Abstract: Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a central role in the activation of B cells and granulocytes, operating downstream of B cell and Fcγ receptors, and is considered an attractive target for treating autoimmune diseases. Preclinical investigations have demonstrated that inhibition of BTK activity holds promise as a potential therapeutic strategy for inflammatory immune responses such as autoimmune diseases and allergies. This review provides an overview of the mechanisms by which BTK contributes to immune-related diseases and summarizes current research on the development of BTK inhibitors for treating these conditions, aiming to offer novel insights into non-oncology applications for BTK inhibitors.

Objective: To investigate the status of occupational health examination institutions in Zhejiang Province, so as to provide suggestions for quality control of occupational health examination institutions. Methods: The 312 occupational health examination institutions in Zhejiang Province that have completed filing before September 30, 2023 were selected. The comprehensive capability, service quality, technical capability, and information reporting status were surveyed and evaluated through on-site inspection and skill assessment. Results: There were 161 public hospitals (51.60%), 147 private organizations (47.12%), and 4 centers for disease control and prevention (CDCs)/ occupational disease prevention and control institutes (1.28%). The pass rates of comprehensive capability, service quality, technical capability and information reporting were 90.02%, 69.89%, 84.07% and 86.78%, respectively. Among the indicators of comprehensive capability, the compliance rate for staffing was the highest at 95.06%, while the qualification rate of quality control in occupational health examinations was the lowest at 84.83%. Among the indicators of service quality, the compliance rate of the physical examination report format was the highest at 95.83%, while the accuracy rate of the audiometry examination was the lowest at 76.60%. In terms of technical capabilities, the qualification rates for blood lead testing, pneumoconiosis reading, and audiogram diagnostic ability were 87.92%, 89.42% and 75.34%, respectively. In terms of information reporting, the qualification rates for reporting completeness, reporting timeliness, suspected occupational disease reporting timeliness, and reporting accuracy were 89.10%, 81.09%, 96.47% and 80.45%, respectively. Among the three types of institutions, private institutions had the lowest average qualification rates for comprehensive capability, service quality, and technical capability, which were 89.83%, 69.06% and 80.00%, respectively. Conclusions Public hospitals and private organizations were the main types of occupational health examination institutions in Zhejiang Province. However, there were deficiencies in quality control, audiogram examination and diagnosis, and the accuracy of information reporting among occupational health examination institutions.

Adenosine has been proved to have immunosuppressive effect in many different diseases, and the activity of ecto-5’-nucleotidase(CD73) on the cell surface is the rate-limiting step of extracellular adenosine production. CD73 has a profound and lasting impact on tumor immune regulation of regulatory T cells, B cells, macrophages and natural killer cells. CD73-mediated adenosine pathway is significant in signal transduction during cancer progression in tumor microenvironment, making CD73 a novel immune checkpoint. Therefore, CD73 inhibition is a emergent and promising strategy for cancer immunotherapy. At present, a variety of monoclonal antibodies and small molecule inhibitors have been in clinical development. This review comprehensively summarizes the frontier research progress of reported small molecule CD73 inhibitors, which can provide guidance for the investigation of novel CD73 inhibitors for cancer therapy.

Objective: To investigate the gravity center and spatial clustering of silicosis in Zhejiang Province, so as to provide the reference for improving silicosis prevention and control measures. Methods: Data on cases of silicosis in Zhejiang Province from 2013 to 2022 was collected from the National Occupational Disease and Health Risk Factors Monitoring Information System. The spatial and temporal characteristics of silicosis incidence in Zhejiang Province were analyzed using the gravity center migration and spatial autocorrelation analysis. Results: Totally 2 902 silicosis cases were reported in Zhejiang Province from 2013 to 2022. The reported cases in 2013, 2019 and 2014 ranked the top three, with 545 (18.78%), 373 (12.85%) and 372 (12.82%) cases, respectively. The silicosis cases were predominantly males, accounting for 99.04% (2 874 cases). The main occupation was mining and related industries, accounting for 50.41% (1 463 cases). Gravity migration analysis showed that the gravity center of silicosis incidence was in Shengzhou City in 2013; from 2014 to 2018, it migrated to the southwest, and was located in Dongyang City and Yiwu City; from 2019 to 2020, it migrated to the southeast, and was located in Xianju County and Tiantai County; then from 2021 to 2022, it migrated to the west, and was located in Pan'an County and Xianju County. Spatial autocorrelation analysis showed that there was spatial correlation of silicosis incidence in 2014, 2016, and 2021 (all Moran's I >0, all P<0.05). Ningbo City, Quzhou City, Wenzhou City and Taizhou City were high-high clustering sites. Conclusions The gravity center of silicosis incidence in Zhejiang Province from 2013 to 2022 had a slight migration, and mainly gathered in the central regions. The high-high clustering sites were migrated from Ningbo City and Quzhou City to Taizhou City.

