Objective To analyze the lung function condition and the prevalence of pulmonary ventilation disorders in the occupational population of Wuhan, and to explore their influencing factors. Methods Physical examination data from the Wuhan Prevention and Treatment Center for Occupational Diseases were used in this study, and finally 9499 people were selected as the study subjects. The linear regression model and logistic regression model were used to analyze the influencing factors of pulmonary ventilation function and pulmonary dysfunction. The restricted cubic spline was used to explore the nonlinear relationship. Results The prevalence of pulmonary ventilation disorders was 1.7%, and the lung function indexes FVC, FEV1, and FEV1/FVC were significantly lower in the population aged >27 years than in the population aged <27 years (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in females than in males (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in underweight occupational groups than in normal-weight groups (P<0.001), and FVC and FEV1 were significantly lower in dust-exposed occupational groups than in groups without dust exposure(P<0.05). Restricted cubic spline plots showed a nonlinear relationship between age and lung function indexes FVC and FEV1 (P_nonlinear< 0.05). Age and BMI were the risk factors for pulmonary ventilation disorders. Conclusion Age, gender, BMI, and dust exposure are risk factors for decreased FVC and FEV1. Age is the risk factor for decreased FEV1/FVC. Age and BMI are the risk factors for pulmonary ventilation disorders.

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Objective To explore the action mechanism of tauroursodeoxycholic acid(TUDCA)promoting intracellular clearance of Burkholderia pseudomallei(B.pseudomallei)in RAW264.7 macrophages.Methods After TUDCA of different concentrations were used to treat RAW264.7 cells pre-infected with B.pseudomallei for 8 h or not,flow cytometry was applied to detect the apoptosis of the infected and control cells.In addition,another endoplasmic reticulum stress(ERS)inhibitor 4-PBA was used to detect the apoptosis and proliferation of host cells after B.pseudomallei infection with Annexin-V/PI double staining and MTT cell proliferation assay.Furthermore,after transfected with CHOP siRNA,Western blotting and flow cytometry were employed to detect the effect of TUDCA on the expression levels of Caspase-3 and Caspase-12 and the changes in apoptotic rate after B.pseudomallei infection,respectively.Finally,the effect of TUDCA on intracellular multiplication of infected RAW264.7 cells were observed to estimate the CFU value in the presence and absence of CHOP siRNA.Results Under different concentrations of TUDCA,100 or 200 μmol/L TUDCA significantly reduced B.pseudomallei-induced apoptosis in RAW264.7 cells(P＜0.05).Meanwhile,both TUDCA and 4-PBA treatment could decrease the apoptosis induced by B.pseudomallei infection by ERS(P＜0.05).Further,the expression levels of Caspase-3 and Caspase-12 were obviously increased after B.pseudomallei infection compared with uninfected groups,but their expression levels in the siCHOP group was significantly lower than that in the siC group.Besides,flow cytometry also showed that TUDCA could reduce apoptosis induced by B.pseudomallei infection(P＜0.05),but no significant effect of TUDCA on apoptosis was observed under CHOP knockdown.Finally,intracellular CFU assay indicated that TUDCA treatment promoted the host cell clearance of B.pseudomallei(P＜0.05),but no such effect was observed in siCHOP group.Conclusion In B.pseudomallei infected RAW264.7 cells,TUDCA promotes the intracellular clearance of the bacteria by inhibiting ERS-induced apoptosis.

BACKGROUND:There are many studies focusing on keloid scars,but the pathogenesis is not fully understood.In recent years,there have been some new research advances in the pathogenesis of keloids,including transforming growth factor-β(TGF-β)/Smad signaling pathway,ischemic hypoxia,hypoxia-inducible factor 1(HIF-1),and mitogen-activated protein kinase(MAPK)pathway.The TGF-β/Smad pathway is now more clearly studied,and activation of the TGF-β/Smad pathway promotes the development of keloid scars. OBJECTIVE:To review the TGF-β/Smad signaling pathway and evaluate the main therapeutic strategies targeting this pathway,with the aim of contributing to the development of more effective clinical treatments. METHODS:PubMed and Web of Science,CNKI and WanFang databases were searched by computer for relevant literature published from January 2017 to April 2023 with the search terms of"keloid,fibroblasts,TGF-β/Smad,extracellular matrix,collagen,treatment measures"in English and Chinese.Seventy-two articles were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The mechanism of TGF-β/Smad signaling pathway in the occurrence and development of keloids is summarized:TGF-β1 and TGF-β2 are overexpressed in keloids,while TGF-β3 shows antifibrotic effects.Smad2/3 and Smad1/5/8 are combined with Smad4 to form a complex that enters the nucleus and plays a fibrotic role,while Smad6/7 can inhibit keloid hyperplasia.The TGF-β/Smad signaling pathway is currently the most clearly studied pathway in keloids,and there are many pathways targeted to inhibit the activation of this pathway,which can inhibit the occurrence and development of keloids to a greater extent.Currently,there is no single clinical gold standard treatment for keloids,and inhibition of the TGF-β/Smad pathway alone cannot completely inhibit the development of keloids.A comprehensive consideration of the association between all systemic systems and keloids is needed.Although many promising targets have been identified in the fibrosis cascade,more research is needed to translate this into targeted therapies in the clinic.

