This paper summarized the experience of professor WANG Yongyan in differentiating and treating vascular cognitive impairment （VCI）. It is believed that the core etiology and pathogenesis of VCI are deficient qi retention and stagnation， and toxin damaging brain collaterals. The essence lies in depletion of essence and qi， and malnutrition of brain collaterals as the root cause， while phlegm， turbidity， stasis， and heat blocking brain collaterals act as the branch aspects. It reveals the pathogenesis essence of VCI as stagnation caused by deficiency and qi stagnation transforming into excess， internal generation of toxin and collateral injury. The overall therapeutic principle is to tonify deficiency， move stagnation， resolve toxin， and unblock the collaterals， guided by the three core treatment methods of nourishing， unblocking， and clearing. Clinically， according to the different characteristics of the plateau phase， fluctuation phase， and decline phase， treatment methods including replenishing qi and blood， tonifying the kidney and supplementing essence； promoting sanjiao （三焦） circulation and activating blood to dredge collaterals； clearing heat and resolving toxin， eliminating phlegm and reducing turbidity are respectively adopted. This provides clinical guidance for the treatment of VCI in traditional Chinese medicine.

BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.

Objective Exploring the application effect of fragmented resistance exercise in the exercise rehabili-tation of elderly patients with chronic obstructive pulmonary disease,providing references for improving their quality of life.Methods From October to December 2024,96 elderly patients with chronic obstructive pulmonary disease admitted to a tertiary hospital in Pingdingshan city were conveniently selected as the research subjects.They were randomly divided into an experimental group and a control group(all n=48)using a random number table method.The experimental group received a fragmented resistance exercise program on the basis of routine pulmonary reha-bilitation,while the control group received routine pulmonary rehabilitation nursing care for a duration of 3 months.The lung function,exercise endurance,quality of life,and exercise compliance were compared between the 2 groups before and after intervention.Results The experimental group ultimately included 46 cases,while the control group ultimately included 47 cases.The lung function of the experimental group was better than that of the control group after 3 months of intervention(P＜0.05),and the exercise compliance scores of the experimental group were high-er than those of the control group after 1 and 3 months of intervention(P＜0.001).Repeated measures ANOVA showed that there was an interaction effect(P＜0.05)in the comparison of exercise endurance and quality of life between the 2 groups.Simple effects analysis showed that the experimental group had better exercise endurance after 3 months of intervention than the control group(P＜0.05),and better quality of life after 1 and 3 months of intervention than the control group(P＜0.05).Conclusion Fragmented resistance exercise can effectively improve lung function,enhance exercise endurance and compliance,and improve quality of life in elderly patients with chronic obstructive pul-monary disease.

Objective:To observe the pregnancy outcomes of patients with unexplained recurrent spontaneous abortion (URSA) after interventional treatment or expectant treatment.Methods:This prospective study followed up 398 patients with recurrent spontaneous abortion from March 2017 to September 2022 in seven hospitals. Among them, 267 patients were diagnosed with URSA, including 124 patients who were initially diagnosed in the interventional treatment hospital and 143 patients who were initially diagnosed in the expectant treatment hospital. All URSA patients were followed up for 33 months. Ongoing pregnancy rates were observed as main outcome indicators.Results:A total of 127 patients became pregnant, and 107 of them had sustained pregnancies, the ongoing pregnancy rate was 84.25% (107/127). The ongoing pregnancy rate was 86.11% (31/36) in the interventional treatment group and 83.52% (76/91) in the expectant treatment group, with no significant difference ( P>0.05). During the follow-up, the ongoing pregnancy rates in the interventional treatment hospital and the expectant treatment hospital were 75.71% (53/70) and 94.74% (54/57), respectively, with a significant difference ( P<0.05). The ongoing pregnancy rate after interventional treatment in the interventional treatment hospital was 82.76% (24/29), which was similar to the 94.00% (47/50) after expectant treatment in the expectant treatment hospital ( P>0.05). Conclusion:The ongoing pregnancy rate of interventional treatment for URSA patients has not been significantly improved, suggesting that it may not be necessary to carry out this treatment.