Objective To compare the anti-inflammatory,antitumor and anti-bacterial effects of the single extract(in granules)and the prepared drug in pieces of Forsythia Suspense(Lianqiao,a traditional Chinese herbal medicine).Methods In zebrafish embryo models of CuSO4 exposure,tail transection and LPS microinjection-induced inflammation,the anti-inflammatory effects of 10 μg/mL DEX,single extract of Forsythia Suspense,and the water extract of the prepared drug(400,600,and 800 μg/mL)were evaluated by observing neutrophil counts,RT-qPCR,HE staining and survival analysis.Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining.The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs.Results In the zebrafish embryo models of inflammation,both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation,reduced the mRNA expressions of TNF-α,IL-6,P38,Jnk,Erk and P65,and increased the survival rate of zebrafish.They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells(HCT116),pancreas adenocarcinoma cells(PANC-1),lung cancer cells(A549),liver cancer cells(Hep3B)and cervical carcinoma cells(Hela)in zebrafish embryos,and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL.Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory,antitumor and antibacterial effects,but their effects for inhibiting IL-6,P65,and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.

Objective To compare the anti-inflammatory,antitumor and anti-bacterial effects of the single extract(in granules)and the prepared drug in pieces of Forsythia Suspense(Lianqiao,a traditional Chinese herbal medicine).Methods In zebrafish embryo models of CuSO4 exposure,tail transection and LPS microinjection-induced inflammation,the anti-inflammatory effects of 10 μg/mL DEX,single extract of Forsythia Suspense,and the water extract of the prepared drug(400,600,and 800 μg/mL)were evaluated by observing neutrophil counts,RT-qPCR,HE staining and survival analysis.Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining.The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs.Results In the zebrafish embryo models of inflammation,both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation,reduced the mRNA expressions of TNF-α,IL-6,P38,Jnk,Erk and P65,and increased the survival rate of zebrafish.They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells(HCT116),pancreas adenocarcinoma cells(PANC-1),lung cancer cells(A549),liver cancer cells(Hep3B)and cervical carcinoma cells(Hela)in zebrafish embryos,and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL.Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory,antitumor and antibacterial effects,but their effects for inhibiting IL-6,P65,and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.

In the face of a serious occupational disease prevention and control situation, the lack of efficient supervision and regulation methods has become a prominent contradiction. This paper reviewed the progress and application of occupational health grading and classification supervision methods for employers in China in recent years, and analyzed the characteristics and limitations of selected methods. The grading and classification supervision methods have gradually developed from considering only inherent health risk of occupational disease hazards, to considering both inherent attributes of occupational disease hazards and exposure duration. Some regional authorities introduced trial measures for grading and classification of occupational health supervision by embracing exposure level of an occupational disease hazard of interest, associated outcome severity, and occupational health management situation of targeted employers. In October 2022, the National Disease Control and Prevention Bureau issued the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement, which further promoted the establishment of a differentiated occupational health supervision model. Grading and classification of occupational health supervision can improve the supervision efficiency of public health administration departments and promote employers to fulfill the main responsibility of occupational disease prevention and control.

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8⁺ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.

Background Occupational hearing loss associated with noise is becoming more and more serious, and occupational noise-induced deafness has become the second most frequently reported occupational disease in China. Objective To characterize occupational hearing loss in Zhejiang Province so as to provide a basis for the formulation of hearing protection strategies and measures. Methods Through the occupational diseases reporting system, the data of new cases of occupational noise-induced deafness in Zhejiang Province from 2006 to 2020 and the audiometry results of laborers who were exposed to occupational noise and participated in physical examinations from 2015 to 2020 were collected. The distribution of new cases of occupational noise-induced deafness were described in categories of region, year, industry, enterprise scale, age, onset age, and length of work, as well as the detection of increased high-frequency hearing threshold of workers who ordered occupational health examination in each year. Results A total of 575 cases of occupational noise-induced deafness were reported in Zhejiang Province from 2006 to 2020, of which 526 cases were male and 49 were female. The mean onset age of patients with noise-induced deafness was (44.8±8.0) years. There was a significant difference in mean onset age between male and female (t=3.420, Ρ=0.001). The median length of work [M (P₂₅, P₇₅)] at the time of onset was 9.0 (5.5, 13.2) years. The number of cases of noise-induced deafness and its proportion to the total number of occupational diseases in a year showed an increasing trend from 2006 to 2020 and the average annual growth rate was 22.11%. The patients were mainly distributed in the Hangzhou, Ningbo, and Jiaxing, and the number of cases were 194, 140, and 112, respectively, accounting for 77.5% of the total cases in Zhejiang Province. Manufacturing industry was dominant one in terms of the number of cases, which accounted for 89.6% (515 cases). Private economic enterprise, in terms of economic type, accounted for 57.4% (330 cases). There were significant differences in the length of work at the time of onset among different economic types of enterprises (H=29.081, Ρ<0.001). There were 215 cases in the medium-sized enterprises and 265 in the small- and micro-sized enterprises, respectively, accounting for 83.5% of the the total number of cases. Conclusions From 2006 to 2020, the cases of occupational noise-induced deafness in Zhejiang Province present an increasing trend, with a relatively short length of work at the time of onset, and regional and industrial agglomeration.

The phenomenon of workers working beyond standard working hours is called long working hours. In recent years, more and more relevant studies at home and abroad have shown the association between long working hours and adverse health effects of occupational populations, such as increased risks of cardiovascular diseases, diabetes, and various psychological conditions such as depression and occupational stress. However, the current research has not yet reached a consistent conclusion. The main reason is that the physiological and psychological effects of exposure to long working hours need to be explored in depth. Therefore, based on the relevant research progress at home and abroad, this article introduced the health effects of long working hours from both physical and psychological aspects, including hypertension, cardiovascular diseases, diabetes, depression, and job burnout, expounded related mechanisms involved, and indicated deficiencies in current research on long working hours and the next research directions.