The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.

Objective: To investigate the current status and influencing factors for cognitive frailty among the elderly in community, so as to provide the evidence for early identification and prevention of cognitive frailty among the elderly. Methods: Residents aged 60 years and above with local household registration from 11 counties (cities, districts) in Zhejiang Province from 2021 to 2023 were selected as study participants using a multistage random sampling method. Demographic information, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were assessed using the Patient Health Questionnaire. Cognitive frailty was evaluated using the FRAIL Scale and the Mini-Mental State Examination. Factors affecting cognitive frailty among the elderly in community were identified using a multivariable logistic regression model. Results: A total of 16 613 individuals were surveyed, including 7 465 males (44.93%) and 9 148 females (55.07%). The average age was (70.97±7.29) years. A total of 784 individuals were detected with depressive symptoms, with a detection rate of 4.72%. A total of 724 individuals were detected with cognitive frailty, with a detection rate of 4.36%. Multivariable logistic regression analysis showed that females (OR=1.419, 95%CI: 1.179-1.708), aged ≥70 years (70-<80 years old, OR=1.869, 95%CI: 1.490-2.345; ≥80 years old, OR=5.017, 95%CI: 3.935-6.398), without a spouse (OR=1.495, 95%CI: 1.234-1.810), sedentary (OR=2.420, 95%CI: 1.829-3.202), chronic diseases (1 type, OR=1.456, 95%CI: 1.175-1.804; ≥2 types, OR=1.639, 95%CI: 1.314-2.045), and depressive symptoms (OR=4.191, 95%CI: 3.361-5.225) were associated with a higher risk of cognitive frailty among the elderly in community. Conversely, a lower risk of cognitive frailty was seen among the elderly in community who had primary school or above (primary school, OR=0.512, 95%CI: 0.389-0.676; junior high school or above, OR=0.464, 95%CI: 0.354-0.608), engaged in physical exercise (OR=0.396, 95%CI: 0.291-0.539), and were reported average or good self-rated health status (average, OR=0.641, 95%CI: 0.475-0.866; good, OR=0.150, 95%CI: 0.109-0.208). Conclusions The detection rate of cognitive frailty among the elderly in community is relatively low and is influenced by demographic factors such as gender, age, education level, as well as lifestyle like sedentary and physical exercise, and health status. It is recommended to reduce the risk of cognitive frailty among the elderly through multidimensional interventions, including health education, promotion of healthy lifestyles, and enhanced mental health support.

Objective: To establish a nomogram prediction model for Alzheimer's disease (AD) among the elderly in community, so as to provide the evidence for early screening and prevention of AD. Methods: Based on the Zhejiang Healthy Aging Cohort Study, the elderly aged 60-90 years who completed the baseline survey were selected as the study subjects. Follow-up surveys were conducted from 2015 to 2016 and from 2019 to 2021. Sociodemographic characteristics, lifestyle factors, medical history, and waist circumference were collected through questionnaire surveys and physical examinations. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and a diagnosis of AD was made based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale and medical history. The participants were randomly divided into training and validation sets at 8∶2 ratio. LASSO regression was used to screen for predictive factors. Multivariable logistic regression model was used to analyze predictive factors and construct a nomogram. The model was analyzed and evaluated using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 6 988 elderly were included at baseline, with a mean age of (68.19±6.63) years. There were 3 438 males (49.20%), and 3 550 females (50.80%). The median follow-up duration was 4.90 (interquartile range, 3.80) years, with 817 new cases of AD were identified, yielding an incidence of 11.69%. LASSO regression and multivariable logistic regression showed that age (OR=1.017, 95%CI: 1.005-1.030), gender (female, OR=1.820, 95%CI: 1.533-2.165), educational level (primary school, OR=0.813, 95%CI: 0.673-0.980), physical exercise (not active, OR=1.572, 95%CI: 1.260-1.980), dining companions (spouse and children, OR=0.771, 95%CI: 0.598-0.995), baseline MMSE score (OR=0.843, 95%CI: 0.821-0.866), and waist circumference (OR=0.981, 95%CI: 0.973-0.989) were risk predictors for AD among the elderly in community. The prediction model demonstrated an area under the ROC curve of 0.740 (95%CI: 0.698-0.783) in the validation set, with a sensitivity of 0.731 and a specificity of 0.667. DCA indicated that when the probability threshold was 0.060 to 0.325, the clinical net benefit was relatively high. Conclusion The AD risk prediction model constructed in this study has good discrimination and clinical practicability, can be used for early screening of AD among the elderly in the community.

