ObjectiveThis study aims to investigate the effect of Liuwei Dihuangwan on the autophagy function in the hippocampus of senescence-accelerated mouse prone 8 （SAMP8） by regulating the expression of glycoprotein non-metastatic melanoma protein B （GPNMB）. Furthermore， it is designed to explore the mechanism of the method of tonifying the kidneys and replenishing essence in the treatment of Alzheimer's disease （AD）. MethodsIn experiment 1， 24 5-month-old SAMP8 mice were randomly and equally divided into the model group， and the low-， middle- and high-dose（0.59，1.18，2.36 g·kg^-1） Liuwei Dihuangwan groups. At the same time， six 5-month-old senescence accelerated mouse resistant 1 （SAMR1） mice were used as the control group. The learning and memory ability was evaluated through novel object recognition experiment. Serum cortisol （Cort）， adrenocorticotropic hormone （ACTH） and urine 17-hydroxycorticosteroid （17-OHCS） levels were detected by enzyme-linked immunosorbent assay （ELISA）. The ultrastructure of hippocampal neurons was observed by transmission electron microscope （TEM）， and the expression levels of hippocampal GPNMB， a disintegrin and metalloproteinase 10 （ADAM10） and autophagy-related proteins were detected by Western blot. In experiment 2， 18 SAMP8 mice were randomly and equally divided into the model group， vector control group （Vector）， and GPNMB overexpression group （GPNMB^OE）. Lentiviral vectors were stereotactically injected into the brain （2 μL per side in the GPNMB^OE group）. Western blot was used to detect the expression of the above target proteins in the hippocampus； In Experiment 3， 24 SAMP8 mice were randomly and equally divided into the model group， Liuwei Dihuangwan group， Liuwei Dihuangwan+negative control （NC） group， and Liuwei Dihuangwan+GPNMB silencing group （shGPNMB）. Before drug treatment， the Liuwei Dihuangwan+NC group and the Liuwei Dihuangwan+shGPNMB group were injected with negative control and GPNMB silencing lentivirus， respectively. Western blot was used to detect the expression of the above target proteins in the hippocampus. ResultsThe novel object discrimination index of mice in the model group was significantly lower than that of mice in the control group （P<0.01）. The novel object discrimination index of mice in the medium- and high-dose Liuwei Dihuangwan groups was significantly higher than that of mice in the model group （P<0.01）. Aggregated autolysosomes were observed in the normal hippocampus tissue by TEM. In the model group， mitochondria were dominant， and no typical characteristic autophagosomes were observed. In the low- and medium-dose Liuwei Dihuangwan groups， a small number of autolysosomes and autophagosomes with double-membrane structures were observed. In the high-dose Liuwei Dihuangwan group， the number of autophagosomes and autolysosomes was greater than that in the low- and medium-dose groups. The results of ELISA and Western blot showed that compared with the control group， the levels of serum Cort， ACTH， and urine 17-OHCS in the model group were substantially increased， while the expression of hippocampal ADAM10， Beclin1， and microtubule associated-protein light chain 3-Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ） was significantly decreased. The expression of GPNMB and ubiquitin binding protein p62 was significantly increased （P<0.05， P<0.01）. Compared with the model group， the serum Cort and ACTH levels in the low-， medium-， and high-dose Liuwei Dihuangwan groups were significantly reduced， while only the urine 17-OHCS level in the high-dose group was significantly reduced. The hippocampal GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ expression levels in the medium-， and high-dose groups of Liuwei Dihuangwan were significantly increased compared to the model group， whereas the expression of p62 was significantly reduced （P<0.01）. The above indicators showed a progressive trend among the three groups. Compared with the model group， the GPNMB^OE group showed a significant increase in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ expression， and a significant decrease in p62 expression （P<0.01）. Compared with the model group， the expression of GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ in the hippocampus of the Liuwei Dihuangwan group significantly increased， while the expression of p62 significantly decreased （P<0.01）. Compared with the Liuwei Dihuangwan group， the Liuwei Dihuangwan+shGPNMB group showed a significant decrease in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ， and a significant increase in p62 expression （P<0.01）. ConclusionLiuwei Dihuangwan can enhance hippocampal autophagy function and improve AD by upregulating GPNMB expression.

Pulmonary arterial hypertension(PAH)is a serious and fatal cardiovascular disease that significantly affects patients'quality of life and survival.Current treatments offer some relief but have limited effectiveness and notable side effects.Sotatercept,as a novel drug,modulates the transforming growth factor-β(TGF-β)signaling pathway and shows promising therapeutic effects in PAH.By summarizing the pharmacological mechanisms and clinical research progress of sotatercept in PAH,assessing its application prospects,and analyzing future research directions in the light of current clinical research results,we provide an important perspective for understanding the clinical application of this drug in China,with a view to promoting its promotion and application in China.

