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.

Objective:To screen differentially expressed genes in the retinas of mice with experimental autoimmune uveitis (EAU) through transcriptome sequencing.Methods:Twenty 8-week-old SPF grade male C57BL/6J mice were randomly divided into EAU group and control group by random number table method, with 10 mice in each group.In the EAU group, an emulsion of interphotoreceptor retinoid-binding protein 1-20 and complete Freund adjuvant was injected subcutaneously into the inner side of the hind limbs and intravenously into the tail vein of the mice, and pertussis toxin was injected intraperitoneally to establish the EAU model.In the control group, mice were subcutaneously injected with the corresponding volume of phosphate buffer solution.On the 21st day after model establishment, the anterior segment inflammation of the mouse eyes was examined using a slit-lamp microscope.Retinal blood vessels were observed by fundus photography and clinical inflammation was scored.Hematoxylin-eosin staining was used to observe the morphological changes in the retinal tissues of the two groups.Retinal tissues were collected from two groups of mice.RNA was extracted and cDNA libraries were constructed for transcriptome sequencing.The clusterProfiler package in R programming language was used to screen for differentially expressed genes in EAU, and to conduct GO and KEGG enrichment analyses.The expression of core differentially expressed genes in the retinal tissues was then verified using real-time fluorescent quantitative PCR.The breeding and use of experimental animals were in compliance with the relevant regulations of the Animal Ethics Committee of Anhui Medical University.The study protocol was approved by the Ethics Committee of Anhui Medical University (No.LLSC20221208).Results:On the 21st day after model establishment, the clinical score of the EAU group was 2.83±0.94, significantly higher than 1.89±0.93 of the control group, and the difference was statistically significant ( t=2.290, P<0.05). The retinal blood vessels of mice in the EAU group showed tortuosity and dilation.Histopathological examination revealed a large number of inflammatory cell infiltrations in the retina, indicating successful establishment of the EAU mouse model.Transcriptome sequencing of the mouse retinal tissues identified a total of 32 473 genes, and 154 differentially expressed genes were screened out.Among them, 79 genes were up-regulated with Gm38574, Tmem81, Ptpn7 being top three and 75 genes were down-regulated with Gm19802, Fga, Cyp3a11 being top three.GO enrichment analysis showed that the differentially expressed genes were mostly related to immune response and cytokine action.KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly enriched in the Toll-like pathway and cytokine signaling pathway.Compared with the control group, the relative expression levels of Gm38574, Tmem81, and Ptpn7 in the retinal tissues of the EAU group were up-regulated, while the expression levels of Gm19802, Fga, and Cyp3a11 were down-regulated, and the differences were statistically significant ( t=9.755, 5.358, 6.289, 4.312, 6.577, 6.118; all P<0.05). Conclusions:There are significant differences in the key genes Gm38574, Tmem81, Ptpn7, Gm19802, Fga, and Cyp3a11 in the retinal tissues of EAU mice, mainly corelated with the cytokine interaction pathway, Toll-like receptor signaling pathway.

Objective To develop a toolkit suitable for assisting community health institutions in the early identification and inter-vention of mild cognitive impairment(MCI)among older adults.Methods A literature review was conducted to construct a draft of the identification and intervention toolkit.Tools with an expert approval rate above 70%were included after expert consultation.The final version of the toolkit was developed by integrating these tools with officially recommended tools in China.Results The expert consultation yielded an authority coefficient of 0.84.The finalized toolkit included the assessment tools of Mini-Mental State Examination,Montreal Cognitive Assessment,General Practitioner Assessment of Cognition,Cognitive Abilities Screening Instrument and Clock Drawing Test,and 18 intervention measures in-cluding pharmacological treatment,cognitive training and psychological interventions,etc.Conclusion The MCI Identification-Intervention Toolkit may serve as a reference for guiding the identification and inter-vention of MCI among older adults for community health institutions.

The advent of bruton tyrosine kinase inhibitors (BTKi) has offered more therapeutic choices for patients with B-cell malignancies. However, with its widespread application in recent years, the use of BTKi increases the risk of severe infections in patients. Here, we report three cases of B-cell malignancies, including one case of chronic lymphocytic leukemia and two cases of diffuse large B-cell lymphoma. During treatment with BTKi zanubrutinib, different degrees of invasive fungal disease (IFD) of the central nervous system occurred in these patients. All patients fully recovered following antifungal therapy. With a median follow-up of 35 months, all patients remained in a continuous remission state, and none of them had a recurrence of IFD.

