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.

AIM: To investigate the mechanism of Hexue Mingmu Tablets(HXMMT)in improving diabetic retinopathy(DR)based on transcriptomics.METHODS: Zebrafish DR models were established by 3-day glucose induction(130 mmol/L)starting at 3 days post-fertilization(dpf). Larvae were randomized into four groups: control group(CG; aquaculture water), model group(MG; 130 mmol/L glucose), low-dose HXMMT treatment group(L-HX; 130 mmol/L glucose +7.5 mg/L HXMMT), and high-dose HXMMT treatment group(H-HX; 130 mmol/L glucose +75 mg/L HXMMT), with a 3-day intervention period until 6 dpf. The area and length of eyes, and body length of zebrafish were observed by stereomicroscopy, retinal morphology was observed by hematoxylin-eosin staining(HE), and retinal vessel diameter was observed under fluorescence microscope. Differentially expressed genes(DEGs)were identified by RNA-sequencing(RNA-seq)technology to further elucidate the molecular mechanism of HXMMT in improving DR in zebrafish, and the sequencing accuracy was validated through quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS: HE staining demonstrated that the intervention with HXMMT significantly improved the disordered cell arrangement, widened gaps, and thickened inner nuclear layer(INL)in ganglion cell layer GCL); retinal vascular diameter quantification revealed that the retinal vessel diameter of the MG significantly increased compared with the CG, and it was significantly changed after the intervention of HXMMT, with significant efficacy in the H-HX(P<0.05); transcriptomics profiling identified 1 470 reversed DEGs, predominantly enriched in the AMPK signaling pathway, FoxO signaling pathway, retinal developmental processes, and tight junction regulation. Technical validation confirmed strong correlation between qRT-PCR and RNA-seq data(R2=0.8571, P<0.05).CONCLUSION: HXMMT may improve retinal vascular microcirculation disorders in DR by regulating core targets including vsx1, pde6c, arr3a, plk1, fbp1b, foxo1a, pcna, and cdk1, as well as synergistically modulating processes such as retinal development in camera-type eyes, visual perception, microtubule cytoskeletal organization, tight junctions, and the AMPK signaling pathway, Foxo signaling pathway.

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 analyze the serological characteristics of anti-Mur antibodies and investigate the distribution frequency of the Mur antigen among voluntary blood donors in Shiyan, thereby providing a basis for guiding clinical transfusion and establishing a Mur blood type database. Methods: ABO blood grouping of donors and patients was performed using an automated blood typing analyzer and the gel card method, respectively. Unexpected antibody screening and identification were performed using the saline, tube anti-human globulin, and polybrene methods. The specificity of anti-Mur antibodies was confirmed using Fisher's exact probability test. Plasma treated with 2-mercaptoethanol was used to distinguish IgM and IgG antibodies. IgM and IgG anti-Mur titers were determined by the saline tube method and the anti-human globulin tube method, respectively, at 4℃, room temperature, and 37℃. A total of 1 659 donor red blood cell samples were initially screened for the Mur antigen phenotype using three samples of human-derived anti-Mur plasma by the micro-tube method. Donors who tested positive for Mur antigen were further tested by the direct antiglobulin test (DAT); those with negative results were confirmed for Mur antigen by the gel card and polybrene methods. Results: Three blood samples were identified to contain mixed IgG and IgM anti-Mur antibodies. The titers of both IgM and IgG anti-Mur antibodies were highest at 4℃, intermediate at room temperature, and lowest at 37℃. The positive frequency of the Mur antigen among voluntary blood donors in Shiyan was 1.99% (33/1 659). Conclusion: anti-Mur antibodies were detected in both blood donors and patients in our region. The Mur antigen shows a certain distribution frequency among voluntary blood donors in Shiyan. Screening for the Mur blood type and establishing a corresponding database could enhance transfusion safety.

