ObjectiveTo explore the role of the histone deacetylase Sirtuin-1 （SIRT1）/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells （NSCLC） induced by the co-stimulatory molecule B7 homolog 3 （B7-H3）. MethodsThe GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7⁃H3 gene expression levels. The Gene Enrichment Analysis （GSEA） method was used to analyze the enrichment characteristics of B7⁃H3 molecules in the gene set of cell apoptosis. In the non-small cell lung cancer A549 cell line， B7⁃H3 was knocked down， and the protein expression levels of SIRT1 and p53 were detected by Western blot. B7⁃H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. Overexpression of B7⁃H3 and knockdown of SIRT1 were performed in A549 cell line. The expression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected respectively by Western blot. Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. ResultsThe overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group （P<0.01）. B7-H3 was significantly enriched in the cell apoptosis signaling pathway and the p53 signaling pathway （P<0.05）. Compared with the control group， the expression of SIRT1 was significantly downregulated， and p53 was significantly upregulated in the B7⁃H3 knockdown group （both P<0.001）. Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression （P<0.05）， down-regulated p53 expression （P<0.01）， and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins （P<0.001）. The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overexpressed B7⁃H3 decreased （the apoptosis rate of the control group was 26.72%±4.13%， while that of the B7⁃H3 overexpression group was 13.87%±0.82%； P<0.01）. In B7-H3-overexpressing cell lines， SIRT1 knockdown significantly reversed apoptosis （P<0.05）， up-regulated p53 protein expression （P<0.001）， and markedly reduced the Bcl-2/Bax ratio （P<0.001）. ConclusionB7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.

ObjectiveTo investigate the efficacy and safety of Babaodan Capsule （BBD） in the treatment of patients with chronic hepatitis B virus （HBV） infection with damp-heat in the liver and gallbladder comorbid with gallbladder polyps. MethodsA randomized， double-blinded， placebo-controlled single-center trial was conducted among 120 patients with chronic HBV infection who were admitted to Beijing YouAn Hospital， Capital Medical University， from August 2020 to April 2023， and they were divided into treatment group （BBD） and control group （placebo）， with 60 patients in each group. The course of treatment was 24 weeks， and follow-up assessments were conducted every 4 weeks. The primary outcome measures were the number and maximum diameter of gallbladder polyps （assessed by ultrasound）， and the secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， blood lipid levels， and liver function parameters. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the Wilcoxon rank-sum test was used for comparison of ranked data between two groups； the generalized estimating equation was used to analyze repeated measures data. ResultsAfter 8 weeks of treatment， the treatment group had a significantly smaller diameter of polyps and a significantly lower number of polyps than the control group （Z=-1.76 and -1.80， both P<0.05）， and after 24 weeks of treatment， the treatment group had a significantly higher polyp reduction rate than the control group （30.51% vs 10.91%， P<0.05）. The subgroup analysis showed that patients receiving combined antiviral therapy， male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps tended to achieve significantly greater benefits. At week 8 of treatment， the treatment group had a significantly better TCM syndrome score than the control group （Z=-2.35， P<0.05）； after treatment， compared with the control group， the treatment group had a significantly greater increase in high-density lipoprotein （Z=-1.85， P<0.05） and significantly lower levels of alanine aminotransferase （Z=-2.06， P <0.05）， aspartate aminotransferase （Z=-2.13， P<0.05）， total bilirubin （Z=-2.12， P<0.05）， and direct bilirubin （Z=-3.09， P<0.05）. No serious adverse events were reported in either group. ConclusionBBD can effectively reduce the size of gallbladder polyps， improve TCM syndrome score， and reduce the level of bilirubin in patients with chronic HBV infection with damp-heat in the liver and gallbladder， with a favorable safety profile， and it may be more suitable for patients receiving combined antiviral therapy and specific subgroups （male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps.

Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ² test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.