OBJECTIVE To analyze the chemical constituents from classical prescription Xiehuang San(XHS)standard decoc-tion by UPLC-Q-TOF-MS technology,and classify the chemical composition and analyze the representative components.METHODS Acquity HSS T3 column(2.1 mm×100 mm,1.8 μm)was used as the chromatographic column,with 0.1%formic acid solution-0.1%formic acid acetonitrile as the mobile phase for gradient elution.The volume flow rate was 0.4 mL·min-1 and the column tem-perature was 40℃.Mass spectrometry data of XHS were collected in positive and negative ion modes.The chemical constituents from classical prescription XHS were analyzed and identified by Masslynx 4.1 software comparison with reference materials,mass spectrome-try data analysis and reference to relevant literature.RESULTS A total of 107 compounds were analyzed and identified from XHS,including 45 flavonoids,27 triterpenoids,11 monoterpenoids,10 phenylpropanoids,6 chromogenic ketones,5 alkaloids and 3 other other compounds.CONCLUSION The study provides an experimental basis for the further research on the substance basis and qual-ity control of XHS.

Hepatocellular carcinoma is a kind of cancer with a strong invasion, a high incidence rate and mortality, and a poor prognosis. At the time of diagnosis, most patients are already in the advanced stages of a tumor and have lost the chance for radical surgical treatment. Advanced hepatocellular carcinoma treatment has a gradual transition from systemic chemotherapy to targeted therapy, immunotherapy, and combination therapy, especially immune checkpoint inhibitor-based immunotherapy combination therapy, such as combination with bevacizumab monoclonal antibodies and other drugs, or combination with TACE, HAIC, radiotherapy, ablation, and other treatment methods. Combination therapy has significant synergistic effects and thus has already become a future treatment trend for hepatocellular carcinoma. An immunotherapy-based combination therapy plan will run through the whole process of systemic therapy, which is expected to bring better survival benefits to patients with hepatocellular carcinoma. This article reviews the latest research progress in aspects of the first-line treatment of advanced hepatocellular carcinoma.

