ObjectiveTo develop a community-family management model for older adults with mild cognitive impairment (MCI) and to formulate detailed application specifications, and to fully leverage the initiative of communities and families under limited resource conditions, for achieving community-based early detection and early intervention for older adults with MCI. MethodsA systematic literature review was conducted to identify pertinent publications. Corpus-based research methodologies were employed to extract, refine, integrate and synthesize management elements, thereby establishing the specific content and service processes for each stage of the management model. Utilizing the 5W2H analytical framework, essential elements such as management stakeholders, target populations, content and methods for each stage were delineated. The model and its application guidelines were finalized through expert consultation and demonstration. ResultsAn expert evaluation of the management model yielded mean scores of 4.84, 4.32 and 4.84 for acceptability, feasibility and systematicity, respectively. By integrating the identified core elements with expert ratings and feedback, the final iteration of the community-family management model for older adults with MCI was formulated. This model comprised of five stages: screening and identification, comprehensive assessment, intervention planning, monitoring and referral pathways to ensure implementation, and enhanced support for communities, family members and caregivers. Additionally, it included 18 specific application guidelines. ConclusionThe proposed management model may theoretically help delay cognitive decline, improve cognitive function and potentially promote reversal from MCI to normal cognition. It may also enhance the awareness and coping capacity of older adults and their families, strengthen community healthcare professionals' ability to early identify and manage MCI.

ObjectiveTo establish a high-performance liquid chromatography（HPLC） for the quantitative analysis of multiple components in Gegen Qinlian tablets， and to comprehensively evaluate the quality of samples from different manufacturers by integrating chemical pattern recognition and technique for order preference by similarity to ideal solution（TOPSIS）， in order to provide a reference basis for quality evaluation and control of Gegen Qinlian tablets. MethodsHPLC was employed to determine the contents of 10 components in 28 batches of Gegen Qinlian tablets collected from 6 manufacturers， and taking the detection results as variables， SIMCA 14.1 and SPSS 26.0 were employed for cluster analysis（CA）， principal component analysis（PCA）， and orthogonal partial least squares-discriminant analysis（OPLS-DA） to identify key components affecting the quality. Then， TOPSIS analysis was employed to rank the quality of Gegen Qinlian tablets from the 6 manufacturers and establish a comprehensive quality evaluation method. ResultsA quantitative method for Gegen Qinlian tablets was established. After methodological validation， the method was found to be stable and reliable， and could be used for the quantitative analysis of this preparation. The contents of 3′-hydroxy puerarin， puerarin， 3′-methoxy puerarin， daidzein， coptisine hydrochloride， epiberberine， jatrorrhizine hydrochloride， berberine hydrochloride， palmatine hydrochloride and baicalin in 28 batches of samples were 3.58-7.35， 24.88-42.32， 4.20-9.36， 4.33-7.60， 2.52-6.44， 0.93-4.10， 0.58-3.05， 10.68-22.92， 0.82-4.82， 11.73-60.16 mg·g^-1， respectively. Among them， puerarin， berberine hydrochloride and baicalin all met the limit requirements for this preparation specified in the 2025 edition of the Pharmacopoeia of the People's Republic of China. CA and PCA clustered the 28 batches of samples into 5 categories， PCA extracted 2 principal components with a cumulative variance contribution rate of 90.588%， and OPLS-DA screened out 4 differential markers with variable importance in the projection（VIP） values>1.0， namely baicalin， 3′-hydroxy puerarin， coptisine hydrochloride and palmatine hydrochloride， which might be the main components affecting the quality of Gegen Qinlian tablets. TOPSIS analysis showed that the comprehensive score of each evaluation index（C_i） values of different manufacturers were different. Among them， the C_i of manufacturer B was ranked higher， indicating potentially superior quality， while the C_i of manufacturer A was ranked lower， suggesting potentially inferior quality. ConclusionThis study establishes a quantitative method for Gegen Qinlian tablets， and the content uniformity of the same manufacturer is good， while there are differences in the contents of active components among different manufacturers. Through the chemical pattern recognition analysis， it is found that the content differences of Gegen Qinlian tablets may be related to baicalin， 3′-hydroxy puerarin， coptisine hydrochloride and palmatine hydrochloride.

