OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

Background Experimental studies have shown that radiofrequency electromagnetic waves emitted by mobile phones can cause adverse effects on male reproductive health, including decreased semen quality and altered sex hormones. However, the results of epidemiological studies on the relationship between mobile phone use and male semen quality are inconsistent. Furthermore, there are few epidemiological studies on the association of mobile phone use with sex hormones. Objective To explore the associations of mobile phone use with male semen quality and sex hormones. Methods A total of 2045 men visited the reproductive medicine center of a hospital in Wuhan and ordered infertility examination were recruited from December 2018 to January 2020. Information on mobile phone use was obtained using a questionnaire. Among them, 1232 and 1694 men were eligible for semen quality analyses and sex hormone analyses, respectively. Multiple linear and logistic regression models were used to analyze the associations of mobile phone use with male semen quality and sex hormones. Results After adjusting for potential confounders, there was no statistically significant associations of mobile phone use with sperm progressive motility, sperm total motility, sperm concentration, sperm count, or serum luteinizing hormone (P>0.05). However, serum total testosterone showed a declined tendency with increasing daily duration of mobile phone use (P_trend=0.08). Compared with men with daily mobile phone use of 0-2 h, men with daily mobile phone use of 2.1-5, 5.1-8, and >8 h showed decreased serum total testosterone concentrations by 6.29% (95%CI: 0.40%-11.84%), 6.01% (95%CI: 0.60%-12.19%), and 7.87% (95%CI: 0.40%-14.79%), respectively. Conclusion Mobile phone use is not associated with male semen quality and serum luteinizing hormone, but increasing daily duration of mobile phone use is potentially associated with a tendency to lower male serum total testosterone.

Objective:To explore the effect of chemotherapy administration sequence combined with programmed cell death protein-1(PD-1)monoclonal antibody on the efficacy and immune-related adverse events(irAEs)in patients with advanced non-small cell lung cancer(NSCLC).Methods:The clinical data of 110 patients with advanced NSCLC treated at The First Affiliated Hospital of Zhengzhou University between November 2019 and January 2022 were retrospectively collected.The factors influencing irAEs were analyzed by univariate and multivariate Logistic regression analyses,while those influencing curative effect were analyzed by Kaplan-Meier curve analysis,Log-rank test,and univariate and multivariate Cox regression analyses.Results:Treatment with PD-1 monoclonal antibody after 2 days of chemotherapy(sequential treatment group,n=36)significantly prolonged progression-free survival(PFS)compared with PD-1 monoclonal antibody admin-istration on the same day of chemotherapy(simultaneous treatment group,n=74)(17.2 months vs.11.3 months,respectively;P＜0.05).The disease control rate(DCR)was better in the sequential treatment group than in the simultaneous treatment group(94.4％vs.79.7％,re-spectively;P=0.045),while the objective response rate(ORR)did not differ significantly(69.4％vs.51.4％,respectively;P=0.072).The Cox re-gression analysis showed that cytokerat in 19 fragment(Cyfra21-1)and d-dimer(D-dimer)affected the efficacy of combination therapy(P＜0.05).The Logistic regression analysis showed that age and lactic dehydrogenase(LDH)influenced the occurrence of irAEs(P＜0.05),while the administration sequence did not significantly affect the occurrence of irAEs(P=0.130).Conclusions:Administration sequence influences the efficacy of combination therapy,and patients with advanced NSCLC who receive sequential therapy may experience better efficacy.Age and LDH are negatively correlated with the occurrence of irAEs.

Objective To investigate the syndrome differentiation characteristics of children with atopic dermatitis(AD)and the immune imbalance status in children with different syndrome types of AD.Methods A total of 159 AD children and 100 normal control children were enrolled.The peripheral blood eosinophil(Eo)count was measured by impedance method,total serum immunoglobulin E(IgE)by immunoturbidimetric assay,and interferon-gamma(IFN-γ),interleukin-4(IL-4),interleukin-5(IL-5)and interleukin-17(IL-17)were measured by multiple microspheres flow immunofluorescence assay.Results Among 159 AD children,syndrome of heart-fire and spleen-deficiency was most commom,accounting for 38.4%,followed by syndrome of blood-deficiency and wind-dryness(22.0%),syndrome of heat accumulation in heart and spleen(20.1%)and syndrome of spleen-deficiency and dampness-accumulation(19.5%).Compared with normal control group,there was no significant difference in serum IFN-γ level among different syndrome types of AD.The levels of peripheral blood Eo,serum total IgE,IL-4 and IL-17 in AD with heart-fire and spleen-deficiency syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo,IL-4,IL-5 and IL-17 in AD with blood-deficiency and wind-dryness syndrome were significantly increased(P<0.05).The levels of IL-4,IL-5 and IL-17 in AD with heat accumulation in heart and spleen syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo and serum IL-4 in AD with spleen-deficiency and dampness-accumulation syndrome were significantly increased(P<0.05).Conclusion Heart-fire and spleen-deficiency syndrome is the most common type in children with AD,however,the main type under 3 years old is heat accumulation in heart and spleen syndrome.Th2/Th17 immune imbalance are the main pathogenesis in heart-fire and spleen-deficiency syndrome,blood-deficiency and wind-dryness syndrome and heat accumulation in heart and spleen syndrome,and Th2 immune imbalance is the main pathogenesis of spleen-deficiency and dampness-accumulation syndrome.