Intraflagellar transport (IFT) is a core mechanism for ciliary assembly, length maintenance, ciliary proteome homeostasis and signal transduction. Most proteins required for ciliary structure and function are synthesized in the cytoplasm. Because the ciliary compartment is separated from the cell body by the selective barrier of the transition zone, these proteins cannot freely equilibrate between the cytoplasm and the cilium. Consequently, axonemal components, membrane proteins and signaling molecules must be actively imported into cilia, retrieved from the ciliary compartment, and recycled or degraded through highly ordered transport and sorting pathways. The IFT system is mainly composed of the IFT-A complex, IFT-B complex, kinesin-2, dynein-2 and the Bardet-Biedl syndrome protein complex (BBSome). Through coordinated anterograde and retrograde transport, these modules mediate the dynamic trafficking of different classes of ciliary cargoes. Anterograde transport delivers structural and membrane-associated components from the ciliary base toward the ciliary tip, whereas retrograde transport retrieves IFT components and selected cargoes back toward the ciliary base and cytoplasm. In this way, IFT not only supports the construction of the axoneme but also contributes to the maintenance of ciliary composition and the regulation of ciliary signaling activity. In recent years, advances in cryo-electron microscopy, in situ cryo-electron tomography and single-molecule imaging have greatly improved our understanding of the molecular mechanisms underlying IFT. These approaches have revealed how IFT trains are assembled at the ciliary base, how they move along axonemal microtubule tracks, how they undergo directional switching at the ciliary tip, and how cargoes are retrieved and recycled. Among the IFT modules, IFT-B acts as the major scaffold of IFT trains. It participates in cargo loading, motor coupling and initiation of anterograde transport. IFT-A is involved in retrograde transport, membrane protein adaptor function and train remodeling. The BBSome, through reversible association with the IFT system, regulates ciliary membrane protein sorting, signaling receptor clearance and renewal of the ciliary proteome. These functions indicate that the IFT machinery is not a simple linear transport pathway, but rather a dynamic and reconfigurable transport system. The conversion of transport direction is a key step in the IFT cycle. This process is closely associated with disassembly of anterograde trains, dissociation of kinesin-2, activation of dynein-2 at the ciliary tip and reassembly of retrograde trains. In terms of pathogenic mechanisms, IFT abnormalities may cause ciliopathies through four major pathways: defects in ciliary assembly and structure, abnormal localization of ciliary cargoes, dysregulation of signaling pathways, and impaired cargo unloading and retrieval. These defects can affect multiple organ systems, including the retina, kidney, skeleton, respiratory tract, reproductive system, and neuro-metabolic system. Current therapeutic strategies are still mainly based on symptomatic support and maintenance of organ function. Overall, IFT is a dynamic transport system jointly regulated by axonemal structure, motor activity, cargo selection and cellular signaling. It links ciliary architecture with protein turnover and signaling regulation, thereby playing a fundamental role in both ciliary homeostasis and ciliopathy pathogenesis. Further elucidation of IFT regulatory mechanisms and their relationships with disease phenotypes will help promote mechanism-based classification, genetic diagnosis and precision intervention for ciliopathies.

In the context of global warming, protecting outdoor workers from occupational heat exposure has become an important public health concern. This review summarized the principle, applicability, and limitation of three categories of wet bulb globe temperature (WBGT) prediction models: empirical regression models, heat-balance models, and machine-learning models. Drawing on international experience from the United States, Europe, and Japan, this review further examined the technical challenges of applying WBGT-based prediction models to large-scale occupational heat stress early warning systems. In response to gaps in occupational heat stress management in China, WBGT should be considered a core assessment indicator to support a transition from passive response to proactive intervention. A localized implementation pathway is proposed, incorporating mechanism-based model calibration, regional parameter adaptation, and multi-source data fusion. Strengthening collaboration between public health and meteorological departments and developing platform-based flexible intervention strategies for workers in new forms of employment may improve the targeting of occupational heat stress early warning and health protection. Future research should focus on physics-constrained machine learning, refined microenvironmental prediction, and individualized risk assessment to support the development of a digitally enabled occupational heat-health protection framework.

