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.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

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.

ObjectiveTo investigate the efficacy of ovarian tissue cryopreservation and autologous transplantation in preserving fertility and ovarian endocrine function in patients with cervical cancer. MethodsA 26-year-old patient with stage ⅡA1 cervical cancer underwent ovarian tissue harvesting and cryopreservation during cancer surgery. Following complete remission of the cancer， autologous ovarian tissue transplantation was performed. Follow-up monitoring included assessment of menopausal symptoms， hormone levels， and follicular development. ResultsSix months after transplantation， follicle-stimulating hormone levels decreased to 6.60 U/L， and estradiol levels increased from ＜10.00 ng/L to 89.00 ng/L. At 10 months after transplantation， ultrasound monitoring confirmed follicular development and physiological ovulation in the transplanted ovarian tissue. By 15 months after transplantation， follicle-stimulating hormone levels remained stable at 7.24 U/L， and estradiol levels further increased to 368.00 ng/L. Over 2 years after transplantation， the patient successfully gave birth to a healthy baby through assisted reproductive technology. ConclusionThe restoration of endocrine and ovulation functions in the transplanted cryopreserved ovarian tissue， followed by successful pregnancy， demonstrates the clinical success of ovarian tissue transplantation.

RNA splicing is an essential cellular process in which a series of protein-nucleic acid complexes cut and splice the products of gene transcription to generate mature RNA， and it plays an important role in maintaining the normal life activities of cells. Extensive studies have shown that proteins and nucleic acids associated with RNA splicing undergo the pathological changes such as aggregation in neurodegenerative diseases， and inadequate RNA splicing is observed in lesions. Genetic alterations within RNA splicing-related genes can cause neurodegenerative diseases. All these findings suggest that abnormalities in RNA splicing pathways may play a significant role in the pathogenesis of neurodegenerative diseases. This article reviews the research advances in the alterations of RNA splicing in common neurodegenerative diseases in terms of histopathology， biochemistry， and genetics， as well as related cell biology and animal models， in order to clarify their role in the pathogenesis of neurodegenerative diseases.
Alzheimer Disease ; Parkinson Disease

Objective: To evaluate the efficacy and safety of plasma exchange (PE) in thymoma-associated myasthenia gravis (MG), thereby to provide theoretical support for its application in the treatment of thymoma-associated MG. Methods: A total of 133 patients with thymoma-associated MG admitted from January 2018 to September 2024 were retrospectively analyzed. Patients were matched using propensity score to reduce selection bias, yielding 22 matched pairs for both PE group (n=22) and non-PE group (n=22). Patient characteristics including gender, age of disease onset, course of disease, history of thymoma resection, clinical absolute scores [clinical absolute scores (CAS) and clinical relative scores (CRS)], and synchronized immunotherapy regimen of the two groups were analyzed. The CAS scores before and after treatment were compared between the two groups, and the CRS was used to assess the treatment efficiency. Safety of the two treatment regimens were also compared. Continuous variables were compared using the t-test or ANOVA, while categorical data were compared by the chi-square test. Results: A total of 133 patients were included and divided into two groups according to whether they underwent plasma exchange treatment: the PE group (n=22) and the non-PE group (n=111). To exclude bias caused by large difference in the number of cases between the two groups, we performed propensity score matching. After matching, the number of cases in both groups was 22. There was no significant difference in baseline clinical characteristics between the two groups (P>0.05), including gender, age of onset, duration of disease course, history of thymectomy and baseline CAS score before treatment. Compared to the non-PE group, patients in the PE group showed more significant improvement in CAS score (5.09±1.95 vs 3.59±1.50, P<0.05) and a higher CRS score (75.00% vs 50.00%, P<0.001). Compared to the non-PE group, PE group had significantly longer ICU stay, longer hospital stay and higher hospitalization cost (P<0.05). There was no statistically significant difference in adverse events between the two groups during treatment (P>0.05). During long-term follow-up, both the PE and non-PE groups showed relatively low 1-, 3-, and 5-year recurrence rate, with no significant difference between the two groups (P>0.05). Conclusion: This study indicates that plasma exchange has clear value in the treatment of patients with thymoma-associated myasthenia gravis. It can not only significantly improve patients' muscle strength to alleviate motor dysfunction and enhance quality of life, but also does not significantly increase the incidence of adverse reactions. Therefore, it can be regarded as one of the preferred treatment options that achieve a "balance between efficacy and safety" for such patients, and provides an important basis for optimizing treatment strategies, improving prognosis, and promoting the application of subsequent treatment regimens.

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.