Objective:To investigate whether beta-sitosterol(BS)can affect the polarization of alveolar macrophages and the nuclear factor kappa B(NF-κB)pathway in a rat model of acute lung injury(ALI)induced by lipopolysaccharides(LPS).Methods:Thirty spe-cific pathogen-free Sprague-Dawley rats were randomly divided into normal saline group(NS group),ALI model group(LPS group),low-dose BS intervention group(BS-L group),high-dose BS intervention group(BS-H group),and dexamethasone group(DX group),with six rats in each group.After successful modeling,the rats were sacrificed for the following examinations:the pathological changes and wet-to-dry(W/D)weight ratio of lung tissue;the levels of tumor necrosis factor α(TNF-α)and interleukin 1β(IL-1β)in bron-choalveolar lavage fluid(BALF);the relative mRNA expression levels of NF-κB p65,IL-1β,and TNF-α in lung tissue;the protein expression levels of NF-κB p65 and TNF-α and the percentage of CD80-positive M1 alveolar macrophages in lung tissue.Results:Ab-normal behaviors and cyanosis were observed in all the groups except the NS group,with milder symptoms in the BS groups and DX group than in the LPS group.Compared with the NS group,the LPS group showed significant increases in the lung tissue pathological injury score,the W/D ratio,the relative mRNA expression levels of NF-κB p65,IL-1β,and TNF-α in lung tissue,the protein expres-sion levels of TNF-α and NF-κB p65 in lung tissue,the percentage of CD80-positive M1 alveolar macrophages,and the levels of the in-flammatory factors TNF-α and IL-1β in BALF(all P<0.01).Com-pared with the LPS group,the BS-L group,BS-H group and DX group showed significant decreases in the lung tissue pathological injury score,the W/D ratio,the relative expression levels of NF-κB p65,IL-1β,and TNF-α mRNAs in lung tissue,the protein expression levels of NF-κB p65 and TNF-α in lung tissue,the percentage of CD80-positive M1 alveolar macrophages,and the levels of TNF-α and IL-1β in BALF(all P<0.001).The above indicators were sig-nificantly lower in the BS-H group than in the BS-L group(all P<0.001).Compared with those in the BS-L and BS-H groups,the above indicators in the DX group were significantly decreased(all P<0.01).Conclusion:BS may alleviate the severity of ALI through inhibiting the activation of the NF-κB pathway and suppressing the polarization of alveolar macrophages towards M1-type macro-phages in ALI rats.

OBJECTIVE To investigate the ultrasound characteristics of category 4 thyroid nodules in the Chinese version of the Thyroid Imaging Reporting and Data System(C-TI-RADS),and to analyze the value of ultrasonography combined with elastography scoring in the correction of nodule properties.METHODS Data from 80 patients with 105 nodules from April 2020 to December 2023 were retrospectively analyzed.Fine-needle aspiration biopsy or surgical pathology was used as the gold standard.The Kappa test was employed to evaluate diagnostic consistency,while the receiver operating characteristic(ROC)curve was utilized to assess the differentiation and accuracy of the diagnostic methods.RESULTS Sixty-eight malignant nodules and 37 benign nodules were confirmed by surgical pathology or puncture biopsy.After enhancement by ultrasonography,the percentage of malignant nodules with low intensity,centripetal enhancement,inhomogeneous enhancement,blurred boundary of enhanced nodules,enlarged enhanced nodules,and irregular enhanced nodules was significantly higher than that of the benign group,while the percentage of circumferential enhancement was lower than that of the benign group(P<0.05).The overall compliance rate of ultrasonography scoring in diagnosing C-TI-RADS category 4 thyroid nodules was 83.81%(88/105),and when compared with the pathological gold standard,the Kappa value was 0.644.The ROC curve analysis showed that the sensitivity of ultrasonography scoring in diagnosing benign and malignant nodules was 84.51%,the specificity was 82.35%,the correctness index was 0.669,the negative likelihood ratio was 0.188,and the positive likelihood ratio was 4.789.The overall compliance rate of elastography score in diagnosing C-TI-RADS category 4 thyroid nodules was 85.71%(90/105),and when compared with the pathological gold standard,the Kappa value was 0.689.The ROC curve analysis revealed that the sensitivity of elastography score in diagnosing benign and malignant nodules was 88.24%,the specificity was 81.08%,the correctness index was 0.693,the negative likelihood ratio was 0.145,and the positive likelihood ratio was 4.664.Ultrasonography enhancement features,along with the combination of ultrasonography score and elastography score,had an AUC=0.922(0.876-0.968),with an accuracy of 92.91%,demonstrating a strong ability to identify truly malignant nodules versus benign nodules.CONCLUSION Ultrasonography combined with elastography scoring is valuable in the correction of C-TI-RADS category 4 nodules in the thyroid gland and helps to improve diagnostic accuracy.

