Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

【Objective】 To investigate the risk factors of frailty syndrome in elderly patients with acute coronary syndrome （ACS） and their impact on prognosis. 【Methods】 The elderly patients with ACS aged 65 and over， who were hospitalized in the Department of Cardiology and Geriatric Cardiology of The First Affiliated Hospital of Xi’an Jiaotong University from September 2020 to February 2021， were selected in the cross-sectional survey. The patients were divided into frailty syndrome and non-frailty syndrome groups via the Chinese revised version of Tilburg Frailty Scale. We collected the patients’ activities of daily living， nutrition， depression， sleep quality， total cholesterol， triglycerides， low-density lipoprotein， and adverse events during hospitalization and within 30 days of discharge. We then performed LOG-BINOMIAL regression to analyze the risk factors of frailty syndrome. 【Results】 A total of 250 elderly ACS patients were enrolled， and 118 patients were diagnosed with frailty syndrome with 47.2% prevalence of frailty syndrome. There was a significant difference in the average score between the frailty syndrome group and the non-frailty syndrome group （11.06±2.53 vs. 5.77±1.54， P<0.01）. Multivariate regression analysis revealed that age （PR=2.01 CI： 1.81-2.22， P<0.001）， hypertension （PR=1.20 CI： 1.09-1.30， P<0.001）， chronic kidney disease （PR=1.16 CI：1.04-1.29， P=0.012）， and NT-proBNP （PR=1.20 CI： 1.07-1.35， P=0.004） were risk factors for frailty syndrome in elderly ACS patients. The incidence of arrhythmia and pulmonary infection during hospitalization and the rate of readmission within 30 days after discharge were significantly higher in the frailty syndrome group than those in the non-frailty syndrome group （P<0.05）. 【Conclusion】 There is a higher incidence of frailty syndrome in elderly patients with ACS. Older age， hypertension， chronic kidney disease and high NT-proBNP can increase the risk of frailty syndrome. In clinical practice， attention should be paid to the above factors， and reasonable intervention should be provided in time.

The pathogenesis of gestational diabetes mellitus (GDM) remains unclear. Recent studies have found that a dysbiosis of gut flora could lead to metabolism and immune system disorders in human beings, resulting in GDM. The gut microbiome changes can be affected by various factors, of which diet and antibiotic exposure are the most dominant. From the perspective of the gut microbiome changes, individualized dietary guidance, evidence-based administration of antibiotics, appropriate intake of prebiotics, and probiotics supplement may help prevent and treat GDM.

ObjectiveTo investigate the clinical effect and safety of robot-assisted laparoscopic hepatectomy (RALH) versus open hepatectomy (OH) in the treatment of liver diseases. MethodsWeb of Science, PubMed, Cochrane Library, Embase, CNKI, CBM, VIP, and Wanfang Data were searched for Chinese and English articles on RALH versus OH in the treatment of liver diseases published up to February 2020. The quality of the articles included was assessed, and RevMan 5.1 was used to perform the meta-analysis. ResultsSeven studies were included, with a total of 754 patients (328 patients in the RALH group and 426 in the OH group). The meta-analysis showed that compared with the OH group, the RALH group had a significantly longer time of operation (mean difference ［MD］=59.41, 95% confidence interval ［CI］: 9.74-109.08, P=0.02), significantly higher blood transfusion rate (relative risk ［RR］=2.24, 95%CI: 1.04-4.82, P=0.04) and rate of hepatic portal occlusion (RR=2.27, 95%CI: 1.37-3.75, P=0.001), a significantly shorter length of hospital stay (MD=-3.87, 95%CI: -5.63 to -2.12,P＜0.001), and significantly lower overall incidence rate of postoperative complications (RR=0.58, 95%CI: 0.41-0.81, P=0.001) and incidence rates of major postoperative complications (RR=0.45, 95%CI: 0.22-0.91, P=0.03). There was no significant difference in intraoperative blood loss between the two groups (P＞0.05). ConclusionFor hepatectomy, RALF can shorten the length of hospital stay and reduce postoperative complications, creating conditions for minimally invasive hepatectomy and rapid recovery.

