Chronic obstructive pulmonary disease(COPD),as a global health challenge,brings heavy economic and psychological burdens to patients and their families.Accurately identifying the risk factors for COPD and excluding false associations are crucial for understanding its pathogenesis and formulating prevention strategies.Mendelian randomization(MR),as a supplementary method,has shown great potential in reducing the interference of confounding factors,lowering the cost of experimental research,and avoiding experimental ethical issues.This article focuses on MR and its main derivative methods,discusses their basic principles and applicable conditions,and analyzes their application effects and limitations in COPD research in combination with specific cases,enabling MR to be more widely applied in the study of influencing factors of COPD.

Objective To investigate the impact of Toxoplasma gondii type I, II and III rhoptry protein 16 (ROP16) on programmed cell death ligand 1 (PD-L1) expression in lung adenocarcinoma cells, and to examine the effects of T. gondii type I ROP16 protein on the relative PD-L1 expression, the relative PD-L1 distribution on the cell membrane surface, and the binding of programmed cell death 1 (PD-1) to PD-L1 in lung adenocarcinoma cells. Methods Lentiviral vectors overexpressing T. gondii type I, II and III ROP16 proteins were generated, and transfected into the human lung adenocarcinoma A549 cell line. A549 cells were used as a blank control group, and A549 cells transfected with an empty lentiviral expression vector were used as a negative control group, while A549 cells transfected with lentiviral vectors overexpressing T. gondii type I, II and III ROP16 proteins served as experimental groups. Stably transfected cells were selected with puromycin and verified using Western blotting, quantitative real-time PCR (RT-qPCR), and immunofluorescence assays. The PD-L1 expression was quantified at translational and transcriptional levels using Western blotting and RT-qPCR assays in A549 cells in the five groups, and the relative PD-L1 distribution was detected on the A549 cell membrane surface using flow cytometry. In addition, the effect of T. gondii type I ROP16 protein on the PD-1/PD-L1 binding was measured in A549 cells using enzyme-linked immunosorbent assay (ELISA). Results The relative ROP16 protein expression was 0, 0, 1.546 ± 0.091, 1.822 ± 0.047 and 2.334 ± 0.089 in the blank control group, negative control group, and the T. gondii type I, II and III ROP16 protein overexpression groups (F = 1 339.00,P < 0.001), and the relative ROP16 mRNA expression was 2.153 ± 0.949, 2.436 ± 1.614, 14.343 ± 0.020, 12.577 ± 0.285 and 15.090 ± 0.420 in the blank control group, negative control group and the T. gondii type I, II and III ROP16 protein overexpression groups, respectively (F = 483.50,P < 0.001). The ROP16 expression was higher in the T. gondii type I, II and III ROP16 protein overexpression groups than in the blank control group at both translational and transcriptional levels (allP values < 0.001). Immunofluorescence assay revealed that T. gondii type I, II and III ROP16 proteins were predominantly localized in A549 cell nuclei. Western blotting showed that the relative PD-L1 protein expression was 0.685 ± 0.109, 0.589 ± 0.114, 1.007 ± 0.117, 0.572 ± 0.151, and 0.426 ± 0.116 in the blank control group, negative control group, and the T. gondii type I, II and III ROP16 protein overexpression groups (F = 9.46,P < 0.05), and RT-qPCR assay quantified that the relative PD-L1 mRNA expression was 1.012 ± 0.190, 1.281 ± 0.465, 1.950 ± 0.175, 0.889 ± 0.251, and 0.230 ± 0.192 in the blank control group, negative control group, and the T. gondii type I, II and III ROP16 protein overexpression groups (F = 14.18,P < 0.05). The PD-L1 expression was higher in the T. gondii type IROP16 protein overexpression group than in the blank control group at both translational and transcriptional levels (both P values < 0.05). Flow cytometry detected that the relative distributions of PD-L1 protein were (10.83 ± 0.60)%, (11.23 ± 0.20)%, and (14.61 ± 0.50)% on the A549 cell membrane surface (F = 28.31, P < 0.05), and the relative distribution of PD-L1 protein was higher in the T. gondii type IROP16 protein overexpression group than in the blank control group and negative control group (both P values < 0.001). ELISA measured significant differences in the absorbance (A) value among the T. gondii type IROP16 protein overexpression group, the blank control group and the negative control group if the concentrations of the recombinant PD-1 protein were 0.04 (F = 10.45, P < 0.05), 0.08 μg/mL (F = 11.68, P < 0.05) and 0.12 μg/mL (F = 52.68, P < 0.05), and the A value was higher in the T. gondii type IROP16 protein overexpression group than in the blank control group and the negative control group (both P values < 0.05), indicating that T. gondii type IROP16 protein promoted the PD-L1/PD-1 binding in A549 cells in a concentration-dose manner. Conclusions T. gondii type IROP16 protein overexpression may up-regulate PD-L1 expression in A549 cells at both transcriptional and translational levels and the relative PD-L1 distribution on the A549 cell membrane surface, and affect the PD-1/PD-L1 binding in a concentration-dependent manner.

