Background Shift work is increasingly common in modern industries as economic globalization continues to advance, and has been associated with type 2 diabetes mellitus (T2DM). Objective To investigate the independent and interactive effects of shift work types and physical labor intensity on the risk of T2DM within an occupational cohort of petroleum workers, aiming to provide a scientific basis for reducing the risk of T2DM among workers engaged in shift work and physical labor. Methods This cohort study enrolled petroleum workers who underwent occupational health examinations at Karamay Central Hospital in Xinjiang from 2013 to 2015. Using stratified sampling, employees aged 20–60 years who had been actively employed and had been working in their current positions for at least one year were selected. A total of 3720 participants completed the baseline questionnaire survey and health examination, and follow-up was conducted in 2023. T2DM was diagnosed according to the 2020 Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes. Shift work type was categorized into fixed day shift, two-shift rotation, three-team two-shift rotation, four-team three-shift rotation, and other shift schedules. Physical labor intensity was classified as light, moderate, heavy, and extremely heavy according to the Classification of Physical Labor Intensity for Petroleum Field Operations (SY/T 6358—2008). Poisson regression models were used to estimate the associations of shift work type, physical labor intensity, and their joint exposure categories with T2DM risk after adjustment for potential confounders. Results A total of 3473 participants completed follow-up. Poisson regression analysis showed that shift work type was associated with T2DM risk. After adjustment for confounders, compared with fixed day shift workers, those engaged in two-shift rotation, three-team two-shift rotation, four-team three-shift rotation, and other shift schedules had higher risks of T2DM, with RRs of 2.17 (95%CI: 1.44, 3.27), 1.86 (95%CI: 1.16, 2.97), 1.85 (95%CI: 1.17, 2.93), and 2.15 (95%CI: 1.20, 3.88), respectively. T2DM risk also differed across physical labor intensity groups, with the extremely heavy group showing the highest risk (RR=2.26, 95%CI: 1.44, 3.56), followed by the heavy group (RR=1.91, 95%CI: 1.29, 2.82). Compared with workers exposed to fixed day shift + light intensity, increased T2DM risks were observed in those exposed to fixed day shift + heavy intensity (RR=2.38, 95%CI: 1.16, 4.72) or extremely heavy intensity (RR=2.64, 95%CI: 1.13, 5.82); two-shift rotation + light (RR=2.71, 95%CI: 1.11, 6.14), moderate (RR=3.38, 95%CI: 1.43, 7.34), heavy (RR=3.61, 95%CI: 1.52, 7.84), or extremely heavy intensity (RR=4.93, 95%CI: 1.87, 11.12); three-shift two-team rotation + light (RR=2.75, 95%CI: 1.14, 6.19), moderate (RR=3.08, 95%CI: 1.14, 7.51), or heavy/extremely heavy intensity (RR=4.06, 95%CI: 1.77, 8.50); four-shift three-team rotation + heavy/extremely heavy intensity (RR=3.89, 95%CI: 1.78, 7.84); and other shift types + heavy/extremely heavy intensity (RR=4.57, 95%CI: 1.55, 11.30). Conclusion This study demonstrates that various types of shift work significantly increase the risk of T2DM, and that concurrent exposure to high physical labor intensity exacerbates this risk. Regular blood glucose monitoring and targeted health interventions are recommended for workers exposed to rotating shift schedules and high physical work intensity.

