Neurological diseases have high morbidity and disability rates， posing a severe threat to human health. Cli nical manifestations include motor， sensory， cognitive and conscious disorders. Chaihu jia longgu muli decoction is derived from Treatise on Febrile Diseases ， with the effects of harmonizing Shaoyang， activating Yang and clearing heat， and tranquilizing the mind. This paper systematically reviews the research progress in clinical application and mechanism of Chaihu jia longgu muli decoction in the field of neurological diseases. It has been found that the decoction shows favorable efficacy in various neurological diseases such as insomnia， depression， epilepsy， vertigo， migraine and vascular dementia. The specific mechanisms are related to regulating neurotransmitter levels， repairing neuronal function， alleviating neuroinflammation， improving mitochondrial dysfunction and regulating intestinal flora. In the future， standardized prospective follow-up cohorts should be established， and core outcome indicators should be clearly defined to strengthen the evidence base. Furthermore， multidisciplinary research should be leveraged to expand the therapeutic value of Chaihu jia longgu muli decoction in the management of neurological diseases.

ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

OBJECTIVE To explore the influencing factors of Shenfukang capsule in the treatment of chronic kidney disease （CKD） and construct a nomogram prediction model for evaluating its therapeutic efficacy. METHODS CKD patients who were hospitalized from July 2019 to August 2022 in the First Affiliated Hospital of Guangxi Medical University and treated with Shenfukang capsule were selected as study subjects. Clinical data of the patients were collected from the hospital’s electronic medical record system， and they were divided into an effective group and an ineffective group based on treatment outcomes. Lasso-Logistic multivariate regression analysis was used to screen the influencing factors of the efficacy of Shenfukang capsule. Using the effectiveness of Shenfukang capsule treatment as the prediction outcome and the screened influencing factors as predictor variables， a nomogram prediction model was constructed using R software. All patients were randomly divided into a training cohort and a validation cohort. The discriminative ability， calibration， and clinical net benefit of the model were evaluated using the receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis， respectively. RESULTS Lasso-Logistic regression analysis revealed that concurrent diabetes mellitus， decreased levels of blood urea nitrogen， triglycerides， and serum phosphorus， as well as prolonged prothrombin time and elevated apolipoprotein AⅠ levels， were influencing factors for reduced efficacy of Shenfukang capsule in CKD treatment. The evaluation results of the nomogram prediction model showed that the area under curve values were 0.745 and 0.797 in the training and validation cohorts， respectively， which were close and both exceeded 0.70， indicating stable predictive performance. The calibration curves demonstrated good agreement in both datasets， suggesting satisfactory calibration performance. The clinical decision curves were positioned above the two extreme reference lines， indicating high clinical benefit of the model. CONCLUSIONS Diabetes mellitus， blood urea nitrogen， triglycerides， apolipoprotein AⅠ， serum phosphorus， and prothrombin time were factors associated with the efficacy of Shenfukang capsule in CKD patients. The nomogram prediction model established in this study may provide a basis for rational clinical application of Shenfukang capsule and for improving its therapeutic efficacy in CKD.

OBJECTIVE To explore the influencing factors of Shenfukang capsule in the treatment of chronic kidney disease （CKD） and construct a nomogram prediction model for evaluating its therapeutic efficacy. METHODS CKD patients who were hospitalized from July 2019 to August 2022 in the First Affiliated Hospital of Guangxi Medical University and treated with Shenfukang capsule were selected as study subjects. Clinical data of the patients were collected from the hospital’s electronic medical record system， and they were divided into an effective group and an ineffective group based on treatment outcomes. Lasso-Logistic multivariate regression analysis was used to screen the influencing factors of the efficacy of Shenfukang capsule. Using the effectiveness of Shenfukang capsule treatment as the prediction outcome and the screened influencing factors as predictor variables， a nomogram prediction model was constructed using R software. All patients were randomly divided into a training cohort and a validation cohort. The discriminative ability， calibration， and clinical net benefit of the model were evaluated using the receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis， respectively. RESULTS Lasso-Logistic regression analysis revealed that concurrent diabetes mellitus， decreased levels of blood urea nitrogen， triglycerides， and serum phosphorus， as well as prolonged prothrombin time and elevated apolipoprotein AⅠ levels， were influencing factors for reduced efficacy of Shenfukang capsule in CKD treatment. The evaluation results of the nomogram prediction model showed that the area under curve values were 0.745 and 0.797 in the training and validation cohorts， respectively， which were close and both exceeded 0.70， indicating stable predictive performance. The calibration curves demonstrated good agreement in both datasets， suggesting satisfactory calibration performance. The clinical decision curves were positioned above the two extreme reference lines， indicating high clinical benefit of the model. CONCLUSIONS Diabetes mellitus， blood urea nitrogen， triglycerides， apolipoprotein AⅠ， serum phosphorus， and prothrombin time were factors associated with the efficacy of Shenfukang capsule in CKD patients. The nomogram prediction model established in this study may provide a basis for rational clinical application of Shenfukang capsule and for improving its therapeutic efficacy in CKD.