Objective:To assess the association between diabetes mellitus and the risk of sudden cardiac death (SCD), and to identify potential contributing factors.Methods:This meta-analysis was an updated version of the original study Diabetes mellitus and the risk of sudden cardiac death： a systematic review and meta-analysis of prospective studies. The original review included all eligible case-control and cohort studies published in PubMed and Embase up to 2017 that investigated the association between diabetes and SCD risk. In this updated study, newly published studies were added, including those available in PubMed, Embase, China National Knowledge Infrastructure (CNKI), and WANFANG MED ONLINE up to December 3, 2023. Search terms included "diabetes""glucose""sudden cardiac death" "cardiac arrest" and their Chinese equivalent. The primary outcome was the risk of SCD, while factors such as country, ethnicity, skin color, follow-up duration, left ventricular ejection fraction (LVEF), baseline comorbidities, and other relevant variables were analyzed as potential influencing factors. Relative risk ( RR) was used as the summary measure. A random-effects model was used when significant heterogeneity was detected, otherwise a fixed-effects model was used. Cochran′s Q test was used for subgroup analysis to assess the influence of factors such as region, baseline diseases, LVEF, and ethnicity (based on skin color) on the outcomes. Results:A total of 32 cohort/case-control studies with a combined sample size of 3 252 954 individuals were included. The meta-analysis showed that the risk of SCD in patients with diabetes was double that of non-diabetics ( RR=2.00, 95% CI: 1.83-2.19, P<0.001). In Asian populations, the risk of SCD in diabetic patients was 1.78 times that of non-diabetic individuals ( RR=1.78, 95% CI: 1.51-2.10), 2.05 times that of in European populations ( RR=2.05, 95% CI: 1.79-2.34), and 2.12 times that of in American populations ( RR=2.12, 95% CI: 1.82-2.47), with no statistically significant heterogeneity between regions ( P=0.287). Among individuals without other baseline comorbidities, the risk of SCD was 2.12 times higher in diabetic patients than in those without diabetes ( RR=2.12, 95% CI: 1.89-2.38). In patients with baseline coronary heart disease, the risk was 1.75 times that of non-diabetics ( RR=1.75, 95% CI: 1.45-2.11). In those with baseline heart failure, the risk was 1.92 times that of non-diabetics ( RR=1.92, 95% CI: 1.51-2.43). In patients with baseline atrial fibrillation, the risk was 4.00 times that of non-diabetic individuals ( RR=4.00, 95% CI: 1.38-11.56). In patients undergoing hemodialysis due to renal failure, the risk was 1.76 times that of non-diabetic individuals ( RR=1.76, 95% CI: 1.25-2.48), with no statistically significant heterogeneity between groups ( P=0.262). In cardiac patients with LVEF>50%, the risk of SCD in diabetic patients was 2.08 times that of non-diabetic individuals ( RR=2.08, 95% CI: 1.57-2.75), and in those with LVEF<50%, the risk was 1.69 times that of non-diabetic individuals ( RR=1.69, 95% CI: 1.30-2.18), with no statistically significant heterogeneity between groups ( P=0.277). In yellow-skinned populations, the risk of SCD in diabetic patients was 1.80 times that of healthy individuals ( RR=1.80, 95% CI: 1.73-1.87), and in white-skinned populations, it was 2.18 times that of healthy individuals ( RR=2.18, 95% CI: 1.88-2.54), with statistically significant heterogeneity between groups ( P=0.014). Conclusions:Diabetes mellitus significantly increased the risk of SCD, and this effect may be more pronounced in white-skinned populations, while region, baseline comorbidities, and LVEF had no further effect.

Objective:To explore the clinical value of recurrent laryngeal nerve dissection in the surgical treatment for congenital pyriform sinus fistula（CPSF）. Methods:The clinical data of 42 patients with CPSF were retrospectively analyzed. All patients were diagnosed and treated in the First Affiliated Hospital of Guangdong Pharmaceutical University. Results:During the operation, all patients' recurrent laryngeal nerves were dissected successfully, and fistulas were resected completely,no patients had complication of recurrent laryngeal nerve's damage.There were no recurrence cases during the 13 to 48 months of follow-up. Conclusion:The trend of congenital pyriform sinus fistula is closely related to recurrent laryngeal nerve, it's important to dissect the recurrent laryngeal nerve during the operation for congenital pyriform sinus fistula.
Humans ; Neck ; Recurrent Laryngeal Nerve/surgery* ; Retrospective Studies ; Pyriform Sinus/surgery* ; Fistula/surgery*

Objective Aiming at the problem of significant anisotropy in the three-dimensional ( 3D) printed polyether-ether-ketone ( PEEK) bone substitutes manufactured by material extrusion technology, taking the femur, the main load-bearing long bone of the lower limb, as an example, the biomechanical properties of the femoral model under different direction in the build chamber were evaluated by the combination of finite element analysis and in-vitro mechanical experiment. Methods A left femoral model was obtained by reconstruction from CT data. The stress and displacement of the 3D printed PEEK femur with different directions in the build chamber under five physiological postures in the human gait cycle were simulated by varying the orthogonal anisotropy mechanical properties. An in-vitro mechanical experiment was conducted to investigate the safety and stability of the femur through a 3D printed PEEK femur. Results When the long axis of the femur model was perpendicular to the building platform of the 3D printer, a better mechanical property was obtained, and the maximum von Mises stress was 46. 56 MPa, which was lower than the yield stress of PEEK, while the maximum displacement was larger than that of the natural femur under same loading condition. Therefore, the 3D printed PEEK femur met the strength requirement, but the stability needs to be improved. Conclusions The long axis is recommended to be perpendicular to the building platform when the material extrusion technology was used for the substitute of the load-bearing long bone, and the effect of its anisotropy on service performance of the substitute should be carefully considered when the 3D printing technology is used for load-bearing bone substitute.

Tumor cells and tumor microenvironment (TME) are closely related. It is known that many factors will change the TME, then affect tumor development, however the change of TME is also inseparable from tumor cells. More and more studies have confirmed that the regulation of TME is the key to anti-tumor therapy. Therefore, it is critical to understand the effect of tumor cells on TME.