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 explore the construction of a machine learning model for the diagnosis of traditional Chinese medicine （TCM） syndromes in chronic cough and the optimization of this model using the Voting ensemble algorithm. MethodsA retrospective analysis was conducted using clinical data from 921 patients with chronic cough treated at the Respiratory Department of Dongfang Hospital， Beijing University of Chinese Medicine. After standardized processing， 84 clinical features were extracted to determine TCM syndrome types. A specialized dataset for TCM syndrome diagnosis in chronic cough was formed by selecting syndrome types with more than 50 cases. The synthetic minority over-sampling technique （SMOTE） was employed to balance the dataset. Four base models， logistic regression （LR）， decision tree （dt）， multilayer perceptron （MLP）， and Bagging， were constructed and integrated using a hard voting strategy to form a Voting ensemble model. Model performance was evaluated using accuracy， recall， precision， F1-score， receiver operating characteristic （ROC） curve， area under the curve （AUC）， and confusion matrix. ResultsAmong the 921 cases， six syndrome types had over 50 cases each， phlegm-heat obstructing the lung （294 cases）， wind pathogen latent in the lung （103 cases）， cold-phlegm obstructing the lung （102 cases）， damp-heat stagnating in the lung （64 cases）， lung yang deficiency （54 cases）， and phlegm-damp obstructing the lung （53 cases）， yielding a total of 670 cases in the specialized dataset. High-frequency symptoms among these patients included cough， expectoration， odor-induced cough， throat itchiness， itch-induced cough， and cough triggered by cold wind. Among the four base models， the MLP model showed the best diagnostic performance （test accuracy： 0.9104； AUC： 0.9828）. Compared with the base models， the Voting ensemble model achieved superior performance with an accuracy of 0.9289 on the training set and 0.9253 on the test set， showing a minimal overfitting gap of 0.0036. It also achieved the highest AUC （0.9836） in the test set， outperforming all base models. The model exhi-bited especially strong diagnostic performance for damp-heat stagnating in the lung （AUC： 0.9984） and wind pathogen latent in the lung （AUC： 0.9970）. ConclusionThe Voting ensemble algorithm effectively integrates the strengths of multiple machine learning models， resulting in an optimized diagnostic model for TCM syndromes in chronic cough with high accuracy and enhanced generalization ability.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

OBJECTIVE: To investigate the clinical effect of transposition of gracilis muscle flap in repairing urethral perineal fistula after Miles operation. METHODS: The clinical data of 3 patients with urethral perineal fistula treated in the Second Affiliated Hospital of Zhejiang University from September 2023 to November 2024 were analyzed retrospectively. All patients were male, aged from 59 to 68 years (mean 63 years). All patients underwent Miles operation because of low rectal cancer. Urethral perineal fistula occurred after 2 months to 13 years of the operation. The underlying comorbidities included diabetes (2/3), preoperative chemoradiotherapy (1/3), and chemotherapy alone (1/3). The endourethral fistula was located in the apical and membranous part of the prostate, with a diameter of 1.5-2.0 cm and a mean of 1.7 cm. Suprapubic cystostomy was performed one month before operation. In all 3 cases, perineal inverted "Y" incision was taken under general anesthesia to expose urethral fistula, cut off necrotic tissue and suture urethral fistula. The gracilis muscle of the right thigh was taken and turned through the perineal subcutaneous tunnel. and 6 stitches were suture at the urethral fistula. RESULTS: The operations of all 3 patients were completed successfully. The follow-up period ranged from 2 months to 12 months, with an average of 8 months. There was no case of urinary incontinence after removal of catheter 3 weeks after operation. In two patients, urethrography was reviewed 1 month after surgery to show no fistula residue and urethral stenosis, and the fistula was removed. In one patient with a history of radiotherapy, urethrography was reviewed 1 month after surgery to show a small amount of contrast overflow around the urethra, and urethrography was reviewed again 3 months after surgery to show no contrast overflow around the urethra. All the 3 patients had no disturbance of movement of the right lower limb, and the pain of different degrees of thigh incision was acceptable and basically relieved half a month after operation. CONCLUSION Gracilis muscle flap is one of the effective methods for repairing urethral perineal fistula after Miles operation，which has a precise surgical result and few complications.
Humans ; Male ; Middle Aged ; Aged ; Gracilis Muscle/transplantation* ; Urinary Fistula/surgery* ; Retrospective Studies ; Surgical Flaps ; Perineum/surgery* ; Rectal Neoplasms/surgery* ; Postoperative Complications/surgery* ; Urethral Diseases/surgery* ; Urethra/surgery*

