AIM: To develop a novel gene-delivery therapeutic based on CRISPR/Cas9 genome editing technology capable of specifically targeting and knocking out the VEGFA gene, thereby achieving sustained suppression of VEGFA expression in retinal pigment epithelial(RPE)cells and providing a new strategy for gene therapy in retinal neovascular diseases.METHODS:Single guide RNAs targeting the human VEGFA gene for knockout were designed, and corresponding recombinant plasmids were constructed. A novel polymer(PTEE)was used to encapsulate the plasmids to prepare a PTEE-loaded anti-VEGFA plasmid(PLAP)gene delivery system. PTEE materials at concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 μg/μL were co-incubated with ARPE-19 cells, and the biocompatibility of PTEE was evaluated using the cell counting kit-8(CCK-8)assay. Recombinant plasmids expressing green fluorescent protein(GFP)were constructed. Lipofectamine 3000 and jetOPTIMUS®DNA transfection reagents were used as control groups, and PTEE nanomaterials were used as the experimental group to encapsulate the plasmids. When the cell confluence reached 80%, the formulations were transfected into ARPE-19 and 293T cells. GFP expression was observed under light microscopy, and the transfection efficiencies of each group were compared. ARPE-19 cells were induced under hypoxia, and PLAP was transfected into the cells. The expression level of VEGFA was detected by enzyme-linked immunosorbent assay(ELISA)to evaluate the efficacy of this novel gene delivery system.RESULTS: After co-incubation of ARPE-19 cells with different concentrations of PTEE for 24 h and 48 h, no significant effect on cell viability was observed in any group. The transfection efficiency of PLAP in ARPE-19 cells was higher than that in the Lipo3000 and jetOPTIMUS groups, with statistically significant differences(P<0.01). Hypoxia for 6 h significantly induced the upregulation of VEGFA mRNA expression in ARPE-19 cells, and under hypoxic conditions, the PTEE group exhibited a significant inhibitory effect on VEGFA expression(P<0.01).CONCLUSION:PLAP exhibits favorable biocompatibility and prominent VEGFA inhibitory effects in vitro, making it a potential candidate drug for gene therapy of retinal neovascular diseases.

Needle removal is an essential component of the entire acupuncture treatment process， and its standardization is directly related to clinical safety and quality control in acupuncture practice. However， in actual clinical work， due to factors such as the accelerated pace of diagnosis and treatment， increased workload， and changes in personnel collaboration patterns， missed needle removel still occurs from time to time， gradually becoming one of the potential safety hazards in acupuncture clinical practice. Based on the clinical practice， this article analyzes the occurrence characteristics and risk factors of missed needle removal， and finds that it is closely associated with personnel collaboration， the spatial distribution and identifiability of acupoints， and changes in patients' body positioning. A risk stratification framework is developed according to acupoint location， patient positioning， and diagnosis and treatment mode， and prevention and control strategies， including standardized handover， stratified checking， and information support proposed for different risk levels， aiming to provide a reference for standardized acupuncture and moxibustion practice and quality and safety management.

AIM: To evaluate the diagnostic value of serum Th1-type cytokine levels and extraocular muscle-related parameters in thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective study was conducted on 45 patients diagnosed with TAO in our hospital from January 2023 to December 2024, and 20 normal volunteers during the same period as controls. Venous blood samples of the patients were collected to detect the concentrations of Th1-type cytokines [interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), and interleukin-12(IL-12)] in the serum. Additionally, the end diastolic velocity(Ved), velocity maximum(Vmax), resistance index(RI)of the central retinal artery, as well as the thickness and left-right diameter of the medial rectus muscle were measured. Logistic regression model was used to analyze the risk factors of TAO, and receiver operating characteristic curve(ROC)was adopted to evaluate the diagnostic efficacy of each index for the occurrence of TAO.RESULTS: The general information of the two groups was comparable. Compared with the normal control group, the serum concentrations of IFN-γ and TNF-α in TAO patients were significantly increased, Ved and Vmax were lower than those in the control group, and RI and the thickness of the medial rectus muscle were higher than those in the control group(all P<0.05). Logistic regression analysis showed that serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle were all risk factors for TAO. ROC curve analysis indicated that the AUCs of serum IFN-γ concentration, Ved, Vmax, and the thickness of the medial rectus muscle for the diagnostic efficacy of TAO were 0.756, 0.769, 0.732, and 0.642, respectively. The combined detection of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle had an AUC of 0.840 and a Youden index of 0.59, which was superior to the detection of a single indicator.CONCLUSION: The levels of serum Th1-type cytokines and extraocular muscle-related ultrasound indicators have certain value in the diagnosis of TAO. The combination of IFN-γ, Ved, Vmax, and the thickness of the medial rectus muscle has better diagnosis efficiency in TAO, which can provide a certain reference for the early diagnosis of TAO.

