ObjectiveTo explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6 （Fas）/cysteine protease-8 （Caspase-8）/cysteine protease-3 （Caspase-3） signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury （CLI）. MethodsAmong 48 Wistar rats，12 rats were randomly selected as the blank group，and the other rats were administered alpha-naphthalene isothiocyanate （ANIT） by gavage to induce a CLI model. The modeling rats were randomly divided into the model group， the ursodeoxycholic acid group（0.1 g·kg^-1） and the Yinchenhao Tang group（9.23 g·kg^-1），with 12 rats in each group. The rats in each group were given corresponding drugs by gavage for three consecutive days. The levels of alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），gamma-glutamyl transpeptidase （γ-GT），total bilirubin （TBil） and total bile acid （TBA） in serum were detected. The levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in liver tissue were detected. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3，B-cell lymphoma-2 （Bcl-2） associated X protein （Bax） and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with those in the blank group，the levels of ALT，AST，ALP，γ-GT，TBA and TBil in serum of the model group were significantly increased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased （P<0.01）. The arrangement of hepatocytes was disordered，and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly increased（P<0.05，P<0.01），while the protein and mRNA expressions of Bcl-2 were significantly decreased （P<0.05，P<0.01）. Compared with those in the model group，the levels of ALP，γ-GT，TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased（P<0.05，P<0.01）. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the mRNA expression of Bcl-2 was significantly increased （P<0.05，）. The levels of ALT，AST，γ-GT，TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased （P<0.05，P<0.01）. The protein expression of Fas and Bax and the mRNA expression of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the protein and mRNA expression of Bcl-2 were significantly increased （P<0.05，P<0.01）. Hepatocyte injury，inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced. ConclusionYinchenhao Tang can ameliorate CLI，and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.

ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury （CLI） by inhibiting toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） pathway via regulating farnesol X receptor （FXR）. MethodsA total of 40 Wistar male rats were randomly selected， with 10 as a blank group，and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate （ANIT）. After modeling，they were randomly divided into the model group， the ursodeoxycholic acid （0.1 g·kg^-1） group and the Yinchenhao Tang （9.23 g·kg^-1） group，with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），γ-glutamyl transpeptidase （γ-GT），total bile acid （TBA），total bilirubin （TBil） and direct bilirubin （DBil） levels in serum were detected. Tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），and interleukin-6 （IL-6） levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR，TLR4，MyD88，NF-κB，F4/80，TNF-α，IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR，TLR4，MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. ResultsCompared with those in the blank group，ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the model group were significantly increased （P<0.01）. The levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were significantly increased （P<0.01），and the mRNA and protein expressions of FXR in liver tissue were decreased （P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased （P<0.05，P<0.01）. Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group，ALT，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.05，P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased （P<0.05，P<0.01）. ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.01）. The mRNA and protein expressions of FXR in liver tissue were significantly increased，and the mRNA expressions of TLR4，MyD88，NF-κB，and F4/80， as well as the protein expressions of TLR4 and NF-κB were obviously decreased （P<0.05，P<0.01）. The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI，and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.

