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 investigate the time-dependent pattern of blue light-induced retinal damage in mice, establish a suitable animal model, and evaluate the protective effects of a compound formula containing lutein esters, DHA algal oil, Lycium ruthenicum, and other ingredients used as both food and medicine. MethodsThirty-two of the 56 SPF-grade male C57BL/6J mice were randomly divided into a control group and model groups (1 h, 3 h, and 6 h irradiation) (n=8 per group) to determine the optimal blue light irradiation time. First, mice were exposed to blue light from a 467 nm light-emitting diode at (5 000±200) lx for 1 h, 3 h, and 6 h, respectively. Retinal histopathology and thickness were examined using hematoxylin‑eosin (HE) staining. Serum malondialdehyde (MDA) and glutathione (GSH) levels were measured using assay kits. Retinal inflammatory cytokine mRNA expression was assessed by real-time fluorescent quantitative reverse transcription PCR. After 3 h of blue light exposure was confirmed as the appropriate modeling condition, the remaining 24 mice were used in an intervention experiment to evaluate the protective effect of the eye-protective compound formula on blue light-induced retinal damage. The mice were administered the compound formula (1 000 mg·kg^-1·d^-1) by gavage for 14 days, followed by 3 h of blue light irradiation, and the same indicators were evaluated as described above. ResultsWith prolonged irradiation time, the thickness of each retinal layer gradually decreased (P<0.05 to P<0.01) and cell arrangement became disordered. Serum MDA levels progressively increased (P<0.01), while GSH levels gradually decreased (P<0.01). The mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in retinal tissue was significantly upregulated with increasing irradiation time. The 1 h irradiation group showed only minor changes (P>0.05), whereas the 6 h irradiation group exhibited the most pronounced changes (P<0.000 1). Therefore, 3 h of blue light irradiation (P<0.001), which showed significant yet moderate differences in all indicators, was selected as the subsequent modeling condition. After intervention with the eye-protective compound formula, compared with the model group, serum MDA level was significantly reduced (P<0.01), and serum GSH level was significantly increased (P<0.05). The expression levels of retinal inflammatory cytokines IL-1β (P<0.000 1), IL-6 (P<0.001), and TNF-α (P<0.01) were significantly downregulated. Total retinal thickness (P<0.01), as well as the thicknesses of the inner plexiform layer (P<0.05), inner nuclear layer (P<0.05), outer plexiform layer (P<0.05), and outer nuclear layer (P<0.01), were significantly increased compared with the model group. Histopathological examination also showed that the regularity and density of retinal cell arrangement were markedly better than those in the model group. ConclusionBlue light irradiation at a specific illuminance for 3 h can establish a stable mouse model of retinal damage. The compound formula alleviates retinal damage through antioxidant and anti-inflammatory pathways, providing an experimental basis for the development of related functional foods.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

Objective To explore the prognostic value of plasma sST2 in the population of coronary heart disease(CHD)complicated with chronic kidney disease(CKD).Methods A total of 326 elderly patients with CHD or CKD undergoing physical examination in the Second Medical Center of Chinese PLA General Hospital from April 2021 to July 2022 were continuously enrolled,and according to whether having CHD or CKD,they were divided into a CHD-CKD comorbidity group(n=117),a CHD group(n=124),and a CKD group(n=85).Their baseline data were compared,and the plasma concentration of sST2 was detected using chemiluminescence assay.Multiple linear regression analysis was used to identify the relevant factors of sST2.Kaplan-Meier survival curve and Cox proportional hazards regression analyses were applied to determine the impact of plasma sST2 on all-cause mortality and major adverse cardiovascular events(MACE).Results There were significant differences among the three groups in terms of age,sST2 and NT-proBNP levels,Log(NT-proBNP),eGFR,ratios of hyperuricemia,cerebral infarction,tumors,and using anti-platelet drugs and statins,PR interval,LVEF,and TC,TG,HDL-C and Hb levels(P＜0.05,P＜0.01).Multiple linear regression analysis showed that the sST2 level was positively correlated with logNT-proBNP and negatively with Hb level in the comorbidity group(t=2.266,P=0.025;t=-2.235,P=0.021).Kaplan-Meier survival curve analysis indicated that during a median fol-low-up of 31.5(22.0,32.2)months,the comorbidity group had a lower survival rate than the two single-disease groups(P＜0.05,P＜0.01),and higher incidence of MACEs than the CKD group(P＜0.01).ROC curve analysis suggests that the AUC value of sST2 in predicting all-cause mor-tality in the comorbid group was 0.692.Cox proportional hazards regression model revealed that after adjustment for cofounders,sST2 was still an independent risk factor for all-cause mortality in the comorbid patients(HR=4.461,95％CI:1.640-8.399,P=0.024),although this prognos-tic value may be influenced by NT-proBNP.Conclusion sST2 can independently predict the risk of mortality in elderly patients with CHD-CKD comorbidity.

