OBJECTIVE To study the differences in toxicity between intravenous(iv)administration and aqueous solution exposure of Dichroa alkali salt(DAS)in zebrafish.METHODS ① Well-devel-oped zebrafish larvae of 2 d post fertilization(2 dpf)were randomly divided into the normal control(no treatment),solvent control(saline,iv),and DAS groups(0.125,0.25,0.50,1.00 and 2.00 mg·kg-1,iv)before being observed for 3 consecutive days after administration.A heart rate of 0 was determined as death of zebrafish,and the mortality rate,maximum non-lethal dose(MNLD),and 10 percent lethal dose(LD10)were calculated.The incidence of venous sinus congestion,pericardial edema,slowing heart rate and blood flow of zebrafish in the 0.50 and 2.00 mg·kg-1 groups were observed and calculated by somatoscopic microscopy at 4 h after drug administration.Zebrafish larvae were iv given DAS at doses of 0.041,0.136,0.412,and 0.452 mg·kg-1 while the malformation phenotypes of zebrafish larvae development were observed under a stereomicroscope for 3 consecutive days,including pericardial edema,abnormal heart rate,slow blood flow,loss of circulation,eye abnormalities,brain malforma-tions,jaw abnormalities,loss/degeneration of the liver,delayed yolk sac absorption,intestinal abnormal-ities,abnormal body coloration,body edema,curvature of the trunk/tail/nodal cord and muscle degener-ation before the incidence was calculated.②Zebrafish larvae were randomly divided into a normal control group and DAS aqueous solution exposure groups at concentrations of 2.5,5.0,10.0,25.0,50.0,75.0,and 100.0 mg·L-1,observed for 3 d until the mortality rate,LD10,and MNLD were calculated.Zebrafish were exposed to DAS aqueous solutions at concentrations of 0.32,1.06,3.20,and 11.00 mg·L-1,and the malformation phenotypes of zebrafish larvae development were observed under a stereomicro-scope for 3 consecutive days to calculate the incidence.RESULTS ① The MNLD and LD10 of DAS iv administered to zebrafish larvae were 0.412 and 0.452 mg·kg-1,respectively.Compared with the solvent control group,4 h after DAS iv administration,the incidence of sinus congestion,slow heart rate and pericardial edema in the 0.50 and 2.00 mg·kg-1 groups significantly increased(P<0.05,P<0.01),so was the incidence of slow blood flow in the 2.00 mg·kg-1 group(P<0.01).The rate of delayed yolk sac absorption was significantly increased in the 0.041,0.136,0.412,and 0.452 mg·kg-1 groups(P<0.05,P<0.01),so was the mortality rate in the 0.452 mg·kg-1 group(P<0.05),with pericardial edema observed in the dead zebrafish.② The MNLD and LD10 of DAS aqueous solution exposure for zebrafish larvae were 3.20 and 11.00 mg·L-1,respectively.Compared with the normal control group,the incidence of decreased heart rate and slow blood flow was significantly increased in the 3.20 and 11.00 mg·L-1 groups(P<0.01),so was the incidence of significantly darkened intestines in the 1.06,3.20,and 11.00 mg·L-1 groups(P<0.01).The incidence of delayed yolk sac absorption was significantly increased in the 0.32,1.06,3.20,and 11.00 mg·L-1 groups(P<0.05,P<0.01),so was the incidence of trunk curvature and lower jaw malformation in the 11.00 mg·L-1 group(P<0.01).CONCLUSION The toxic phenotypes of DAS are different between iv administration and aqueous solution exposure in zebrafish larvae.DAS aqueous solution exposure can not only lead to slow heart rate,slow blood rheology,delayed yolk sac absorption and intestinal blackening,but also induce neurodevelopmental toxicity.However,iv adminis-tration can effectively ward off significant gastrointestinal damage and neurodevelopmental toxicity.