In recent studies some urea derivatives have been identified as potent anti-tuberculosis agents by targeting mycobacterial membrane protein large 3 (MmpL3). However, this compound series as exemplified by AU1235 exhibited poor in vitro pharmacokinetic profile. With AU1235 as the lead, we have identified a novel benzimidazole series as potential anti-tuberculosis agents by using scaffold hopping approach. Among these synthesized compounds, 2-aminobenzimidazole derivative 8b showed the potent anti-tuberculosis activity with the MIC value of 0.03 microg x mL(-1). This compound also showed improved metabolic stability compared to AU1235. Our investigation indicated that benzimidazole derivatives are the promising lead for further optimization as anti-tuberculosis agents.

Objective To determine risk factors of postoperative pulmonary complications within 1 month in patients undergoing thoracic surgery in Day Care Unit.Methods The total of 200 patients routinely scheduled for VATS under centralized management were enrolled in this study.On the postoperative day 1,lung ultrasound(LUS)was conducted by one physician in the ward.The patients received at least once Chest X-ray or CT in outpatient department within 30 days after discharge.The composite of out-of-hospital PPCs,and the value of LUSS in predicting the PPCs was appraised.Furthermore,we identified the perioperative risk factors associated with PPCs in VATS patients.Results Of 200 recruited VATS patients eligible in the Nanjing Drum Tower Hospital,188 participants received LUS examination and finally completed the 30 days follow-up.Of whom,68 patients developed the varied types of PPCs.Multivariable Logistic regression analysis indicated that comorbidity of immune system disease(P = 0.021),lobar resection(P = 0.031)and the postoperative 24 hours LUSS(P = 0.002)were independent risk factors for PPCs within 30 days after VATS.Conclusion Comorbidity of immune system disease,lobar resection and the postoperative 24 h LUSS were independent risk factors for PPCs within 30 days after VATS.

Objective To investigate the changes in cognitive function in patients with early Parkinson's disease (PD) in a 5-year follow-up.Methods A total of 181 PD and 173 normal participants were recruited between January 2009 and January 2012 at the Department of Neurology,the Second Hospital of Jiaxing City.Regression analysis was used to evaluate the risk factors of cognitive impairment,and changes in subdomains of the Montreal Cognitive Assessment (MoCA) were compared annually with baseline data.Results Baseline clinical data were similar between the two groups.The level of cognitive impairment was positively correlated to the age of onset and the Hamilton Anxiety Scale (H AMD) (t =3.326,P＜ 0.05;t =5.211,P＜0.01),and negatively correlated to education level (t=-2.505,P＜0.05).There were no statistical differences in the first (26.5 ± 2.6),second (26.3±3.2) and third year (25.9±2.9) in the total scores of MoCA,which significantly increased in the forth (24.4 ± 2.3,P＜0.05) and fifth (24.1 ± 1.2,P＜0.05) year compared with baseline levels (26.7±2.9).However,in the control group,differences between any two years in total scores were not statistically significant (all P＞0.05).Seven subdomains of MoCA were attenuated,and four of them were significant different between the groups,including delayed recall,attention,abstraction task and orientation after the forth year of follow-up (all P ＜ 0.05).Meanwhile,visuospatial execution capacity was attenuated before the third year,and then rose markedly (P＜0.05).In the control group,the between-year differences of seven subdomains were not statistically significant (all P＞0.05).Conclusions Cognitive function of PD patients decreases significantly in some domains,such as delayed recall,attention,abstraction task and orientation after a five-year followup.

Objective To investigate the solubility and stability of Tetrodotoxin (TTX) in different solvents, and the effect of temperature and pH on its stability. Methods Solutions of TTX in different matrices were prepared. Their concentrations at different temperatures and pH buffers were determined by high performance liquid chromatography and their solubility and stability were analyzed and calculated. Results TTX was most soluble at pH 3.5 and its solubility decreased as the pH increased. TTX degraded most rapidly under strong alkali conditions, with complete degradation after 20 min of reaction at 0.1 mol/L sodium hydroxide and 70 ℃. The stability test results similarly demonstrated that TTX was least stable under alkaline conditions. In a PBS buffered solution at 37 ℃, pH 7.4, TTX concentration began to decrease consistently at 1~10h, with a degradation rate of 88.07±0.27% after 28 days. Conclusion TTX is readily soluble in acidic aqueous solutions at pH 3.5 and almost insoluble in alkaline aqueous solutions. Its stability is closely related to the temperature and pH of the medium. It is more stable in acidic aqueous solutions and easily degrades under alkaline conditions, and its degradation process could be accelerated by increasing temperature.