Hepatitis B virus (HBV) infection is a major global public health problem. There will be about 257 million chronic HBV-infected patients worldwide, according to the World Health Organization's estimation by 2025. Currently, the main drugs for the treatment of chronic HBV infection are nucleos(t)ide analogues and pegylated interferon (PEG-IFN). However, previous research results show that whether it is nucleos(t)ide analogues and PEG-IFN-α monotherapy or combination therapy, or sequential combination therapy, the rate of hepatitis B surface antigen seroconversion in patients is low, and there is still a high risk of disease progression after a certain course of antiviral treatment. Therefore, to achieve the ambitious target of "eliminating viral hepatitis by 2030" set by the World Health Organization and help more hepatitis B patients achieve functional cure, a large number of new drugs have been developed and entered clinical trials. This paper summarizes and reviews the types, safety, and efficacy of new drugs to further promote advancements in the field of treatment of chronic HBV infection.

Objective:To evaluate the value of deep-inhaled breath-hold (DIBH)-30s scanning with total-body PET/CT under half-dose injection mode in improving the poor alignment of thoracic and upper abdominal tumors.Methods:Forty-six patients (28 males, 18 females, age (57.3±11.4) years) who underwent half-dose 18F-FDG total-body DIBH-30s PET/CT examination because of suspect or confirmed thoracic and upper abdominal tumors in Sun Yat-Sen University Cancer Center between October 2022 and February 2023 were analyzed retrospectively. SUV, standard deviation (SD) and signal-to-noise ratio (SNR) of the liver and mediastinal blood pool in free breath (FB)-8min, FB-30s and DIBH-30s PET images were measured; SUV of lesions, metabolic tumor volume (MTV) and tumor-to-background ratio (TBR) in DIBH-30s and FB-8min images were also measured; maximum diameter of contraposition offset and offset rate in coronal, transverse and sagittal directions of lesions in DIBH-30s and FB-8min images were calculated. Five-point Likert scale was used to score the overall image quality, image noise level and diagnostic confidence of fused images. Kruskal-Wallis rank sum test, Nemenyi test or Mann-Whitney U test was used to compare the parameters of different groups. Results:Among the 46 patients, 38 successfully completed breath-holding collection, and 80 lesions were detected, including 37 in the lungs and 43 in the livers. The liver SUV max (3.40(3.15, 3.63), 3.44(3.06, 3.70)) and SD (0.36(0.32, 0.41), 0.35(0.30, 0.40)) in DIBH-30s group and FB-30s group were higher than those (SUV max: 2.73(2.45, 2.92), SD: 0.15(0.13, 0.17)) in FB-8min group ( H values: 49.79, 85.27, χ2 values: 3.26-3.65, all P<0.001). The SUV max and the SD of mediastinal blood pool in DIBH-30s group and FB-30s group were also higher ( H values: 9.31, 59.73, χ2 values: 2.13-2.75, all P<0.01), while SNR liver and SNR med in those 2 groups were lower ( H values: 87.90, 54.11, χ2 values: 3.36-5.47, all P<0.001). The image noise scores of DIBH-30s group and FB-30s group were lower than the score of FB-8min group (3(3, 3) vs 3(3, 4) vs 5(5, 5); H=93.02, χ2 values: 2.13, 2.23, all P<0.001). The overall image quality score and diagnostic confidence score of DIBH-30s group were higher than those of FB-30s group and FB-8min group ( H values: 70.13, 24.22, χ2 values: 2.11-2.48, all P<0.001). The SUV and TBR of lesions in DIBH-30s group were higher than those of FB-8min group ( Z values: from -3.82 to -2.44, all P<0.05), while the MTV, contraposition offset and offset rate were lower than those of FB-8min group ( Z values: from -6.20 to -3.18, all P<0.001). Conclusions:DIBH-30s scanning with total-body PET/CT can make the focus alignment more accurate, which is suitable for short-time collection or low drug administration activity. It has a unique value in improving the poor focus alignment of chest and upper abdomen tumors.