Chronic obstructive pulmonary disease(COPD),as a global health challenge,brings heavy economic and psychological burdens to patients and their families.Accurately identifying the risk factors for COPD and excluding false associations are crucial for understanding its pathogenesis and formulating prevention strategies.Mendelian randomization(MR),as a supplementary method,has shown great potential in reducing the interference of confounding factors,lowering the cost of experimental research,and avoiding experimental ethical issues.This article focuses on MR and its main derivative methods,discusses their basic principles and applicable conditions,and analyzes their application effects and limitations in COPD research in combination with specific cases,enabling MR to be more widely applied in the study of influencing factors of COPD.

ObjectiveTo investigate the chemical hazards in the production line of lithium batteries, so as to provide a scientific basis for the management of occupational-health risk and to promote the healthy and sustainable development of the lithium battery industry. MethodsAn on-site survey on the process flow of the production of lithium battery was conducted in an enterprise. Volatile organic compounds (VOCs) in the occupational environment were collected by Summa canisters, carbonates and N-methyl pyrrolidone (NMP) were collected using activated carbon tubes, and airborne metals were collected using filter membranes. VOCs, carbonates and NMP were detected by gas chromatography-mass spectrometry (GC-MS), and airborne metal elements in the dust samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). ResultsNon-targeted environmental monitoring results indicated that NMP was detected in the negative /positive electrode coating, assembly and drying filling workstations, dimethyl carbonate (DMC) was detected in the assembly, drying and electrolyte injection workstations, and ethyl methyl carbonate (EMC) was detected solely in the electrolyte injection workstation. Semi-quantitative analyses of VOCs identified 136 pollutants, including acrylonitrile and halohydrocarbons. Quantitative targeted environmental monitoring results revealed the highest geometric mean (GM) concentration of EMC (31.450 mg·m^-3) was found in the assembly and drying workstations, diethyl carbonate (DEC) was detected in all workstations. While vinylene carbonate (VC) and ethylene carbonate (EC) were detected only in electrolyte injection, assembly and drying workstations. NMP was detected in all positive electrode coating samples, with a GM concentration of 5.68 mg·m^-3 (concentration range: 4.0‒ 7.4 mg·m^-³). Lithium was exclusively detected in dust samples from the liquid injection workstation (GM: 0.014 μg·m^-³). ConclusionNMP, EMC, DEC, and other chemicals are identified at the key workstations such as the positive electrode coating, electrolyte injection, assembly and drying in the lithium production line. Furthermore, semi-quantitative VOCs analyses identified 136 pollutants, demonstrating a characteristic of multicomponent chemical exposure.