Objective:To analyze the applied effect of artificial intelligence(AI)rehabilitation system combined with telemedicine platform in individualized rehabilitation treatment for patients with long-term coma,so as to realize individual management for them.Methods:An AI rehabilitation system that aimed to patients with long-term coma was designed by integrating data of multimodal sensors included inertial sensor,image sensor and bioelectric sensor.A telemedicine platform,which included seven modules(patient management,consultation management,video communication,data transmission,electronic medical records,cost management and system maintenance),was designed by using a browser/server(B/S)architecture.The changes of patients'condition were followed up,and the full process of the management for rehabilitation treatment and the individualization of treatment plan were realized.A total of 60 inpatients whose coma duration exceeded 28 days were selected from the Coma Awakening Center of Dongguan Shipai Hospital between October 1,2021 and September 30,2022.They were randomly divided into control group(n=30)and observation group(n=30)by random number table.The control group received physical therapy and rehabilitation training based on evaluation results of rehabilitation,while the observation group adopted AI rehabilitation system combined with the telemedicine platform to conduct intervention.The consciousness levels,quality of life,hospital stay duration and treatment costs of two group were compared after intervention.Results:The Glasgow Coma Scale(GCS)scores,Coma Recovery Scale-Revised(CRS-R)scores,and Persistent Vegetative State(PVS)scores of two groups after intervention were significantly higher than those before intervention,and these indicators of observation group were significantly higher than them of control group after intervention,and the differences were significant(t=7.187,15.586,9.293,P<0.05),respectively.There were not significant differences in Glasgow Outcome Scale(GOS)scores and Activities of Daily Living(ADL)scores between two groups before intervention(P>0.05),and these scores of two groups were significantly increased after intervention,and these scores of observation group were significantly higher than them of control group after intervention,and the differences were significant(t=7.584,6.755,P<0.05).Additionally,the hospital stay duration and treatment costs of observation group were significantly less than those of control group,and the differences were significant(t=20.965,9.503,P<0.05).Conclusion:The intervention of AI rehabilitation system combines with a telemedicine platform on patients with long-term coma can enhance GCS,CRS-R,PVS,GOS and ADL scores,and reduce hospital stay duration and treatment cost.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:Dehydrated hereditary stomatocytosis (DHS), a rare condition caused by pathogenic PIEZO1 or KCNN4 mutations, remains under-recognized. This study aimed to improve the diagnosis and management of DHS in China by retrospectively analyzing clinical and genetic characteristics.Methods:Patients diagnosed with DHS at Peking Union Medical College Hospital between 2018 and 2024 were included. All had suspected congenital hemolytic anemia and were confirmed by next-generation sequencing to harbor pathogenic PIEZO1 or KCNN4 mutations. Clinical features, genotypes, iron overload, and treatment outcomes were collected and analyzed.Results:Twenty-three DHS patients were identified, including 21 with PIEZO1 and 2 with KCNN4 mutations. Common manifestations were splenomegaly, jaundice, cholelithiasis, and secondary iron overload. Mild and moderate anemia occurred in 8.7% and 17.4% of patients, respectively, and stomatocytes were present in only 17.4%. The median time from symptom onset to diagnosis was 11 years. The predominant PIEZO1 variants were c.7367G > A and c.6328C > T, with nine novel mutations identified. Both KCNN4 mutations involved c.1055G > A. No clear genotype–phenotype correlation was observed. Secondary hepatic iron overload was found in 21.7% of patients.Conclusion:DHS is often underdiagnosed or misdiagnosed. Genetic testing enables accurate identification, and regular monitoring for secondary hepatic iron overload is crucial for long-term management.

