Objective To investigate the awareness of radon exposure hazards among non-uranium miners in Chongqing, China. Methods A survey was conducted among 177 male miners from eight non-uranium metal mines in Chongqing to collect data on basic information, personal habits, and the rate of radon awareness. Factors affecting radon awareness were analyzed using chi-square test and logistic regression model. Results The awareness rate of radon among miners was 23.73%. The chi-square test indicated significant difference in the radon awareness rate among miners with different levels of education (χ² = 10.28, P < 0.05), while there was no significant difference across different ages, years of work, labor relations, job categories, and types of miners (P > 0.05). Binary logistic regression analysis showed that a college (junior college) or higher level of education, a high school level of education, and working in mines were factors affecting the radon awareness among miners (χ² = 4.030, 9.150, 11.776, P < 0.05). Conclusion Miners lack awareness of radon, and there is an urgent need to strengthen education and propaganda regarding the hazards of radon.

OBJECTIVES: In the early stage of central cervical disc herniation, clinical symptoms may be mild. However, as the spinal cord becomes compressed by herniated nucleus pulposus tissue, progressive edema and degeneration may occur, resulting in more severe clinical manifestations, including limb weakness, bladder and bowel dysfunction, spastic paraplegia of the lower extremities, and even respiratory difficulty. The spinal endoscopic Key-hole technique is widely applied in treating radiculopathic cervical spondylosis and has demonstrated good clinical outcomes. This study aims to analyze and summarize the technical points and therapeutic efficacy of the far lateral Key-hole technique in the treatment of central cervical disc herniation, providing reference for clinical application. METHODS: Eight patients with central cervical disc herniation treated with the far lateral Key-hole technique were included as the experimental group. Another 8 patients who underwent single-level anterior cervical diskectomy and fusion (ACDF) during the same period were selected as the control group. Data collected included gender, age, intraoperative blood loss, incision length, and length of hospitalization. Pain severity was evaluated using the Visual Analogue Scale (VAS); cervical function was assessed using the Japanese Orthopaedic Association (JOA) score; and cervical disability was measured by the neck disability index (NDI). Radiological outcomes were assessed using disc height index (DHI), cervical Cobb angle, and operative segment Cobb angle. RESULTS: Compared with the control group, the experimental group had significantly less intraoperative blood loss, shorter incision length, and shorter hospital stay (all P<0.05), while there was no significant difference in operation time (P>0.05). Postoperative VAS and NDI scores in both groups were significantly lower than preoperative values, and JOA scores significantly improved (P<0.05). No significant differences were noted between the two groups preoperatively (P>0.05). Postoperatively, the experimental group showed significantly lower VAS and NDI scores and higher JOA scores than the control group (P<0.05). There was no statistical significance in DHI before and after surgery in the experimental group (P>0.05), while the DHI increased significantly postoperatively in the control group (P<0.05). Postoperative DHI in the experimental group was significantly lower than in the control group (P<0.05). No significant differences were observed in the cervical Cobb angle either within or between groups (all P>0.05). The operative segment Cobb angle increased significantly after surgery in the control group (P<0.05), while no other operative segment angle changes were statistically significant (all P>0.05). CONCLUSIONS The far lateral Key-hole technique offers advantages in treating central cervical disc herniation, including reduced intraoperative bleeding, smaller incision length, shorter hospitalization, and improved postoperative pain relief. Additionally, the technique does not affect cervical physiological curvature or stability in the short term, making it suitable for clinical application.
Humans ; Intervertebral Disc Displacement/surgery* ; Cervical Vertebrae/surgery* ; Male ; Female ; Middle Aged ; Adult ; Diskectomy/methods* ; Treatment Outcome ; Spinal Fusion/methods* ; Endoscopy/methods*

