Objective To explore the applicability of four risk assessment methods in evaluating occupational health risks associated with low-level benzene homologues exposure in key work sites within the automobile manufacturing industry. Methods The work sites (paint mixing and spray painting) with exposure to benzene homologues among six automobile manufacturing enterprises in Guangdong Province were selected as the study subjects using the judgmental sampling method. Qualitative risk assessment, exposure index method, non-carcinogenic risk assessment, and the International Council on Mining and Metals risk rating method were independently applied to evaluate the occupational health risks of benzene homologues at these work sites. Accuracy, consistency, and correlation of the four methods were compared. Results The air levels of benzene, toluene, xylene, and ethylbenzene in work sites of paint mixing and spray painting across all six enterprises met national occupational health standards. The median ratios of occupational exposure limits for benzene and toluene in spray painting site were higher than those in paint mixing site (0.017 vs 0.010, P<0.05). Using this ratio as a reference for evaluating method accuracy, the non-carcinogenic risk assessment method could distinguish paint mixing site from spray painting site in terms of risk level (P<0.05), whereas the other three methods could not (both P>0.05). The result of consistency testing revealed that the Kappa coefficients between the four methods ranged from -0.13-0.26, indicating poor consistency. The result of Spearman correlation analysis showed that the non-carcinogenic risk assessment and exposure index methods had higher correlation with occupational exposure limits ratios (Spearman correlation coefficients were 0.501 and 0.656, respectively, all P<0.05). Conclusion Occupational health risk assessment can serve as a supplementary tool to evaluate the hazard level of key work sites in the automobile manufacturing industry. Non-carcinogenic risk assessment shows higher accuracy.

Objective:To explore the clinical and genetic characteristics of dyskeratosis congenita (DC).Methods:A retrospective analysis was conducted on the clinical, laboratory, imaging, pathological, genetic, and treatment data of 6 DC patients diagnosed at the Children′s Hospital of Zhejiang University School of Medicine from January 2010 to June 2025.Results:Among the 6 DC patients, 1 case was of Hoyeraal-Hreidarsson syndrome, 4 were male, and 2 were female. The diagnosis age 0.9-6.1 years. All 6 cases presented with bone marrow failure; 5 cases had a classic triad of skin and mucous membrane (mucosal leukoplakia, abnormal skin pigmentation, nail dystrophy); 5 cases had growth retardation, among which 2 cases had intrauterine growth retardation. Two cases had diarrhea and 1 case had abnormal liver function; 1 case had stiff and deformed limbs, accompanied by limited mobility, and dry and obstructive balanitis; 1 case had recurrent eyelid inflammation, middle ear inflammation, and nasal inflammation. All 6 cases had decreased B cell numbers, and 4 cases also had decreased natural killer cell numbers. There were 3 cases of children with cytomegalovirus (CMV) infection, of which 1 case of CMV infection led to retinal frosted branch angiitis and subsequent intracranial CMV infection resulting in death, and 1 case had CMV enteritis and died of hemophagocytic syndrome. Among 4 cases of boys, 3 cases had DKC1 gene variations and 1 case had an unknown variation gene; 2 cases of girls had TINF2 gene variations. The TINF2 c.860T>A (p.L287Q) variation site was a new mutation. Among 6 patients with DC, 2 cases died, 3 cases survived and 1 case was lost to follow-up.Conclusions:The DKC1 and TINF2 genes are common pathogenic genes in patients with DC. Bone marrow failure is a clue for the early identification of DC. The triad of skin and mucous membrane is its typical clinical manifestation. Children with DC generally have reduced B cells and natural killer killer cells, and have a high risk of fatal CMV infection. The overall prognosis is poor.

Objective To analyze the feasibility of probiotics in delaying the progression of early Alzheimer's disease(AD)based on the changes of brain-gut-microbiota axis factors.Methods A total of 100 patients with early AD who visited Shaoxing 7th People's Hospital from December 2023 to December 2024 were selected and divided into control group(40 cases)and study group(60 cases)based on different treatment methods.The control group was treated with donepezil hydrochloride,while study group was treated with donepezil hydrochloride combined with probiotic preparations.The cognitive function,daily living ability,intestinal flora,and relative expression levels of brain-gut-microbiota axis factors,interleukin(IL)-6,tumor necrosis factor-α(TNF-α),5-hydroxytryptamine(5-HT),γ-aminobutyric acid(GABA),and lipopolysaccharide(LPS)/Toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)axis factors were compared before and after treatment in both groups.The clinical efficacy and prognosis monitoring results were also compared.Results The total effective rate and the proportion of patients with a clinical dementia rating score of 0 in study group were higher than those in control group(P＜0.05).The cognitive function and daily living ability scores in study group were higher than those in control group(P＜0.05).The copy numbers of lactobacillus and bifidobacterium in study group were higher than those in control group,while the copy numbers of enterococcus and escherichia coli were lower(P＜0.05).The relative expression levels of amyloid-β protein 1-42,IL-6,TNF-α,TLR4,and NF-κB in study group were lower than those in control group,and the levels of 5-HT and GABA were higher(P＜0.05).Conclusion Probiotics can delay the progression of early AD patients and improve clinical efficacy.It is speculated that the mechanism of action may be related to regulating the brain-gut-microbiota axis-mediated LPS/TLR4/NF-κB pathway to restore the intestinal microecology and alleviate neurological inflammation.