Dent disease is a rare X-linked recessive inherited renal tubular disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and other clinical features, and can lead to progressive renal failure. It is primarily caused by mutations in the CLCN5 gene. This article reports the case of a 10-year-old male patient of Chinese descent who was incidentally found to have asymptomatic proteinuria during a routine health examination. Comprehensive biochemical testing and clinical evaluation revealed significant LMWP and hypercalciuria, while renal biopsy showed mesangial cell and matrix proliferation. Whole exome sequencing identified a novel deletion mutation in the CLCN5 gene (NM_001127899.4, c.1158delC, p.F387Lfs*42) causing a frameshift and premature termination, which is likely to disrupt its role in chloride/hydrogen ion exchange and endosomal acidification. Bioinformatic analysis indicated the variant is pathogenic. Genetic testing plays an important role in diagnosing rare kidney diseases. Early identification of pathogenic mutations is essential for facilitating timely intervention and appropriate management, potentially enhancing patient outcomes. This report expands the CLCN5 mutation spectrum and contributes to understanding the genetic and molecular mechanisms of Dent disease.
Humans ; Chloride Channels/genetics* ; Dent Disease/genetics* ; Male ; Child ; Computational Biology ; Mutation ; Proteinuria/genetics* ; Hypercalciuria/genetics*

Objective Currently, there is no commercially available quantitative detection kit for the main Felis domestic allergen (Fel d 1) in China. To establish a rapid detection method for Fel d 1, this study aims to prepare monoclonal antibodies against Fel d 1 protein. Methods The codon preference of Escherichia coli was utilized to optimize and synthesize the Fel d 1 gene. The prokaryotic expression plasmid pET-28a-Fel d 1 was constructed and used to express and purify the recombinant Fel d 1 protein. Subsequently, the recombinant protein was immunized into BALB/c mice and monoclonal antibodies (mAbs) were prepared by the hybridoma technique. An indirect ELISA was established using the recombinant Fel d 1 as the coating antigen, and hybridoma cell lines were screened for positive clones. The specificity and antigenic epitopes of the mAbs were confirmed by Western blot analysis. Finally, the selected hybridoma cells were injected into the peritoneal cavities of BALB/c mice for large-scale monoclonal antibody production. Results The recombinant plasmid pET-28a-Fel d 1 was successfully constructed, and soluble Fel d 1 protein was obtained after optimizing the expression conditions. Western blot and antibody titer assays confirmed the successful isolation of two hybridoma cell lines, 7D11 and 5H4, which stably secreted mAbs specific to Fel d 1. Antibody characterization revealed that the 5H4 mAb was of the IgG2a subtype and could recognize the amino acid region 105-163 of Fel d 1, while the 7D11 mAb was the IgG1 subtype and could recognize the amino acid region 1-59. Conclusion The high-purity recombinant Fel d 1 protein produced in this study provides a promising alternative for clinical immunotherapy of cat allergies. Furthermore, the monoclonal antibody prepared in this experiment lays a material foundation for the in-depth study of the biological function of Fel d 1 and the development of ELISA detection.
Animals ; Antibodies, Monoclonal/biosynthesis* ; Mice, Inbred BALB C ; Cats ; Mice ; Allergens/genetics* ; Glycoproteins/genetics* ; Enzyme-Linked Immunosorbent Assay ; Hybridomas/immunology* ; Recombinant Proteins/genetics* ; Female ; Antibody Specificity