ObjectiveTo explore the mechanism by which Yinchenhao Tang intervenes in α-naphthylisothiocyanate （ANIT）-induced cholestatic liver injury by regulating the Takeda G-protein-coupled receptor 5（TGR5）/NOD-like receptor protein 3（NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1） pyroptosis signaling pathway. MethodsForty male Wistar rats were randomly assigned into blank， model， ursodeoxycholic acid， and Yinchenhao Tang groups. Except the blank group， other groups were treated with ANIT dissolved in olive oil for the modeling of cholestatic liver injury. Ursodeoxycholic acid （0.1 g·kg^-1） and Yinchenhao Tang （9.23 g·kg^-1） were administered by gavage. The blank group and the model group were administrated with the same amount of pure water， once a day for 3 days. The blood and liver tissue samples were collected， and the serum levels of liver function indicators were measured by an automatic biochemical analyzer. Hematoxylin-eosin staining was employed to observe the pathological changes of the liver. The levels of interleukin （IL）-1β and IL-18 in the liver tissue were determined by ELISA. The mRNA levels of IL-1β， IL-18， TGR5， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， and GSDMD in the liver tissue were assessed by Real-time PCR. The protein levels of TGR5， NLRP3， ASC， Caspase-1， and GSDMD in the liver tissue were determined by Western blot. ResultsCompared with the blank group， the model group showed elevated levels of alanine amino-transferase （ALT）， aspartate transferase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， and total bilirubin （TBil） in the serum （P<0.01）， inflammatory cell infiltration， hepatocyte swelling， and bile duct epithelial cell proliferation in the liver， raised levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA and protein levels of TGR5 （P<0.01）， up-regulated mRNA levels of IL-18 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， and NLRP3 （P<0.05）， and up-regulated protein levels of NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， and GSDMD （P<0.05）. Compared with the model group， the ursodeoxycholic acid group showed declined levels of AST （P<0.01）， TBA （P<0.01）， TBil （P<0.01）， and ALT （P<0.05） in the serum， lowered levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of NLRP3 （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， IL-18 （P<0.05）， and ASC （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.05）， and down-regulated protein levels of NLRP3， ASC， Caspase-1， and GSDMD （P<0.05）. Compared with the model group， the Yinchenhao Tang group showed lowered levels of ALT， AST， ALP， TBA， and TBil in the serum （P<0.01）， declined levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of IL-1β （P<0.01）， NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， and IL-18 （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.01）， and down-regulated protein levels of Caspase-1 and GSDMD （P<0.05）. The liver tissue of the administration groups showed reduced infiltration of inflammatory cells， reduced swelling of hepatocytes， and alleviated proliferation of bile duct epithelial cells. ConclusionYinchenhao Tang can ameliorate ANIT-induced cholestatic liver injury by regulating the hepatocyte pyroptosis mediated by the TGR5/NLRP3/Caspase-1 signaling pathway.

Cholestatic liver injury refers to the bile production， secretion， and excretion disorder caused by various reasons. It induces liver injury， metabolic disorders， and dysfunction of the hepatobiliary system， which can further develop into liver fibrosis， cirrhosis， liver failure， and even death. At present， the preferred drug for clinical treatment is ursodeoxycholic acid， which， however， induces adverse reactions and is intolerant in some patients. Yinchenhao Tang is a representative prescription of traditional Chinese medicine for the treatment of jaundice due to Yang jaundice. It has the effects of clearing heat， eliminating dampness， and removing jaundice and has shown good therapeutic effect in long-term clinical application. Modern pharmacological studies have found that this prescription has anti-inflammatory， anti-oxidation， bile acid balance-regulating， hepatocyte apoptosis-inhibiting and other liver-protecting effects. This paper reviews the relevant clinical and animal experimental studies on Yinchenhao Tang in the treatment of cholestatic liver injury in recent years. Yinchenhao Tang can intervene in the progression of cholestatic liver injury by regulating bile acid metabolism and excretion， reducing inflammatory response， inhibiting oxidative stress， alleviating endoplasmic reticulum stress， inhibiting hepatocyte apoptosis， and protecting intestinal mucosal barrier. This paper systematically expounds the molecular mechanisms by which Yinchenhao Tang regulates cholestatic liver injury that are confirmed by current research， aiming to provide reference for the clinical application and in-depth study of Yinchenhao Tang.

