ObjectiveTo analyze the factors influencing meropenem-related liver injury （MRLI） and to explore their clinical predictive value. MethodsA retrospective case-control study was conducted， and the Chinese Hospital Pharmacovigilance System （CHPS） was used to establish a retrieval scheme. A total of 1 625 hospitalized cases using meropenem from January 2018 to December 2022 were collected. Patients were divided into case group （n=62） and control group （n=1 563） based on the presence or absence of liver injury. Clinical data and laboratory indicators from both groups were collected and analyzed. The t-test was used for comparison of normally distributed continuous data between the two groups， while the Mann-Whitney U test was used for comparison of continuous data not conforming to a normal distribution. The chi-square test was used for comparison of categorical data between the two groups. A multivariate Logistic regression analysis was performed to identify the influencing factors for MRLI. A Logistic regression equation was established， and the predictive value of these factors was assessed using the receiver operating characteristic （ROC） curve. ResultsThe results of univariate analysis indicated that the rates of male patients， hypoproteinemia， shock， intensive care unit （ICU） admissions， sepsis， and liver， gallbladder， and cardiovascular diseases， the levels of alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， aspartate aminotransferase （AST）， creatinine （CREA）， and procalcitonin （PCT）， and the number of hospitalization days were significantly higher in the case group than in the control group （P<0.05）， and that the platelet levels in the case group were significantly lower than those in the control group （P<0.05）. The multivariate Logistic regression analysis showed that male sex （odds ratio ［OR］=2.080， 95% confidence interval ［CI］： 1.050 — 4.123， P=0.036）， admission to the ICU （OR=8.207， 95%CI： 4.094‍ ‍—‍ ‍16.453， P<0.001）， comorbidity with gallbladder disease （OR=8.240， 95%CI： 3.605‍ ‍—‍ ‍18.832， P<0.001）， ALP （OR=1.012， 95%CI： 1.004‍ ‍—‍ ‍1.019， P=0.004）， GGT （OR=1.010， 95%CI： 1.005‍ ‍—‍ ‍1.015， P<0.001）， and PLT （OR=0.997， 95%CI： 0.994‍ ‍—‍ ‍0.999， P=0.020） were the influential factors for MRLI. The areas under the ROC curve of ALP， GGT， and PLT were 0.589， 0.637， and 0.595， respectively， and the AUC of them combined was 0.837. ConclusionMale sex， ICU admission， comorbidity with gallbladder disease， increased ALP， increased GGT， and decreased PLT were influencing factors for MRLI， and a combination of factors has a better predictive value for the occurrence of MRLI.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective To observe the toxicity of low concentration Mn²⁺ compound combined with autophagy inhibitor chloroquine on nerve cell line PC12 cells for long-term and its mechanism. Methods PC12 cells at logarithmic growth stage were treated with 0 (control), 5, 10, 25, 50, 100, and 200 μM manganous chloride, and 5, 10, 25, 50, and 100 μM chloroquine for 24 h, respectively. The effect of manganous chloride and chloroquine on cell viability was detected by MTT assay. The combined effect of the two compounds on cell viability was determined at 24, 48 and 72 h, respectively. The mitochondrial respiratory function was further examined to explore the possible toxicity mechanism of manganous chloride and chloroquine. Results Compared with the control group, manganous chloride and chloroquine alone had inhibitory effect on cells survival in a concentration-dependent manner. Manganous chloride and chloroquine at concentrations of 40 μM and 2.5 μM, respectively, had no significant effect on cell survival. Compared with the control group, administration of 2.5 μM chloroquine alone for 24, 48 and 72 h did not significantly change cell survival and mitochondrial respiratory function. Treatment of cells with manganous chloride alone at the concentration of 40 μM for 72 h did affect mitochondrial respiratory function. However, the cell survival and mitochondrial respiratory function in the combined administration of manganous chloride and chloroquine for 72 h were significant decreased (P< 0.05). Conclusion The long-term combination of low-concentration manganous chloride and chloroquine produced an additive cytotoxicity on PC12 cells, and the toxicity mechanism may be related to the damage of mitochondrial function.