Objective To explore the characteristic changes in white matter microstructure in Parkinson's disease(PD)patients via automated fiber quantification(AFQ)technology,providing a basis for the identification and diagnosis of PD,and to analyze the feasibility of combining the AFQ method with support vector machine(SVM)in the diagnosis of PD.Methods Forty patients with primary PD(PD group)and 20 healthy controls(HC)(HC group)were prospectively selected.The AFQ technology was applied for white matter fiber tract analysis.Statistical analyses were performed using FSL(v6.0)software and SPSS 27.0 software.Independent-sample t-tests were conducted for comparisons between groups in AFQ analysis.The AFQ method was used to analyze the relationship between diffusion tensor imaging(DTI)parameters and Montreal Cognitive Assessment(MoCA)scores.Results(1)The results of AFQ analysis revealed that compared with the HC group,the PD group exhibited significantly lower fractional anisotropy(FA)values in the right cingulum bundle,left cingulum bundle hippocampus,and left uncinate fasciculus,with no differences in the FA values of the remaining 17 fiber tracts.Moreover,PD group demonstrated higher mean diffusivity(MD)values in the left cingulum bundle,left cingulum bundle hippocampus,left inferior frontal occipital fasciculus,left inferior longitudinal fasciculus,left superior longitudinal fasciculus,and left uncinate fasciculus.These differences were statistically significant(P<0.05),while no significant differences were found in the MD values of the remaining 14 fiber tracts.Furthermore,the MD values of the left inferior frontal occipital fasciculus,and left inferior longitudinal fasciculus were negatively correlated with the MoCA scores.(2)The classification results of SVM showed that the best results were achieved when combining the differential nodes of FA and MD as classification features,with an area under the curve(AUC)of 0.922,an accuracy of 84.81%,a sensitivity of 87.50%,and a specificity of 82.05%.Conclusion The DTI parameters in PD patients can serve as potential biomarkers for diagnosis.The AFQ methods provides an effective approach for detecting alterations white matter tract integrity,offering important insights for the identification and diagnosis of PD.The best results are achieved when combining the differential nodes of FA and MD as classification features.

T follicular helper cells(Tfh)are a group of helper T cell subsets located in germinal center area of lymphoid tissue,which can modulate germinal center response and promote humoral immune response of B cells.Tfh cells,with differentiation regulated by Bcl-6,express phenotypic markers including CXCR5,PD-1 and ICOS.New evidence indicates that thymocyte selection-associated high mobility group box(TOX)influences Bcl-6 expression through epigenetic regulation and further regulates differentia-tion of Tfh cells.Recent studies have demonstrated that Tfh cells are positively correlated with aberrant activity of B cells and disease activity in pathogenesis of primary Sj?gren's syndrome(pSS),rheumatoid arthritis(RA)and systemic lupus erythematosus(SLE).It has been shown that IFN-α inhibitor(Anifrolumab),JAK inhibitors(Tofacitinib,Ruxolitinib)and STAT1 specific inhibitor(Fludara-bine)can suppress overexpression of TOX,inhibitors of IFN-α-JAK/STAT-TOX pathway may represent a new therapeutic strategy to target Tfh cells for treatment of autoimmune diseases.

Objective To study the effect of Liuwei Dihuangwan on autophagy level and its mechanism in SAMP8 mice and Aβ-stimulated BV2 cell model,and to explore the molecular mechanism of tonifying the kidney and filling up the essence to prevent and control Alzheimer's disease(AD)through interfering with autophagy.Methods Ten 7-month-old male anti-aging mice(SAMR1)were taken as the normal group,and 40 7-month-old male rapid aging mice(SAMP8)were randomly control and model groups,equal volumes of saline were administered by gavage twice a day for 4 weeks,and the levels of Aβ expression in the hippocampus of the mice in each group were detected by immunofluorescence;The expression levels of FcγRⅡB,c-Src and SHP-1 in the hippocampus of each group were detected by Western blot;BV2 cells were cultured and Fcγ receptor Ⅱ-b(FcγRⅡB)overexpression vectors were constructed;the AD state cell model was established by treating the BV2 cells with 5 μmol·L-1 Aβ1-42,and the Liuwei Dihuangwan drug-containing serum was prepared.The cells were divided into NC group,Aβ1-42 group,blank serum group,drug-containing serum group,Vector group,FcγRⅡB OE group,and drug-containing serum+FcγRⅡB OE group;immunofluorescence was used to detect the expression level of Aβ protein in the cells of each group;Western blot was used to detect the expression level of p62,LC3 Ⅱ/Ⅰ,FcγRⅡB,SHP-1,and c-Src in cells of each group.Results Compared with the normal group,the hippocampal Aβ,FcγRⅡB,SHP-1,and c-Src expression levels in the model group of mice were significantly higher(P<0.01),and compared with the model group,the expression levels of Aβ,FcγRⅡB,SHP-1,and c-Src in the low-,medium-,and high-dose groups of Liuwei Dihuangwan were significantly lower(P<0.01),it also showed a significant dose dependent relationship.Compared with NC group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in Aβ1-42 group were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with Aβ1-42 group and blank serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in drug-containing serum group were significantly decreased(P<0.01),and LC3Ⅱ/Ⅰ was significantly increased(P<0.01);Compared with NC group and Vector group,the expression of Aβ in FcγRⅡB OE group was increased,the protein expressions of p62,FcγRⅡB,SHP-1 and c-Src were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with the drug-containing serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in the drug-containing serum+FcγRⅡB OE group were significantly increased(P<0.01),and the protein expression levels of LC3Ⅱ/Ⅰ were significantly decreased(P<0.01).Conclusion Liuwei Dihuangwan improved AD by inhibiting microglia FcγRⅡB/c-Src pathway and increasing autophagy level.

Objective To study the effect of Liuwei Dihuangwan on autophagy level and its mechanism in SAMP8 mice and Aβ-stimulated BV2 cell model,and to explore the molecular mechanism of tonifying the kidney and filling up the essence to prevent and control Alzheimer's disease(AD)through interfering with autophagy.Methods Ten 7-month-old male anti-aging mice(SAMR1)were taken as the normal group,and 40 7-month-old male rapid aging mice(SAMP8)were randomly control and model groups,equal volumes of saline were administered by gavage twice a day for 4 weeks,and the levels of Aβ expression in the hippocampus of the mice in each group were detected by immunofluorescence;The expression levels of FcγRⅡB,c-Src and SHP-1 in the hippocampus of each group were detected by Western blot;BV2 cells were cultured and Fcγ receptor Ⅱ-b(FcγRⅡB)overexpression vectors were constructed;the AD state cell model was established by treating the BV2 cells with 5 μmol·L-1 Aβ1-42,and the Liuwei Dihuangwan drug-containing serum was prepared.The cells were divided into NC group,Aβ1-42 group,blank serum group,drug-containing serum group,Vector group,FcγRⅡB OE group,and drug-containing serum+FcγRⅡB OE group;immunofluorescence was used to detect the expression level of Aβ protein in the cells of each group;Western blot was used to detect the expression level of p62,LC3 Ⅱ/Ⅰ,FcγRⅡB,SHP-1,and c-Src in cells of each group.Results Compared with the normal group,the hippocampal Aβ,FcγRⅡB,SHP-1,and c-Src expression levels in the model group of mice were significantly higher(P<0.01),and compared with the model group,the expression levels of Aβ,FcγRⅡB,SHP-1,and c-Src in the low-,medium-,and high-dose groups of Liuwei Dihuangwan were significantly lower(P<0.01),it also showed a significant dose dependent relationship.Compared with NC group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in Aβ1-42 group were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with Aβ1-42 group and blank serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in drug-containing serum group were significantly decreased(P<0.01),and LC3Ⅱ/Ⅰ was significantly increased(P<0.01);Compared with NC group and Vector group,the expression of Aβ in FcγRⅡB OE group was increased,the protein expressions of p62,FcγRⅡB,SHP-1 and c-Src were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with the drug-containing serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in the drug-containing serum+FcγRⅡB OE group were significantly increased(P<0.01),and the protein expression levels of LC3Ⅱ/Ⅰ were significantly decreased(P<0.01).Conclusion Liuwei Dihuangwan improved AD by inhibiting microglia FcγRⅡB/c-Src pathway and increasing autophagy level.