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Background Agitated behaviour in male patients with schizophrenia can lead to serious consequences for the individual and the society.Non-invasive drug delivery may help to rapidly control agitation and improve the overall patient satisfaction,but there are limited studies on the efficacy of olanzapine oral soluble film for the treatment of agitated behaviour in patients with schizophrenia.Objective To compare the efficacy and safety profile of olanzapine oral soluble film versus intramuscular haloperidol against agitated behaviour in male patients with schizophrenia,so as to provide a reference for the treatment of agitated behaviour.Methods From May 2022 to July 2023,a consecutive sample of schizophrenic patients(n=44)with agitated behaviour who met the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)were recruited in the male psychiatric closed ward of the Third People's Hospital of Fuyang.Patients were assigned into two groups using the random number table method,each with 22 cases.Study group was treated with olanzapine oral soluble film 10 mg/d,while control group was given intramuscular haloperidol 8 mg/d.The severity of agitated behaviour was determined using Positive and Negative Syndrome Scale-Excited Component(PANSS-EC)and Agitation Calmness Evaluation Scale(ACES)at the baseline and after 6 h of drug administration.The treatment response rate was calculated based on the reduction of PANSS-EC score,and the drug side effects were assessed using Rating Scale for Extrapyramidal Side Effects(RSESE)and Barnes Akathisia Rating Scale(BARS)after 6 h of drug administration.Results After 6 h of drug administration,no statistical difference was reported in PANSS-EC score and ACES score between two groups(F=0.039,0.082,P>0.05),and the treatment response rate yielded no statistical difference between two groups(χ2=0.419,P=0.517),while study group reported a lower incidence rate of adverse reactions compared with control group,with statistically significant difference(P=0.031).BARS scores noted no statistical significant difference between two groups(t=0.587,P=0.561),whereas study group scored lower on RSES compared to control group,with a statistical difference(t=-7.367,P<0.01).Conclusion In the treatment of agitation in male patients with schizophrenia,the efficacy of olanzapine oral soluble film is comparable to that of intramuscular haloperidol,while the safety profile of the former is superior to that of the latter.

Objective Compare and analyze the clinical efficacy and imaging differences of zero-profile interbody fusion cage and interbody fusion cage combined with titanium plate in anterior cervical discectomy and fusion(ACDF).Methods The clinical data of 40 patients who underwent ACDF in our hospital from February 2017 to November 2021 were retrospectively analyzed.Among them,22 patients were treated with zero-profile interbody fusion cage(zero-profile group),and 18 patients were treated with interbody fusion cage combined with titanium plate(titanium plate group).Record the operation time and intraoperative blood loss of the two groups.Japa-nese Orthopaedic Association(JOA)score,neck disability index(NDI)score and postoperative dysphagia were used to evaluate the clinical efficacy.Measure the cervical Cobb angle(C2-C7),fusion segment Cobb angle,aver-age intervertebral space height,and fusion segment height.Evaluate the fusion and subsidence of the cage by observ-ing the internal and external bone bridging of the cage through postoperative CT.Results There was no significant difference in operation time and intraoperative blood loss between the two groups(P>0.05).The JOA score,NDI score,average intervertebral space height,and fusion segment height of the two groups after operation were signifi-cantly improved compared with those before operation(P<0.05).The incidence of postoperative dysphagia in the zero-profile group was significantly lower than that in the titanium plate group(P<0.05).The Cobb angle of the fusion segment in the zero-profile group at 3 months after operation was significantly improved compared with that before operation(P<0.05).There was no significant difference in the other radiographic parameters between the two groups at each follow-up time point(P>0.05),except for the Cobb angle of the fusion segment at 3 months after operation and at the last follow-up(P<0.05)and the difference in the extra-fusion bone bridge(ExGBB)between the two groups at the last follow-up(P<0.05).Conclusions In ACDF,the clinical efficacy of zero-profile interbody fusion cage and interbody fusion cage combined with titanium plate is similar,both of which can significantly improve cervical function and postoperative imaging indicators.However,the zero-profile interbody fusion cage sig-nificantly reduced the incidence of dysphagia compared with the interbody fusion cage combined with titanium plate.In the end-stage follow-up,the former is better than the latter in improving the Cobb angle of the fusion segment and ExGBB,which is more conducive to promoting bone graft fusion.Both fuses have the risk of sinking.