Objective:To systematically elucidate the molecular mechanism of hesperetin in the treatment of heart failure by network pharmacology, molecular docking, and molecular dynamics, and to clarify its key targets and pathway regulatory networks.Methods:Potential targets of hesperetin were retrieved from the PubChem, Pharmmapper, SwissTargetPrediction, and Similarity ensemble approach databases. Heart failure-related targets were obtained from the OMIM, GeneCards, and TTD databases. Intersection targets were identified using Venny 2.1. A protein-protein interaction (PPI) network of potential targets was constructed using the STRING database and Cytoscape 3.9.0 software. Gene ontology (GO) functional and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses of key targets were performed using the Metascape database. Molecular docking was carried out using Autodock vina1.1.2. GROMACS (2024.03) was employed to conduct a 100 ns molecular dynamics simulation on the optimal affinity complex. The thermodynamic stability of the candidate complex during simulation was evaluated by analyzing the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and binding free energy. Data were analyzed by an independent sample t test or one-way analysis of variance. Results:A total of 356 related targets of hesperetin and 2 923 related targets of heart failure were screened, with 152 intersection targets identified as potential targets for hesperetin intervention in heart failure. PPI network topological analysis revealed key targets for hesperetin intervention in heart failure, including insulin-like growth factor 1, estrogen receptor 1 (ER1), cysteine aspartic acid specific protease-3, sarcoma proto-oncogene, matrix metalloproteinase 9 (MMP9), MMP2, Janus kinase 2 (JAK2), albumin, heat shock protein 90 alpha family class A member 1, epidermal growth factor receptor, and B-cell lymphoma-2 (Bcl-2). GO functional enrichment analysis indicated that biological processes were mainly enriched in response to hormone stimulation, positive regulation of cell migration, gland development, response to nutritional levels, regulation of system processes, and response to trauma. Molecular functions were primarily enriched in phosphotransferase activity, nuclear receptor activity, endopeptidase activity, kinase binding, heme binding, hormone binding and protease binding. Cellular components were mainly enriched in membrane-related structures such as vesicle cavity, membrane raft, vacuole cavity, receptor complex and extracellular matrix containing collagen. KEGG pathway enrichment analysis showed that these key targets were significantly enriched in lipid and atherosclerosis, diabetic cardiomyopathy, and the hypoxia-inducible factor-1 signaling pathway. Molecular docking results indicated that the binding energy of hesperetin to MMP9 (?46.442 kJ/mol) was significantly lower than that to other key targets. Molecular dynamics simulations revealed that the hesperetin-MMP9 complex maintained structural stability, with an average RMSD of 1.60 ?. The average RMSF values of MMP9 residues (0.83 ?) and ligand atoms (0.68 ?) indicated stable protein conformation and ligand-binding states. The Rg values of MMP9 [(15.04±0.60) ?] and hesperetin [(4.19±0.35) ?] showed minimal fluctuations, further supporting structural compactness. The total binding free energy of the hesperetin-MMP9 complex during the 100 ns simulation was (?142.3±6.3) kJ/mol, with minimal energy fluctuations, confirming that the complex remained structurally stable without significant energy transition throughout the simulation.Conclusions:Hesperetin may bind effectively to targets such as MMP9, JAK2, Bcl-2, and ER1, and form a stable complex with MMP9. It is suggested to influence biological processes related to lipids and signaling pathways such as atherosclerosis, diabetic cardiomyopathy, and hypoxia-inducible factor-1, thereby playing a role in heart failure intervention.