Objective:To investigate the inhibitory effect of astragaloside Ⅳ(AS-Ⅳ)on cisplatin(CDDP)-induced liver injury in the mice,and to elucidate its possible mechanism.Methods:Forty male C57BL/6 mice with body weights of 18-22 g were randomly divided into control group,model group,AS-Ⅳ group and adenosine 5'-monophosphate-activated protein kinase(AMPK)inhibitor(Compound C)+AS-Ⅳ group.The mice in control group and model group were gavaged with the same volume of normal saline,and the drug was administered continuously for 9 d.The mice in AS-Ⅳ group and Compound C+AS-Ⅳ group were given AS-Ⅳ aqueous solution(150 mg·kg-1·d-1),respectively.On the 6th day of experiment,the mice in Compound C+AS-Ⅳ group were intraperitoneally injected with Compound C(20 mg·kg-1),and on the 7th day,except for control group,the mice in other groups were intraperitoneally injected with 20 mg·kg-1 CDDP to establish the mouse liver injury models,and the mice were sacrificed 48 h later.Serum and liver tissues were collected,and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in the serum of the mice,as well as the activities of superoxide dismutase(SOD)and catalase(CAT)and the levels of malondialdehyde(MDA)in the liver tissue of the mice in various groups were detected by kits.The pathomorphology of liver tissue of the mice in various groups were detected by HE staining.The expression levels of glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and ferroptosis inhibitory protein 1(FSP1)proteins in liver tissue of the mice in various groups were detected by immunohistochemical staining,and the expression levels of nuclear factor-E2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and AMPK proteins in liver tissue of the mice in various groups were detected by Western blotting method.Results:Compared with control group,the levels of AST and ALT in serum of the mice in model group were increased(P＜0.01),the activities of SOD and CAT in the liver tissue were significantly decreased(P＜0.01),and the MDA level was increased(P＜0.01);compared with model group,the levels of AST and ALT in serum of the mice in AS-Ⅳ group were decreased(P＜0.01),the MDA level in the liver tissue was decreased(P＜0.01),and the activities of SOD and CAT were increased(P＜0.01);compared with AS-Ⅳ group(P＜0.01),the levels of AST and ALT in serum of the mice in Compound C+AS-Ⅳ group were increased(P＜0.01),the level of MDA in liver tissue was increased(P＜0.05),and the activities SOD and CAT were decreased(P＜0.01).The HE staining results showed that compared with control group,the liver damage degree of the mice in model group was enhanced,the hepatocyte arrangement was disordered,and some hepatocyte edema were increased;compared with model group,the liver morphology of the mice in AS-Ⅳ group returned to normal;compared with AS-Ⅳ group,the hepatocyte arrangement of the mice in Compound C+AS-Ⅳ group was disordered and the edges were blurred.The immunohistochemistry results showed that compared with control group,the expression levels of GPX4,FTH1 and FSP1 proteins in liver tissue of the mice in model group were decreased(P＜0.05);compared with model group,the expression levels of GPX4,FTH1 and FSP1 proteins in liver tissue of the mice in AS-Ⅳ group were increased(P＜0.05);compared with AS-Ⅳ group,the expression levels of GPX4,FTH1 and FSP1 proteins in liver tissue of the mice in Compound C+AS-Ⅳ group were decreased(P＜0.05 or P＜0.01).The Western blotting results showed that compared with control group,the expression levels of Nrf2,HO-1 and AMPK proteins in liver tissue of the mice in model group were decreased(P＜0.01);compared with model group,the expression levels of Nrf2,HO-1 and AMPK proteins in liver tissue of the mice in AS-Ⅳgroup were increased(P＜0.01);compared with AS-Ⅳ group,the expression levels of Nrf2,HO-1 and AMPK proteins in liver tissue of the mice in Compound C+AS-Ⅳ group were decreased(P＜0.01).Conclusion:AS-Ⅳ can alleviate the CDDP-induced liver injury,and its mechanism may be related to the regulation of AMPK/Nrf2/HO-1 signal pathway and ferroptosis by AS-Ⅳ.

Radiotherapy can cause varying degrees of damage to surrounding normal tissues while treating tumors. In recent years, single-cell RNA sequencing (scRNA-Seq), an emerging technology in modern biology, has gradually played a significant role in research on radiation-induced injuries. Researchers have delved into a variety of radiation-induced brain injuries, including radiation-induced brain injury (RIBI), cardiovascular injury, lung injury, intestinal injury, skin injury, and hematopoietic injury. Their studies provide novel perspectives for revealing the mechanisms behind radiation-induced injuries, assessing the degree of injury, and exploring potential therapies. This study reviews the advances in the application of scRNA-seq to research on radiation-induced injuries.