Objective:To explore the efficacy and safety of domestic bortezomib in combination with lenalidomide and dexamethasone in the treatment of newly diagnosed multiple myeloma (NDMM) .Methods:This multicenter, prospective, single-arm clinical study included 126 patients with NDMM admitted to seven hospitals between December 2019 and January 2022. All patients received domestic bortezomib in combination with lenalidomide and dexamethasone (BLD regimen), and the efficacy, prognostic factors, and safety were analyzed.Results:Among the 126 patients with NDMM, 118 completed four cycles of treatment, with an overall response rate (ORR) of 93.22% (110/118) and a ≥very good partial response (VGPR) rate of 68.64% (81/118). Ultimately, 114 patients completed at least eight cycles of treatment, with an ORR of 92.98% (106/114) and a ≥VGPR rate of 77.19% (88/114). Eighteen patients underwent autologous hematopoietic stem cell transplantation after completing 6-8 cycles of the BLD regimen, with an ORR of 100% (18/18) and a ≥VGPR rate of 88.9% (16/18). The proportion of patients achieving ≥VGPR increased with the treatment duration, and factors such as staging and age did not significantly affect efficacy. Single-factor analysis showed that R2-ISS stage Ⅲ/Ⅳ, blood calcium >2.27 mmol/L, and failure to achieve VGPR after six cycles were adverse prognostic factors for progression-free survival (PFS) ( P<0.05), whereas failure to achieve VGPR after six cycles was an adverse prognostic factor for overall survival (OS) ( P<0.001). Multifactor analysis demonstrated that failure to achieve VGPR after six cycles is an independent adverse prognostic factor for PFS ( P=0.002). The incidence of hematologic adverse reactions was 16.7% (19/114), and nonhematologic adverse reactions were mainly mild to moderate, with no significant cardiac or renal adverse reactions observed. Conclusion:The BLD regimen is effective in treating NDMM, in which patients with high-risk genetic features are still achieving a high ≥VGPR rate, and the overall safety is good.

AIM:To explore the molecular mechanism of Tiaopi Chengqi decoction (TpCqD) improving hyperthermia and high-protein food-induced hyperphagia mice based on transcriptomics. METHODS:C57 mice were randomly divided into a control group, model group, low-dose TpCqD group, high-dose TpCqD group, and domperidone group. The general condition of the experimental mice was observed and the average food intake was counted, and the rate of gastric emptying and intestinal propulsion was determined for each group of mice. H&E staining was used to observe pathological changes in gastric tissue. PAS staining was used to observe glycogen changes in gastric tissue. Pepsin activity was determined by colorimetry. pH value of gastric contents was measured by acid-base titration. Transcriptome sequencing was used to analyze the differential genes in gastric tissue, a volcano map and a cluster heat map were made for the differential genes, and KEGG was used to analyze the signal pathway enrichment of the differential genes. RT-qPCR verified the differential genes obtained by screening. RESULTS:After treatment with TpCqD, the body weight and average food intake of mice with food accumulation increased (P<0.05), and the intestinal propulsion rate and gastric emptying speed of mice with food accumulation accelerated (P<0.05). TpCqD could protect gastric tissue structure and glycogen degradation, increase pepsin activity (P<0.05), and reduce gastric content pH (P<0.05). Transcriptome results showed that TpCqD could regulate the expression of Acox2 and cilp2, regulate fat digestion and absorption, protein digestion and absorption, and pancreatic secretion signals. RT-qPCR showed that compare with model group, TpCqD up-regulated Acox2 (P<0.05) and down-regulated the mRNA level of cilp2 (P<0.05). CONCLUSION:TpCqD ameliorated digestive dysfunction in mice with high-calorie and high-protein diets leading to food accumulation involving the regulation of the fat and sugar metabolism genes Acox2 and cilp2, and pancreatic secretory signaling.