ObjectiveThis study aimed to investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through regulating ferroptosis， and to screen key metabolites and analyze their association with ferroptosis. MethodsClinical samples of normal endometrium from patients without EMs and eutopic and ectopic endometrium from EMs patients （10 cases each） were collected and divided into control group， eutopic group， and EMs group. Hematoxylin-eosin （HE） staining was performed to observe ectopic lesions of EMs. Immunohistochemistry was used to detect the expression of solute carrier family 7 member 11 （SLC7A11） and glutathione peroxidase 4 （GPX4）. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of malondialdehyde （MDA）， ferrous ion （Fe²⁺）， GPX4 and glutathione （GSH） in endometrial tissues， as well as serum levels of Fe²⁺， GPX4 and GSH. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of SLC7A11， GPX4， transferrin receptor （TFR） and ferritin heavy chain 1 （FTH1）. In the in vitro experiment， primary stromal cells were isolated from ectopic lesions of EMs patients. Cell counting kit-8 （CCK-8） was used to determine the optimal concentration of drug-containing serum for intervention. The level of reactive oxygen species （ROS） was measured， and Real-time PCR was applied to detect ferroptosis-related indicators. In the animal experiments， an EM rat model was established， and the rats were randomly assigned to the sham operation group， EMs group， low-dose Luoshi Neiyi Formula group （7.87 g·kg^-1）， high-dose Luoshi Neiyi prescription group （15.74 g·kg^-1）， and danazol group （42 mg·kg^-1）. Untargeted metabolomics detection and pathway enrichment analysis were conducted on serum samples from patients and rats. Spearman correlation analysis was performed to assess the relationship between differential metabolites and ferroptosis indicators. The correlations between differential metabolites in patient endometrium and serum and key ferroptosis indicators （GPX4， Fe²⁺， MDA， GSH） as well as ferroptosis-related mRNAs （GPX4， SLC7A11， FTH1） were analyzed， and correlation heatmaps were generated accordingly. ResultsCompared with normal eutopic endometrium， ectopic lesions in EMs patients showed glandular disorganization and stromal fibrosis. In ectopic endometrium， the contents of MDA， ROS， and Fe²⁺ decreased， while GPX4 level increased， and the mRNA expression of SLC7A11 and GPX4 was upregulated （P<0.05， P<0.01）. In serum， the levels of GPX4 and Fe²⁺ were elevated， whereas the GSH level declined， suggesting abnormalities in ferroptosis-related pathways in ectopic lesions （P<0.05， P<0.01）. After intervention with Luoshi Neiyi prescription-containing serum， the intracellular ROS level in ectopic endometrial stromal cells was elevated， the mRNA expression of SLC7A11 and GPX4 was downregulated， and TFR mRNA expression was upregulated （P<0.05， P<0.01）. Metabolomics analysis revealed 1104 and 198 differential metabolites in EMs patients and EMs rats， respectively， compared with their corresponding control groups， and both low-dose and high-dose Luoshi Neiyi prescription were found to regulate this metabolic disturbance， with the core regulatory pathways mainly involving arginine and proline metabolism. Correlation analysis showed that the glycerophospholipids including PI（16∶0/17∶0） and PI［18∶2（9Z，12Z）］ were negatively correlated with GPX4 and positively correlated with MDA， while 17α-hydroxyprogesterone was positively correlated with GPX4， SLC7A11， and FTH1 q<0.05）. ConclusionLuoshi Neiyi prescription may systematically ameliorate disease-associated metabolic dysregulation via modulation of the serum arginine and proline metabolism pathway， and may regulate ferroptosis in ectopic lesions through a mechanism potentially linked to the serum glycerophospholipid and steroid metabolism pathways. Collectively， these findings provide experimental evidence for the clinical application of Luoshi Neiyi prescription.

ObjectiveThis study aimed to investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis （EMs） through regulating ferroptosis， and to screen key metabolites and analyze their association with ferroptosis. MethodsClinical samples of normal endometrium from patients without EMs and eutopic and ectopic endometrium from EMs patients （10 cases each） were collected and divided into control group， eutopic group， and EMs group. Hematoxylin-eosin （HE） staining was performed to observe ectopic lesions of EMs. Immunohistochemistry was used to detect the expression of solute carrier family 7 member 11 （SLC7A11） and glutathione peroxidase 4 （GPX4）. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of malondialdehyde （MDA）， ferrous ion （Fe²⁺）， GPX4 and glutathione （GSH） in endometrial tissues， as well as serum levels of Fe²⁺， GPX4 and GSH. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of SLC7A11， GPX4， transferrin receptor （TFR） and ferritin heavy chain 1 （FTH1）. In the in vitro experiment， primary stromal cells were isolated from ectopic lesions of EMs patients. Cell counting kit-8 （CCK-8） was used to determine the optimal concentration of drug-containing serum for intervention. The level of reactive oxygen species （ROS） was measured， and Real-time PCR was applied to detect ferroptosis-related indicators. In the animal experiments， an EM rat model was established， and the rats were randomly assigned to the sham operation group， EMs group， low-dose Luoshi Neiyi Formula group （7.87 g·kg^-1）， high-dose Luoshi Neiyi prescription group （15.74 g·kg^-1）， and danazol group （42 mg·kg^-1）. Untargeted metabolomics detection and pathway enrichment analysis were conducted on serum samples from patients and rats. Spearman correlation analysis was performed to assess the relationship between differential metabolites and ferroptosis indicators. The correlations between differential metabolites in patient endometrium and serum and key ferroptosis indicators （GPX4， Fe²⁺， MDA， GSH） as well as ferroptosis-related mRNAs （GPX4， SLC7A11， FTH1） were analyzed， and correlation heatmaps were generated accordingly. ResultsCompared with normal eutopic endometrium， ectopic lesions in EMs patients showed glandular disorganization and stromal fibrosis. In ectopic endometrium， the contents of MDA， ROS， and Fe²⁺ decreased， while GPX4 level increased， and the mRNA expression of SLC7A11 and GPX4 was upregulated （P<0.05， P<0.01）. In serum， the levels of GPX4 and Fe²⁺ were elevated， whereas the GSH level declined， suggesting abnormalities in ferroptosis-related pathways in ectopic lesions （P<0.05， P<0.01）. After intervention with Luoshi Neiyi prescription-containing serum， the intracellular ROS level in ectopic endometrial stromal cells was elevated， the mRNA expression of SLC7A11 and GPX4 was downregulated， and TFR mRNA expression was upregulated （P<0.05， P<0.01）. Metabolomics analysis revealed 1104 and 198 differential metabolites in EMs patients and EMs rats， respectively， compared with their corresponding control groups， and both low-dose and high-dose Luoshi Neiyi prescription were found to regulate this metabolic disturbance， with the core regulatory pathways mainly involving arginine and proline metabolism. Correlation analysis showed that the glycerophospholipids including PI（16∶0/17∶0） and PI［18∶2（9Z，12Z）］ were negatively correlated with GPX4 and positively correlated with MDA， while 17α-hydroxyprogesterone was positively correlated with GPX4， SLC7A11， and FTH1 q<0.05）. ConclusionLuoshi Neiyi prescription may systematically ameliorate disease-associated metabolic dysregulation via modulation of the serum arginine and proline metabolism pathway， and may regulate ferroptosis in ectopic lesions through a mechanism potentially linked to the serum glycerophospholipid and steroid metabolism pathways. Collectively， these findings provide experimental evidence for the clinical application of Luoshi Neiyi prescription.