Objective To understand the epidemiological characteristics and incidence trend of syphilis in Shiyan City, and to provide a scientific basis for formulating syphilis control strategies. Methods Descriptive epidemiological statistical analysis on the data of syphilis cases from 2008 to 2020 in Shiyan City was performed. Results A total of 9 578 syphilis cases were reported in Shiyan City from 2008 to 2020, with the reported incidence rate ranging from 16.80/100 000 to 27.48/100 000. The reported incidence rate of syphilis showed a downward trend from 2008 to 2014 (χ² trend=44.869, P=0.000), and an upward trend from 2015 to 2020 (χ² trend=69.642, P=0.000). The composition ratio of syphilis in each stage had changed, with a decreasing trend in stage I and II syphilis. The composition ratio of recessive syphilis cases increased from 58.90% in 2008 to 93.10% in 2020, and gradually became the main epidemic type. No cases of fetal syphilis were reported in the past three years. The incidence rate of syphilis reported from 2008 to 2020 was generally higher in women than that in men, with a male to female ratio of 0.67:1. Occupations were mainly farmer, housework, and unemployment. The high incidence areas of syphilis in Shiyan City included mainly Maojian District, Zhangwan District, and Fangxian County, with the annual reported incidence rates being 38.40/100 000, 37.97/100 000, and 29.37/100 000, respectively. Conclusion The syphilis epidemic in Shiyan City from 2008 to 2020 has showed a trend of first decline and then rise. The prevention and treatment of syphilis in key populations and key areas should be strengthened according to the epidemiological characteristics of syphilis to control the spread of syphilis and reduce the harm to the public.

: To explore the relationship between metal exposure level and blood pressure, so as to provide a scientific basis for verifying the relationship between metal exposure and elevated blood pressure among primary school students. Methods: In July 2022, a total of 555 students of second to sixth grade were selected by cluster random sampling method from two primary schools in Zhuxi County, Shiyan City, Hubei Province. A questionnaire survey was conducted to obtain the socio demographic characteristics and living habits of the participants. The height, weight, body mass index(BMI) and blood pressure were obtained by physical examination. At the same time, the urine of the subjects was collected, and the metal mass fraction in urine was detected by inductively coupled plasma mass spectrometry. The relationship between metal mass fraction in urine and blood pressure was analyzed by generalized linear regression. Results: The detection rate of elevated blood pressure in primary school students was 15.86% , and there was a statistically significant difference in the detection rate of elevated blood pressure among obese primary school students (yes:37.25%,no:13.69%, χ 2=19.28, P <0.01).There were statistically significant differences in BMI[15.80( 14.69 ， 17.92 )，17.87(15.49，20.89)kg/m 2] between the non elevated blood pressure group and the elevated blood pressure group of elementary school students ( Z =-4.67, P <0.01). The geometric mean mass fraction of zinc in urine was the highest ( 6 942.86 μg/g), titanium was the lowest (2.20 μg/g). Zinc and lead were positively correlated with elevated systolic blood pressure( β = 0.054 , 0.014), zinc and cadmium were positively correlated with elevated diastolic blood pressure ( β =0.038,0.029) ( P <0.05). Conclusions Metal zinc, lead and cadmium concentration are associated with elevated blood pressure. It is necessary to intervene and control the exposure of zinc, lead and cadmium in the environment to promote the blood pressure health of primary school students.

Objective:To explore the clinical and genetic characteristics of five children with epilepsies due to variants of SCN8A gene. Methods:Clinical data of five children (four males and one female) admitted to Linyi People′s Hospital due to hereditary epilepsies between August 2015 and August 2022 were collected. Whole exome sequencing was carried out for these children, and candidate variants were verified by Sanger sequencing.Results:All of the five children were found to harbor variants of the SCN8A gene. Case 1, who had benign familial infantile epilepsy, inherited a known pathogenic c. 4840A>G variant from his father with similar symptoms. Cases 2 to 4 had presented with intermediate epilepsy. Among these, case 2 has harbored a de novo c. 3967G>A variant which was rated as pathogenic (PS1+ PS2+ PM1+ PM2_Supporting+ PP3) based on the guidelines from the American College of Medical Genetics and Genomics. Cases 3 and 4 were found to respectively harbor a de novo c. 415A>T and a c. 4697C>T variant, which were both rated as likely pathogenic (PS2+ PM1+ PM2_Supporting+ PP3). Case 5, who had early-onset infantile epileptic encephalopathy transformed into Lennox Gastaut-like syndrome, has harbored a de novo c. 5615G>A variant, which was known to be pathogenic. The children had their age of onset ranging from 2 to 14 months, and all had focal seizures and generalized tonic clonic seizures. Four children (cases 1, 2, 3 and 5) had cluster seizures, four (cases 1 to 4) had become seizure-free after single or dual treatment and showed normal growth and development, whilst case 5 was drug-resistant and showed severe developmental retardation. Conclusion:The five children had new features such as cluster seizures, occasional benign seizures in adulthood, and intermediate epilepsy which are prone to relapse after discontinuation of medication, which may be attributed to the pathogenic variants of the SCN8A gene.