Objective To analyze the feasibility of probiotics in delaying the progression of early Alzheimer's disease(AD)based on the changes of brain-gut-microbiota axis factors.Methods A total of 100 patients with early AD who visited Shaoxing 7th People's Hospital from December 2023 to December 2024 were selected and divided into control group(40 cases)and study group(60 cases)based on different treatment methods.The control group was treated with donepezil hydrochloride,while study group was treated with donepezil hydrochloride combined with probiotic preparations.The cognitive function,daily living ability,intestinal flora,and relative expression levels of brain-gut-microbiota axis factors,interleukin(IL)-6,tumor necrosis factor-α(TNF-α),5-hydroxytryptamine(5-HT),γ-aminobutyric acid(GABA),and lipopolysaccharide(LPS)/Toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)axis factors were compared before and after treatment in both groups.The clinical efficacy and prognosis monitoring results were also compared.Results The total effective rate and the proportion of patients with a clinical dementia rating score of 0 in study group were higher than those in control group(P＜0.05).The cognitive function and daily living ability scores in study group were higher than those in control group(P＜0.05).The copy numbers of lactobacillus and bifidobacterium in study group were higher than those in control group,while the copy numbers of enterococcus and escherichia coli were lower(P＜0.05).The relative expression levels of amyloid-β protein 1-42,IL-6,TNF-α,TLR4,and NF-κB in study group were lower than those in control group,and the levels of 5-HT and GABA were higher(P＜0.05).Conclusion Probiotics can delay the progression of early AD patients and improve clinical efficacy.It is speculated that the mechanism of action may be related to regulating the brain-gut-microbiota axis-mediated LPS/TLR4/NF-κB pathway to restore the intestinal microecology and alleviate neurological inflammation.

Objective:To explore the clinical and genetic characteristics of dyskeratosis congenita (DC).Methods:A retrospective analysis was conducted on the clinical, laboratory, imaging, pathological, genetic, and treatment data of 6 DC patients diagnosed at the Children′s Hospital of Zhejiang University School of Medicine from January 2010 to June 2025.Results:Among the 6 DC patients, 1 case was of Hoyeraal-Hreidarsson syndrome, 4 were male, and 2 were female. The diagnosis age 0.9-6.1 years. All 6 cases presented with bone marrow failure; 5 cases had a classic triad of skin and mucous membrane (mucosal leukoplakia, abnormal skin pigmentation, nail dystrophy); 5 cases had growth retardation, among which 2 cases had intrauterine growth retardation. Two cases had diarrhea and 1 case had abnormal liver function; 1 case had stiff and deformed limbs, accompanied by limited mobility, and dry and obstructive balanitis; 1 case had recurrent eyelid inflammation, middle ear inflammation, and nasal inflammation. All 6 cases had decreased B cell numbers, and 4 cases also had decreased natural killer cell numbers. There were 3 cases of children with cytomegalovirus (CMV) infection, of which 1 case of CMV infection led to retinal frosted branch angiitis and subsequent intracranial CMV infection resulting in death, and 1 case had CMV enteritis and died of hemophagocytic syndrome. Among 4 cases of boys, 3 cases had DKC1 gene variations and 1 case had an unknown variation gene; 2 cases of girls had TINF2 gene variations. The TINF2 c.860T>A (p.L287Q) variation site was a new mutation. Among 6 patients with DC, 2 cases died, 3 cases survived and 1 case was lost to follow-up.Conclusions:The DKC1 and TINF2 genes are common pathogenic genes in patients with DC. Bone marrow failure is a clue for the early identification of DC. The triad of skin and mucous membrane is its typical clinical manifestation. Children with DC generally have reduced B cells and natural killer killer cells, and have a high risk of fatal CMV infection. The overall prognosis is poor.

Objective To investigate the predictive value of labor progress angle (AOP), fetal head descent distance (HPD) and their change rates in the outcome of vaginal trial of cesarean scar uterus. Methods A total of 170 pregnant women who underwent vaginal trial production of scar uterus after cesarean section were selected as study subjects, and were divided into successful group and failed group based on the trial production outcomes. Advanced oxidation processes (AOP) and head-perineum distance (HPD) were measured by ultrasound during the active phase of the first stage of labor when the cervix dilated to 4 cm and at 1 hour after the cervix dilated to 4 cm, respectively. The AOP change rate and HPD change rate after 1 hour of progress were calculated. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of AOP, HPD and their change rates in the outcome of vaginal trial production of scar uterus after cesarean section. Delong test was used to compare the differences in area under curves (AUCs). Results Among 170 pregnant women with scarred uterus after cesarean section who were pregnant again, 139 cases (success group) were succeed in transvaginal delivery, while 31 cases failed trial delivery, and transferred to cesarean section (failure group). The AOP of the successful group was significantly larger than that of the failed group when the cervix was opened to 4 cm, and the HPD was significantly shorter than that of the failure group (P < 0.05). The AOP change rate and the change rate of HPD of the successful group were significantly higher than that of the failed group when the cervix dilated to 4 cm and at 1 hour (P < 0.05). The AUC of AOP and HPD in predicting the outcome of vaginal trial delivery of scar uterus after cesarean section were 0.846 and 0.812 respectively, and AUC predicted jointly by AOP and HPD showed no significant differences compared with AUC predicted separately (P>0.05). The AUC of the change rate of AOP and HPD in predicting the outcome of vaginal trial delivery of scarred uterus after cesarean section was 0.899 and 0.852 respectively, and the combined prediction of AOP change rate and HPD change rate had a higher AUC value than the AUC predicted separately. Its AUC value was higher than that of AOP combined with HPD (P < 0.05). Conclusion The AOP, HPD and their change rates when the uterine orifice expands to 4 cm in the active phase of the first stage of labor have predictive value for the outcome of vaginal trial production of scarred uterus after cesarean section.