Objective:To investigate the effect and influencing factors of anti-retroviral therapy (ART) in human immunodeficiency virus (HIV)-positive female commercial sex workers (CSW) in Guangxi Zhuang Autonomous Region.Methods:A retrospective cohort study was used in this study. A total of 661 HIV-positive CSW receiving ART from the Guangxi Zhuang Autonomous Region′s municipal and county-level Centers for Disease Control and Prevention (CDC) reported to Guangxi Zhuang Autonomous Region CDC from January 1, 2009 to December 31, 2018 were included.The demographic information of the patients, marital status, past medical history, acquired immunodeficiency syndrome (AIDS)-related diseases after six to 12 months of ART, medications, CD4 + T lymphocytes, virological and immunological effects after receiving ART for six to 12 months were collected. Logistic regression model was used to analyze the influencing factors of virological failure and immunological failure of HIV-positive CSW after six to 12 months of ART. Results:Among 661 HIV-positive CSW, 50(7.6%) cases experienced virological failure, 80(12.1%) cases experienced immunological failure, and 13(2.0%) had both virological failure and immunological failure.There were 85 cases (12.9%) who had a history of sexually transmitted diseases. Multivariate logistic regression analysis showed that unmarried (adjusted odds ratio (a OR)=3.298, 95% confidence interval ( CI) 1.285 to 8.461), AIDS-related diseases after six to 12 months of ART (a OR=4.391, 95% CI 1.555 to 12.402) and missed medications in the last seven days (a OR=3.731, 95% CI 1.942 to 7.166) were risk factors for virological failure. Compared with CD4 + T lymphocytes<200.00/μL at baseline, 350.00≤CD4 + T lymphocytes <500.00/μL (a OR=3.543, 95% CI 1.631 to 7.701) and CD4 + T lymphocytes≥500.00/μL (a OR=2.358, 95% CI 1.002 to 5.547) were risk factors for immunological failure. Conclusions:HIV-positive CSW in Guangxi Zhuang Autonomous Region have a better treatment effect, with low rates of virological failure and immunological failure. Marital status, baseline CD4 + T lymphocyte counts, AIDS-related diseases after six to 12 months of ART, and missed medication in the last seven days are factors influencing the effect of six to 12 months of ART.

Objective To construct a new biomechanical testing system of in vitro spine based on LabVIEW and six-axis robot arm and conduct preliminary reliability studies, so as to make preparation for further studies on coupled motion testing. Methods By programming on LabVIEW platform, using Ethernet and Profibus to communicate the data of the robot arm with PC in real time, the displacement control and load control were realized, and the end position and rotation angle of the robot arm were read in real time. Through the force/torque sensor and data acquisition (DAQ), board DAQ, processing, storage and other functions were acquired. Using the digital micrometer and special stationary fixture, the 6-direction translation accuracy test was completed, and the data were analyzed. The flexion, extension, lateral flexion and rotation were applied on sheep spine specimen to draw the load-displacement curve, analyze and compare the experimental result, and verify the effectiveness of the biomechanical platform. Results A biomechanical test system with high precision for spine in vitro based on LabVIEW and 6-axis robot arm was developed and established, of which the average translational precision was 8.1 μm and the average translational accuracy was 56.7 μm. The program of control, data acquisition, data processing and storage were written, and the biomechanical test of the sheep spine was completed effectively. Conclusions This biomechanical test system based on Labview and 6-axis robot arm could complete the conventional three-dimensional spinal motion test with high precision and be used to conduct coupled motion test research in the next step.