Objective:To screen differentially expressed genes in the retinas of mice with experimental autoimmune uveitis (EAU) through transcriptome sequencing.Methods:Twenty 8-week-old SPF grade male C57BL/6J mice were randomly divided into EAU group and control group by random number table method, with 10 mice in each group.In the EAU group, an emulsion of interphotoreceptor retinoid-binding protein 1-20 and complete Freund adjuvant was injected subcutaneously into the inner side of the hind limbs and intravenously into the tail vein of the mice, and pertussis toxin was injected intraperitoneally to establish the EAU model.In the control group, mice were subcutaneously injected with the corresponding volume of phosphate buffer solution.On the 21st day after model establishment, the anterior segment inflammation of the mouse eyes was examined using a slit-lamp microscope.Retinal blood vessels were observed by fundus photography and clinical inflammation was scored.Hematoxylin-eosin staining was used to observe the morphological changes in the retinal tissues of the two groups.Retinal tissues were collected from two groups of mice.RNA was extracted and cDNA libraries were constructed for transcriptome sequencing.The clusterProfiler package in R programming language was used to screen for differentially expressed genes in EAU, and to conduct GO and KEGG enrichment analyses.The expression of core differentially expressed genes in the retinal tissues was then verified using real-time fluorescent quantitative PCR.The breeding and use of experimental animals were in compliance with the relevant regulations of the Animal Ethics Committee of Anhui Medical University.The study protocol was approved by the Ethics Committee of Anhui Medical University (No.LLSC20221208).Results:On the 21st day after model establishment, the clinical score of the EAU group was 2.83±0.94, significantly higher than 1.89±0.93 of the control group, and the difference was statistically significant ( t=2.290, P<0.05). The retinal blood vessels of mice in the EAU group showed tortuosity and dilation.Histopathological examination revealed a large number of inflammatory cell infiltrations in the retina, indicating successful establishment of the EAU mouse model.Transcriptome sequencing of the mouse retinal tissues identified a total of 32 473 genes, and 154 differentially expressed genes were screened out.Among them, 79 genes were up-regulated with Gm38574, Tmem81, Ptpn7 being top three and 75 genes were down-regulated with Gm19802, Fga, Cyp3a11 being top three.GO enrichment analysis showed that the differentially expressed genes were mostly related to immune response and cytokine action.KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly enriched in the Toll-like pathway and cytokine signaling pathway.Compared with the control group, the relative expression levels of Gm38574, Tmem81, and Ptpn7 in the retinal tissues of the EAU group were up-regulated, while the expression levels of Gm19802, Fga, and Cyp3a11 were down-regulated, and the differences were statistically significant ( t=9.755, 5.358, 6.289, 4.312, 6.577, 6.118; all P<0.05). Conclusions:There are significant differences in the key genes Gm38574, Tmem81, Ptpn7, Gm19802, Fga, and Cyp3a11 in the retinal tissues of EAU mice, mainly corelated with the cytokine interaction pathway, Toll-like receptor signaling pathway.

To summarize the first aid and nursing experience of a patient with enterobacter aerogenes infection complicated by septic shock after oral floor cancer surgery. The patient was admitted to the Department of Oral and Maxillofacial Surgery at the Second Affiliated Hospital of Zhejiang University School of Medicine in August 2023. This patient who developed enterobacter aerogenes infection complicated by septic shock after surgery for oral floor cancer was treated with a comprehensive approach. In response to the patient's rapid onset, rapid progression of the condition, and critical situation, the following key points of nursing care were formulated and implemented: this included the rapid identification of septic shock, precise execution of emergency interventions; effectiveion of airway management, active prevention of airway obstruction; implement refined nursing care, awareness of leukocyte crisis, preventing secondary infection; establishing blood alert mechanism, implementing monitoring and protection management; implementing phased progressive nutritional support, improveing the nutritional status of patients. After 21 days of intensive treatment and nursing care, the patient made a full recovery and was discharged. A 6-month follow-up revealed that the patient remained in stable condition with no recurrence.