Objective:To establish the reference interval of 12 types of cytokines(IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17,IFN-γ,IFN-α,TNF-α)in adult plasma based on multiple microsphere flow immunofluorescence(MBFFI).Methods:A total of 140 healthy adult patients who were examined at Xuzhou Central Hospital between January 2022 and December 2023 were included in the study.Plasma cytokine levels were detected and reference intervals were established by the flow cytometer and the assay kits produced by Qingdao Raisecare Biotechnology Co.,Ltd and Jiangsu BioPredia Biotechnology Co.,Ltd.Results:All of the cytokines exhibited a non-normal distribution,and there was a discrepancy in the 95％reference interval between the two re-agents.The reference intervals for the 12 cytokine kits produced by Qingdao Raisecare Biotechnology Co.,Ltd.were as follows:IFN-α:<4.91 pg/ml,IL-12 p70:<1.95 pg/ml,IL-5:<12.72 pg/ml,IL-8:<60.68 pg/ml,IL-1β:<27.67 pg/ml,IL-2:<5.01 pg/ml,IL-4:<1.22 pg/ml,IL-6:<6.11 pg/ml,TNF-α:<2.92 pg/ml,IL-17:<10.27 pg/ml,IL-10:<6.88 pg/ml,IFN-γ:<17.68 pg/ml.The reference intervals of the 12 cytokines produced by Jiangsu BioPredia Biotechnology Co.,Ltd.were as follows:IFN-α:<4.05 pg/ml,IL-12 p70:<7.33 pg/ml,IL-5:<7.80 pg/ml,IL-8:<13.24 pg/ml,IL-1β:<19.24 pg/ml,IL-2:<2.42 pg/ml,IL-4:<0.99 pg/ml,IL-6:<2.10 pg/ml,TNF-α:<0.87 pg/ml,IL-17:<1.42 pg/ml,IL-10:<1.10 pg/ml,IFN-γ:<1.34 pg/ml.Conclusion:In this study,the ref-erence range of two reagents for the detection of 12 kinds of cytokines in plasma of healthy adults is established by MBFFI,which pro-vides a valuable reference for the diagnosis and treatment of clinical-related diseases.

AIM:To investigate the possible mechanism how orphan nuclear receptor 4A1(NR4A1)affects renal fibrosis in unilateral ureteral obstruction(UUO)mice.METHODS:(1)Specific pathogen-free(SPF)male C57BL/6J mice(5 to 6 weeks old)were randomly divided into sh-Con+sham group(n=6),sham+sh-NR4A1 group(n=6),sh-NR4A1+UUO group(n=6),and sh-NR4A1+UUO group(n=6).Renal NR4A1 knockdown mice were prepared by intrarenal injection of NR4A1 viral vector.(2)SPF male C57BL/6J mice(5 to 6 weeks old)were randomly assigned to in sham group,UUO group,and UUO+cytosporone-B(Csn-B)group.An animal model of renal fibrosis was prepared by UUO,and Csn-B was intervened for 14 days.HE,Masson,and Sirius red staining were used to observe renal pathological damage.Immunohistochemistry and Western blot were performed to detect the expression of NR4A1,interferon-γ(IFN-γ),α-smooth muscle actin(α-SMA)and vimentin.The purpose of this study is to observe the regulatory effect of NR4A1 on UUO-induced renal fibrosis.RESULTS:(1)The expression of NR4A1 was decreased in kidney tissues of UUO mice(P<0.05).(2)HE staining results showed that there are tubular dilation,atrophy,and massive inflammatory cell infiltra-tion in sh-Con+UUO group,and NR4A1 knockdown can aggravate UUO-induced kidney damage(P<0.05).The results of Masson and Sirius red staining showed a banded distribution of collagen deposition in the sh-Con+UUO group,and colla-gen deposition increased significantly after NR4A1 knockdown(P<0.05).Treatment with Csn-B could improve renal path-ological damage and reduce collagen deposition.(3)UUO could upregulate the expression of α-SMA and vimentin,and NR4A1 knockdown could significantly increase UUO-induced their expression(P<0.05).In addition,Csn-B could im-prove UUO-induced renal fibrosis(P<0.05).(4)The expression of IFN-γ was increased in UUO mice,and NR4A1 knockdown could upregulate UUO-induced IFN-γ expression(P<0.05).Moreover,Csn-B could down-regulate UUO-in-duced IFN-γ expression(P<0.05).CONCLUSION:NR4A1 can affect renal fibrosis by regulating IFN-γ in UUO mice.

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.