Objective To investigate the correlation between hemoglobin A1c(HbA1c)levels and excessive daytime sleepiness(EDS)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 132 T2DM patients and 40 healthy people(NC group)who were treated in the outpatient department of Nanjing Meishan Hospital from December 2020 to December 2022 were selected.General clinical data of the subjects were collected,and their Epworth sleepiness scale(ESS)scores,Pittsburgh sleep quality index(PSQI),and apnea-hypopnea index(AHI)were measured.Based on ESS scores,T2DM patients were divided into simple T2DM group(ESS score<9,n=99)and EDS group(ESS score≥9,n=33)according to ESS score.The baseline data were compared for each group.Spearman correlation analysis and multivariate logistic regression model were used to evaluate the correlation between HbA1c levels and EDS.The receiver operating characteristic(ROC)curve was used to calculate the area under the curve(AUC)to evaluate the predictive value of HbA1c levels for EDS.Results HbA1c,fasting plasma glucose,AHI index and PSQI score in EDS group were higher than those in T2DM and NC group(P<0.05).Spearman correlation analysis showed that ESS score was positively correlated with HbA1c in T2DM patients(P<0.05).Multivariate logistic regression analysis revealed that elevated HbA1c levels emerged as a significant and independent risk factor for the onset of EDS.The ROC curve indicated that the AUC of HbA1c for predicting EDS was 0.736.Conclusions There is an independent positive correlation between HbA1c levels and EDS in T2DM patients,which provides clues for early identification and treatment of EDS in clinical practice.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

OBJECTIVE To analyze the ethanol extracts,total phenols,total flavonoids contents and HPLC fingerprints of typi-cal propolis samples from 6 foreign countries and 5 domestic regions,optimize the extraction process and evaluate the antioxidant activi-ty,so as to provide data support for improving the quality control system of propolis.METHODS The optimization of the propolis ex-traction process utilized flavonoid content as an indicator.Three flavonoid detection methods-namely,the aluminum trichloride meth-od,aluminum nitrate method,and polyamide method-were compared.The content of ethanol extract,total phenol content,and the scavenging ability of DPPH free radicals for each sample were determined.Further analysis was conducted using HPLC fingerprint pro-filing.RESULTS The propolis extract with the highest flavonoid content was obtained using 80%ethanol as the extraction solvent,operating at 50℃,with a stirring time of 3 h,ultrasonic power of 180 W,and ultrasonic time of 15 min.The aluminum trichloride method was proved to be the most effective for determining total flavonoids in propolis.While the ethanol extract,total flavonoids,and total phenols of propolis from Xinjiang,China were relatively low,their antioxidant activity exhibited superiority.HPLC analysis re-vealed,Brazilian red propolis lacked of chrysin,galangin,caffeic acid phenethyl ester and Brazilian green propolis lacked ferulic acid,apigenin,p-coumaric acid,chrysin,and pinocembrin.In contrast,the content of these four compounds in other samples varied,with the antioxidant capacity of the extracts not precisely corresponding to the compound content.CONCLUSION Propolis exhibits a complex chemical composition with significant variations among varieties.Key quality control indexes must be comprehensively consid-ered,encompassing physicochemical characteristics and biological activity.Establishing a multi-angle assessment system with a mate-rial basis-functional linkage is essential.This approach facilitates the realization of high quality and cost-effectiveness,thereby promo-ting the healthy development of the industry.