OBJECTIVE To evaluate the potential of nanopore sequencing technology for rapid diagnosis of Talaro-myces marneffei(TM)infection.METHODS Nine patients with TM infection admitted to the Fourth People's Hospital of Nanning from May 13,2022 to Aug.3,2023 were retrospectively analyzed.Rapid diagnosis was con-ducted by nanopore sequencing technology,and a comprehensive analysis of their clinical characteristics and treat-ment processes was performed.RESULTS The 9 patients included in the study had infections in various sites such as the lungs,buttocks,blood and cervical lymph nodes.Comorbidities included AIDS,secondary pulmonary tuberculosis,non-tuberculous mycobacterial disease and adult-onset immune deficiency.Patients generally exhibited elevated C-reactive protein levels and erythrocyte sedimentation rates,along with increased neutrophil counts.Some patients had abnormal lymphocyte counts and CD4+/CD8+ratios.Microbiological tests showed positive cultures in 3 cases,positive smears in 2 cases and positive targeted detection in 6 cases.Nanopore sequencing detected various pathogens in the 9 patients.The treatment results indicated that 8 patients improved after medication,with 6 patients having medication regimens adjusted based on nanopore sequencing results.CONCLUSION Nanopore sequencing technology has shown potentials in the auxiliary diagnosis of TM infection,providing timely etiological diagnostic evidence for clinical practice.

