Objective To investigate the expression of Thymosinβ10(TMSB10)in gastric cancer and its molecular mechanism in promoting the progression of gastric cancer.Methods We collected pathological sections of 70 patients with gastric cancer in our hospital,detected expression of TMSB10 in gastric adenocarcinoma by immunohistochemistry,and analyzed its prognostic effect.In order to study the mechanism of action,the effects of TMSB10 on the proliferation and glycolysis of gastric cancer cells and its related mechanism were observed by trans-fection technique,CCK8 test,EDU assay,Transwell assay,scratch test,glycolysis assay and Western blot.Results Immunohistochemistry showed that TMSB10 was highly expressed in gastric cancer,while the expression level of TMSB10 was correlated with tumor size(P=0.032),TNM stage(P=0.002)and distant metastasis.In the mechanism study,we found that overexpression of TMSB10 promoted the proliferation,invasion,migration and glycolytic phenotype of gastric cancer cells through in vitro CCK-8 test,EDU assay,Transwel assay and glycolysis assay,and vice versa.Western blot results showed that overexpression of TMSB10 may regulate the occurrence of gastric cancer through up-regulation of the AMPK/mTOR signaling pathway.Conclusions TMSB10 promotes the proliferation,invasion,migration and glycolysis gastric cancer through the AMPK/mTOR signaling pathway.

Objective:To explore the effect of perioperative aspirin administration on intraoperative and postoperative bleeding in patients undergoing video-assisted thoracoscopic (VATS) pulmonary wedge resection.Methods:Sixty-three patients scheduled for VATS pulmonary wedge resection in Shougang Hospital of Peking University from November 2020 to April 2022 were randomly assigned in 2 groups. All patients had a history of aspirin taking, patients in study group ( n=32) continued aspirin taking perioperatively, and patients in the control group ( n=31) stopped taking aspirin for 7 days before surgery and resumed taking 3 days after surgery. The volume of intraoperative blood lost, operation time, postoperative drainage volume, thoracic drainage tube placement time, postoperative hospital stay, postoperative thrombosis of lower extremity, perioperative cardiovascular and cerebrovascular events, and postoperative wound healing were documented and compared between the two groups. Results:There were no significant differences in age, gender, oral aspirin time, lesion location, lesion nature, localization, lesion size and underlying disease between the two groups (all P>0.05). All patients successfully completed the operation, and no patients switched to thoracotomy. The intraoperative blood loss in study group and control group was (27.72±12.86) ml and (31.35±13.81) ml ( t=1.08, P=0.283); the operation time was (61.16±10.24) minutes and (61.39±13.79) minutes, respectively ( t=0.08, P=0.940). There were no significant differences in postoperative thoracic drainage, drainage tube placement time, length of hospital stay, incidence of lower extremity thrombosis, incidence of cardiovascular and cerebrovascular events, and rate of poor wound healing between the two groups (all P>0.05). Conclusion:Perioperative administration of aspirin may not increase intraoperative and postoperative bleeding, and the incidence of operation-related complications in patients undergoing VATS pulmonary wedge resection.

Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; China

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.

Objective:To establish a double antibody sandwich ELISA for detecting the specific antigen of Seoul virus (SEOV) L99 strain and to provide a means for antigen detection in the development, production and verification of vaccine against hemorrhagic fever with renal syndrome (HFRS).Methods:Monoclonal antibodies (McAbs) aganist L99 virus were induced in mice using four hybridoma cell lines and purified by Protein-A affinity chromatography. The purity, titer and specificity of McAbs were determined by SDS-PAGE, indirect ELISA and Western blot, respectively. Four McAbs were paired with each other and the additivity indices of paired McAbs were analyzed. After labeling McAbs with horseradish peroxidase (HRP), the concentrations of the coated and labeled antibodies were optimized by orthogonal test, and then a double antibody sandwich ELISA for virus antigen detection was established. Type Ⅱ HFRS inactivated vaccine standard was used as a quantitative standard to verify the sensitivity, linearity, specificity, accuracy and precision of the developed method. The applicability of the method was verified by testing three batches of vaccine stock solutions.Results:Four McAbs were at titers of greater than 1∶10 6 and their purity was all greater than 98%. The McAbs secreted by 1D5, 3A4 and 5B7 cells could specifically recognize the nucleocapsid protein of SEOV L99. There was cross-reaction between McAb secreted by 1D5 cells and Hantaan virus PS-6. The McAbs secreted by 3A4 and 1D5 were used as coating and labeling antibodies based on the results of antibody pairs. The working concentrations of the coating antibody and the horseradish peroxidase (HRP)-labeled antibody were 20 μg/ml and 1∶4 000, respectively. The minimum detection limit of the established method for the detection of SEOV L99 antigen was 0.078 1 μg/ml, and the linear range was 0.078 1-2.500 0 μg/ml with a R2 value of more than 0.99. There was no cross reaction with other HFRS vaccine. The virus antigen recovery rate was between 95.8% and 108.7%, and the coefficients of variation of precision was less than 10%. Three batches of Type II HFRS inactivated vaccine stocks were detected by this method and the results was dose-dependent. Conclusions:This study successfully established a double antibody sandwich ELISA method for specific detection of SEOV L99 strain antigen in the production of bivalent HFRS vaccines produced from hamster kidney cells.

Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely

Objective:To develop and validate a clinical prediction model for the risk of malignant ventricular arrhythmia in patients with acute myocardial infarction (AMI) during hospitalization, and evaluate the effect of the prediction model.Methods:A retrospective study was conducted. A total of 2 649 patients with AMI admitted to cardiology department of Changzhou No.2 People's Hospital of Nanjing Medical University from December 2012 to August 2020 were enrolled. The clinical characteristics including gender, age, medical history, discharge diagnosis, vital signs during hospitalization, electrocardiogram characteristics at admission, laboratory examination indexes, interventional treatment, drug usage, malignant ventricular arrhythmias [mainly included sustained ventricular tachycardia (VT), ventricular flutter or ventricular fibrillation (VF)], and death were recorded. All patients were divided into two groups according to whether VT/VF occurred during their hospitalization. Independent risk factors for VT/VF during hospitalization were evaluated by multivariate Logistic regression analysis, and a clinical prediction model was constructed. The receiver operating characteristic curve (ROC curve) was plotted, and the area under ROC curve (AUC) was calculated to evaluate the accuracy of the prediction model.Results:A total of 2 649 eligible patients with AMI were enrolled, of whom 134 (5.06%) developed VT/VF during hospitalization. The in-hospital mortality rate in VT/VF group was significantly higher than that in non-VT/VF group (38.1% vs. 1.7%, P < 0.01). Compared with the non-VT/VF group, the patients in the VT/VF group with lower systolic blood pressure [SBP (mmHg, 1 mmHg = 0.133 kPa): 125.9±28.2 vs. 132.0±24.2], higher random blood glucose (mmol/L: 8.6±4.8 vs. 7.4±3.7), worse cardiac function [Killip heart function grade ≥ 3: 36.6% vs. 10.7%, left ventricular ejection fraction (LVEF) < 0.50: 56.7% vs. 33.6%, frequent premature ventricular contractions: 12.7% vs. 1.2%] and more hypokalemia (46.3% vs. 17.3%), with significant differences (all P < 0.05). Multivariate Logistic regression analysis showed that Killip classification of cardiac function ≥ 3 [odds ratio ( OR) = 3.540, 95% confidence interval (95% CI) was 2.336-5.363], random blood glucose > 11.1 mmol/L ( OR = 1.841, 95% CI was 1.171-2.893), LVEF < 0.50 ( OR = 0.546, 95% CI was 0.374-0.797), frequent premature ventricular contractions ( OR = 12.361, 95% CI was 6.077-25.144), potassium < 3.5 mmol/L ( OR = 4.268, 95% CI was 2.910-6.259), SBP < 90 mmHg ( OR = 0.299, 95% CI was 0.150-0.597) and creatinine (Cr) > 100 μmol/L ( OR = 2.498, 95% CI was 1.170-5.334) were independent risk factors for VT/VF in patients with AMI (all P < 0.05). The clinical prediction model of VT/VF risk was constructed based on the variables selected by multivariate regression analysis. The ROC curve analysis showed that the AUC of the model in predicting VT/VF was 0.779 (95% CI was 0.735-0.823, P < 0.001); the optimal cut-off value of the model was 17, the sensitivity was 76.1%, the specificity was 67.3%. Conclusions:The incidence of VT/VF during hospitalization of AMI patients significantly increases the risk of in-hospital death. The independent risk factors of VT/VF are Killip grade ≥ 3, random blood glucose > 11.1 mmol/L, LVEF < 0.50, frequent ventricular premature beats, potassium < 3.5 mmol/L, SBP < 90 mmHg and Cr > 100 μmol/L. The newly constructed clinical prediction model has certain predictive value for the occurrence risk of VT/VF.