Objective: To investigate the clinical application of indocyanine green fluorescence imaging in open hepatectomy. Methods: A total of forty-five patients who underwent liver resection in Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University from July 2017 to December 2018 were included in this prospective study. There were 26 males and 19 females, aged between 29 to 74 (51±10) years. Indocyanine green was injected intravenously 72~96 hours prior to surgery in all these patients. An intraoperative fluorescence imaging system was used to locate and remove the tumor, the liver parenchymal transection planes and surgical margins were detected by fluorescence again after tumor resection. The fluorescence profiles of the tumor specimens in relation to the tumor differentiation were analyzed. Results: Indocyanine green fluorescence imaging was performed in 45 patients. A total of 66 lesions were detected by preoperative CT (or MRI), abdominal ultrasound and intraoperative fluorescence imaging. After excision of the primary liver cancer, the surgical margins of the remnant liver stumps and fluorescence in the excised liver specimens were studied. Thirteen small lesions were found in 10 patients, most of which were located at the surgical margin, and the smallest tumors detected were less than 5 mm in diameter. Five venous cancer emboli were found in 5 patients, 3 of which were not detected by preoperative imaging examinations. The fluorescence profile images of the excised hepatocellular carcinoma specimens showed homogeneous fluorescence in most highly differentiated hepatocellular carcinoma, and partial fluorescence or ring fluorescence in moderately differentiated hepatocellular carcinoma. Conclusion Indocyanine green fluorescence imaging technology can identify liver surface lesions, as well as detect small residual lesions at the cutting edge and venous thrombus, which improves the efficiency of hepatocellular carcinoma resection.

Objective: To explore the safety and feasibility of transumbilical single channel laparoscopic cryptorchidopexy with conventional instruments in treatment of cryptorchidism in children. Methods: Thirty-five children with cryptorchidism were treated by transumbilical single channel laparoscopic cryptorchidopexy with conventional instruments from November 2017 to March 2018 at Department of Pediatric Surgery, the First Affiliated Hospital of Guangxi Medical University.Clinical data were recorded including the general information, operation time, intraoperative blood loss, postoperative testicular position and postoperative complications, etc. Results: All 35 patients completed the cryptorchidopexy in one operation.Among those 35 patients, 28 patients had unilateral lesions and 7 patients had bilateral lesions, with a total of 42 sides.Twenty-six patients were of groin type(33 sides), 9 patients abdominal type(9 sides). The average operation time was (40.4±8.2) min for unilateral lesion, and (62.5±15.3) min for bilateral lesions; the average intraoperative blood loss was (3.0±1.8) mL; and the average postoperative hospital stay was (6.4±2.1) h. Testis of 32 patients (40 sides) were fixed in the middle and bottoms of the scrotum, and testis of 2 patients (2 sides) were fixed on the top of the scrotum.One case had poor healing of naval incision, which was recovered in 1 week after dressing change.There were no postoperative complications such as scrotum hematoma, infection of incision, testicular epididymitis, testicular necrosis, testicular retraction or testicular atrophy, etc.No obvious visible scar was found in the abdomen review 2 weeks postoperatively, with the incidence of complications was 2.9%(1/35 cases). Conclusions Transumbilical single channel laparoscopic cryptorchidopexy with conventional instruments in treatment of cryptorchidism is characterized by small trauma, quick recovery, low complication rate and visible scar free result, which is worthy of clinical promotion, but the operation is relatively complex and the correct procedures are required.