AIM: To investigate the effects of placement of the absorbable packing material Nasopore around the anastomosis site on postoperative re-bleeding, discomfort, and on the success rate of endoscopic dacryocystorhinostomy(En-DCR).METHODS: Prospective randomized controlled study. A total of 101 patients(101 eyes)diagnosed with chronic dacryocystitis that underwent En-DCR in the ophthalmology department, Renmin Hospital, Hubei University of Medicine from November 2020 to October 2021 were collected. The patients were randomly divided into two groups according to whether they were packed with Nasopore at the end of operation, namely, the packed group(49 eyes)and the non-packed group(52 eyes). The postoperative follow-up was 9 mo, the degree of re-bleeding, discomfort, and postoperative success rate(including anatomical success rate and functional success rate)were compared between the two groups of patients.RESULTS: This study included 94 patients, including 45(45 eyes)and 49(49 eyes)in packed group and non-packed group, respectively. The En-DCR was performed successfully in all patients. Postoperative re-bleeding occurred in 1 eye(2%)in the packed group, and 9 eyes(18%)in the non-packed group(P<0.05); postoperative nasal discomfort occurred in 2 cases(4%)in the packed group, and 9 cases(18%)in the non-packed group(P<0.05); The success rate of postoperative anatomical success rate was 93%(42/45)in the packed group and 88%(43/49)in the non-packed group(P>0.05). The postoperative functional success rate was 89%(40/45)in the packed group and 86%(42/49)in the non-packed group(P>0.05). Other complications such as orbital fat prolapse, cerebrospinal fluid leakage, sinusitis, visual impairment and double vision were not observed in all patients during the follow-up.CONCLUSION: Nasal packing absorbable material Nasopore around the anastomosis at the end of En-DCR operation can reduce postoperative re-bleeding and postoperative discomfort of patients, and it has no obvious effect on the postoperative success rate.

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Adult ; Humans ; Cardiovascular Diseases/prevention & control* ; East Asian People ; Prospective Studies ; Risk Factors ; Smoking

Objective: To investigate the current situation and related factors of the ecological environment and health literacy level of medical college students in Shiyan City, so as to propose relevant countermeasures and suggestions for improvement in these domains. Methods: From May to June 2023, 1 312 medical students from Hubei University of Medicine in Shiyan City were selected by accidental sampling to investigate the level and influencing factors of the ecological environment and health literacy among this population. The Chi square test and binary multivariate Logistic regression analysis were performed to analyze the different characteristics and main influencing factors of the ecological environment and health literacy levels in this population. Results: The level of the ecological environment and health literacy level among medical students in Shiyan City was 24.3%. Different levels of ecological environmental and health literacy were observed among medical students by gender, grade, major and ethnicity ( χ 2=5.13, 54.87 , 64.71, 5.99, P <0.05). Higher rates were also observed among public health major students than among students of other majors. The first three classification literacy levels consisting of basic literacy, basic knowledge, and basic skills were 4.6%, 49.5 % and 50.4%, respectively. The possession rates of six secondary classification indicators were as follows:basic cognition ( 53.2 %), basic attitudes (34.5%), scientific knowledge (3.0%), behavioral knowledge (22.5%), cognitive skills (59.5%) and operational skills (48.6%). The results of multivariate Logistic regression showed that ethnic minorities and biomedical majors were negatively correlated with medical students ecological environment and health literacy ( OR =0.61,0.52), while female students, public health majors, sophomores and seniors were positively correlated with medical students ecological environment and health literacy ( OR=1.44, 1.95, 2.16, 2.24, P <0.05). Conclusions The overall level of ecological environment and health literacy among medical students in Shiyan City is low. Schools should popularize environmental health knowledge from different perspectives in order to improve the overall literacy level of environmental health literacy among medical students.