Objective:To investigate the effect of thoracic X-ray irradiation on the spermatogenesis of adult male mice.Methods:A total of 24 healthy adult male C57BL/6 mice (6-8 weeks old) were randomly divided into radiation group (Radiation) and sham-radiation group (Sham), 12 mice in each group. The area of thoracic irradiation was 1.5 cm× 2 cm, and the dose rate was 3.04 Gy/min, 8 Gy/d for 3 consecutive days, 24 Gy in total. At 7 d and 21 d after thoracic irradiation, the bilateral testes and epididymal tails were stripped and the testicular index was calculated. The morphology of testis was examined by haematoxylin-eosin (HE) staining, then the diameter of seminiferous tubules and the thickness of seminiferous epithelium were measured. The sperms were collected from the bilateral epididymal tails for sperm counting. The level of apoptosis in testis and levels of apoptosis-related proteins were detected by TUNEL and Western blot, respectively.Results:Compared with Sham group, the morphology of testis and epididymis was seriously damaged, the diameter of seminiferous tubules significantly decreased at 21 d after irradiation ( t = 8.93, P < 0.05), and the seminiferous epithelium significantly decreased at 7 d and 21 d after irradiation ( t = 4.24, 12.77, P < 0.05). In addition, the number of sperms significantly decreased ( t = 4.30, 2.98, P < 0.05). The number of TUNEL positive cells in the seminiferous epithelium significantly increased at 7 d and 21 d after irradiation ( t = -2.73, -3.74, P < 0.05). Meanwhile, the level of cleaved Caspase-3 protein significantly increased at 7 d and 21 d after irradiation ( t = -2.96, -2.46, P < 0.05). The concentrations of SCF and GDNF did not change at 7 d after irradiation, but were significantly increased at 21 d after irradiation ( t = -10.46, -5.42, P < 0.05). Conclusions:The thoracic X-ray irradiation could lead to spermatogenesis disorder in male adult mice, and the induction of spermatogenic cell apoptosis and the secretory dysfunction of sertoli cells may be involved.

Objective:to review the clinical features, diagnosis and treatment of spinal Rosai-Dorfman disease(RDD).Methods:we conducted a systemic review and collected the cases reported from 2010. The key words were Rosai-Dorfman disease, spine/central nervous system. We screened both English and Chinese database. There were 43 reports finally included in the study, containing 52 cases. We distracted the information of interest and, subsequently, analyzed the harvested data using specific statistical software packages. The study focused on the summary and description of the clinical features, diagnosis and treatment and prognosis of spinal RDD.Results:The included articles reported 52 cases. The average age was 32.1±17.1 years (ranging from 6 to 76 years old). The ratio of male to female was 1.9/1. The median follow-up period was 19.9 months. The initial symptoms of 41 patients (78.8%) were spinal lesion-related. The cases with painless lymph nodes enlargement, other organ lesions and abnormal lab tests were 11.5%, 36.5% and 23.1%, respectively. The frequent infringed segments were cervical (43.1%) and thoracic (39.2%) spine. 53.2% lesions were dura-based, while 17.0% and 10.6% for bone and cord, respectively. Surgery was the mainstream of the treatment armamentarium, composing 83.7% cases, among which 46.3% underwent total resection. Cases only treated with radiotherapy, chemotherapy and steroids were 10.2%. Very Few cases remitted spontaneously (2.0%). The risk of recurrence and occurrence at other vertebral levels was 22.0%.Conclusion:It is rare for spinal involvement of RDD. This entity has no pathognomonic clinical and imaging features. RDD has a tendency of multi-organ involvement and recurrence. Surgery remains the mainstay of the treatment, but the efficacy of other adjuvant therapies is not sure. A wait and watch strategy is employed for asymptomatic patients.