Background The global prevalence of obesity is on the rise and is closely associated with various chronic non-communicable diseases such as cardiovascular diseases and diabetes. There is a relative lack of long-term dynamic studies on compound obesity among occupational populations. Objective To explore the changing trends of compound obesity among different occupational groups aged 18–59 years in nine provinces (autonomous regions, municipalities) of China from 1993 to 2018, and to provide a scientific basis for formulating targeted weight management strategies for occupational populations. Methods A total of 34519 employed adults aged 18–59 years from nine waves of the China Health and Nutrition Survey in1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, and 2018 were included. Obesity types were determined according to the Chinese Adult Weight Management Guidelines. The Joinpoint regression model was used to calculate the average annual percentage change (AAPC) and annual percentage change (APC) of compound obesity rates. Results From 1993 to 2018, the age-standardized compound obesity rate among the occupational population aged 18–59 years showed an upward trend (AAPC=6.24%, 95%CI: 5.09%, 7.41%, P<0.05). The AAPCs (95%CI) for age-standardized compound obesity rates among agricultural workers, blue-collar workers, other occupational groups, service workers, and white-collar workers were 9.55% (7.51%, 11.64%), 6.18% (4.70%, 7.69%), 5.53% (2.27%, 8.90%), 4.07% (2.40%, 5.77%), and 3.89% (2.16%, 5.65%), respectively, with statistically significant differences (P<0.05). Among males, the AAPCs (95%CI) for age-standardized compound obesity rates among agricultural workers, blue-collar workers, other occupational groups, service workers, and white-collar workers were 11.52% (7.71%, 15.47%), 7.28% (6.18%, 8.40%), 5.92% (2.28%, 9.69%), 5.56% (2.11%, 9.12%), and 4.22% (2.33%, 6.15%), respectively, with statistically significant differences (P<0.05). Among females, the AAPCs (95%CI) for age-standardized compound obesity rates among agricultural workers, blue-collar workers, and white-collar workers were 7.45% (6.22%, 8.69%), 3.72% (0.84%, 6.67%), and 2.41% (0.17%, 4.70%), respectively, with statistically significant differences (P<0.05). A turning point was observed in the compound obesity rate among female white-collar workers in 2006, with an APC (95%CI) of 9.69% (5.24%, 14.33%) from 2006 to 2008, showing a statistically significant difference (P<0.05), while no significant trend was found from 1993 to 2006 (P>0.05). No significant trends were observed in the age-standardized compound obesity rates among females in other occupational groups and service workers (P>0.05). Conclusion The compound obesity rate among China's occupational population is increasing rapidly, with the growth rate among agricultural workers being particularly prominent. In 2018, male white-collar workers and female agricultural workers exhibit relatively high compound obesity rates, warranting focused attention. Although the overall growth rate among service workers is slower, the expanding workforce in this sector indicates that obesity remains a serious issue. Targeted occupational health and weight management interventions are needed in the future.

Autoimmune myositis （AIM） is a group of autoimmune diseases that primarily affect muscle fibers， often accompanied by the involvement of multiple organs such as the skin，lungs，and joints.It is the most common treatable skeletal muscle disease in adults. Although most patients with AIM can achieve remission with traditional immunosuppressive therapies， their quality of life can be heavily reduced due to drug-related adverse effects and the high relapse rate and high disability rate of the disease. With the deepening understanding of the immunopathological mechanisms of AIM，various biologics targeting different components of these mechanisms have brought new hope for patients with AIM. This article reviews the advances in the treatment of AIM.

Sporadic late-onset nemaline myopathy （SLONM） is a rare， acquired， and treatable myopathy with a subacute or chronic progressive clinical course， characterized by asymmetric muscle atrophy and weakness in the axial and limb muscles， with or without involvement of respiratory and cardiac muscles. The only definitive diagnostic method at present is the identification of rods accumulation in muscle fibers by muscle biopsy pathology. This article provides a review of the clinical manifestations， diagnostic evaluations， muscle pathology， and advances in the treatment of SLONM.
Immunotherapy

ObjectiveTo investigate the infection characteristics of respiratory syncytial virus (RSV) in children with acute respiratory tract infection (ARI) in Pudong New Area, Shanghai, from 2013 to 2023, so as to provide an evidence for the prevention and control of RSV in Shanghai. MethodsChildren who sought medical care at sentinel healthcare facilities in Pudong New Area, Shanghai, between January 2013 and December 2023 and met the case definition of ARI were included in the study. Nasopharyngeal swab samples were collected and tested for viral pathogens using real-time fluorescene PCR, and the clinical information of whom was collected simultaneously. ResultsA total of 4 980 children were included in the ARI surveillance, among whom 231 tested positive for RSV, with an overall detection rate of 4.64%. Of these, 106 cases were type A and 125 were type B. From 2013 to 2023, the detection rate of RSV in children showed an overall trend of initial increase followed by a decline, with higher detection rates in autumn and winter and lower rates in spring and summer. The RSV detection rate gradually decreased with age, with the highest rate observed in children <1 year old, accounting for 16.33% (80/490) of RSV-detection cases. Cough was the most common clinical symptom. Among the RSV-positive cases, 36 involved co-infection with another virus, 6 co-infected with three viruses, and 1 with mixed infection of four viruses. The most frequent co-infection was RSV and human coronavirus. ConclusionChildren under 1 year of age are more susceptible to RSV infection, with cough being the predominant symptom. RSV infection in Pudong New Area, Shanghai, mainly occurs in winter. Targeted prevention and control measures should be taken for children under 1 year old during the winter season to reduce the risk of both RSV infection and co-infection with human coronavirus and influenza virus.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.