Objective To retrospectively analyze the results of serum beta-amyloid 42(Aβ42)tests conducted in the laboratory and explore potential issues associated with this testing.Methods All the Aβ42 test data collected up to the initiation of this study were compiled,and the positive rates for various diagnoses,including Alzheimer's disease(AD),cognitive decline,and dementia were ana-lyzed.Accuracy of the test kit was preliminarily validated using the kit's own reference,mouse brain tissue,and in vitro cultured cell-based reference samples.Results Data from 546 patients were col-lected,with 166 positive cases(positive rate of 30.4％).Among them,3 out of 6 AD patients tested positive;among 149 patients diagnosed with cognitive decline and 59 dementia patients,there were 29 and 24 positive cases respectively,with positive rates of 19.5％and 40.7％.The kit's detection of its own reference was affected by the serum matrix and failed to effectively detect positive mouse brain tissue and cellular reference samples.The kit's detection was generally unaffected by the amyloid precursor protein(APP)of Aβ,but it did not demonstrate good recovery rates for its own reference samples added to various clinical serum specimens.Conclusion The positive rate of serum Aβ42 test results in laboratory is lower than expected,and the accuracy of the test kit may require further improvement.

OBJECTIVE To investigate the deglycosylation metabolism of dioscin in vivo and the changes of its anti-tumor activi-ty of its deglycosylated metabolites.METHODS An LC-MS/MS analysis method for simultaneous determination of dioscin and its deglycosylation metabolites was established to study the cumulative excretion amount of dioscin and its deglycosylated metabolites in rat feces after oral administration.To mimic its deglycosylation metabolism,HPLC method was applied to investigate the time-dependent changes in the prototype components and metabolites of dioscin after incubation in artificial gastric juice.Solid-phase extraction tech-nology was employed to isolate the product of dioscin following hydrolysis by artificial gastric juice.The cytotoxic effects of this product on human colon cancer cells HCT-116 were assessed using the CCK-8 assay across different hydrolysis time periods.Concurrently,the enzymatic activities of caspase-3 and caspase-9,along with the expression levels of cytochrome C,were measured to elucidate the impact of dioscin post-hydrolysis on the cytotoxicity against HCT-116 cells.RESULTS Dioscin and its series of deglycosylated me-tabolites were detected in rat feces,revealing no significant differences in the cumulative excretion amounts of Polyphyllin Ⅴ and Pro-genin Ⅱ.Dioscin was shown to generate a range of deglycosylated metabolites in artificial gastric juice.Furthermore,dioscin and its deglycosylated metabolites inhibited the proliferation of HCT-116 cells,induced morphological changes,and increased the enzymatic activities of caspase-3 and caspase-9,as well as cytochrome C expression.However,it was observed that the antitumor activity of the deglycosylated metabolites diminished with prolonged hydrolysis time.CONCLUSION The deglycosylation metabolism of dioscin sig-nificantly attenuates its inhibitory effect on the proliferation of HCT-116 cells.Suppressing the acid-mediated or gut microbiota-medi-ated deglycosylation metabolism may be a promising strategy to preserve its antitumor activity.