ObjectiveTo analyze the research status and trends in low-level occupational benzene exposure. Methods Articles on low-level occupational benzene exposure from Chinese and English journals from January 1st, 2000, to December 31th, 2022 were retrieved using the Web of Science and the China National Knowledge Infrastructure, and a bibliometric analysis was conducted. Results A total of 327 articles were included in the analysis, comprising 216 English articles and 111 Chinese articles. i) The number of articles published in English fluctuates greatly over the years, without a trend of continuous growth or decline. Authors from 359 research institutions in 45 countries and regions have published relevant English articles in 97 kinds of journals, involving 281 grants from 226 foundations. The top three countries in terms of articles amount were the United States, Italy, and China, with 81, 46, and 43 papers, respectively. The English articles mainly focused on mechanistic research at the genetic level, such as hematotoxicity, oxidative stress, and DNA damage. ii) The number of Chinese articles increased gradually after 2012, with the growth peak in 2017. Authors from 127 research institutions in 26 provinces, autonomous regions, and municipalities published Chinese articles in 51 kinds of journals, involving 154 grants from 78 foundations. Chinese articles tended to focus on benzene-induced hematotoxicity and occupational health damage. Conclusion Most studies on low-level occupational benzene exposure were conducted in China, the United States and Italy, focused on hematotoxicity. Monitoring international research topics and hotspots of the field has certain reference value for related research in China.

The scientific rigor and efficacy of methodologies employed in drafting emergency health systems guidance documents （HSGs） are paramount in guaranteeing the quality， reliability， and applicability of HSGs. According to the Appraisal of Guidelines for Research and Evaluation- Health Systems （AGREE-HS）， we demonstratively assessed both global coronavirus disease-2019 （COVID-19） emergency HSGs and World Health Organization （WHO） standard HSGs to uncover the core attributes of methods employed in the development of emergency HSGs. Our evaluation findings revealed that across the five assessment items of AGREE-HS， methods in the 34 emergency HSGs evaluated ranked third， trailing behind topic and recommendations. Notably， criterion 2 （the best available and most contextually relevant evidence is considered） received the highest score， whereas criterion 5 （evidence of cost and cost-effectiveness of the potential options is described） scored the lowest. Compared with the WHO standard HSGs， the COVID-19 emergency HSGs exhibited low scores in methods （P<0.05）， which was reflected in nine criteria （P<0.05）， especially in criteria 1 （systematic and transparent methods are used to identify and review the evidence） and 9 （systematic and transparent methods are used to agree upon the final recommendations）. Among the COVID-19 emergency HSGs， that developed by the WHO achieved higher scores in eight out of all nine criteria， excluding criterion 8 （P<0.05）. The clinically relevant emergency HSGs had higher scores in the criteria 3 （the evidence base is current） and 8 （the rationale behind the recommendations is clear） than other types of emergency HSGs. Collectively， the methodology for developing emergency HSGs， represented by the COVID-19 emergency HSG， underscores evidence orientation and integrates expert consensus. It is characterized by adaptable evidence synthesis strategies， streamlined evidence review protocols， and contextual relevance， all of which are influenced by external， internal， and implementation-specific factors.

The construction of the comprehensive evaluation index system of the famous classical formula preparations after the marketing has both theoretical and practical significance. In this study， literature related to the post-marketing comprehensive evaluation of traditional Chinese medicine（TCM） compound preparations was retrieved from China National Knowledge Infrastructure（CNKI）， China Science and Technology Journal Database（VIP）， Wanfang Data Knowledge Service Platform（WanFang） and SinoMed from January 1， 2000 to April 30， 2022. CiteSpace 6.1.R2， a scientometrics software， was used to visualize the keywords involved， and to analyze the dynamic evolution trend and research hotspots in this field. Then， the existing comprehensive post-marketing evaluation index system of TCM compound preparations was screened and extracted， and the research status was systematically analyzed by mathematical statistics. It was found that there were problems such as the generalized boundaries between assessment dimensions and assessment elements， the lack of data sources for individual evaluation indexes， unset weight of some index system and insufficient application degree. In addition， according to the characteristics of famous classical formulas， the authors discuss the importance of evidence evaluation based on combination of disease and syndrome， pharmacovigilance of famous classical formulas preparations， and whole-process quality control of famous classical formulas， and put forward the construction strategy of comprehensive post-marketing evaluation of the famous classical formula preparations， which is oriented by clinical value， centered on evidence evaluation， and guaranteed by the whole-process quality control.