P<0.01). At 6 and 12 months after operation, the difference of external rotation angle of both knees was -2.0(-3.2, 1.3)° and -1.4(-3.0, 1.7)° respectively, which were significantly improved compared with 16.8(13.9, 18.4)° before operation ( P<0.05), while there was no significant difference at 6 and 12 months after operation ( P>0.05). IKDC objective classification of external rotation stability of the knee joint was grade A in 14 patients, grade B in one and grade C in one at 6 or 12 months after operation, and showed statistical difference from grade C in 14 patients and grade D in 2 before operation ( P<0.01). At 6 and 12 months after operation and at the last follow-up, the IKDC 2000 subjective scores [(76.3±4.7)points, (80.3±4.4)points, (79.9±3.8)points respectively] and the Lysholm scores [(76.1±3.9)points, (81.1±4.3)points, (82.8±3.2)points respectively] were significantly improved compared with those before operation [(48.6±3.7)points and (52.6±2.4)points] ( P<0.05). The IKDC 2000 subjective scores and Lysholm scores were significantly improved at 12 months after operation and at the last follow-up than those at 6 months after operation ( P<0.05). There were no significant differences in the IKDC 2000 subjective scores and Lysholm scores at 12 months after operation and at the last follow-up ( P>0.05). There were no complications such as wound infection, vascular and nerve injury, joint stiffness or ectopic ossification. Conclusion:For Fanelli type C PLC injury, tibiofibular-based reconstruction technique with single femoral tunnel reduces the interference between the lateral femoral tunnels, significantly improves the varus and external rotation stability and the function of the knee joint, and has few complications and satisfactory short-term clinical efficacy.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Arrhythmogenic cardiomyopathy (ACM), a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes, accounts for 20% of sudden cardiac death and lacks effective treatment. It is often caused by mutations in desmosome proteins, with Desmoglein-2 (DSG2) mutations as a common etiology. However, the mechanism underlying the accumulation of fibrofatty in ACM remains unknown, which impedes the development of curative treatment. Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2 (CS-Dsg2 ^-/-). Heart failure and cardiac lipid accumulation were observed in CS-Dsg2 ^-/- mice. We demonstrated that these phenotypes were caused by decline of fatty acid (FA) β-oxidation resulted from impaired mammalian target of rapamycin (mTOR) signaling. Rapamycin worsened while overexpression of mTOR and 4EBP1 rescued the FA β-oxidation pathway in CS-Dsg2 ^-/- mice. Reactivation of PPARα by fenofibrate or AAV9-Pparα significantly alleviated the lipid accumulation and restored cardiac function. Our results suggest that impaired mTOR-4EBP1-PPARα-dependent FA β-oxidation contributes to myocardial lipid accumulation in ACM and PPARα may be a potential target for curative treatment of ACM.