Current formulation of objective performance criteria （OPC） in traditional Chinese medicine （TCM） faces methodological challenges， including poor reporting quality， insufficient standardization of methods， limited comparability of study populations， and inadequate consideration of the genetic and environment particularities of ethnic minority populations. In response to these issues， this paper proposes optimization strategies for setting OPC in TCM， with particular attention to ethnic minority medicine. These include improving methodological techniques and statistical descriptions， ensuring transparency in meta-analyses and data sources； standardizing the estimation of point estimates and confidence intervals， and incorporating multidisciplinary expert consensus for value determination； introducing local real-world data from the same period， especially cohort study evidence， to compensate for the lack of high-quality randomized controlled trial data. Through process transparency and dynamic updating mechanisms， the credibility of OPC method can be enhanced， thereby providing methodological support for strengthening evidence-based research capacity in this field.

OBJECTIVE: To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. METHODS: A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5' and 3' untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). RESULTS: The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ:C) and FⅫ antigen (FⅫ:Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c.712_713insT (p.Cys238Leufs *73) in exon 8 and c.1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p.Cys238Leufs*73 variant, while her older son was heterozygous for the p.Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p.Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. CONCLUSION The c.712_713insT and c.1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c.712_713insT (NM_000505) was unreported previously.
Adult ; Female ; Humans ; Male ; Middle Aged ; Base Sequence ; China ; Factor XII/genetics* ; Heterozygote ; Mutation ; Pedigree ; Factor XII Deficiency/genetics* ; East Asian People

OBJECTIVE: To analyze the phenotype and genotype of a family with hereditary coagulation factor Ⅹ (FⅩ) deficiency and preliminarily explore its molecular pathogenesis. METHODS: A hereditary FⅩ deficiency pedigree presented at the First Affiliated Hospital of Wenzhou Medical University on August 13, 2024 was selected as the study subject. Coagulation parameters of the proband and her family members (7 individuals from 3 generations) were measured using a one-stage clotting assay. All of the 8 exons and flanking sequences of the F10 gene were amplified by PCR and directly sequenced. Bioinformatics software was used to analyze the functional impact and pathogenicity of the variant proteins, as well as the spatial conformational changes and evolutionary conservation of the mutation sites. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: The proband exhibited significantly abnormal prothrombin time (PT, 33.3 s), activated partial thromboplastin time (APTT, 47.7 s), and FⅩ activity (FⅩ:C, 3%), while other coagulation parameters remained normal. The plasma thromboplastin generation test (PTGT) demonstrated that the proband and her children had lower thromboplastin generation levels compared with the healthy control group, and the proband's thromboplastin generation capacity was more severely impaired. Genetic analysis revealed that the proband, her daughter, and grandson have all harbored a heterozygous missense variant c.212T>C (p.Phe71Ser) in exon 2 of the F10 gene, which was located in the β-sheet core region of the Gla domain. The variant has altered surrounding hydrogen bonds and disrupted calcium-binding sites. Additionally, the proband, her son, and granddaughter have all carried a heterozygous missense variant c.1270G>T (p.Val424Phe) in exon 8, which increased the side-chain volume, leading to steric hindrance in the catalytic domain and impaired coagulation function. Bioinformatics analysis confirmed that both p.Phe71Ser and p.Val424Phe were pathogenic variants, with Phe71 and Val424 being highly conserved residues. CONCLUSION The reduced FⅩ levels in this hereditary FⅩ-deficient family may be attributed to the heterozygous missense variants c.212T>C (p.Phe71Ser) in the exon 2 and c.1270G>T (p.Val424Phe) in the exon 8 of the F10 gene.
Humans ; Female ; Male ; Pedigree ; Adult ; Heterozygote ; Mutation ; Middle Aged ; Factor X/genetics* ; Exons ; Factor X Deficiency/genetics*