Objective To assess the effect of PCI on quality of life in very old CHD patients.Methods One hundred and ninety-six ≥80 years old CHD patients were divided into PCI group (n=92) and drug therapy group (n=104).Their clinical data were retrospectively analyzed.The patients were followed up for 12 months during which non-event survival rate,readmission rate,and incidence of recurrent arrhythmia,cardiogenic death,bleeding events were recorded.Results The incidence of 3-vessel lesions and serum creatinine level were significantly higher in PCI group than in drug therapy group (70.65％ vs 25.00％,82.63±25.35 μmol/L vs 71.09±22.71 μmol/L,P＜0.01).The non-event survival rate was significantly higher while the readmission rate was significantly lower in PCI group than in drug therapy group (66.30％ vs 50.96％,25.00％ vs 44.23％,P＜0.05).No significant difference was found in recurrent arrhythmia and cardiogenic death between the two groups (P＞0.05).Conclusion PCI can effectively improve the quality of life in very old CHD patients.

Objective To study the protective effect of Trimetazidine on myocardial injury in mice.Methods 6 to 7 week-old male BALB/c mice were randomly divided into 3 groups at twelve for each group:normal saline (NS) group,ISO group and TMZ group,N.S group for blank control group,ISO group for damage group,TMZ as treatment group.After 4 weeks,cardiac index (HW/BW) was calculated,serum lactate dehydrogenase (LDH) activity were measured by enzyme standard method.Malondialdehyde(MDA) was detected by thiobarbituric acid method(TBA).Superoxide dismutase (SOD) activity were determined by WST-1 method.The concentrations of serum Klotho were measured by ELSIA.The cardiac muscular tissue was imbedded with paraffin and colored with HE,Massion and caspase-3.Results The experiment model meets the requirements.In TMZ groups' HW/BW,LDH activity and MDA level were significantly lower than those of the ISO group(P ＜ 0.01).SOD energy,concentration of Klotho was significantly higher than those of the ISO group(P ＜ 0.01).HE color results showed that the myocardial cell diameter of ISO group was obviously larger than that of NS group,combined with disordered muscle fibers and hyperplastic myocardial interstitial fibroblasts.The cardiomyocytes diameter of TMZ groups was much smaller than that of the ISO group.Masson color results showed that the level of collagen fiber distribution in the myocardial interstitial and hemal wall of TMZ group was lower than that of ISO group.Caspase 3 color results showed that the number of tan dye distribution was significantly lower in TMZ group than that of the ISO group(Color positive results showed obvious practical color distribution).Conclusion Trimetazidine could prevent myocardial injury and its mechanism might be related to raised Klotho level.

Objective To assess the protective effect of the proteasome inhibitor bortezomib on rat liver subjected to bile duct obstruction. Methods Thirty rats were divided randomly into three groups, which were sham-operation group (SO group), bile duct ligation control group (Con group) and bortezomib group (Bor group). All rats in the Con group underwent ligation of the common bile duct, and rats in the Bor group were given bortezomib intrabominally at-1 d, 4 d post-ligation of the common bile duct. All the rats were sacrificed at 7 d post-surgery. ALT, TB and TBA levels were determined. The expression of NF-κB p65 was assessed using immunohistological staining. RT-PCR was employed to detect TNF-α mRNA levels in liver samples. Results There was no significance in the levels of TB and TBA between Con and Bor groups. The ALT revel in the Bor group [(92.4±21.4)μmol/L]was significantly lower than that in the Con group [(145.7 ±33.5) μmol/L], P＜0.05. The positive staining rate of NF-κB p65 subunit in the Bor group showed significant lower value (11.6% ±2.7 % ) compared to that in the Con group (15.5 %±4.3 % ), P＜0.05. The expression ratio of TNF-α mRNA in the Bor group was 1.0± 0. 2, which also significantly lower than that in the Con group (1.3±0.4), P＜0. 05. Conclusion These data suggest that the proteasome inhibitor bortezomib reduces rat hepatocyte injury in the bile duct ligation by mechanisms associated with the inhibition of NF-κB as well as the attenuation of inflammation.