Objective:To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI.Methods:In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time.Results:The median age ( P5- P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service ( P5- P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group ( P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion:The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.

Objective:To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI.Methods:In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time.Results:The median age ( P5- P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service ( P5- P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group ( P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion:The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.

OBJECTIVE To establish an in vitro test method and to evaluate the genotoxicity of chemicals using primary cultured mouse hepatocytes and the changes in phosphorylated histone H2AX(γH2AX)expression levels to provide a more reliable marker of the identification of genotoxicity. METHODS Hepatocytes were isolated from BALB/c mice by an improved two-step collagenase diges?tion method and then cultured in sandwich configuration. The primary cultured hepatocytes were treat?ed with various concentrations of four known genotoxic agents bleomycin(BLM),benzo(a)pyrene〔B (a)p〕,styrene and styrene-7,8-oxide(SO)within the range of 40 μmol · L-1 and two non-genotoxic agents azathioprine(Aza)and ciclosporin A(CsA)at different time points within 24 h. The cytotoxicity induced by these toxicants was assessed by CCK-8 assay. Then,the changes in γH2AX expression levels in treated cells were determined by flow cytometry. RESULTS The four genotoxic agents could be detected and two non-genotoxic agents could not be detected by this method. The γH2AX expression level was the highest when hepatocytes were exposed to BLM and SO for 3 h,or B(a)p and styrene for 6 h(P<0.01). The production of γH2AX was 25.67,18.36,12.43 and 14.25 for the four types of genotoxic agents,respectively,and was approximately 19,13,9 and 11 times that of the vehicle control group(P<0.01)at the optimum time point and concentration. There was a significant positive corre?lation between the indicated concentrations of genotoxic chemicals and γH2AX expression levels(P<0.01). In addition,the production ofγH2AX indicated no marked increase in two non-genotoxic agents such as Aza and CsA in comparison with the control group. CONCLUSION This test method can effec?tively distinguish genotoxic agents from non-genotoxic agents,and direct genotoxic agents from indirect genotoxic agents in the absence of S9. γH2AX might be a reliable marker for the identification of the potential genotoxicity of chemicals.

OBJECTIVETo investigate the effect of occupational exposure to toluene diisocyanate (TDI) on the workers' health.

METHODSA total of 76 workers exposed to TDI (exposure group) and 64 management staff members (control group) were selected from a factory as the study subjects. Area sampling was performed for the place with exposure to TDI according to the method in GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace, and gas chromatography was applied to measure the concentration of TDI in workplace air. The workers' personal information was collected with questionnaire, pulmonary ventilation function was determined with a portable spirometer, hematological parameters were analyzed by automatic blood analyzer and blood chemistry analyzer, and the indicators of oxidative damage and energy metabolism were measured by the reagent kit provided by Nanjing Jiancheng Bioengineering Institute. SPSS 17 software was applied for statistical analysis.

RESULTSThe exposure group had significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second(FEV1.0), and FEV1.0/FVC ratio than the control group (P <0.05). Compared with the control group, the exposure group had significantly higher red blood cell count, platelet distribution width, mean platelet volume, lymphocyte count, and neutrophil count(P<0.01), and significantly lower activities of lactate dehydrogenase(LDH), superoxide dismutase, and succinodehydrogenase (SDH)(P <0.01). In the exposure group, the length of exposure was negatively correlated with the activities of SDH and LDH in the serum (r=-0.319, P <0.05; r=-0.239, P <0.05), and the length of exposure was not found to be correlated with the activity of SOD and pulmonary function indices.

CONCLUSIONTDI can induce inflammatory response and lung ventilation function impairment in workers exposed to TDI, as well as oxidative stress and imbalance of energy metabolism. Therefore, it can cause damage to workers' health, and protective measures should be enhanced.

Case-Control Studies ; Erythrocyte Count ; Forced Expiratory Volume ; Humans ; Inflammation ; physiopathology ; L-Lactate Dehydrogenase ; blood ; metabolism ; Leukocyte Count ; Lung ; physiopathology ; Occupational Exposure ; adverse effects ; Pulmonary Ventilation ; Succinate Dehydrogenase ; blood ; metabolism ; Superoxide Dismutase ; metabolism ; Toluene 2,4-Diisocyanate ; adverse effects ; Vital Capacity