[Objective]To analyze the pathogenesis of liver cirrhosis and provide ideas for clinical treatment.[Methods]Through the exposition of the theory of"liver essence Yin and function Yang"and the application of"taking images and comparing classes"thinking mode,the macroscopic and microcosmic mechanism of liver cirrhosis progression was analyzed.[Results]Liver cirrhosis is the final stage of many liver diseases.Liver apraxia is an important pathological mechanism of progressive progression of liver cirrhosis.Macroscopically,it can lead to pathological changes such as Qi stagnation,water stagnation,blood stasis and so on.Microscopically,it can lead to the degeneration and necrosis of hepatocytes,the formation of extracellular matrix(ECM),the reduction of liver sinusoidal endothelial cell(LSEC)window,sinusoidal capillarization and other pathological mechanisms.These are important factors in the progression of liver cirrhosis.Therefore,based on the theory of"liver essence Yin and function Yang",the methods of nourishing Yin and soothing the liver,activating blood circulation and removing blood stasis,invigorating Qi and spleen can be adopted in the treatment of patients with liver cirrhosis.[Conclusion]The theory of liver essence Yin and function Yang is a high summary of the physiological characteristics of the liver and has an enlightening effect on the clinical diagnosis and treatment of liver cirrhosis.

Objective To analyze the influencing factors and action paths of frailty in elderly patients with col-orectal cancer,so as to provide a theoretical clinical intervention.Methods A convenience sampling method was adopted.A total of 254 elderly patients with colorectal cancer who were scheduled for elective surgery in a tertiary A hospital in Shanxi Province from March 2023 to September 2024 were selected as the research subjects.General information questionnaires,Fried frailty phenotype,Perceived Ageism Scale,Multidimensional Assessment Scale of In-teroceptive Awareness Version 2-Chinese,Cancer Patient Self-Management Assessment Scale,and Anderson Symptom Inventory were used for the investigation,and a structural equation model was constructed.Results The incidence of frailty in elderly colorectal cancer patients before surgery is 38.98％.Anderson Symptom Assessment and Per-ceived Ageism were positively correlated with frailty(r=0.534,0.568,P＜0.01),while interoceptive sensitivity and the self-management level were negatively correlated with frailty(r=-0.444,-0.659,P＜0.01).Self-management behavior had only a direct effect on patients' frailty(β=-0.349,P＜0.001),while Anderson Symptom Assessment,perceived age discrimination and interoceptive sensitivity had both direct and indirect effects on patients' frailty(direct effects β=0.235,0.287,-0.220;indirect effects β=0.147,0.090,-0.113;all P＜0.001).Conclusion The incidence of frailty in elderly patients with colorectal cancer before surgery is high.Attention should be paid to patients who are elderly,female and have a low level of education.Medical staff can take targeted measures to enhance patients' interocep-tive concentration and stability,so that patients can better monitor and regulate their bodies and emotions,and im-prove their health-promoting decisions and behaviors.At the same time,attention should also be paid to the prob-lem of age discrimination to create a good medical environment for patients.

Objective:To analyze the protective effect of a respiratory syncytial virus (RSV) vaccine based on bacterial outer membrane vesicle (OMV) in mice.Methods:The pre-fusion protein (preF) of RSV was linked to the surface of OMV through the transmembrane protein cytolysin A (ClyA) to form the nanovaccine OMV-preF. The morphological characteristics of OMV and OMV-preF were observed under a transmission electron microscope. OMV-preF was intramuscularly injected into BALB/c mice and the elicited humoral and cellular immune responses were evaluated. The protective effect of OMV-preF was assessed by challenging the immunized mice with RSV Long strain. One-way analysis of variance and Tukey test were used for statistical analysis.Results:The results showed that preF was stably expressed in OMV, and both OMV-preF and OMV exhibited a double-layer vesicle structures under the microscope. OMV-preF could significantly activate the cellular and humoral immune responses in mice, causing a significant increase in CD8 + T cells and CD19 + B cells as well as a significant increase in the serum level of specific IgG. The neutralizing antibodies produced in the immunized mice could significantly inhibit the replication of RSV Long strain in vivo. Conclusions:The nanovaccine OMV-preF can induce high-level humoral and cellular immune responses, and the antibodies produced following immunization can effectively inhibit viral replication. This study provides a new strategy for RSV subunit vaccines.