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Objective:To analyze the relationship between gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibitor-1 (PAI-1) and lower limb deep venous thrombosis (DVT) after colorectal cancer surgery.Methods:The clinical data of patients with colorectal cancer who underwent surgical treatment in Zhangjiakou First Hospital from February 2020 to February 2023 were analyzed retrospectively. According to the presence or absence of lower limb DVT after surgery, the patients were divided into DVT group (20 cases) and non-DVT group (80 cases). The polymorphism of MTHFR C677T and PAI-1 promoter 4G/5G were detected by polymerase chain reaction method. The relationship between the polymorphisms of MTHFR C677T and PAI-1 promoter 4G/5G and lower limb DVT after colorectal cancer surgery was discussed by logistic regression analysis.Results:TT genotype frequency and T allele frequency of MTHFR C677T in the DVT group were higher than those in the non-DVT group: 65.00% (13/20) vs. 25.00% (20/80), 80.00% (32/40) vs. 38.75% (62/160). CC genotype frequency and C allele frequency were lower than those in the non-DVT group: 5.00% (1/20) vs. 47.50% (38/80), 20.00% (8/40) vs. 61.25% (98/160), with statistically significant differences ( P<0.05). There was no significant difference in CT genotype frequency between the two groups ( P>0.05). 4G/4G gene frequency and 4G allele frequency of PAI-1 gene in the DVT group were higher than those in the non-DVT group: 50.00% (10/20) vs. 21.25% (17/80), 67.50% (27/40) vs. 38.75% (62/160). 5G/5G gene frequency and 5G allele frequency were lower than those in the non-DVT group: 15.00% (3/20) vs. 43.75% (35/80), 32.50% (13/40) vs. 61.25% (98/160), with statistically significant differences ( P<0.05). There was no significant difference in 4G/5G gene frequency between the two groups ( P>0.05). The distribution frequency of TT genotype of MTHFR C677T and 4G/4G genotype of PAI-1 promoter in DVT group was higher than that in non-DVT group: 55.00% (11/20) vs. 22.50% (18/80), with a statistically significant difference ( P<0.05). Multivariate Logistic regression analysis showed that MTHFR C677T TT genotype ( OR = 1.499, 95% CI 1.201 to 1.871), PAI-1 promoter 4G/4G genotype ( OR = 1.471, 95% CI 1.170 to 1.850) and MTHFR The C677T loci TT genotype combined with the 4G/4G genotype of the PAI-1 promoter ( OR = 1.592, 95% CI 1.258 to 2.014) were risk factors for lower limb DVT after colorectal cancer surgery ( P<0.05). Conclusions:The TT genotype of MTHFR C677T site and the 4G/4G genotype of PAI-1 promoter are closely related to the formation of lower limb DVT after colorectal cancer surgery, and the risk of lower limb DVT is higher in patients with both genotype TT and 4G/4G.