ObjectiveTo analyze the research hotpots and development trends of international nursing ethical decision-making in the past 10 years by bibliometric methods. MethodsLiterature related to nursing ethical decision-making published in the Web of Science core collection database from 2014 to 2023 was retrieved. VOSviewer 1.6.18 software was utilized to visually present and analyze data regarding the number of publications， journal sources， countries of origin， author information， research institutions， key terms， co-cited references， and others. ResultsA total of 149 articles were included， involving 85 source journals， of which Nursing Ethics and BMC Medical Ethics were the most prolific. The number of publications on nursing ethical decision-making showed an overall upward trend， with the United States leading other countries in the number of publications. These publications involved 567 authors from 302 research institutions， and the degree of inter-institutional collaboration was relatively low. Keyword clustering， timeline overlay， and density analysis revealed that current research hotspots and trends included the ethical issues and decision-making in clinical nursing practice， the ethical decision-making level and competence of university nursing undergraduates， the ethical decision-making of nursing managers， and ethical decision-making dilemmas encountered by nursing staff during public health emergencies. ConclusionResearch on nursing ethical decision-making is gradually deepening but remains fragmented， lacking sustainability and collaboration. The ethical decision-making levels and competencies of university nursing students， as well as the field of ethical decision-making among nursing managers， may emerge as novel research hotspots in the future. Henceforth， it is necessary to strengthen in-depth exchanges among authors and institutions， pay close attention to international research frontiers， and enhance both the depth and breadth of research.

Objective:To explore the feasibility of joint screening of the two primary immunodeficiency diseases [severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia(XLA)] and spinal muscular atrophy(SMA) in newborns by multiplex real-time quantitative PCR technology, and to provide evidence for early screening, diagnosis and treatment of children.Methods:Cross-sectional study. From July 2021 to January 2023, a total of 103 240 dry blood spots samples of newborns were collected which were delivered to Neonatal Disease Screening Center of Zhejiang by cold chain transportation. The concentrations of the T cell receptor excision ring (TREC), Kappa deletion of the recombinant excision loop (KREC), and exon 7 deletion of Survival Motor Neuron 1 (SMN1) gene in dry blood spots were simultaneously detected by multiplex real-time fluorescence quantitative PCR, taken ribonuclease P/MRP 30 000 subunits (RPP30) as an internal reference gene. The positive newborns were further diagnosed by other laboratory tests and gene sequencing was taken as gold standard. Children samples from 1 case of SCID, 3 cases of XLA and 2 cases of SMA were used for positive verification. The correlation between detected concentration of TREC/KREC and basic information in newborns were analyzed. The differences among groups for each factor were analyzed.Results:One case of SCID, 2 cases of XLA, 9 cases of SMA and 7 cases of other genetic diseases (4 cases of DiGeorge syndrome, 1 case of trisomy 21 syndrome, 1 case of Noonan syndrome and 1 case of super male syndrome) were identified by multiplex real-time fluorescence quantitative PCR. The positive predictive values of screening neonatal SCID, XLA and SMA were 2.44% (1/41), 2.78% (2/72) and 9/9 respectively. Taking the samples from clinically diagnosed 1 case of SCID, 3 cases of XLA and 2 cases of SMA as positive validation samples, which were all identified. The detected results of TREC/KREC correlated with time of blood collection, sex, weight, gestational age and delivery mode of newborns, whose r values were 0.162/0.187, 0.066/0.032, 0.045/0.042, ?0.015/?0.088 and 0.014/0.068 respectively (all P<0.05). Conclusions:Relying on current neonatal screening platform in Zhejiang, it is feasible to screen jointly two kinds of primary immunodeficiency diseases and spinal muscular atrophy in newborns by multiple real-time fluorescence quantitative PCR technology.