Objective:To evaluate the feasibility of training physicians from secondary comprehensive hospitals in the clinical assessment of brain death and to provide recommendations for nationwide implementation.Methods:This prospective cohort study enrolled physicians who completed standardized training in clinical brain death determination at five pilot hospitals between June and December 2023. Participants were from internal medicine, neurology, critical care, emergency, or anesthesiology departments of secondary comprehensive hospitals and had ≥5 years of clinical experience. Organ donation coordinators and surgeons involved in organ donation or transplantation were excluded. The training program comprised four modules: didactic lectures, bedside demonstrations, simulation-based practice, and written theoretical assessment with review. The theoretical assessment was considered qualified if the score was 60 or above. Participants were categorized into ≥80 and <80 groups based on assessment scores. Between-group comparisons were conducted using rank-sum or chi-square tests.Results:A total of 191 physicians from 74 secondary comprehensive hospitals were enrolled. Most held a bachelor's degree [89.5%(171/191)] and had intermediate [47.1%(90/191)] or associate senior [36.1%(69/191)] professional titles; [59.7%(114/191)] were from non-neurology specialties. The overall pass rate was 99.5% (190/191), with a mean score of 82.4±7.1. Compared with those scoring<80 (56 participants), physicians scoring ≥80 (135 participants) differed significantly by professional title, province, and department ( P=0.014, 0.019 and 0.039). The proportion scoring<80 was higher among junior/intermediate versus senior titles [38.0%(41/108) vs 18.1%(15/83), P=0.003), and among non-neurology/critical care departments (emergency, internal medicine, anesthesiology) versus neurology/critical care [39.7%(31/78) vs 22.1%(25/113), P=0.009]. Only 2.09%(4/191) achieved a perfect score. Across all test items, the overall error rate was 14.99%(700/4 670). The five knowledge points with the highest error rates were mistriggering of mechanical ventilation [96.97%(32/33)], corneal reflex [42.25%(30/71)], spinal reflexes [24.25%(65/268)], documentation of the determination [21.21%(7/33)], and the apnea test procedure [20.73%(57/275)]. Conclusions:The pilot hospitals can effectively deliver clinical training for brain death determination, supporting nationwide promotion. However, physicians' theoretical grounding in neurology at secondary comprehensive hospitals appears relatively weak. Training curricula should be optimized to further improve training quality.

Background:Acute pancreatitis(AP)is a common disease of the digestive system,among which severe acute pancreatitis(SAP)has a high mortality rate.Finding more accurate and convenient methods for early recognition of SAP is one of the major challenges in clinical treatment.Aims:To explore the application value of the controlled attenuation parameter(CAP)of ultrasound elastography in predicting SAP.Methods:A retrospective cohort study was conducted involving 135 AP patients admitted to Jiading Branch of Shanghai General Hospital from February to October 2024.Patients were categorized into non-SAP and SAP groups according to the severity of the disease.Clinical data,local complications,laboratory indicators,and CAP were compared between the two groups.Univariate and multivariate Logistic regression analyses were used to identify independent risk factors for SAP.A SAP prediction model based on CAP was constructed according to the identified risk factors and the minimum Akaike information criterion(AIC).ROC curve and Bootstrap method were used to evaluate the efficacy of the prediction model and conduct internal validation,respectively.Results:There were statistically significant differences between the non-SAP group and SAP group in body mass index(BMI),incidence of hyperlipidemia,etiological composition,incidence of pleural and ascitic fluid,length of hospital stay,incidence of peripancreatic effusion,incidence of pancreatic necrosis,white blood cell count(WBC),D-dimer(D-D)level,blood glucose,triglyceride(TG),C-reactive protein(CRP),neutrophil count,procalcitonin(PCT),interleukin-6(IL-6),free triiodothyronine(FT3),and CAP(all P<0.05).Multivariate Logistic regression analysis showed that pancreatic necrosis(OR=13.39,95%CI:3.10-57.94,P<0.001)and CAP(OR=1.01,95%CI:1.01-1.02,P=0.038)were independent risk factors for SAP.The SAP prediction model based on CAP was formulated as:Logit(P)=-5.884+0.010×CAP+2.839×pancreatic necrosis+0.169×D-D+0.132×blood glucose+0.006×CRP.The model showed an area under the curve(AUC)of 0.834 for predicting SAP,which was superior to CAP alone(P<0.05).Internal validation indicated that the prediction model had high stability and accuracy(C-index=0.808).Conclusions:The prediction model constructed based on CAP has good clinical value for predicting SAP,providing a new perspective and tool for early identification and prognostic assessment of AP.