Investigation on how nature produces natural compounds with chemical and biological diversity at the genetic level offers inspiration for the discovery of new natural products and even their biological targets. The polyketide rumbrin ( 1) is a lipid peroxide production and calcium accumulation inhibitor, which contains a chlorinated pyrrole moiety that is a rare chemical feature in fungal natural products. Here, we identify the biosynthetic gene cluster (BGC) rum of 1 and its isomer 12E-rumbrin ( 2) from Auxarthron umbrinum DSM3193, and elucidate their biosynthetic pathway based on heterologous expression, chemical complementation, and isotopic labeling. We show that rumbrins are assembled by a highly reducing polyketide synthase (HRPKS) that uniquely incorporates a proline-derived pyrrolyl-CoA starer unit, and followed by methylation and chlorination. Sequent precursor-directed biosynthesis was able to yield a group of rumbrin analogues. Remarkably, inspired by the presence of a human immunodeficiency virus (HIV)-Nef-associated gene in the rum cluster, we predicted and pharmacologically demonstrated rumbrins as potent inhibitors of HIV at the nanomolar level. This work enriches the recognition of unconventional starter units of fungal PKSs and provides a new strategy for genome mining-guided drug discovery.

An epidemiological investigation was carried out on a local cluster of outbreak caused by imported cases of Coronavirus Disease 2019 (COVID-19) in rural areas of Chengdu in December 2020, to find out the source of infection and the chain of transmission. According to
COVID-19 ; Disease Outbreaks ; Epidemics ; Humans ; Quarantine ; SARS-CoV-2

Objective: To assess the clinical characteristics and identify the risk factors in the acute myocardial infarction (AMI) patients complicating with ventricular septal rupture (VSR). Methods: A retrospective study was performed on 96 AMI patients complicating with VSR, who were hospitalized in the Second Xiangya Hospital of Central South University, Hunan Provincial Peoples′ Hospital, the First Affiliated Hospital of University of South China, the Second Affiliated hospital of University of south China, Xiangtan Central Hospital from December 2007 to May 2017. There were 46 females and the age was (66.2±10.7) years (from 43 to 90 years). Patients were divided into in-hospital survival group (n=64) and in-hospital death group (n=32). The 96 patients were also divided into the early death group (survived ≤2 weeks after admission, n=50) and non-early death group (survived>2 weeks after admission, n=46). Multivariate logistic regression was used to analyze the independent risk factors of the early death. Results: Location of VSR was available in 71 patients, VSR was located at the apical or anterior septum near the apical region in 64.0% (32/50) patients with the anterior AMI, VSR was located at the posterior wall and basal inferior segment in 57.1% (12/21) patients with non-anterior AMI. Compared to the in-hospital survival group, patients in the in-hospital death group were older ((69.6±11.3) years vs. (64.6±10.1) years, P=0.031), incidence of non-ventricular aneurysm (71.9% (23/32) vs. 37.5% (24/64), P=0.001) and anterior AMI (84.4%(27/32) vs. 62.5%(40/64), P=0.028) was significantly higher in the in-hospital death group than in the in-hospital survival group. The comparison between the early death group and non-early death group showed that older age, female, no history of angina or myocardial infarction, Killip grade>Ⅲ, and non-ventricular aneurysm were related to increased risk of the early mortality in this patient cohort. Logistic regression analysis revealed that female (OR=5.109,95%CI 1.19-22.00, P=0.012), no history of angina or myocardial infarction (OR=23.34, 95%CI 3.44-158.37, P=0.001), Killip grade>Ⅲ(OR=5.35, 95%CI 1.26-22.66, P=0.019) and non-ventricular aneurysm (OR=6.30,95%CI 1.67-23.73, P=0.005) were independent risk factors for early death in this patient cohort. Conclusion The risk factors of in-hospital death include older age, non-ventricular aneurysm and anterior AMI. Female, no history of angina or myocardial infarction, Killip grade>Ⅲ and non-ventricular aneurysm are independent risk factors for the early death of AMI patients complicating VSR.

Objective To investigate the impact of 1,25(OH)2D3 on histological changes and activation of STAT3 in BLM?induced pulmonary fibrosis mice. Methods 30 male C57BL/6 mice were randomly divided into control group ,BLM group and BLM+VD group. Mice in BLM group and BLM+VD group received intratracheal injection of BLM(3 U/kg). Control group were intratracheally injected equal volume of sterile saline. From the first day after the surgery,mice in BLM+VD group received intraperitoneal injection of VD (5μg/kg·d). After 21 days, H&E and Masson′s trichrome staining were carried out. Aschroft score were used to evaluate histological changes in lungs. IL?6,IL?4 and INF?γin BALF were assessed by Elisa. p?STAT3,α?SMA and Collagen I were detected by western blot (WB) and immunohistochemistry. Results Fibrosis score and level of α?SMA,Collagen I in BLM group were significantly higher than that in control group (P < 0.05). However ,treatment with VD effectively at?tenuated fibrosis (P<0.05). IL?6 and IL?4 increased while INF?γwas decreased in BALF of BLM group (P<0.05). VD could ameliorate these changes. Upregulation and neuclear translocation of p?STAT3 were observed in BLM group,while VD intervention could inhibit phosphorylation of STAT3. Conclusions VD attenuate BLM?induced pulmonary fibrosis and regulate inflammatory cytokines probably by blocking STAT3 activation.