Objective:To establish the normal reference value of lumbar bone mineral density (BMD) under quantitative CT (QCT) in Chinese healthy adult females and to explore the regional differences.Methods:Total of 35 431 healthy women who met the inclusion criteria of Chinese health quantitative CT big data program were selected in this study. The BMD of the central plane of L 1 and L 2 vertebrae was measured by Mindways′s QCT system, and the mean value was taken. One-way analysis of variance was used to compare the BMD differences of lumbar vertebrae in women of different ages and regions. The subjects were grouped by an age interval of 10 years, and the level of BMD in different regions of the same age group were compaired. Results:The peak BMD of Chinese healthy adult women appeared in the age group of 20-29 years (Northeast China(183.01±24.58) mg/cm 3, North China (188.93±24.80) mg/cm 3, East China (187.54±27.71) mg/cm 3, South China (186.22±33.72) mg/cm 3, Central China (176.33±24.91) mg/cm 3, Southwest China(182.25±28.00) mg/cm 3), and then it decreased with age. The level of BMD in different regions decreased with the age. Before the age of 70 years, BMD in Central and Southwest China was always at a low level((176.23±24.91) to (90.38±28.12) mg/cm 3, 182.25±28.00 to (88.55±25.68) mg/cm 3), lower than those in Northeast China ((183.01±24.58) to (99.69±27.85) mg/cm 3), North China ((188.93±24.80) to (95.89±26.12) mg/cm 3), East China ((187.54±27.71) to (95.65±27.86) mg/cm 3). After 70 years of age, BMD tended to be the same in different regions ( P>0.05). The BMD values in Central China and Southwest China were similar in the age group of 40-60 years ( P>0.05). The BMD values in the health adult femles in the age group of 60 years in different regions of Chinawere all lower than those of bone mass abnormality (all P<0.05). The detection rate of osteoporosis in females over 50 years was the highest in Southwest China (25.65%) and it was the lowest in North China (17.30%). Conclusions:This study establishes reference values of BMD under QCT in healthy Chinese women, which can be used as a reference basis for identifying women with low BMD who are at risk of osteoporosis. The BMD value is the lowest in Southwest China and the highest in South China.