Objective To investigate the clinicopathological characteristics of colon cancer patients with different mismatch repair gene (MMR) status and evaluate the value of MMR status combined with preoperative blood neutrophil-lymphocyte ratio (NLR) in predicting postoperative recurrence of colon cancer. Methods We retrospectively analyzed the pathological MMR immunohistochemistry results of 125 colon cancer patients after radical resection. Patients were divided into deficient mismatch repair (dMMR) group (n=55) and proficient mismatch repair (pMMR) group (n=70), and further divided into four groups according to MMR status and NLR level. Results Compared with the pMMR group, the patients in the dMMR group had younger onset age, larger tumor size, lower differentiation and more nerve invasion, and were more likely to occur in the right hemicolon (P < 0.05). According to the ROC curve, the NLR threshold was determined as 3. The proportion of low NLR in dMMR group was significantly higher than that in pMMR group (P < 0.05). The 3-year recurrence-free survival rate of the dMMR with low NLR group was 85.0%, significantly higher than those of the other three groups (P < 0.05); Survival analysis showed a significant advantage of the dMMR with low NLR group comparing with the pMMR with high NLR group. Conclusion dMMR colon cancer has unique clinicopathological characteristics. MMR status combined with NLR value can be used to evaluate the postoperative recurrence risk of colon cancer patients.

Objective:To investigate the clinical effect of free fibula flap transplantation in repairing the defect of mandibular osteoradionecrosis (ORN).Methods:A total of 151 mandibular ORN patients undergoing free fibular flap transplantation were selected from August 2005 to September 2020 in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University. Among them, 109 patients were males and 42 patients were females, aged (54.1±10.1) (ranged 31-85) years old. The clinical data of the patients was collected and the survival rate of the flaps and postoperative function were calculated to evaluate the surgical efficacy. The χ 2 test was used for difference analysis. Results:Among the 151 patients, mandibular ORN caused by radiotherapy for nasopharyngeal carcinoma accounted for 79.5% (120/151). The average time for mandibular ORN appeared was 5(6) years after radiotherapy. Facial artery [57.2%(87/152)] and superior thyroid artery [32.9%(50/152)] were the main anastomotic arteries in the recipient area. There was no significant difference in the necrosis rates of the two flaps [10.3%(9/87) and 12.5% (5/50), respectively, P=0.949]. The main anastomotic veins in the recipient area were the external jugular vein [48.4%(135/279)] and the common facial vein [26.5%(74/279)]. Twenty-five cases (16.6%) had one vein anastomosed, and 126 cases (83.44%) had two veins anastomosed. There was no significant difference in the flap necrosis rate between the two conditions [20.0%(5/25) and 7.1%(9/126), respectively, P=0.100]. Ninety-seven cases (64.2%) used the peroneal musculocutaneous-fascia composite flap to repair the maxillofacial soft and hard tissue defects. Thirteen cases (8.6%) underwent the restorations with digital virtual surgery design, of which 5 cases were repaired with dental implants at the same time. After the operations, lower respiratory tract infection occurred in 17 patients (11.3%), and upper respiratory tract obstruction occurred in 3 cases (2.0%). The survival rate of the flap after operation was 90.7% (136/151), and 21 patients (13.9%) had flap vascular crisis. Delayed healing of maxillofacial wounds occurred in 33 cases (21.9%). After 3 to 24 months of follow-ups, 110 patients (76.9%) had no fistula inside/outside the oral cavity, 118 patients (82.5%) had an improvement in opening mouth of increasing (≥0.5 cm) after surgery, 135 patients (94.4%) had pain relief, 97 cases (67.8%) could eat normal diet, semi-liquid or soft food, and 137 cases (95.8%) were satisfied or basically satisfied with the treatment effects. Conclusions:The free fibular flap transplantation is an effective method to repair mandibular ORN defects. Preoperative vascular assessment is helpful for the selection of recipient vessels. Facial artery, superior thyroid artery, external jugular vein and common facial vein can be used as the main recipient vessels. The repair of the peroneal musculocutaneous-fascia composite flap facilitates the closure of internal and external fistulas. Digital technology can help to restore the maxillofacial shape more accurately, improve the patient′s occlusal and chewing function and enhance the quality of life of mandibular ORN patients.

COVID-19, an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. China has achieved rapid containment of this highly infectious disease following the principles of early detection, early quarantine and early treatment with integrated traditional Chinese and Western medicine. The inclusion of traditional Chinese medicine (TCM) in the Chinese protocol is based on its successful historic experience in fighting against pestilence. Current findings have shown that the Chinese medicine can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever. To date there are over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. The three Chinese patent medicines (/ (Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules), (Honeysuckle Flower Cold-Relieving Granules) and (Stasis-Resolving & Toxin-Removing) were officially approved by the National Medical Products Administration to list COVID-19 as an additional indication. The pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.