Diagnosis-related groups (DRG) payment is an important component of deepening the reform of medical insurance payment methods. In June 2023, a tertiary hospital launched an intelligent DRG grouping audit system to enhance grouping accuracy. By establishing a multi departmental collaborative organizational structure, building a standardized knowledge base and a rule base covering five categories (diagnosis, fees, testing, nursing, and pathology), and integrating electronic medical records, medical orders, testing, and imaging data throughout the entire diagnosis and treatment process, the intelligent DRG grouping audit system with data collection, identification, extraction, comparison, and output modules was constructed to achieve intelligent audit. At the same time, it was formed a closed-loop management system for pre reporting quality control, in-process group entry control, and post data analysis and assessment, which would prevent the risk of differentiated behaviors such as high coding and high sets, and ensure the reasonable use of medical insurance funds. By January 2024, the system had covered 89 ADRG groups, and improved the efficiency and quality of DRG grouping audit. Compared with February to May 2023, the monthly average rejection rate of medical records on the first page decreased by 9.4% after the system was put into operation (June to December 2023), and core medical indicators such as the number of DRG groups, medical insurance settlement cases, and time consumption index continued to improve. The practical experience could provide reference and inspiration for other hospitals in China.

Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

This paper presents a comprehensive study of Pulsatillae Radix,encompassing its pharmacognostic investigation,chemical constituents,and pharmacological effects.Pulsatillae Radix,first recorded in the Shen Nong's Herbal Classic,is known for its efficacy in cooling blood to stop dysentery,clearing heat,and detoxifying,and has been used to treat diseases such as enteritis caused by parasites,demonstrating potential as an antiviral candidate.Research has revealed that its major chemical constituents include triterpenoid saponins,triterpenic acids,and various other components,which collectively constitute the pharmacological foundation of Pulsatillae Radix.Significant pharmacological activities have been observed in antitumor,anti-inflammatory,antimicrobial,and antiviral aspects,providing a scientific basis for its broad application in the pharmaceutical field.

Objective To investigate the bacterial contamination of water specimens at different pre-discharge time of flexible endoscopic final rinse water before daily use,and provide reference basis for choosing the optimal pre-dis-charge time in clinical work.Methods From August to December 2023,the water produced by the purified water equipment of the digestive endoscopy centers of 4 tertiary first-class medical institutions in Jiangxi Province,as well as the final rinsing water at the terminal-point at different pre-discharge times(before pre-discharge,discharge of 1,3,5,and 10 minutes)were subjected to on-site sampling,the collected water specimens were performed microbio-logical cultures by pouring and filter membrane methods,unqualified water specimens were performed bacterial i-dentification.Results 48 specimens of water produced by purified water equipment were collected,with qualified rate of 100％.480 final water specimens were collected,with a qualified rate of 0 before pre-discharge.The quali-fied rates of pre-discharge at 1,3,5,and 10 minutes were 0,21.88％,55.21％,and 73.96％,respectively.Bac-terial colony counts in the final rinse water with different pre-discharge times in 4 medical institutions showed statis-tically significant differences(all P＜0.001).As the pre-discharge time increased,bacterial colony counts in the fi-nal rinse water of all four medical institutions showed a decreasing trend.The pairwise comparison of the overall bacterial colony count of the final rinse water at different pre-discharge time showed that there was no statistically significant difference in the bacterial colony count of the final rinse water at 5 and 10 minutes of pre-discharge(P＞0.05),while the pairwise comparison between other time points showed statistically significant differences(all P＜0.001).Environmental contaminated bacteria such as Micrococcus luteus,Cupriavidus paucula,and Sphin-gononas paucimobilis were detected from the unqualified water specimens.Conclusion With the extension of pre-discharge time,the degree of bacterial contamination in the final rinse water significantly decreases.All levels of medical institutions need to pre-discharge the final rinse water daily,and the pre-discharge time should last for at least 5 minutes.