Objective To explore the feasibility, safety, and efficacy of transesophageal endoscopic surgery for mediastinal tumors. Methods A retrospective analysis was conducted on the clinical data of 17 patients who underwent transesophageal endoscopic resection for benign mediastinal tumors at the Endoscopy Center of Zhongshan Hospital, Fudan University, between January 1, 2016 and December 31, 2024. Epidemiological characteristics, surgical parameters, adverse events, and follow-up outcomes were analyzed. Results Among the 17 patients, there were 9 males and 8 females, with an average age of (42.4±14.5) years and an average tumor size of (2.6±1.6) cm. Pathological types included esophageal duplication cysts (6 cases, 35.3%), bronchogenic cysts (5 cases, 29.4%), gastroenteric cysts (3 cases, 17.6%), schwannomas (2 cases, 11.8%), and lymphangioma (1 case, 5.9%). Fourteen patients (82.4%) underwent submucosal tunneling endoscopic resection (STER), 3 patients (17.6%) underwent natural orifice transluminal endoscopic mediastinal surgery. All surgeries were successfully completed without conversion to open surgery. En bloc resection was achieved in 11 patients (64.7%), with an average operative time of (60.9±32.6) min. No intraoperative bleeding or mucosal injury occurred, and 4 patients (23.5%) experienced minor complications (pneumothorax, fever, recurrent laryngeal nerve injury), all of which resolved with conservative treatment. The average postoperative hospital stay was (3.2±1.5) days, and no recurrence was observed during the follow-up period. Conclusions Transesophageal endoscopic resection of benign mediastinal tumors is a safe, effective, and minimally invasive treatment method. Further validation of its efficacy and safety through large-scale prospective studies is warranted.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective The long-term epidemiological and etiological characteristics of hand, foot and mouth disease (HFMD) in Huai’an, Jiangsu were analyzed to provide scientific evidence for the prevention of HFMD. Methods The data of HFMD reports, etiological diagnosis and in Huai’an from 2009 to 2022 were described and analyzed. Results A total of 78 535 cases were reported from 2009 to 2022 , with 14-year average annual incidence rate of 114.71/100 000. Before 2020, the incidence rate of HFMD in Huai’an showed the epidemic intensity increased every other year on the whole, and the average annual incidence rate during the COVID-19 pandemic (2020-2022) (55.69/100 000) was significantly lower than that in previous years (2009-2019) (129.95/100 000). The joinpoint regression analysis showed that the best fitting model from 2009 to 2022 had no joinpoints, APC=AAPC=-1.24%. The overall trend showed a monotonously decreasing trend, but the trend was not statistically significant. The male-to-female distribution ratio was 1.53:1, and the age distribution was mainly under 5 years old, especially in scattered children. The epidemic season was from April to July. The results of etiological surveillance showed that the co-epidemic of Coxsackievirus A16 (CV-A16) and Enterovirus A71 (EV-A71) during the early stages had changed to the co-epidemic of CV-A16 and CV-A6 in the current period. Conclusion The burden of HFMD in Huai’an was large, and the epidemic intensity increased every other year was affected by the COVID-19 pandemic. The epidemiological features after the COVID-19 pandemic should be further monitored.

Objective To explore the value of serum stearoyl sphingosine(C18∶1-Cer)and 1-stearoyl-sn-glycero-3-phospho-choline(LPC 18∶0)levels in pregnant women's serum samples during pregnancy in predicting gestational diabetes mellitus(GDM).Methods The clinical data and laboratory indicators of 126 pregnant women were retrospectively analyzed.The sub-jects were divided into GDM group(n=66)and control group(n=60)according to the GDM diagnosis results.Mass spec-trometry was used to detect the serum C18∶1-Cer and LPC18∶0 levels of the subjects in early and mid pregnancy.Logistic re-gression analysis was used to screen out the risk factors for GDM.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of C18∶1-Cer,LPC18∶0 and their combination for GDM.Results Compared with the control group,the serum C18∶1-Cer and LPC18∶0 levels of the subjects in the GDM group were significantly increased in early(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)and mid pregnancy(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml),and the differences were statistically significant(t=7.127,15.637;-5.984,2.174,all P＜0.05)C18∶1-Cer was positively correlated with fasting plasma glucose(FPG),fasting plasma insulin(FPI),homeostasis model assessment of insulin resistance(HOMA-IR),glycated hemoglobin(HbA1c)and triglyceride(TG)(r=0.458,0.209,0.317,0.223,0.219,all P<0.05).LPC18.0 was positively correlated with FPG,FPI,HOMA-IR,HbA1c,total cholesterol(TC)and TG(r= 0.715,0.426,0.580,0.465,0.232,0.372,all P<0.05).Logistic regression analysis results showed that C18∶1-Cer[OR(95%CI):1.522(1.136～2.039),P<0.05]and LPC18:0[OR(95%CI):1.198(1.102～1.302),P<0.001]were independent risk factors for GDM.ROC curve analysis results showed that the area under the curve(AUC)of serum C18∶1-Cer,LPC18∶0 and the combination of the two indicators were 0.819,0.971 and 0.986,respectively.The predictive performance of the combination of the two indicators was better than that of the single detection.Conclusion Serum C18∶1-Cer and LPC18∶0 in early pregnancy were closely related to the occurrence of GDM.C18∶1-Cer combined with LPC 18∶0 has a certain predictive value for the early diagnosis of GDM.