Objective:To evaluate the clinical efficacy of the modified medial gastrocnemius myocutaneous flap (MGMF) with extended anterior, posterior and (or) inferior boundaries.Methods:From January 2002 to September 2022, modified MGMFs were applied onto 33 patients who received reconstructive surgery for soft-tissue defects around knee or in calf, in the Department of Orthopaedics, the Second Xiangya Hospital of Central South University. The size of defects ranged from 10 cm×4 cm to 22 cm×12 cm, and the flap size ranged from 15 cm×6 cm to 28 cm×14 cm. Twenty-five patients had the complication of chronic osteomyelitis. The boundaries of a modified MGMF were as follows: the anterior boundary was the anterior border of the tibia, where the posterior boundary at 3.0 cm lateral to the posterior midline, the proximal boundary at the popliteal fossa crease, and the distal boundary at the plane 2.0 cm above the tip of medial malleolus. The anterior edge of the modified MGMF was designed running along the medial edge of the defect and its curved extension line. Pretibial skin was equally divided into 9 zones, with the 1st to 9th zones from proximal to distal in sequence. Postoperative routine anti-infection treatment was offered. All patients were included in the postoperative follow-up through outpatient visits, telephone or WeChat interviews. Flap viability and wound healing in both donor and recipient sites were evaluated. Function of the affected limb was assessed using the evaluation criteria established by Punor et al.Results:All patients were included in the follow-up for 1 to 169 (median duration: 9)months. The 33 modified MGMFs included MGMFs with extended boundary of anterior ( n=18), inferior ( n=5), anterior combined with inferior ( n=6), posterior combined with anterior ( n=2), and posterior combined with inferior ( n=2) boundaries. Twenty-nine (87.9%) flaps survived completely. Partial necrosis occurred in 4 flaps(12.1%)(2 flaps with extended anterior boundary and 2 flaps with extended inferior boundary). The anterior margins of 26 flaps (78.7%) with extended anterior boundary alone or in combination with extended inferior or posterior boundary exceeded the medial edge of the tibia by 1.0-4.5 (mean, 2.1) cm, and 3 of them reached the anterior edge of tibia. Fourteen (42.4%) modified MGMFs were used to reconstruct the defects involving 1/3 of distal calf, and the distal ends of these defects were located in the 7th ( n=8) or 8th ( n= 6) zone. All the skin grafts in the donor sites survived. During follow-up, 31 patients (93.9%) showed no sign of infection, and 2 patients (6.1%) who had recurrence of chronic osteomyelitis. Functions of the affected limbs were excellent ( n=25), good ( n=6) and fair ( n=2) by Punor et al. Conclusion:Modified MGMF with extended anterior, posterior and (or) inferior boundaries is clinically feasible. It offers advantages of easier design and operation. It can be used to reconstruct a more distal, wider and larger defect as well as broadens the application of the MGMF.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Objective To explore the the detection of MMP-2,-7,-9,and-12 enzymatic activity using the CEACAM1-derived fluorescent peptide substrate Site 84,investigating the application of substrate Site 84 to distinguishing between MMP-2 and MMP-9 in the gelatinase spectrum of MMPs.Methods The fluorescent enzymatic method was employed to observe the detection of MMP-2,-7,-9,and-12 enzymatic activity using substrate Site 84;further observations were made on the sensitivity and specificity of substrate Site 84 to enzymatic activity of MMP-2 and MMP-9 within the gelatinase spectrum;the kinetic parameters(Km and Kcat)of the enzymatic reaction between substrate Site 84 and MMP-2 were obtained.Results Using Site 84 as a substrate,enzymic kinetics curves for MMP-12,-7,-2 were obtained,but no enzymatic activity curve for MMP-9 was observed.Furthermore,Site 84 specifically detected the enzymatic activity of MMP-2 within the gelatinase spectrum,capable of detecting low concentration(0.6 μM)of MMP-2 enzymatic activity,but no obvious enzymatic reaction was observed for high concentration(6 μM)of MMP-9;the kinetics parameters for the enzymatic reaction between Site 84 and MMP-2 were Km=315 μM,Kcat/Km=2 565/MS.Conclusion The CEACAM1-derived substrate Site 84 serves as a novel fluorescent peptide substrate,enabling the acquisition of enzymatic activity curves for MMP-12,-7 and-2,and specifically detecting the enzymatic activity of MMP-2 within the MMP gelatinase spectrum.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique