OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objective    To investigate the clinical effect of thoracoscopic lobectomy versus segmentectomy in the treatment of T1bN0M0 non-small cell lung cancer (NSCLC). Methods    Clinical data of 181 patients with T1bN0M0 NSCLC admitted to our hospital from 2012 to 2015 were retrospectively analyzed. They were divided into a lobectomy group and a segmentectomy group according to surgical methods. There were 117 patients in the lobectomy group (46 males and 71 females aged 61.32±8.94 years) and 64 patients in the segmentectomy group (20 males and 44 females aged 58.55±12.57 years). Perioperative indicators and prognosis were compared between the two groups. Results    The segmentectomy group had longer operation time, less intraoperative blood loss, shorter postoperative hospital stay and more preservation of lung function compared with the lobectomy group (P<0.05). The lobectomy group had higher consolidation tumor ratio, bigger tumor diameter, and more lymph node sampling compared with the segmentectomy group (P<0.05). There was no statistical difference in 5-year overall survival or recurrence-free survival between the two groups (P<0.05). Conclusion    For patients with T1bN0M0 NSCLC, thoracoscopic segmentectomy and lobectomy have similar prognosis, but segmentectomy has advantages with less injury and faster recovery over lobectomy.

BACKGROUND: Chronic obstructive pulmonary diseases (COPD) affects 45%-63% of lung cancer patients worldwide. Lung cancer patients complicated with COPD have decreased cardiopulmonary function and increased perioperative risk, and their postoperative exercise endurance and lung function are significantly lower than those with conventional lung cancer. Previous studies have shown that postoperative exercise training can improve the exercise endurance of unselected lung cancer patients, but it is unclear whether lung cancer patients with COPD can also benefit from postoperative exercise training. This study intends to explore the effects of postoperative exercise training on exercise endurance, daily activity and lung function of lung cancer patients with COPD. METHODS: Seventy-four patients with non-small cell lung cancer (NSCLC) complicated with COPD who underwent pneumonectomy in the lung cancer center of West China Hospital of Sichuan University from August 5, 2020 to August 25, 2021 were prospectively analyzed. They were randomly divided into exercise group and control group; The patients in the two groups received routine postoperative rehabilitation in the first week after operation, and the control group was given routine nursing from the second week. On this basis, the exercise group received postoperative exercise rehabilitation training for two weeks. Baseline evaluation was performed 3 days before operation and endpoint evaluation was performed 3 weeks after operation. RESULTS: The exercise endurance, daily activity and pulmonary function test results of the two groups decreased from baseline to the end point. However, after the operation and intervention program, the maximum oxygen consumption of Cardiopulmonary Exercise Test and the walking distance of 6-Minute Walking Test in the exercise group were significantly better than those in the control group [(13.09±1.46) mL/kg/min vs (11.89±1.38) mL/kg/min, P=0.033; (297±46) m vs (243±43) m, P=0.041]. The average number of we-chat steps in the exercise group was also significantly better than that in the control group (4,381±397 vs 3,478±342, P=0.035). Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in the exercise group were better than those in the control group, but the difference did not reach a statistically significant level [(1.76±0.19) L vs (1.60±0.28) L, P=0.084; (1.01±0.17) L vs (0.96±0.21) L, P=0.467]. CONCLUSIONS Postoperative exercise rehabilitation training can improve exercise endurance and daily activity ability of patients with lung cancer complicated with COPD and promote postoperative rehabilitation.
Carcinoma, Non-Small-Cell Lung/surgery* ; Exercise ; Forced Expiratory Volume ; Humans ; Lung Neoplasms/surgery* ; Pulmonary Disease, Chronic Obstructive/complications*