Objective:To investigate the efficiency, safety and complication of 0.7 mg dexamethasone sustained release agent (Ozurdex ?) vitreous cavity implantation for macular edema secondary to vitrectomy. Methods:A total of 15 patients (16 eyes) were included in this retrospective case series study. There were 7 males (8 eyes) and 8 females (8 eyes). Age ranged from 47 to 72 years old with an average age of (60.2±8.6)years. Among them, 8 cases were diabetic retinopathy (6 cases combined cataract surgery). 4 cases were silicone oil removal after retinal detachment surgery (all combined cataract surgery). 2 cases were epi-macular membrane (all combined with cataract surgery) and 1 case was vitreous hemorrhage (combined with cataract surgery). Ozurdex ? was implanted for macular edema after vitrectomy. The number of implantation was from 1 to 3 times (mean 1.67 times). The follow-up time was from 3 to 12 months, with an average of (7.33±3.50)months. Results:The best corrected visual acuity (BCVA) was improved in 10 cases (11 eyes), unchanged in 4 cases and decreased in 1 case within 3 months after Ozurdex ? implantation in the 15 cases (16 eyes). The macular edema was significantly improved in all cases. The central macular thickness (CMT) measured by optical coherence tomography (OCT) was from 350 to 1 370 γm before surgery with average thickness (621.60±235.48)γm, and the CMT postoperative was 118 to 556 γm with average thickness (269.87±118.14)γm, with statistically significant difference ( P<0.001). Cataract was not progressive after Ozurdex ? implantation. Macular edema was recurrent in 7 cases after first implantation and stable for additional 1-2 injections. Intraocular pressure elevation occurred in 3 cases 1 to 2 months after implantation with the highest intraocular pressure of 36 mmHg, which were controlled by local anti-glaucoma eye drops. Drugs entered into the anterior chamber in 2 cases and was taken out in 1 case. Conclusions:The efficiency of Ozurdex ? vitreous cavity implantation is definite and the complications are controllable, so it is a safe and effective method to treat macular edema after vitrectomy.

Objective:To investigate the clinical features and treatment status of immune-related myositis (IRM) caused by immune checkpoint inhibitors (ICIs) in order to improve the diagnosis and treatment rate of the disease.Methods:Two cases of IRM combined with the diagnosis and treatment were described and the literature about IRM in the past 10 years was reviewed, and the clinical data of 59 patients were analyzed.Results:IRM was more common in males, with a total of 47 (79.7%). IRM usually occurred after 45 days of medication or after two doses. The clinical manifestations were mainly myalgia and muscle weakness, which were more common in the limbs. The initial symptoms were ptosis and diplopia. Fifty patients (84.7%) had serum creatine kinase (CK) levels higher than twice the upper limit of normal (UNL). In immunological examinations, 18 patients were found to be positive for anti-rhabdoid muscle antibody (AsM-Ab), while most of the myositisspecific antibodies (MSAs) and myositis-associated antibodies (MAAs) were negative. Thirty-four patients (75.6%) had abnormal EMG, and most patients showed myogenic injury. Muscle magnetic resonance imaging (MRI) showed muscle edema and inflammation in 8 patients. Muscle biopsies from 18 (45.0%) patients showed varying degrees of necrotic myofibers. Fifty-seven patients (96.6%) discontinued ICIs after developing IRM, 54(91.5%) received cortico-steroids, and 20(33.9%) received other treatments including intravenous immuno-globulin (IVIG), plasma exchange.Conclusion:IRM can occur in the early stage of ICIs treatment. Electro-myography, muscle MRI and muscle biopsy in suspicious cases can improve the diagnosis rate of the disease. Early use of corticoteroid, IVIG and other immunotherapy can effectively alleviate the disease.

Psoriatic arthritis is a chronic systemic autoimmune disease, characterized by psoriasis skin lesions and inflammation of the spine and joint. It has complicated clinical manifestations and individual variations. Nearly half of the patients will have joints erosion in two years, which is crippling. The severity of the skin and joint disease frequently do not correlate with each other. Currently, the understanding of the disease is insufficient in China with the lack of standardized diagnosis and treatment. Therefore, researchers from the Chinese Rheumatology Association formulated this specification based on the diagnosis and management experience together with guidelines at home and abroad. The specification summarizes the present situation of domestic diagnosis and treatment, aiming to standardize the diagnosis process and treatment protocols of psoriatic arthritis. Furthermore, it can reduce misdiagnosis and missed diagnosis, as well as improve the prognosis.

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEPO6 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.