Objective To explore effects and potential mechanisms of high insulin environment on high density lipoprotein (HDL) generation-related functional protein ABCA1.Methods [3 H] labeled cholesterol efflux from mature 3T3-L1 adipocytes was detected by liquid scintillation counting.ABCA1 mRNA and protein expression in mature 3T3-L1 adipocytes post stimulation with various concentrations of insulin was detected by real-time fluorescence-based quantitative techniques and Western blot,respectively,in the absence and presence of CHX (cycloheximide,CHX),calpeptin (calpain pathway inhibitor) or MG-132 (proteasome pathway inhibitor).Results Cholesterol efflux rates were reduced post insulin stimulation in a dose-dependent manner ((7.06 ± 0.27) ％,(6.59 ± 0.30) ％,(6.34 ± 0.24) ％,(5.07 ± 0.40) ％,and (4.71 ±0.40)％ at 0,1,10,102,and 103 nmol/L of insulin,P ＜0.05).Cholesterol efflux rates decreased in a time-dependent manner post 103 nmol/L insulin stimulation (6.52 ± 0.30) ％,(5.59 ± 0.71)％,(5.44 ± 0.37)％,(4.52 ± 0.32)％,and (4.38 ± 0.33)％ at 0,2,4,6,12 h,respectively).ABCA1mRNA levels were not affected by insulin(P ＞ 0.05).ABCA1 protein level was significantly downregulated in 103 nmol/L insulin group compared to 0 nmol/L insulin group (P ＜ 0.01).Compared with the 0 h group,ABCA1 protein level was significantly reduced in 6 h group (P ＜ 0.05) and further reduced in 12 h group (P ＜ 0.01).Both calpeptin and MG-132 could partly reduce insulin-induced degradation of ABCA1.Compared with the negative control group,ABCA1 protein levels were significantly upregulated by cotreatment with calpeptin and MG-132,respectively (both P ＜ 0.01).Conclusion Our data suggest that high insulin level could promote the ABCA1 protein degradation and reduce cholesterol efflux from mature 3T3-L1 adipocytes through calpain and proteasome pathway,thus,produce a circumference not suitable for nascent HDL formation in 3T3-L1 adipocytes.

Music and speech may share the same neural pathway, and the role of music therapy in speech rehabilitation gradually attracts the attention from the rehabilitation medical profession in recent years. This article reviewed the effect, mechanism, and strategy of music therapy in speech rehabilitation.

Objective To compare the number of lymph node dissected by intraoperative lymphatic mapping guided D2 gastrectomy and that by standard D2 gastrectomy plus lymphadenectomy in patients of advanced gastric cancer. Methods In this study 20 advanced gastric cancer cases received intraoperative peritumor injection of carbon nanoparticles suspension ( group 1 ) and D2 lymphadenectomy was guided by the black-stained lymph nodes. 21 cases undergoing standard D2 lymphadenectomy served as controls (group 2). The number of lymph nodes removed and the condition of lymphatic metastasis in two groups, blackstained lymph nodes in group 1, and postoperative complications were compared. Results The average lymph nodes dissected in group 1 (35. 1 ± 13.4) were higher than in control group (26.2 ±7.8). The differences were statistically significant (t =2. 126, P =0. 034). The number of removed N2 and N3 lymph nodes in group 1 were more than that in control group. The total black-stained ration of lymph nodes was 52. 7% in group 1. The positive rate of lymph nodes was higher in black-stained lymph nodes (27.6%) than in unstained lymph nodes ( 10. 8% ) in group 1 and in control group ( 16. 9% ). The differences were also statistically significant ( x2 = 6. 034, P = 0. 016; x2 = 5. 142, P = 0. 023 ). Postoperative afferent loop obstruction developed in one case in group 1. Conclusions Lymphatic mapping guided D2 radical gastrectomy plus lymphadenectomy increases the number of lymph nodes dessected and improves the efficiency of positive lymph nodes excision for patients of advanced gastric cancer.