Objective:To investigate the influence of bundled ligation of the pancreatic stump on postoperative pancreatic fistula (POPF) of distal pancreatectomy (DP).Methods:The retrospective case-control study was conducted. The clinical data of 60 patients with diseases in pancreatic body and tail who underwent DP in the Affiliated Hospital of Inner Mongolia Medical University from January 2011 to August 2018 were collected. There were 24 males and 36 females, aged from 19 to 68 years, with a median age of 45 years. Of the 60 patients, 36 cases undergoing dissection of pancreas with Endo-GIA stapler were allocated into non-bundled group, and 24 cases undergoing bundled ligation of the pancreatic stump with No.10 or No.7 suture at the site over 1 cm of the resection site before dissection of pancreas were allocated into bundled group. Observation indicators: (1) postoperative situations; (2) analysis of risk factors for POPF of DP. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test or ANOVA test. Measurement data with skewed distribution were represented as M (range).Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the chi-square test and multivariate analysis was conducted using the Logistic regression model. Results:(1) Postoperative situations: the amylase concentration, cases with biochemical fistula, cases with grade B pancreatic fistula, cases with complications, time to extubation, duration of postoperative hospital stay, total hospital expenses were (2 629±592)U/L, 14, 5, 7, (11.9±0.7)days, (13.6±0.7)days, (49 430±1 626)yuan in non-bundled group and (683±312)U/L, 3, 1, 2, (9.7±0.6)days, (11.3±0.5)days, (44 767±1 163)yuan in bundled group, respectively. There were significant differences in the amylase concentration, cases with biochemical fistula, time to extubation, duration of hospital stay, total hospital expenses between the two groups ( t=2.528, χ2=1.512, t=2.341, 2.311, 2.111, P<0.05), and there was no significant difference in the cases with grade B pancreatic fistula or cases with complications between the two groups ( χ2=1.512, 1.394, P>0.05). (2) Analysis of risk factors for POPF of DP. Results of univariate analysis showed that tumor diameter and bundled ligation of the pancreatic stump were related factors of patients undergoing pancreatic fistula after DP ( χ2=4.462, 5.061, P<0.05). Results of multivariate analysis showed that bundled ligation of the pancreatic stump was an independent influencing factor of patients undergoing pancreatic fistula after DP ( odds ratio=0.187, 95% confidence interval as 0.037-0.954, P<0.05). Conclusions:Bundled ligation of the pancreatic stump was an independent influencing factor of patients undergoing pancreatic fistula after DP. Bundled ligation of the pancreatic stump can effectively reduce the incidence of POPF, especially biochemical fistula, the time to extubation, duration of postoperative hospital stay and total hospital expenses, and promote patient recovery after DP.

Clinical data of 46 patients with trans-sphincter anal fistula treated by fistulectomy with external anal sphincter bareness in Department of Anorectal Surgery, Jiaxing TCM Hospital from July 2018 to July 2019 were retrospectively analyzed. All operations were performed successfully. There were no significant differences in Wexner incontinence scores (2.00±0.68 vs.1.99±0.70, P<0.05), mean anal resting pressure [(75.60±8.60) vs.(73.60±8.20)mmHg(1 mmHg=0.133 kPa), P<0.05] and maximum systolic pressure [(109.60±7.80) vs.(107.20±8.30)mmHg, P<0.05] before and 6 months after operation. There were 1 case with postoperative incision bleeding and 2 cases with postoperative infection. All patients were followed up for 6 months and there was no recurrence and changes in anal shape during the follow-up. Results indicate that the fistulectomy external anal sphincter bareness is safe, efficient with well preserved sphincter function for patients with trans-sphincter anal fistula.

Objective To investigate the clinical features and risk factors of multidrug－resistant bacteria (multi drug resistant organisms, MDROs) infection in Department of Neurosurgery, and to provide evidence for the prevention and control of MDRO infection. Methods Data from 437 cases of infection in hospitalized patients on January 2012－2016 year in December Third Affiliated Hospital of Guizhou Medical University were retrospectively analyzed. Patients were divided into MDROs group and non MDROs group based on the results of MDROs detection. Multi factor Logistic regression analysis model was used to analyze risk factors. Results The infection rate of MDROs was 35.51%, and the detection rate of MDROs was 33.23% . ESBLs, CR－AB and MRSA were the most common bacterial species, and the infection of respiratory tract, urinary tract and wound infection were the main infection sites. Multivariate logistic regression analysis showed that hospitalization time ＞20 d, level of consciousness (coma), occupancy of ICU ≥7 d, ventilation (invasive), number of antibiotics used≥3, combined use of antibiotics≥3, mechanical ventilation Time≥7 d were possible risk factors for MDROs infection in neurosurgical patients (P＜0.05). Conclusion The situation of MDROs infection in neurosurgery is severe. To reduce MDROs infection, it is important to shorten unnecessary hospitalization time, promptly assess and transfer out of ICU as soon as possible, improve microbial examination, avoid frequent change of antibiotics or unnecessary use of use of broad－spectrum antibiotics, reduce unnecessary mechanical ventilation time, change to non－invasive ventilation as far as possible when the condition permits, focus on patients with poor consciousness, and prevent aspiration by mistake.