In terms of the complexity of the"left"and"right"concepts,these directional terms not only indicate spatial orientation but also embody hierarchical order,official titles,systemic imbalances,and temporal sequences.This study explains the medical theory of"liver is born on the left and lung is hidden on the right,"and reveals its implications for ascending and descending of qi movement pathways,sequential patterns,non-equilibrium states,and the centrality of the middle,thus linking the connotation of this theory and its application.In view of this,the theory of"liver is born on the left and lung is hidden on the right"can be used in the clinical diagnosis and treatment of qi-blood-body fluid and emotional diseases,and guides disease prevention and treatment,as well as enhances the subjective initiative of health maintenance and longevity.This study not only deepens the modern interpretation of the classical theory but also provides novel perspectives for its application in disease prevention and treatment.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To compare the diagnostic value of semi-quantitative parameters of fluorine 18-labelled prostate-specific membrane antigen( 18F-PSMA)positron emission tomography /computed tomography(PET/CT)and the Prostate-specific Membrane Antigen Reporting and Data System(PSMA-RADS)score for identifying benign and malignant oligo-PSMA-avid bone lesions(1-5 lesions)in elderly patients with prostate cancer. Methods:A retrospective analysis was conducted on 157 prostate cancer patients who underwent 18F-PSMA PET/CT examinations at Beijing Hospital from October 2022 to August 2024.According to the inclusion and exclusion criteria, a total of 63 patients were selected.All patients underwent 18F-PSMA PET/CT examination for the purpose of initial staging or detecting lesions with biochemical recurrence.PSMA-avid bone lesions were evaluated using the PSMA-RADS version 2.0 scoring system and the semi-quantitative parameters were measured on PSMA PET/CT images.According to the comprehensive diagnostic criteria, PSMA-avid bone lesions were divided into metastatic group and non-metastatic group.The differences in PSMA-RADS scores, semi-quantitative parameters, bone density abnormalities, and lesion distribution were compared between the two groups.Multivariate logistic regression analysis was performed to determine the factors related to the bone metastasis in prostate cancer.By plotting the receiver operating characteristic(ROC)curves and calculating the area under the curve(AUC), factors with better diagnostic performance were evaluated and screened, and the optimal diagnostic threshold for each factor in diagnosing bone metastasis was determined. Results:There were a total of 129 PSMA-avid bone lesions for 63 patients(aged 60-84 years, median age 69 years), including 35 lesions(27.1%)in the metastatic group and 94 lesions(72.9%)in the non-metastatic group.The differences between metastatic group and non-metastatic group in PSMA-RADS scores[5(4, 5) vs.3(3, 3)], maximum standardized uptake value(SUV max)[12.6(7.0, 18.4) vs.4.7(3.5, 5.9)], lesion SUV max/mediastinal blood pool SUV max ratio(lesion-to-blood pool ratio, LBR)[5.4(3.0, 8.3) vs.1.7(1.4, 2.2)], lesion SUV max/liver SUV max ratio(lesion-to-liver ratio, LLR)[2.6(1.6, 4.1) vs.0.8(0.7, 1.1)], PSMA receptor expressing tumor volume(PSMA-TV)[0.6(0.3, 1.0) vs.1.0(0.7, 1.5)], total lesion of PSMA(TL-PSMA)[4.4(2.4, 7.0) vs.2.4(1.7, 3.9)], proportion of changes in osteogenic bone density[77.1%(27/35) vs.2.1%(2/94)], proportion of lesions located in the ribs[14.3%(5/35) vs.46.8%(44/94)], and proportion of lesions located in the pelvis[54.3%(19/35) vs.20.2%(19/94)]were all statistically significant(all P<0.05). Multivariate logistic regression analysis indicated that none of the variables with statistically significant differences between groups above were independent risk factors for osseous metastasis in prostate cancer(all P>0.05). Among them, The PSMA-RADS score, LLR, LBR, and SUV max all had good diagnostic efficacy for osseous metastasis, with 0.995(95% CI: 0.987-1.000), 0.923(95% CI: 0.869-0.977), 0.898(95% CI: 0.828-0.967), and 0.890(95% CI: 0.820-0.961), respectively.The cut-off values for diagnosing osseous metastasis were 4 score for PSMA-RADS score, 0.934 for LLR, 1.990 for LBR, and 5.47 for SUV max, respectively.According to Delong's test, there were statistically significant differences in AUC between PSMA-RADS score and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)( Z-values were 2.677, 2.776, and 2.929, respectively, and P-values were 0.007, 0.006, and 0.003, respectively). Conclusions:The PSMA-RADS score(Version 2.0)and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)both have good diagnostic value in differentiating benign and malignant PSMA-avid bone lesions in elderly patients with prostate cancer, among which the PSMA-RADS score has the best diagnostic efficacy.

