Squalene epoxidase (SQLE) is a potential target for the treatment of liver cancer. Bioinformatics analysis indicated that the high expression of SQLE was closely related to the clinical stage and poor prognosis of patients with liver cancer. However, the existing inhibitors against SQLE 195 tyrosine residue (Y195) cannot be used clinically due to severe side effects. In this study, 35 small-molecule compounds targeting SQLE 335 tyrosine residue (Y335) were selected by computer virtual screening. Combined with MTT assay, 3 candidate compounds (19^#, 31^# and 35^#) with significant inhibitory effects on the proliferation of Huh7 cell line were obtained. Further studies showed that these 3 compounds could inhibit the migration of Huh7 cells, reduce the contents of total and free cholesterol, up-regulate the expression of tumor suppressor gene PTEN, and down-regulate the expression of PI3K and AKT proteins. The results showed that the novel inhibitors 19^#, 31^# and 35^# targeting SQLE Y335 could reduce cholesterol content, inhibit the proliferation and migration of Huh7, thus playing an anti-liver cancer role.

Objective To establish an animal model of sparganosis mansoni through oral administration of Cyclops infected with procercoids. Methods Domestic cats were infected with Sparganum mansoni under laboratory conditions, and fresh cat stool samples were collected, washed in dechlorinated water, and filtered. Spirometra mansoni eggs were collected and prepared into suspensions. Twenty C57BL/6j mice were randomly divided into the experimental group (n = 15) and the control group (n = 5). Wild Cyclops were infected with Spirometra mansoni coracidia to allow 3 to 5 procercoids in each Cyclop. Then, each mouse in the experimental group was given 15 Cyclops infected with procercoids by gavage, while mice in the control group were orally administered with the same volume of dechlorinated water. All mice were sacrificed after 5 months, and dissected, and suspicious Sparganum mansoni worms were collected. The serum specific IgG antibody against Sparganum mansoni was measured in mice using enzyme-linked immunosorbent assay (ELISA). Genomic DNA was isolated from suspicious Sparganum mansoni worms, and the specific Sparganum mansoni cytochrome oxidase I (COI) gene was amplified using PCR assay. Results Among the 15 mice in the experimental group, six were positive for the serum specific IgG antibody against Sparganum mansoni, and milky white worms were found and collected from the subcutaneous regions of 4 out of 6 mice. Only one worm was detected in each mouse, and the worm morphology was similar to Sparganum mansoni. Capillary electrophoresis of the PCR amplification products of COI gene presented a specific band with 151 bp in size, and sequencing analysis revealed 100% homology with Sparganum mansoni. Conclusions A mouse model of sparganosis mansoni is successfully created through oral administration of Cyclops infected with Spirometra mansoni procercoids.

ObjectivesTo evaluate the learning curve for percutaneous endoscopic transforaminal discectomy（PETD）at L4/5 level and L5/S1 level respectively， and to evaluate the differences of learning curve for PETD between the two levels. MethodsTwo batches of the first 51 cases who were each treated with PETD for L4/5 or for L5/S1 disc herniation respectively in the department between December 2019 and November 2020 were reviewed. The operation time， radiation exposure time， VAS score， preoperative ODI score， and the postoperative follow-up were reviewed. Each level was divided into three groups： for the earliest stage， Patients #1~17 were assigned to Group A； for the middle stage， Patients #18~34 were assigned to Group B； and for the latest stage， Patients #35~51 were assigned to Group C. ResultsAll patients were observed postoperatively for 8.4 months ［range： 6 months-12 months， M （P₂₅~P₇₅） = 8.0（7.0~9.3）months］. Significant differences were observed in the mean operation time for L4/5 level both between Group A and Group B （P=0.006） and between Group A and Group C （P=0.000）， while for the average operation time for L5/S1 level there was significant difference between Group A and Group C （P=0.000）， but not between Group A and Group B （P=0.344）. Compared with the operation time at L4/5 level， the operation time at L5/S1 was significantly longer for each stage （Group A： P=0.080， Group B： P=0.000， Group C： P=0.016， Total： P=0.000）. The average X-ray exposure period at each Group A L4/5 level was shortened successively， and there were significant differences between Group A and Group B （P=0.000）， also between Group A and Group C （P=0.000）. However， the mean radiation time of the three stages in L5/S1 level improved less rapidly than that in L4/5 level， in which significant difference was not observed between Group A and Group B （P=0.995）， but was between Group A and Group C （P=0.000）. The radiation exposure time at L5/S1 was significantly longer than L4/5 level for each stage （Group A： P=0.000， Group B： P=0.000， Group C： P=0.000， Total： P=0.000）. In the improvement of VAS score among 3 stages for L4/5 level， no significant differences were observed neither between Group A and Group B （P=0.967） nor between Group A and Group C （P=0.927）. Higher improvement in the ODI score was observed in L4/5 level both between Group A and Group B （P=0.036） and between Group A and Group C （P=0.011）. There was no significant difference in the improvement of VAS score for L5/S1 level neither between Group A and Group B （P=0.397） nor between Group A and Group C （P=0.960）； neither was there any significant difference in the improvement of ODI score both between Group A and Group B （P=0.207） and between Group A and Group C （P=0.109）. ConclusionsThe learning curve in the L4/5 level is steeper than that in the L5/S1 level. Suitable patient selection is of much importance for shortening the learning curve for PETD.