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

Objective:To investigate the effect of age factor on glymphatic function in patients with Parkinson′s disease (PD) and its potential correlation with overall cognitive performance based on diffusion tensor imaging analysis along the perivascular space(DTI-ALPS) index.Methods:The study was cross-sectional. Clinical and imaging data of 77 PD patients (PD group) who attended the Provincial Hospital of Shandong First Medical University from October 2021 to June 2024 were retrospectively analyzed. In the same period, 30 healthy volunteers matched by age and gender were collected as the normal control (NC) group. All subjects underwent MRI scanning and DTI-ALPS index was calculated based on diffusion tensor imaging. Cognitive functions of 46 patients in the PD group were assessed using the mini-mental state examination (MMSE) and montreal cognitive assessment (MoCA) scores. Independent samples t-tests were used to compare the differences in DTI-ALPS index between the PD and NC groups. After adjusting for confounders, the relationship between DTI-ALPS and age was explored using partial correlation analyses, multiple linear regression models. A mediation model was further developed to explore the mediating effect of DTI-ALPS index between age and cognitive function scores. Results:The DTI-ALPS indices of PD and NC groups were 1.66±0.20 and 1.44±0.17, respectively, and the differences were statistically significant ( t=5.27, P<0.001). The age of patients in the PD group was negatively correlated with the DTI-ALPS index ( r=-0.54, P<0.001), and age (β=-0.467, P<0.001) was an independent influencer of DTI-ALPS index. The DTI-ALPS index was positively correlated with MMSE scores ( r=0.53, P<0.001) and positively correlated with MoCA scores ( r=0.56, P<0.001). The mediation model showed that the DTI-ALPS index fully mediated between age and MMSE scores and partially mediated between age and MoCA scores, with an effect share of 33.25%. Conclusion:Age is an independent risk factor for impaired glymphatic pathway in PD patients, and it may induce cognitive decline in PD patients by exacerbating glymphatic pathway impairment.

Objective:To explore brain MRI features of methylmalonic acidemia (MMA).Methods:This observational study retrospectively analyzed the clinical and imaging data of 123 patients with MMA diagnosed at Shandong Provincial Hospital Affiliated to Shandong First Medical University and Qilu Hospital of Shandong University from January 2010 to November 2022. The 123 patients were divided into 7 stages according to age of onset, neonatal period (0 to<1 month), infancy (1 month to<1 year), early childhood (1 to<4 years), preschool (4 to<7 years), school age (7 to<13 years), adolescent (13 to 17 years) and adult (>17 years). All patients underwent brain MRI scanning. The imaging performances were evaluated, including the number, location, morphology of the lesions.Results:Of the 123 patients, 40 were in the neonatal period, 29 in infancy, 13 in early childhood, 9 in preschool, 6 in school age, 13 in adolescence, and 13 in adulthood. The first symptoms of patients in the neonatal period were mainly digestive system abnormalities, such as difficulty in breastfeeding (37.5%, 15/40) and vomiting (25.0%, 10/40), with neurological symptoms gradually becoming the main manifestations from infancy. Seventy-three cases (59.3%) showed significant abnormalities on cranial MRI, including 17 cases with 33 foci in the neonatal period, 23 cases with 53 foci in infancy, 11 cases with 16 foci in early childhood, 2 cases with 2 foci in preschool, 3 cases with 7 foci in school age, 7 cases with 9 foci in adolescence, and 10 cases with 16 foci in adulthood. In neonatal period, the main manifestations were myelin dysplasia (18%,6/33), dilatation of the lateral ventricular system (18%,6/33), and pallidal bulb infarct foci (18%,6/33); in infancy, the main manifestations were hypoplasia or thinning of the corpus callosum (30%,16/53); in early childhood, the main manifestations were pallidal bulb infarct foci (38%,6/16); and the two MRI abnormalities in preschool were pallidum and thalamic infarct foci; in school age, the main manifestations were infarct foci in the chiasmatic nucleus (29%,2/7) and in the caudate nucleus (29%,2/7); in adolescence, the main manifestation was dilatation of the lateral ventricular system (33%,3/9); and in adulthood, the main manifestation was dilatation of the lateral ventricular system (19%,3/16).Conclusion:By staging the age of onset, it is found that the imaging manifestations of MMA patients show significant differences with age, suggesting that there is a dynamic nature of MMA damage to brain structures at different developmental stages.