Objective To identify key acoustic features associated with the progression of Alzheimer's disease(AD)through voice analysis combined with machine learning and feature selection techniques,thereby constructing classification models that serve as candidate tools for the early screening of AD.Methods Voice samples from AD,mild cognitive impairment(MCI)and healthy(HC)elderly individuals were obtained from the NCMMSC2021 AD voice dataset.The voice samples underwent data preprocessing,followed by feature extraction from the eGeMAPS feature set via the OpenSmile toolkit.Classification models were obtained utilizing random forest and support vector machine(SVM)algorithms.Significance testing and feature importance ranking were conducted using Python,and the further selection of the optimal features was performed through sequential forward selection(SFS).The classification performance before and after feature selection was compared and evaluated using accuracy and the area under the receiver operating characteristic curve(AUC).Results The significant acoustic features in the classification models primarily derived from spectral slope,formant,fundamental frequency,and loudness.The optimal classification performance was achieved with the SVM model following SFS feature selection,with recognition accuracies of 0.926(AUC=0.974)for AD/MCI group,0.875(AUC=0.956)for AD/HC group,and 0.879(AUC=0.904)for MCI/HC group.Conclusion SVM model performs better than random forest model,and the use of SFS for feature selection can effectively enhance model performance.Voice analysis has the potential to serve as a valuable supplementary tool for the rapid AD assessment and screening.

Objective To explore practical pathways for the connotation quality control of Zhuang medical records by le-veraging the reform of DRG-based medical insurance payment systems as an opportunity,thereby enhancing record quality and fostering the coordinated development of ethnic medicine with modern medical insurance payment systems.Methods By analy-zing the requirements imposed by the DRG-based payment reform on the quality management of Zhuang medical records,a quality control management system focused on the connotation quality control of these records was established.A scoring standard for the connotation quality of Zhuang medical records,supplemented by DRG,was developed.Dynamic quality control was implemented through a combination of information-based intelligent review and expert manual review to ensure rectification.Results Key in-dicators,such as the qualification rate of the first page of medical records,the A-level rate of inpatient records,and the DRG en-rollment rate,showed significant improvements.The documentations of surgical and procedural records were standardized,and the records of ward rounds and case discussions by senior physicians were comprehensive and detailed,accurately reflecting the diagnostic and therapeutic methods and outcomes of Zhuang medicine.Conclusion The DRG-based quality control model for Zhuang medical records effectively aligns medical insurance payment with the unique characteristics of ethnic medicine,offering a replicable model for the quality management of medical records in ethnic medicine institutions under DRG-based reforms.

Objective To investigate the expression changes and clinical significance of serum pepsinogen(PG)and triggering receptor expressed on myeloid cells-1(TREM-1)in patients with reflux esophagitis(RE).Methods A total of 140 patients with RE who were treated from October 2021 to October 2023 were selected as the observation group,and 140 healthy adults who underwent physical examination during the same period were selected as the control group.Serum PG(PGⅠ and PGⅡ)and TREM-1 were detected by ELISA.Multivariate logistic regression was used to analyze the influencing factors of RE.Receiver operating characteristic(ROC)was used to analyze the diagnostic efficacy of serum PGⅠ,PGⅡ and TREM-1 levels for RE.Results The levels of interleukin(IL)-2,IL-6,Il-1β,PGⅡ,TREM-1 and tumor necrosis factor-α(TNF-α)in the observation group were significantly higher than those in the control group,while the level of PGⅠ was significantly lower than that in the control group(P<0.01).Serum IL-2,IL-6,IL-1β,TNF-α,PGⅡ and TREM-1 were risk factors for RE,while serum PGⅠ was a protective factor for RE(P<0.01).ROC curve analysis showed that the area under the ROC curve(AUC)of combined detection of PGⅠ,PGⅡ and TREM-1 in the diagnosis of RE was significantly higher than that of PGⅠ alone(Z=5.940,P<0.001)and PGⅡ alone(Z=6.764,P<0.001)and TREM-1 alone(Z=6.791,P<0.001).Conclusion The expression levels of serum PGⅡ and TREM-1 in patients with RE are increased,while the expression level of PGⅠ is decreased.The combined detection of the three can improve the diagnostic efficacy of RE.

T follicular helper cells(Tfh)are a group of helper T cell subsets located in germinal center area of lymphoid tissue,which can modulate germinal center response and promote humoral immune response of B cells.Tfh cells,with differentiation regulated by Bcl-6,express phenotypic markers including CXCR5,PD-1 and ICOS.New evidence indicates that thymocyte selection-associated high mobility group box(TOX)influences Bcl-6 expression through epigenetic regulation and further regulates differentia-tion of Tfh cells.Recent studies have demonstrated that Tfh cells are positively correlated with aberrant activity of B cells and disease activity in pathogenesis of primary Sj?gren's syndrome(pSS),rheumatoid arthritis(RA)and systemic lupus erythematosus(SLE).It has been shown that IFN-α inhibitor(Anifrolumab),JAK inhibitors(Tofacitinib,Ruxolitinib)and STAT1 specific inhibitor(Fludara-bine)can suppress overexpression of TOX,inhibitors of IFN-α-JAK/STAT-TOX pathway may represent a new therapeutic strategy to target Tfh cells for treatment of autoimmune diseases.