Objective:To identify the characteristics of nailfold capillaroscopy (NFC) of systemic sclerosis (SSc) and investigate whether more severe peripheral microangiopathy at NFC were related to the development of SSc.Methods:① The study included 115 patients (60 cases with SSc and 55 patients with other connective tissue diseases). All patients were treated with neither prednisone nor immunosuppressive drugs within 3 months before enrollment. We collected the following data: age, disease duration, disease onset, mRSS, high-resolution chest tomography (HRCT), echocardiography, pulmonary function, nailfold capillaroscopy and routine laboratory assessments. ② All the NFC definitions were used for semi-quantitatively scoring and Cutolo's qualitative assessment. ③ The relationship between NFC changes and joint, visceral involvement and autoantibodies in SSc patients was analyzed. ④ T test, Rank sum test and chi-square test were applied to analyze data. Results:① According to Cutoloqualitative assessment of NFC, patients of SSc with active/late pattern ( n=52) were very common than other CTD ( n=21) ( Z=-3.853, P<0.01). ② According to semiquantitative assessment, the scores of loss of capillaries [(1.67±0.60) vs (0.72±0.46), t=8.347, P<0.01)], irregular enlarged capillaries [(1.22±0.88) vs (0.74±0.50), t=3.178, P<0.01)], hemorrhage [(0.30±0.39) vs (0.10±0.21), t=3.090, P<0.01)], disorganization of the microvascular array [(0.38±0.38) vs (0.18±0.32), t=2.729, P<0.01)] were significantly higher than CTD. ③ The NFC of SSc patients was significantly different from CTD. The number of capillary loss ( Z=-4.194, P<0.01), input capillary dimensions ( t=3.704, P<0.01), output capillary dimensions ( t=3.913, P<0.01), wide diameter of capillary ( t=4.586, P<0.01), tortuous capillaries ( Z=-2.677, P<0.01), gaint capillary ( χ2=8.040, P=0.013), effusion ( Z=-2.278, P=0.023) were more increased than CTD. ④ The NFC pattern of SSc with lung involvement were mainly active and late (66%, 33/50), whereas early and active pattern (60%, 6/10) for those without respiratory system involvement ( Z=10.114, P=0.045) . The NFC pattern of SSc patients with joint involvement were mainly active and late (75%, 12/16), whereas early and active (66%, 29/44) for those without joint involvement ( Z=5.550, P=0.057) . Conclusion:The NFC of SSc patients is significantly different from CTD. NFC may be a suitable tool for disease evaluation.

Objective:To investigate the clinical efficacy of locking proximal femur plates (LPFP) revision and artificial hip joint revision after failure of proximal femoral nail antirotation (PFNA) internal fixation in elderly patients with intertrochanteric fracture.Methods:A retrospective case control study was conducted on the clinical data of 43 patients with PFNA internal fixation failure in the elderly admitted to Henan Provincial People's Hospital between March 2014 and October 2018. There were 23 males and 20 females, aged 65-83 years [(71.2±2.0)years]. The course of disease was 60-267 days [(83.1±3.6)days]. According to Evans classification, there were 11 patients with type II fractures, 13 with type III and 19 with type IV. There were 23 patients in artificial hip joint revision group and 20 patients in LPFP revision group. The operation time, intraoperative blood loss, postoperative hospitalization time, total hospitalization time, Harris score and complications were recorded and evaluated in two groups.Results:All patients were followed up for 12-28 months, with an average of 13.6 months. Between artificial joint revision group and LPFP revision group, the operation time and intraoperative blood loss were similar ( P>0.05), but there were significant difference in postoperative hospitalization time [(7.1±3.2)days vs. (13.2±2.9)days] and total hospitalization time [(10.2±2.8)days vs. (16.4±3.4)days] ( P<0.05). In artificial joint revision group, the Harris hip score was (21.1±3.7)points preoperatively, and was respective (70.7±4.8)points, (74.6±4.1)points, (78.6±3.3)points, (82.9±5.2)points, (83.8±5.8)points and (84.9±6.4)points at postoperative 1, 2, 3, 6, 9, 12 months. In LPFP revision group, the Harris score was (21.7±3.2)points preoperatively, and was respective (59.9±2.1)points, (64.79±3.4)points, (70.1±4.2)points, (73.9±4.2)points, (76.2±6.3)points and (77.9±6.8)points at postoperative 1, 2, 3, 6, 9, 12 months. The Harris score in artificial joint revision group was gradually improved compared with LPFP revision group ( P<0.05). One patient with superficial wound infection occurred in each group, and the wound healed after frequent dressing changes. Distal femoral fractures occurred in one patient of artificial joint revision group and distal femoral fractures in three patients of LPFP revision group, but all patients were healed after being fixed with wire. Conclusion:For elderly patients with PFNA internal fixation failure of intertrochanteric fracture, artificial hip revision has shorter hospital stay and better hip joint function recovery than LPFP internal fixation, although the effect in operation time and intraoperative blood loss are similar.