Objective:To explore the effect of NOD-like receptor thermal protein 3 ( NLRP3) knockout in γ-aminobutyric acid (GABA)-ergic neurons in the hippocampal CA1 area on improving cognitive dysfunction in mice after traumatic brain injury (TBI). Methods:Forty-eight healthy male NLRP3 flox/flox mice weighing 25-28 g were randomly divided into 4 groups ( n=12): sham-operated+control virus group (SV group), sham-operated+ NLRP3 specific knockout group (SG group), TBI+control virus group (TV group), TBI+ NLRP3 specific knockout group (TG group). TBI in the TV and TG groups was established by free-fall method, while surgical procedures such as scalp incision and cranial window opening without impact were given to the SV and SG groups. Adenovirus was injected into the hippocampal CA1 area of SG and TG groups 21 d before TBI to induce NLRP3 specific knockout in GABA-ergic neurons in the hippocampal CA1 area; empty virus was injected into the CA1 area of SV and TV groups. Cognitive function was evaluated using novel object recognition test 30 and 31 d after TBI, and learning and memory functions were assessed using Morris water maze test 32-36 d after TBI. Field potentials in the hippocampal CA1 area were recorded during novel object recognition 31 d after TBI. After behavioral tests, these mice were sacrificed. Immunofluorescent staining was used to detect the fluorescent intensity of microtubule-associated protein2 (MAP2), glutamic acid decarboxylase 67 (GAD67), and postsynaptic density protein 95 (PSD95) in the hippocampal CA1 area, as well as percentage of pyroptosis-associated inflammatory factor interleukin-18 (IL-18)/GAD67 double-positive neurons in total GAD67 positive neurons. Results:Compared with the SV and SG groups, the TV and TG groups had decreased novel object recognition index, decreased number of platform crossings during the experimental period, increased escape latency on day 3 and day 4 of the training period in Morris water maze test, decreased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, decreased fluorescent intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, increased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Compared with the TV group, the TG group had increased novel object recognition index, increased number of platform crossings in Morris water maze test, decreased escape latency during the training period, increased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, increased fluorescence intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, decreased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Conclusion:Specific inhibition of NLRP3 expression in GABA-ergic neurons in the hippocampal CA1 area can improve cognitive dysfunction in mice after TBI, whose mechanism may be related to inhibited GABA-ergic neuronal pyroptosis in the hippocampal CA1 area.

Objective To investigate the influence of individual factors and labor organization factors on work-related musculoskeletal disorders (WMSDs) in automobile manufacturing workers, and to provide a scientific basis for the prevention and treatment of WMSDs in automobile manufacturing workers. Methods In April 2020, 5564 workers in an automobile factory were selected by cluster sampling method. The prevalence of WMSDs was investigated by using the Musculoskeletal Disorders Questionnaire, and the influence of individual factors and labor organization factors on WMSDs was investigated by using generalized estimation equation. Results The prevalence rate of WMSDs was 79.00% (4396/5564), and the prevalence rate of multisite WMSDs was 67.95% (3781/5564). The analysis of generalized estimation equation showed that doing the same job every day (OR= 1.478, P < 0.05), age ≥40 years (OR=1.416, P< 0.05), personnel shortage (OR= 1.356, P < 0.05), and work length of 6～10 years and 11～15 years (OR= 1.349, P< 0.05) were the main risk factors for WMSDs in automobile manufacturing workers. Shift work and working time > 40 hours per week increased the risk of WMSDs (P< 0.05). Male and adequate rest time were protective factors for WMSDs. The job correlation matrix showed that WMSDs in most parts had a positive correlation. Conclusions The prevalence of multisite WMSDs of workers in automobile manufacturing industry is high, and unreasonable labor organization is the main risk factor of WMSDs. Appropriate work breaks can effectively reduce the risk of WMSDs, and effective intervention measures should be carried out to prevent the occurrence of WMSDs in workers in automobile manufacturing industry. The generalized estimation equation can better analyze the influencing factors of WMSDs.

This paper summarized the game mechanism, application status and application effect of serious games in self-management education for children and adolescents with type 1 diabetes mellitus (T1DM), and put forward the existing shortcomings and suggestions, which can provide references for Chinese medical personnel to carry out health education and develop relevant serious games in the future.

Objective:To investigate the main occupational hazards,occupational protection facilities and workers'health examination in 17 plywood manufacturing enterprises in Guangxi,so as to provide valuable basis for ensuring workers'physical and mental health.Methods:A total of 17 plywood enterprises in Guangxi were selected as the observation objects.Through the occupational hazard assessment survey,the occupational hazards in the working environment and the collection of workers'occupational health examination data,the main occupational health problems were comprehensively analyzed and evaluated.Results:The over-standard rates of wood dust,formaldehyde,noise,and high temperature in 17 plywood manufacturing enterprises were 5.6%,28.1%,24.9%,and 29.1%,respectively.The noise in 17 enterprises exceeded standards,the mood dust and formaldehyde in 5 enterprises exceeded standards,and high temperature in 2 enterprises exceeded standards.The coincidence rate of dustproof and poisonproof facilities in production protection was 98.3%,the coincidence rate of heat-proof facilities was 88.2%and the coincidence rate of noise protection facilities was 76.5%.The coincidence rate of wearing and using personal protective equipment was 52.9%,and the coincidence rate of installing eyewash spray devices was 58.8%.The total physical examination rate in 17 enterprises was 42.6%(705/1 654),and the abnormal detection rate of physical examination was 14.6%,among which the abnormal detection rates of hearing,chest X-ray,and lung function were 7.4%,2.1%,and 1.7%,respectively.Conclusions:The main occupational health problems in 17 plywood manufacturing enterprises in Guangxi are wood dust,formaldehyde,noise,and high temperature,especially noise.The prevention and control effects of wood dust and formaldehyde are good,but the prevention and control measures for high temperature and noise need to be further strengthened.