Objective To investigate the clinical features and genetic characteristics of patients with late-onset Pompe disease(LOPD).Methods A total of 13 patients diagnosed with LOPD in the First Affilia-ted Hospital of Zhejiang University School of Medicine from September 2020 to December 2023 were selected,and all patients were subjected to clinical investigation,GAA activity detection and GAA gene testing.Results Among the 13 patients,7 were males and 6 were females;5 were family patients and 8 were sporadic patients;and the median age of onset was 17 years(8-52 years),the median age of presentation was 24 years(10-52 years),and the median age of diagnosis was 31 years(14-58 years).In terms of the first symptoms,10 pa-tients presented with limb weakness and 3 patients presented with dyspnea.The average serum creatine kinase level was 552 U/L(55-1084 U/L),and the serum creatine kinase level was normal in one patient.All pa-tients had scoliosis and different degrees of restrictive ventilatory dysfunction.Neuroelectrophysiological exami-nations of 9 patients showed myogenic damage,and 8 of them had muscle tonic discharge.The mean value of GAA activity was 0.3 μmol/(L·h)[0.17-0.5 μmol/(L·h)].A total of 13 mutations were detected in GAA gene,and the most common mutation was c.2238G＞C(p.W746C).There were five new variant sites:c.543del(p.F181Lfs*40),c.839_840insCC(p.R281Pfs*34),c.1800_1823del(p.S601_R608del),c.2296T＞C(p.Y766H)and c.995C＞A(p.S332*).Conclusions LOPD is a rare disease that tends to delay diagnosis.Proximal limb weakness,decreased respiratory function,mild-to-moderate elevation of creatine kinase,scoliosis,and clinical inferior tonic discharge on electromyography are high-risk images of LOPD.c.2238G＞C(p.W746C)is a hotspot mutation,and the discovery of five new mutations enriches the GAA gene mutations lineage.

ObjectiveTo explore the research status and hot spots of virtual reality in the field of stroke rehabilitation. MethodsThe literature related to the application of virtual reality technology in stroke rehabilitation was retrieved in CNKI and Web of Science core collection from establishiment to August, 2024. The knowledge map of authors, institutions and keywords was drawn by Citespace 6.2.R7. ResultsA total of 485 papers were retreived, including 201 in Chinese and 284 in English. The number of articles published in both Chinese and English was on the rise. Qu Yun was the Chinese author with the most articles, and Rocco Salvatore Calabro was the English author. The Third Affiliated Hospital of Sun Yat-Sen University and IRCCS Bonino Pulejo published the most papers respectively. The results of keyword co-occurrence and clustering were consistent in the Chinese and English keywords, mainly included hemiplegia, balance function, upper limb function and cognitive function. The keywords with high bursting intensity in Chinese included motor function, cognitive function and upper limb function, while those with high bursting intensity in English included upper limb, cognitive impairment and environment. The hot spots in this field focused on the virtual reality technology for stroke patients' motor function rehabilitation, cognitive function rehabilitation, limb function rehabilitation and virtual reality technology combined with conventional treatment. ConclusionVirtual reality technology, as a simulation information technology, has been widely applied in the fields of motor function rehabilitation, cognitive function rehabilitation and limb function rehabilitation for stroke patients. The combination of virtual reality technology with conventional rehabilitation therapy could enhance the functional level and activities of daily living. More researches may focus on conjunctions of virtual reality technology with new technologies such as digital therapeutics and brain-computer interfaces, to improve the gait and upper limb functions of stroke patients.

Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

The aging has become the focus of social attention. It is of great significance to improve the physical function of the elderly and improve their frailty condition for the realization of healthy aging. Exercise intervention is the main intervention method to improve the frailty of the elderly. This paper reviews the exercise intervention for the aged with frailty from the aspects of the definition and performance of frailty of the elderly, the implementation of exercise intervention, and the effect of exercise intervention, in order to provide reference for the aged to formulate exercise programs.