Objective:To compare the effects of early orthodontic intervention and conventional sequential periodontal-orthodontic treatment to periodontal health in patients with stage Ⅳ periodontitis.Methods:A total of 30 patients with stage Ⅳ periodontitis, who underwent combined periodontal and orthodontic therapies at the Department of Periodontology, the Second Affiliated Hospital of Zhejiang University School of Medicine, from January 2018 to August 2024, were included. Patients who underwent early orthodontic intervention were initiated simultaneously or within one month after supragingival scaling and subgingival root planning ( n=15). While patients in control group accomplished supragingival scaling, subgingival root planning, and corresponding periodontal surgeries to achieve inflammation control before starting orthodontic treatment ( n=15). Periodontal parameters, including clinical attachment loss (CAL), probing depth (PD), and bleeding on probing (+) % [BOP (+) %], were measured at baseline, one year after orthodontic treatment, and at the end of combined periodontal-orthodontic therapy respectively. Improvements in periodontal parameters and differences in tooth loss between the two groups were compared. Results:After receiving combined periodontal-orthodontic treatment, the CAL of the early orthodontic intervention group significantly decreased from (4.39±0.90) mm before treatment to (2.41±0.35) mm at the end of treatment ( t=7.92, P<0.001). Similarly, the PD significantly reduced from (4.20±1.04) mm before treatment to (2.20±0.38) mm at the end of treatment ( t=7.01, P<0.001). The BOP(+)% also showed a significant improvement, decreasing from 89.29% (68.00%, 100.00%) before treatment to 13.04% (7.14%, 17.86%) at the end of treatment ( Z=-3.41, P<0.001). There were no statistically significant differences between the early orthodontic intervention group and control group in terms of baseline mean CAL, mean PD, and BOP(+)% ( t=1.30, P=0.205; t=1.28, P=0.212; Z=0.58, P=0.559). Furthermore, the improvements in CAL and PD between the two groups were not significantly different compared to baseline ( Z=-1.10, P=0.272; Z=-0.93, P=0.351). However, the number of missing teeth was significantly lower in the early orthodontic intervention group than in the control group (χ2=3.96, P=0.047). The duration of combined periodontal-orthodontic treatment in the early orthodontic intervention group was [33.13 (23.37, 36.20) months], which was significantly shorter than that in the control group [37.47 (32.33, 50.90) months] ( Z=2.07, P=0.037). Conclusions:Both early orthodontic intervention and conventional periodontal-orthodontic treatment significantly improved CAL, PD, and BOP(+)% in stage Ⅳ periodontitis patients. Early orthodontic intervention contributed to the preservation of natural teeth and shortened the treatment duration of stage Ⅳ periodontitis.

Objective:To investigate the efficacy and safety of dupilumab in the treatment of elderly patients (≥ 60 years old) with atopic dermatitis (AD), with particular attention paid to rare adverse reactions.Methods:A single-center retrospective analysis was conducted on data collected from 281 elderly AD patients who received the standard regimen of dupilumab at the Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2020 to May 2024. Clinical characteristics such as gender, disease duration, skin lesion manifestations, and itch severity were analyzed. Changes in skin lesions and itch severity, as well as related adverse events were recorded during the follow-up period of 0 - 16 weeks. The efficacy and safety of dupilumab in the treatment of elderly AD patients were evaluated.Results:Among the 281 elderly AD patients, 214 were males (76.16%) and 67 were females (23.84%), with the age being 71.13 ± 7.91 years and the age at onset being 59.92 ± 15.72 years. The disease duration ( M[ IQR]) was 5.00 (13.00) years. After standard-regimen dupilumab treatment, the improvement rates of clinical outcome indicators SCORing Atopic Dermatitis (SCORAD) and pruritus numerical rating scale (NRS) scores gradually increased. At week 16, the improvement rates of SCORAD and NRS scores ( M[ IQR]) reached the maxima of 72.37% (23.89%) and 75.00% (29.72%), respectively. The overall incidence of adverse events was relatively low, with only 16 patients (6.05%) reporting adverse events. Common adverse reactions such as conjunctivitis (2 cases, 0.71%) and facial erythema (1 case, 0.36%) were mild and well-tolerated. Phenotype switching occurred in 10 cases (3.56%) . Conclusion:Dupilumab was an effective and safe treatment for elderly AD, but phenotype switching may occur.