Objective To explore the value of dynamic contrast-enhanced(DCE)-MRI quantitative parameters based on differential sub-sampling with Cartesian ordering(DISCO)technology for differentiating high-and low-grade breast cancer.Methods A total of 80 patients with single breast cancer confirmed by biopsy pathology were retrospectively enrolled,including 40 cases of low-grade(L group)and 40 cases of high-grade breast cancer(H group).Then quantitative parameters obtained from DISCO-DCE-MRI before treatment were compared between groups,including extravascular extracellular volume fraction(Ve),rate constant(Kep),contrast enhancement ratio(CER),maximum slope(MaxSlope)and volume transfer constant(Ktrans),and their correlations with histological grade were analyzed.Receiver operating characteristic(ROC)curves of DISCO-DCE-MRI quantitative parameters being significantly different between groups were plotted,and the area under the curves(AUC)were calculated to evaluate their efficacy for differentiating high-and low-grade breast cancer.Results Ve(0.91[0.59,0.99]),CER(2.76±0.54)and MaxSlope(0.02[0.01,0.03])in L group were all higher than those in H group(0.52[0.34,0.73],[2.31±0.74],0.01[0.01,0.02],all P＜0.05),and no significant difference of Kep nor Ktrans was found between groups(both P＞0.05).Ve,CER and MaxSlope of breast cancer were all negatively correlated with histological grade(rs=-0.43,-0.39,-0.35,all P＜0.05),while Kep andKtranshad no significant correlation with histological grade(both P＞0.05).The AUC of Ve,CER and MaxSlope for differentiating high-and low-grade breast cancer was 0.749,0.725 and 0.700,respectively.Conclusion Among DISCO-DCE-MRI quantitative parameters,Ve,CER and MaxSlope could be used for differentiating high-and low-grade breast cancer.

Objective To explore the value of dynamic contrast-enhanced(DCE)-MRI quantitative parameters based on differential sub-sampling with Cartesian ordering(DISCO)technology for differentiating high-and low-grade breast cancer.Methods A total of 80 patients with single breast cancer confirmed by biopsy pathology were retrospectively enrolled,including 40 cases of low-grade(L group)and 40 cases of high-grade breast cancer(H group).Then quantitative parameters obtained from DISCO-DCE-MRI before treatment were compared between groups,including extravascular extracellular volume fraction(Ve),rate constant(Kep),contrast enhancement ratio(CER),maximum slope(MaxSlope)and volume transfer constant(Ktrans),and their correlations with histological grade were analyzed.Receiver operating characteristic(ROC)curves of DISCO-DCE-MRI quantitative parameters being significantly different between groups were plotted,and the area under the curves(AUC)were calculated to evaluate their efficacy for differentiating high-and low-grade breast cancer.Results Ve(0.91[0.59,0.99]),CER(2.76±0.54)and MaxSlope(0.02[0.01,0.03])in L group were all higher than those in H group(0.52[0.34,0.73],[2.31±0.74],0.01[0.01,0.02],all P＜0.05),and no significant difference of Kep nor Ktrans was found between groups(both P＞0.05).Ve,CER and MaxSlope of breast cancer were all negatively correlated with histological grade(rs=-0.43,-0.39,-0.35,all P＜0.05),while Kep andKtranshad no significant correlation with histological grade(both P＞0.05).The AUC of Ve,CER and MaxSlope for differentiating high-and low-grade breast cancer was 0.749,0.725 and 0.700,respectively.Conclusion Among DISCO-DCE-MRI quantitative parameters,Ve,CER and MaxSlope could be used for differentiating high-and low-grade breast cancer.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Objective:To explore the differences of the circadian rhythm gene polymorphisms between patients with major depressive disorder and those with bipolar disorder, providing a genetic basis for differential diagnosis.Methods:70 patients who were still diagnosed with major depressive disorder after 5 years and 68 patients who were still diagnosed with bipolar disorder from Zhongda Hospital affiliated to Southeast University from 2012 to 2018 were included in this study. Single nucleotide polymorphisms (SNPs) of circadian rhythm gene were selected for genetic testing. And the differences in genotype frequency, allele frequency, and haplotypes of each SNP between major depressive disorder and bipolar disorder were analyzed using UNPHASED 3.1.7.Results:The analysis of genotype frequency revealed statistically significant differences in genotype frequency of PER1rs2253820, PER1rs2735611, PER3rs12566042, PER3rs17031614, and PER3rs79372391 between the two groups ( OR(95% CI)=2.386(1.173-4.854), 2.357(1.166-4.764), 0.351(0.176-0.703), 0.389(0.196-0.773), 0.389(0.196-0.773) respectively; all P<0.05). Haplotype analysis showed that the T-C-C-T-G haplotype, in CLOCK loci (rs12505266, rs2272073, rs3817444, rs11133389 and rs12505265) was significantly different between major depressive disorder group and bipolar disorder group ( OR(95% CI)=0.108(0.010-1.185), P=0.027). Conclusion:There are significant differences in circadian rhythm gene polymorphisms between patients with major depressive disorder and bipolar disorder. Carrying the PER1rs2253820TT and PER1rs2735611GG genotypes is a risk factors for bipolar disorder.