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.
Antibodies, Monoclonal ; immunology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; immunology ; therapeutic use ; B7-H1 Antigen ; antagonists & inhibitors ; immunology ; Humans ; Neoplasms ; drug therapy ; immunology ; pathology ; Programmed Cell Death 1 Receptor ; antagonists & inhibitors ; immunology ; Signal Transduction ; drug effects ; immunology ; T-Lymphocytes ; immunology

Objective:To investigate the protective mechanism of resveratrol in reducing cardiac ischemia‐reperfusion injury (I/R) of diabetic rats and its effect on autophagy of cardiomyocytes .Methods:Streptozotocin(STZ)‐induced diabetic rat model was constructed and 35 diabetic model rats were randomly divided into five groups ,the sham group ,the resveratrol non‐surgery group ,the I/R group ,the resveratrol treatment group ,and the resveratrol+insulin group ,with 7 rats in each .Then I/R model was built by ligating‐relaxing the left coronary .The change of myocardial infarction size was observed by methylene blue stalning . Autophagic vacuoles were observed with transmission electron microscope (TEM ) . The expression of microtubule‐associated protein 1 light chaln 3(LC3)‐Ⅰ and Ⅱ ,autophagy related gene 5(Atg5) ,Beclin‐1 ,as well as the expression and phosphorylation levels of AMP‐activated protein kinase(AMPK) and mammalian target of rapamycin(mTOR) , were detected by Western blotting .Results:The infarction size in resveratrol treatment group and resveratrol+ insulin group was significantly smaller than that in I/R group(P<0 .05) .TEM showed that in resveratrol treatment group and resveratrol+insulin group ,autophagy of cardiomyocytes could be promoted and the structure of cardiomyocytes could be improved ,when I/R of occurred .The expression levels of LC3‐Ⅱ ,Atg5 ,Beclin‐1 in I/R group were significantly lower than those in sham group (P<0 .05) ,whereas the change of expression levels of LC3‐Ⅰ had no significant difference(P> 0 .05) .Meanwhile ,the expression levels of Atg5 and Beclin‐1 in resveratrol treatment group and resveratrol+ insulin group were significantly higher than those in I/R group ,and the expression level of Beclin‐1 in resveratrol+insulin group was higher than that in resveratrol treatment group(P< 0 .05) .There was no significant difference in the expression level of AMPK and mTOR among the 5 groups(P> 0 .05) .However ,the expression level of p‐AMPK was significantly higher in resveratrol treatment group and resveratrol+insulin group than that in I/R group ,and the expression level of p‐mTOR was significantly lower in resveratrol treatment group and resveratrol+ insulin group than that in I/R group ( P< 0 .05 ) .Conclusions:Resveratrol may protect cardiomyocytes of diabetic rats by activating AMPK pathway ,inhibiting mTOR pathway ,increasing the expression of LC3‐Ⅱ , Atg5 and Beclin‐1 ,promoting autophagy ,suppressing I/R ,and reducing infarction size .

The effects of PEG10 on hydrogen peroxide (H(2)O(2))-induced apoptosis in human normal liver cell line L0(2) were investigated. The PEG10 gene was transfected into L0(2) cells by lipofectamine, the positive clone was screened by G418 and defined as L0(2)/PEG10, while the cell transfected with empty expression vector (pEGFP-N1) was defined as L0(2)/vector. L0(2)/vector and parental L0(2) cells served as control. RT-PCR and Western blotting were employed to detect the expression of target genes. H(2)O(2) (50-400 mmol/L) was administered to induce the apoptosis of L0(2) cells. Cells viability was measured by MTT and the morphological changes of apoptotic cells were determined by fluorescence microscopy using hoechst33342 nuclei staining. DNA fragmentation was observed by agarose gel electrophoresis. PEG10 mRNA and protein levels in L0(2)/PEG10 cells were significantly increased as compared with those in the control cells. After treatment with 400 mmol/L H(2)O(2) for 24 h, the cellular growth inhibition rate of L0(2)/PEG10 cells was significantly lower (58.2%) than that of L0(2) (92.5%) and L0(2)/vector (88%). Distinct morphological changes characteristic of cell apoptosis such as karyopyknosis and conglomeration were not observed in L0(2)/PEG10. Ladder-like DNA fragmentation in a dose-dependent manner was observed in both L0(2) and L0(2)/vector cell lines, but not in L0(2)/PEG10. PEG10 over-expression significantly inhibited cytotoxicity induced by H2O2 on human normal liver cell line L0(2) by antagonizing H(2)O(2)-induced apoptosis.