Seven triterpenoids were isolated and purified from the 95% aqueous EtOH extract whole plants of P. villosa by various chromatographic techniques, such as silica gel, ODS, Sephadex LH-20 gel column chromatography and preparative high performance liquid chromatography. Based on physicochemical properties and spectral analyses, the structures of the seven compounds were identified as 29-acetoxyoleanolic acid-3-O-α-L-arabinopyranoside (1), oleanolic acid (2), 3β-hydroxy-24-norursa-4(23),12,20(30)-trien-28-oic acid (3), 3β-hydroxy-24-nor-urs-4(23),12-dien-28-oic acid (4), ursolic acid (5), hederagenin (6), oleanolic acid 3-O-arabinoside (7). Compound 1 is a new compound. Compounds 3, 4, 6, and 7 are isolated from P. villosa for the first time. All compounds were assayed for their anti-inflammatory activity by the prodution of NO in lipopolysaccharide-stimulated RAW 264.7 cells. The results showed that compounds 1, 2, 3, 4, 6, and 7 significantly inhibited the NO release.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

Objective:To analyze a Chinese pedigree with a recombination occurring between the HLA- A/ C loci in both parents. Methods:A patient who was planning to undergo hematopoietic stem cell transplantation due to "aplastic anemia" in February 2022 was selected as the study subject. Peripheral blood samples were collected from the patient, his parents and brother. HLA- A/ C/ B/ DRB1/ DQB1 high-resolution typing was carried out by using sequence-based typing and sequence-specific oligonucleotides. The recombination was identified by pedigree analysis. The HLA haplotype of each individual was identified by genealogical analysis. The parentage possibility was determined by short tandem repeat analysis. HLA- A/ C/ B/ DRB1/ DRB345/ DQA1/ DQB1/ DPA1/ DPB1 were determined with next-generation high-throughput sequence-based typing. The recombination sites were analyzed by family study. Results:The high parentage possibilities of the family was confirmed by short tandem repeat analysis. Recombination was found between the HLA- A* 24: 02 A* 33: 03/ C* 14: 03 in the paternally transmitted haplotype, whilst HLA- A* 01: 01 A* 03: 01/ C* 08: 02 was found in the maternally transmitted haplotype, which had resulted in two novel HLA haplotypes in the proband. Conclusion:A rare case with simultaneous recombination of the paternal and maternal HLA- A/ C loci has been discovered, which may facilitate further study of the mechanisms of the HLA recombination.

Objective To investigate the effect of non-alcoholic fatty liver disease(NAFLD)induced by high-fat diet(HFD)on the kidneys of mice and the protective effect and mechanism of Xiayuxue Decoction.Methods A total of 25 healthy controls and 25 NAFLD patients who attended Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from September 2020 to September 2021 were enrolled,and the levels of total cholesterol(TC),triglyceride(TG),blood urea nitrogen(BUN),creatinine(Cr),and uric acid(UA)were measured.A total of 24 male C57BL/6 mice were randomly divided into low-fat diet(LFD)group,HFD group,and HFD+Xiayuxue Decoction group(XYXD group),with 8 mice in each group,and since week 13,XYXD was administered by gavage once a day for 6 weeks till the end of week 18.The level of TC,TG,BUN,and Cr were measured for each group.HE staining and oil red staining were used to observe the pathological changes of the liver and the kidneys;immunohistochemical double staining was used to measure the expression levels of CD68 and alpha-smooth muscle actin(α-SMA);quantitative real-time PCR was used to measure the expression levels of sterol regulatory element binding protein 1(SREBP1),fatty acid synthase(FASN),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),Desmin,and α-SMA in renal tissue;Western blot was used to measure the protein expression levels of SREBP1 and TNF-α.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for pairwise comparison;the independent-samples t-test was used for comparison between two groups.Results Compared with the healthy controls,NAFLD patients showed significant increases in the levels of TC,TG,BUN,Cr,and UA(all P<0.05).Compared with the LFD group,the HFD group had significant increases in body weight,TC,TG,BUN,and Cr(all P<0.001),and compared with the HFD group,the XYXD group showed significant inhibition of the expression of TC,TG,BUN,and Cr(all P<0.001).Liver pathological examination showed that compared with the LFD group,the HFD group showed significant increases in hepatic steatosis and inflammatory infiltration,while the XYXD group showed significant alleviation of lesions.Renal pathological examination showed that compared with the LFD group,the HFD group had significant inflammatory infiltration,steatosis,and collagen formation in renal tissue,and compared with the HFD group,XYXD significantly alleviated inflammatory infiltration and inhibited steatosis and collagen formation.Quantitative real-time PCR showed that compared with the LFD group,the HFD group had significant increases in the relative mRNA expression levels of SREBP1,FASN,IL-6,TNF-α,Desmin,and α-SMA in renal tissue(all P<0.001),and compared with the HFD group,the XYXD group had significant reductions in the relative expression levels of these indicators(all P<0.001).Western blot showed that compared with the LFD group,the HFD group had significant increases in the protein expression levels of SREBP1 and TNF-α(P<0.05),and compared with the HFD group,the XYXD group had significant reductions in the protein expression levels of SREBP1 and TNF-α(P<0.05).Immunohistochemical staining showed that compared with the LFD group,the HFD group had significant increases in the positive staining or the double positive staining of α-SMA and CD68(P<0.05),and compared with the HFD group,the XYXD group showed significant reductions(P<0.05).Conclusion HFD can induce renal steatosis,inflammatory infiltration,and collagen formation,and XYXD might exert a protective effect on the kidneys by inhibiting the expression of macrophages and myofibroblasts in renal tissue.

Objective To study and verify the function of de novo interferon regulatory factor(IRF8)frameshift mutation detected in an etiology screening of the cohort of children with recurrent pneumonia at the molecular level.Methods The recombinant overexpression plasmids with wildtype or mutated IRF8 genes were constructed to transiently transfect HEK293T cells,or packed into lentivirus to infect two kinds of immune cell lines.Q-PCR,Western blot,immunofluorescence and other experimental assays were performed to explore the differences of expression and the regulatory effect on downstream genes associated with inflammation.Results The recombinant vectors with wildtype or mutated IRF8 genes were constructed successfully,and the efficiency of transfection by plasmids and infection by packed lentivirus was remarkable as well.Compared with wildtype,the molecular weight of IRF8 variant was slightly increased,while the expression level presents in opposition,even if on transcription level.Moreover,the localization of IRF8 variant was detected in abundance in nucleus rather than cytoplasm,and its inhibition effect was enhanced on the downstream ISRE element in comparison with the wildtype IRF8 protein.Conclusion The de novo frameshift mutation was presumed as gain-of-function(GOF)mutation.

Objective To evaluate the degree of brain atrophy in spinocerebellar ataxia type 3(SCA3)patients based on artificial intelligence(AI)technology,and to explore the correlation between the degree of brain atrophy and the severity of the disease.Methods The clinical and imaging data of 23 SCA3 patients(SCA3 group)and 24 healthy controls(HC)(HC group)were collected.The International Cooperative Ataxia Rating Scale(ICARS)was used to evaluate the severity of ataxia in patients with SCA3.AI technology was used to process the 3D-T1 WI MR image data of the SCA3 and HC groups to segment and measure the volume and volume percentage of brain,followed by correlation analyses between brain structural alterations and the severity of ataxia in SCA3 patients.Results There were no significant differences in gender and age between the two groups(P＞0.05).The SCA3 group had a significant reduction in the volume and volume percentage of various brain regions,such as the frontal,temporal,parietal,occipital,limbic,right cerebral white mat-ter,subcortical gray matter,cerebellum and brainstem,compared to the HC group(multiple hypothesis testing adjusted P＜0.01).In the SCA3 group,the ICARS showed positive correlation with patient age(r=0.571,P=0.004)and negative correlation with the vol-ume of the left cerebellar white matter,vermis,medulla oblongata,and the volume percentages of bilateral cerebellar white matter,vermis,pons,medulla oblongata(P＜0.05).Conclusion The significant atrophy of the supratentorial and subtentorial regions of the brain in SCA3 patients.The globus pallidus exhibits the most substantial atrophy,suggesting its potential as an imaging diagnostic marker of SC A3.