ObjectiveTo evaluate the clinical efficacy of Xu's Shenqiyizhu （SQYZ） decoction combined with chemotherapy in the treatment of cancer-related fatigue （CRF） of stagnated-toxin spleen deficiency type after gastric cancer surgery and explore its possible mechanism. MethodsFifty postoperative gastric cancer patients with CRF of stagnated-toxin spleen deficiency type were selected and randomly divided into an experimental group and a control group by using a random number table，with 25 cases in each group. The control group was treated with FLOT chemotherapy （50 mg·m^-2 docetaxel （iv drip on day 1） + 85 mg·m^-2 oxaliplatin （iv drip on day 1） + 200 mg·m^-2 calcium folinate （iv drip on day 1） + 2 600 mg·m^-2 fluorouracil （iv drip for 24 h on day 1），once every three weeks） and basic and symptomatic supportive treatment. The experimental group was treated with Xu's SQYZ decoction （decocted twice，200 mL taken orally twice a day） in addition to the treatment of the control group. One course of treatment lasted for three weeks，with a total of four courses conducted. Observation was performed on the piper fatigue scale （PFS） scores，karnofsky performance status （KPS） scores，European Organization for Research and Treatment of cancer quality of life questionnaire （EORTC QLQ-C30） scores，traditional Chinese medicine syndrome scores，and serum levels of tumor necrosis factor-α （TNF-α），interferon-γ （IFN-γ），and interleukin-6 （IL-6）detected via enzyme linked immunosorbent assay （ELISA） before and after treatment in the two groups. The safety test results before and after treatment for the two groups of patients，as well as the occurrence of adverse events during treatment， were recorded. Transcriptome sequencing data of peripheral blood samples from gastric adenocarcinoma patients and normal individuals were downloaded from the gene expression omnibus （GEO） database，and differentially expressed genes between the tumor and normal groups were identified. Differential gene enrichment analysis was made based on the Kyoto Encyclopedia of Genes and Genomes （KEGG） and Gene Ontology （GO）. The CRF relevance scores of genes were retrieved from the GeneCards database. Results① Compared with that before treatment，the total PFS score in the experimental group was significantly reduced （P<0.05）. Compared with the control group after treatment，the experimental group showed significantly reduced total PFS score （P<0.05）. ② Compared with that before treatment，the KPS score in the experimental group decreased significantly （P<0.05）. Compared with the control group after treatment，the experimental group exhibited a significantly decreased KPS score （P<0.05）. The experimental group demonstrated significantly increased functional scores （physical function，role function，emotional function，social function，and overall health） （P<0.05） and significantly reduced symptom scores （fatigue，shortness of breath，loss of appetite，constipation，and diarrhea） of the EORTC QLQ-C30 scale after treatment compared with before treatment. Compared with the control group after treatment，the experimental group presented significantly increased functional scores （physical function，emotional function，social function，and overall health） （P<0.05） and significantly reduced symptom scores （fatigue，nausea and vomiting，shortness of breath，loss of appetite，and diarrhea） of the EORTC QLQ-C30 scale （P<0.05）. Compared with those before treatment，the traditional Chinese medicine syndrome scores （eating too little and poor digestion，fatigue and weakness，postprandial bloating，abnormal bowel movements，lassitude and weakness，and total score） in the experimental group were significantly reduced （P<0.05）. Compared with the control group after treatment，the experimental group had significantly reduced traditional Chinese medicine syndrome scores （eating too little and poor digestion，fatigue and weakness，nausea and vomiting，and sallow complexion） （P<0.05）， which indicated better efficacy in the experimental group than in the control group （χ²=7.996，P<0.05）. The serum levels of TNF-α，IL-6，and IFN-γ were significantly correlated with each other （P<0.01）. Compared with those before treatment，the levels of serum cytokines TNF-α，IL-6，and IFN-γ in the experimental group were significantly reduced （P<0.05）. Compared with the control group after treatment，the experimental group showed significantly reduced serum levels of cytokines TNF-α，IL-6，and IFN-γ （P<0.05）. ③ There were no significant intra-group and inter-group differences in the safety test results of the two groups before and after treatment. During the treatment period，there was no significant difference in the incidence of adverse reactions between the two groups of patients. ④ Compared with the normal group，the tumor group exhibited a total of 328 significantly up-regulated genes in the peripheral blood （P<0.05），and KEGG and GO analyses showed that they were significantly enriched in signaling pathways such as TNF （P<0.05）. ⑤ TNF，IL6，IFNG， and other cytokine encoding genes may be key pathogenic genes for CRF. ConclusionXu's SQYZ decoction can alleviate symptoms such as fatigue in postoperative chemotherapy patients with gastric cancer and improve their functional status and quality of life. Its mechanism may be related to improving cytokine imbalance.

Objective To explore the perioperative safety of video-assisted thoracic surgery (VATS) in Day Care Unit and the risk factors for delayed discharge under centralized management model. Methods The patients with VATS managed by the Day Care Unit of the Drum Tower Hospital Affiliated to Nanjing University Medical School in 2021 were retrospectively collected. The patients’ postoperative data and risk factors for delayed discharge were analyzed. Results A total of 383 patients were enrolled, including 179 males and 204 females with an average age of 46.09±14.82 years. Eleven (2.87%) patients developed grade 3-4 postoperative complications during the hospitalization. Eighteen (4.70%) patients visited unscheduled outpatient clinic within 7 days, and 6 (1.57%) patients were re-hospitalized within 30 days after discharge. The remaining patients had no significant adverse events during the 30-day follow-up. The average length of hospital stay was 2.27±0.35 d. The length of hospital stay was over 48 h in 48 (12.53%) patients. The independent risk factor for delayed discharge was lobectomy or combined resection (OR=3.015, 95%CI 1.174-7.745, P=0.022). Conclusion VATS can be safely conducted under the centralized management in Day Care Unit. The risk factor for delayed discharge is the extent of surgical resection.