Objective To investigate the prevalence of Spirometra mansoni infections in hosts in Jiangsu Province, so as to provide the scientific basis for the management of sparganosis mansoni. Methods From 2018 to 2019, nine counties (cities, districts) were randomly selected from Jiangsu Province as the survey sites, and 100 healthy individuals were randomly selected to perform the serological test of S. mansoni infections and the detection of S. mansoni eggs. The procercoids were detected in the intermediate host Cyclops, and the S. mansoni eggs were identified in the stool samples of the definitive hosts cats and dogs. Results The prevalence of S. mansoni human infections was 0 (0/900) in the 9 survey sites of Jiangsu Province, and the sero-prevalence of the specific IgG antibody against S. mansoni was 1.22% (11/900). The positive rate of procercoids was 0.33% (3/900) in Cyclops. In addition, the S. mansoni egg-positive rate was 1.48% (2/135) in cats and dogs. Conclusions Sparganosis mansoni is prevalent in Jiangsu Province. Health education pertaining to the damages of sparganosis mansoni and the route of S. mansoni infections should be improved.

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

BACKGROUND: Unawareness of stroke symptoms and low income are two barriers that affect the seeking of emergency medical service (EMS). This study aimed to assess the effect of unawareness and low income on seeking EMS and to investigate the regional distribution of the unawareness and low-income status and their associations with failing to call EMS in China. METHODS: A total of 187,723 samples from the China National Stroke Screening Survey was interviewed cross-sectionally. Four status of awareness and annual income were identified: unaware and low-income, unaware-only, low-income-only, and aware and regular income. The outcomes were whether they intended to call EMS or not. The regional distribution of each status and their associations with not calling EMS were presented. RESULTS: The status of unaware and low-income, unaware-only, and low-income-only accounted for 6.3% (11,806/187,673), 11.9% (22,241/187,673), and 21.5% (40,289/187,673) of the total sample, respectively. Not calling EMS was significantly associated with the status of unaware and low-income (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 3.07-3.35), unaware-only (OR: 2.38, 95% CI: 2.31-2.46), and low-income-only (OR: 1.67, 95% CI: 1.63-1.71), compared with the aware and regular income status. The Midwest regions had higher percentages of people in the unaware and low-income status; the East, South, and Central had higher percentages of unaware-only status; the North and Northeast regions had a higher percentage of low-income-only status, compared with other regions. CONCLUSION The existence of the regional difference in unawareness and low income justifies the specific stroke education strategies for the targeted regions and population.
China ; Emergency Medical Services ; Humans ; Odds Ratio ; Socioeconomic Factors ; Stroke

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B e Antigens ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Medicine, Chinese Traditional ; Organophosphonates ; therapeutic use ; Young Adult

Objective To analyze the prognosis of pediatric burns and its influencing factors. Methods Clinical data of 1 737 children with burns from January 2013 to December 2017 in the First Affiliated Hospital of Anhui Medical University was analyzed by retrospective method. The demographic, clinical features, and related factors affecting prognosis . Results Log-binominal regression model showed that the care rate was higher in children aged 1- and 3- compared with children aged 7-12 (all P<0.05); Boiling water burns had a higher care rate than electric shock and flame burns (including chemical burn) (all P<0.05); Moderate and severe burns had a higher care rate than heavy severe burns (all P<0.05); The unhealed rate of pediatric burns in summer was higher than burned in winter (RR=0.861,95% CI:0.690-1.074); Children without complications had a higher care rate (P<0.05); Children lived in rural areas have a higher unhealed rate than lived in urban areas (RR=0.713，95% CI:0.618-0.824). Conclusions The care rate of pediatric burns was 51.1%. Major influencing factors included children aged 7-12, burned by electric and flame (including chemical burns), burned severe extraordinarily, burned in summer, and with complications, lived in rural.