Objective This study investigated the use of interventional bronchoscopic techniques in management of patients with tracheobronchial tuberculosis.Methods In this retrospective study,we analyzed the clinical data of 76 patients with endobronchial tuberculosis.All patients underwent bronchoscopy examination and diagnosed by pathology.According to different treatments,the patients were divided into two groups,the observation group (56 cases) adopted by bronchoscopy and chemotherapy and the control group (20 cases) adopted by chemotherapy only.The general features,treatment effectiveness in the two groups were compared and analyzed.Results Compared with the control group,the sputum negative rate,the recovery rate of symptom,and the total effective rate were higher (P ＜ 0.05).No severe side effects were found in the two groups.There was a positive relationship among frequency of bronchoscopy,the area of lesion (r =0.296,P =0.025 ＜ 0.05) and the type of histology (r =0.323,P =0.014 ＜ 0.05).Conclusions It is concluded that interventional bronchoseopic techniques are useful in management of patients with endobronchial tuberculosis.

Objective To investigate the predictive value of central venous-to-arterial carbon dioxide difference (Pcv-aCO2) on the prognosis of elderly patients with sepsis.Methods 208 elderly patients who met the diagnostic criteria of the Sepsis-3 and with the age of more than 60 years old, and admitted to intensive care unit (ICU) of Guangdong General Hospital from January to December in 2017 were enrolled. According to the prognosis, the patients were divided into death group (n = 46) and survival group (n = 162). The Pcv-aCO2, central venous oxygen saturation (ScvO2), serum procalcitonin (PCT), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluationⅡ (APACHEⅡ) were collected for all patients. The differences of each index between the two groups were compared. The correlations between Pcv-aCO2 and ScvO2, PCT, CRP, SOFA, APACHEⅡscores were analyzed respectively with Pearson correlation. The prognostic value of Pcv-aCO2 in elderly patients with sepsis was assessed by receiver operating characteristic curve (ROC).Results Compared with survival group, the Pcv-aCO2, PCT, CRP, SOFA and APACHEⅡscores in death group were significantly increased [Pcv-aCO2 (mmHg, 1 mmHg = 0.133 kPa): 6.13±3.33 vs. 4.40±2.65, PCT (μg/L): 31.41±12.83 vs. 3.01±2.69, CRP (mg/L): 130.51± 42.23 vs. 104.46±50.12, SOFA: 12.01±2.25 vs. 9.05±2.06, APACHEⅡ: 29.52±5.03 vs. 20.01±3.21, allP < 0.05], and ScvO2 in death group was significantly decreased (0.571±0.136 vs. 0.685±0.106,P < 0.01). Correlation analysis showed that the Pcv-aCO2 was negatively correlated with ScvO2 (r = -0.762,P = 0.001) and was positively correlated with PCT, CRP, SOFA and APACHEⅡscores (r value was 0.737, 0.625, 0.738, 0.713, respectively, allP < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of Pcv-aCO2 prediction of death in patients with sepsis was 0.826, the cut-off was 6.62 mmHg, the sensitivity was 84.7％, the specificity was 77.5％, the positive likelihood ratio was 3.76, and the negative likelihood ratio was 0.19.Conclusion Pcv-aCO2 has a great value in evaluating the prognosis of elderly patients with sepsis and can accurately determine the prognosis of sepsis.