Objective:To investigate effect of galangin(Gal)on immune function in nephrotic syndrome(NS)rats by regula-ting stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)signaling pathway.Methods:A NS rat model was established by injecting doxorubicin into tail vein.After successful modeling,rats were randomly grouped into Model group,Gal low,medium and high doses groups,activator group.Twelve rats were randomly selected as control group,and each group was given corre-sponding drug by gavage and intraperitoneal injection,once a day for 6 consecutive weeks.Biochemical indicators such as 24-hour urine protein,urea nitrogen(BUN),creatinine(Scr)and total cholesterol(TC)were detected in rats;HE staining was applied to observe pathological damage in rat kidney tissue;spleen and thymus were taken and weighed,and organ index was calculated;flow cytometry was applied to detect levels of CD3+T,CD4+T,CD8+T,Th1 and Th2 cells in rat peripheral blood;ELISA was applied to detect IL-10,IL-2,TNF-α,IgG and IgM in serum;qRT-PCR and Western blot were applied to detect mRNA and protein expressions of SDF-1 and CXCR4.Results:Compared with control group,24-hour urine protein,BUN,Scr,TC,triglyceride(TG)contents,CD8+T,Th1,Th1/Th2,IL-2,TNF-α,SDF-1,CXCR4 mRNA and protein expressions of rats in Model group were obviously in-creased,albumin(ALB)content,spleen index,thymus index,CD3+T,CD4+T,Th2 cell proportions,CD4+T/CD8+T,IL-10,IgG,and IgM levels were obviously reduced(P<0.05);compared with Model group,24-hour urine protein,BUN,Scr,TC,TG contents,CD8+T,Th1,Th1/Th2,IL-2,TNF-α,SDF-1,CXCR4 mRNA and protein expressions of rats in Gal low,medium and high doses groups were gradually decreased,ALB content,spleen index,thymus index,CD3+T,CD4+T,Th2 cell proportions,CD4+T/CD8+T,IL-10,IgG and IgM levels were gradually increased(P<0.05);compared with high-dose Gal group,changes in above indicators in activator group of rats were obviously reversed(P<0.05).Conclusion:Gal may enhance T lymphocyte immune function by inhibiting SDF-1/CXCR4 pathway,thereby alleviating renal injury in NS rats.

To enhance hospital operational management capability,the sample hospital initiated a financial talent development program aligned with current development needs and policy directions.This program established a talent development framework encompassing hierarchical training,employment mechanisms,and digital empowerment,forming a three-tier financial talent echelon comprising senior,intermediate,and junior professionals.It effectively facilitated the transformation of financial functions toward"strategic support,business service,risk prevention and control,and value creation".It analyzes the hospital's practical experience in financial talent development,aiming to offer insights for financial workforce development in public hospitals.These efforts synergize with the modernization of governance systems and capabilities in health economics,driving high-quality development in public healthcare institutions.

Objective To establish atopic dermatitis(AD)-like models in BALB/c mice using three chemical inducers,calcipotriol(MC903),2,4-dinitrochlorobenzene(DNCB),and oxazolone(OXA),and to explore the occurrence of ferroptosis in the different models.Methods Healthy 7-week-old female BALB/c mice were divided randomly into eight groups(n=8 mice per group)based on the induction site(ear/dorsal skin)and inducer:ear/dorsal control groups,MC903 ear/dorsal model groups,DNCB ear/dorsal model groups,and OXA ear/dorsal model groups.Models were established by topical application of the respective agents at specified concentrations.Mice in the MC903 ear/dorsal groups underwent continuous induction for 14 d.Mice in the DNCB and OXA ear/dorsal groups were sensitized for 3 consecutive days,4 days after the sensitization was completedand then challenged 12 times on day 8 and every other day for up to day 30.Skin lesions were observed and skin thickness was measured.Plasma levels of reactive oxygen species(ROS),interleukin(IL)-4,interferon(IFN)-γ,and malondialdehyde(MDA)were detected,the skin was examined by histopathological staining and ultrastructural observation,and expression levels of ferroptosis-related proteins(glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1),long-chain-fatty-acid-CoA ligase 4(ACSL4),transferrin receptor 1(TfR1))were detected by Western Blot.Results Compared with each control mice,all model mice exhibited obvious redness,swelling,scratching,desquamation,and rough thickening of the skin,and skin thickness was significantly increased(P＜0.01).ROS,IFN-γ,IL-4,and MDA levels were elevated to varying extents(P＜0.05)and histopathological features,including epidermal hyperplasia,keratinocyte degeneration,dermal vascular congestion,and immune cell infiltration,were detected in model mice.Transmission electron microscopy also revealed mitochondrial membrane rupture,increased density,and cristae reduction.Expression levels of ferroptosis markers were dysregulated,including significantly decreased GPX4/FTH1(P＜0.05)and increased ACSL4/TfR1 expression(P＜0.05).Conclusions All three chemicals successfully induced AD-like phenotypes in BALB/c mice through site-specific applications.Ferroptosis is involved in the pathological process of AD,but heterogeneity exists among inducers and modeling sites.