Background Photovoltaic (PV) cells can convert solar energy into electricity and alleviate the dilemma of energy supply shortage. Shanghai's PV module industry is booming, but there are few reports on the health status of the workers and there is an urgent need for health risk assessment. Objective To evaluate the health status of PV module production workers and the association between work and health status, in order to provide a direction for the health management of the workers. Methods Among the PV module production workers who completed prescriptive occupational health examination by a designated medical institution in 2021, 2453 workers with more than one year of working age were selected as the exposure group and 538 newly hired workers as the control group. On the basis of the Technical specifications for occupational health surveillance (GBZ 188−2014), the health examination included physical examination and laboratory examination and information such as sociodemographics, living habits, and disease history. We compared the indicators of pure-tone hearing test, blood routine examination, electrocardiogram (ECG), liver function, and kidney function between the two groups. The blood routine results included erythrocyte-related indicators, leukocyte-related indicators, and platelet-related indicators, and the results of liver function included hepatocyte injury indicators, hepatic secretory function indicators, and hepatic synthesis function indicators. The workers were divided into four groups by quartiles of working age. Trend chi-square test was used to analyze differences in health status between the four working age groups. Multiple logistic regression models were used to evaluate the association between working age and health indicators. Results Among the exposure group workers, 2035 (83.0%) were male and 418 (17.0%) were female. The median (P₂₅, P₇₅) age was 34.0 (30.0, 39.0) years and the median (P₂₅, P₇₅) working age was 6.0 (3.0, 10.0) years. The abnormality rate of blood routine was 61.7%. Among them, the abnormality rates of platelet-related indicators and liver secretory function indicators were 39.8% and 48.1% respectively. The risks of abnormal hepatocyte injury-related indicators, fatty liver, and platelet-related indicator abnormalities among the exposure group were 1.471 (95%CI: 1.060, 2.054), 1.691 (95%CI: 1.208, 2.385), and 7.576 (95%CI: 4.967, 11.994) times higher than those in the control group respectively. The single-factor analysis demonstrated a positively linear trend between working age and hypertension prevalence, electrical audiometry abnormality rate, or liver secretory function indicator abnormality rate. Corrected for gender, age, smoking status, hypertension, etc., the results of logistic analysis showed that quartile working age was positively related to abnormal liver secretion function and abnormal platelet-related indicators respectively (OR=1.047, P=0.005; OR=1.037, P=0.014), and inversely associated with the abnormal rate of renal function (OR=0.953, P=0.044). Conclusion Negative associations between health status and working age are identified in PV module production workers. The target PV module production employees are in younger age, and with the increase of working age, the abnormalities of liver function and platelets may increase. Therefore, the enterprises should extend occupational health work from workplace to workers.

N1-methyladenosine(m1A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels.Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach.