Objective To investigate the species of sandflies and the prevalence of Leishmania infections in sandflies from selected areas of northern and northwestern China, so as to provide insights into identification of leishmaniasis vectors and assessment of epidemiological trends of leishmaniasis in China. Methods Sandfly samples were collected from Mentougou District of Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County of Karamay District of Karamay City, Gaochang District of Turpan City in Xinjiang Uygur Autonomous Region from July 2023 to July 2024. Approximately 100 intact female sandfly samples were randomly selected from each site and the species of sandflies was identified according to morphological characteristics and molecular assays. Female sandflies originating from the same habitat were grouped into pools of 10 individuals. Leishmania infection was detected using polymerase chain reaction (PCR) assay targeting the internal transcribed spacer 1 (ITS-1) gene, and the prevalence of Leishmania infection was calculated in sandflies from different sampling sites using the minimum infection rate (MIR) method. In addition, positive amplicons were sequenced and subjected to phylogenetic analysis. Results A total of 6 155 sandflies were collected from different environments at sampling sites across the six aforementioned regions from July 2023 to July 2024. Phlebotomus chinensis (96.00%) was the dominant sandfly species in Mentougou District, Beijing Municipality, with a small proportion of Ph. sergenti (4.00%), and only Ph. chinensis was found in Xiangning County, Linfen City, Shanxi Province. Ph. wui was the only sandfly species detected in Ejin Banner, Alxa League, Inner Mongolia Autonomous Region, and Payzawat County, Kashgar City, Xinjiang Uygur Autonomous Region, and Ph. caucasicus (97.70%) was the dominant sandfly species in Karamay District, Karamay City, Xinjiang Uygur Autonomous Region, with a small proportion of Ph. wui (2.30%), while Ph. alexandri was the only species in Gaochang District, Turpan City, Xinjiang Uygur Autonomous Region. A total of 40, 60, 34, 18, 18, and 22 pools of sandfly samples were tested from Mentougou District in Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, Payzawat County in Kashgar City, Karamay District in Karamay City, and Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region, respectively. L. infantum was detected in Ph. chinensis samples from Mentougou District in Beijing Municipality, and Xiangning County of Linfen City in Shanxi Province, with MIR of 0.25% to 1.00%, and L. donovani was detected in Ph. wui from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region, with MIR of 0.56% to 0.88%; however, no Leishmania infection was detected in Ph. caucasicus from Karamay District in Karamay City or Ph. alexandri from Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region. Phylogenetic analysis showed that the Leishmania ITS-1 gene sequences obtained from Mentougou District in Beijing Municipality and Xiangning County in Linfen City of Shanxi Province were clustered into the same clade with the reference sequences of L. infantum ITS-1 gene, while the Leishmania ITS-1 gene sequences obtained from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region were clustered into the same clade with the reference sequences of L. donovani ITS-1 gene. Conclusions There are variations in sandfly species in selected areas of northern and northwestern China, and variations in the species of Leishmania infecting sandflies. Improved surveillance of sandfly vectors and targeted control strategies with adaptations to geographical features and leishmaniasis vectors are recommended.

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Objective To compare and analyze the germicidal efficacy of continuous ultraviolet and pulsed ultravio-let(UV)lasers on pathogenic microorganisms.Methods Spore slides of Escherichia coli and Bacillus atrophaeus were irradiated using a 254 nm ultraviolet mercury lamp and UV laser.The carrier quantitative germicidal test was conducted to determine the disinfection efficacy at different irradiation doses.Results When the irradiation dose of the ultraviolet mercury lamp was 245.52 mJ/cm2,the logarithmic killing values of Escherichia coli and Bacillus atro-phaeus spores were 5.00 and 2.92,respectively,and the mean logarithmic killing doses were 49.10 and 84.08 mJ/cm2,respectively;When the UV laser irradiation doses were 208.39 and 206.80 mJ/cm2,the logarithmic killing values for the two microorganisms were 6.29 and 3.32,respectively,and the mean logarithmic killing doses were 33.13 and 62.29 mJ/cm2,respectively.Conclusion Compared with continuous UV radiation,pulsed UV laser has stron-ger penetration ability,better killing efficacy on pathogenic microorganisms at the same radiation dose,and can con-duct targeted disinfection and sterilization on the surface of objects directionally.

Objective:To explore the distribution of cardiovascular disease(CVD)and cardiovascular risk fac-tors(CVRF)in patients with epithelial ovarian cancer before treatment and their correlation with the histological type,stage and grade of ovarian cancer.Methods:A total of 401 newly diagnosed epithelial ovarian cancer pa-tients admitted to The First Affiliated Hospital of Dalian Medical University from January 1,2015 to December 31,2022 were enrolled.Analyze the distribution of CVD(including hypertension,coronary heart disease,stroke,etc.)and CVRF(including diabetes,dyslipidemia,high level of uric acid)in epithelial ovarian cancer patients.Univari-ate analysis and multivariate Logistic regression were performed on the association between CVD,CVRF and the histological type,grade and stage of epithelial ovarian cancer.Results:①Among 401 epithelial ovarian cancer pa-tients,43.6％had at least one CVD before therapy.The most common CVD was hypertension(41.1％),and the most common CVRF was dyslipidemia(57.9％).②Multivariate Logistic regression analysis showed that age ≥60 years was an independent risk factor for serous,high-grade,and advanced epithelial ovarian cancer(OR＞1,P＜0.05).Dyslipidemia was an independent risk factor for high-grade and advanced epithelial ovarian cancer(OR＞1,P＜0.05).High level of uric acid was an independent risk factor for advanced epithelial ovarian cancer(OR＞1,P＜0.05).③The proportion of high-density lipoprotein cholesterol(HDL-C)and lipoprotein A[Lp(A)]abnor-malities in patients with advanced epithelial ovarian cancer was significantly higher than in those with early stage epithelial ovarian cancer(P＜0.05),and the proportion of number of abnormal lipid components was higher in pa-tients with high grade and advanced epithelial ovarian cancer than in patients with low grade and early stage epi-thelial ovarian cancer,respectively(P＜0.05).Conclusions:Patients with epithelial ovarian cancer bear a signifi-cant burden of CVD and CVRF.Hypertension is the most common CVD,and dyslipidemia is the most common CVRF.Dyslipidemia was associated with epithelial ovarian cancer grade and stage.High level of uric acid was as-sociated with epithelial ovarian cancer stage.Active control of blood pressure and blood lipid levels is very impor-tant for epithelial ovarian cancer patients.

Aim To establish the pyroptosis model of rat chondrocytes induced by tumor necrosis factor α(TNF-α)in order to study the effect of lysine acetyl-transferase 7(KAT7)on pyroptosis of chondrocytes.Methods Chondrocytes of rat knee joint were isolated by type Ⅱ collagenase digestion,and were identified by toluidine blue staining and Col Ⅱ immunofluorescence.CCK-8 was used to evaluate cell viability.Western blot was used to detect the expression of pyroptosis-related proteins NLRP3,GSDMD,caspase-8 and KAT7 in cells intervened with TNF-α,adenovirus overexpression of KAT7(KAT7-oe)and KAT7 inhibitor WM-3835.The microstructure of the cells was observed by scanning e-lectron microscopy.Pyroptosis was detected by TUNEL staining,and the expression of pyroptosis-related pro-tein and KAT7 was detected by immunofluorescence.Results Compared with the empty virus group,KAT7-oe inhibited cell viability,promoted the expression of pyroptosis-related proteins,and TNF-α enhanced this effect.At the same time,the expression of KAT7 and pyroptosis-related proteins in the TNF-α stimulation group increased,and WM-3835 reduced the related proteins expression.Electron microscopy showed that KAT7-oe caused cell swelling,deformation,membrane perforation and rupture,while WM-3835 could restore cell morphology.TUNEL staining and immunofluores-cence results also confirmed that KAT7-oe induced chondrocyte pyroptosis,and WM-3835 could down-reg-ulate the fluorescence of pyroptosis-related proteins.Conclusions The expression of KAT7 increases in rat chondrocyte pyroptosis model,and the intervention of KAT7 expression affects signal molecules related to py-roptosis pathway,suggesting that KAT7 may be related to chondrocyte pyroptosis.

Following extensive interdisciplinary research and development over several years,mechanical circulatory support devices(MCSD),including ventricular assist device(VAD)and total artificial heart(TAH),are now established as vital treatment options for patients with advanced heart failure.These devices have proven to be crucial in assisting or replacing a failing heart,offering patients a new lease of life and improving their quality of life.Currently,mechanical circulatory support(MCS)has become a well-recognised,long-term treatment option for patients who are unable to undergo heart transplantation due to donor organ shortages or contraindications.Given their continuous availability independent of donor organ limitations,these devices are poised to play an increasingly vital role in the future of medicine.This article aims to summarize the evolution,clinical applications,categorization,and potential complications of MCSD.

Objective To investigate the predictive value of pan-immune-inflammation value(PIV),blood urea nitrogen to albumin ratio(BAR),collateral circulation and National Institutes of Health stroke scale(NIHSS)score for disease progression and short-term prognosis in patients with acute perforating artery cerebral infarction(APACI).Methods Patients with APACI admitted to the Neurology Department of Anhui NO.2 Provincial People's Hospital from January 2019 to October 2024 were retrospectively enrolled in this study.General and clinical data,including age,gender,previous history(hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,drinking history,NIHSS scores at admission were collected.Fasting venous blood samples were collected from the patients within 24 h after admission to detect levels of neutrophils,lymphocytes,monocytes,platelets,blood urea nitrogen,and serum albumin.PIV(PIV=neutrophils × platelets × monocytes/lymphocytes)and BAR were calculated.The location of lesions and Fazekas classification of white matter lesions were evaluated using head MRI and MR angiography at admission.Collateral circulation status was assessed based on CT angiography upon admission.Disease progression was defined through comparing the NIHSS score at 72-hour after admission to the score at admission(an increase of 2 or more points in NIHSS score indicating disease progression).The patients were divided into a progression group and a non-progression group based on the increase in NIHSS score,as aforementioned.Patients follow-up was conducted through phone call or outpatient visits at 90 d after discharge.The modified Rankin scale(mRS)was used to evaluate the prognosis,with a mRS score of 0-2 indicates good prognosis,and a 3-6 indicates poor prognosis.Factors with statistically significant differences in univariate analysis were included in a multivariate Logistic regression analysis to explore the influencing factors of disease progression and poor prognosis in patients with APACI.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each indicator for disease progression and poor prognosis in patients with APACI.Results A total of 165 patients with APACI were enrolled in this study,including 121 males and 44 females,aged 27-86 years,with an average of(61±11)years.Among all patients enrolled,56 patients were included in the progression group and 109 patients in the non-progression group,124 patients showed good prognosis and 41 patients had poor prognosis.No statistically significant differences were found in age,gender,smoking history,drinking history,hypertension,diabetes,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and Fazekas classification of white matter lesions between the progression group and the non-progression group(all P＞0.05).While the NIHSS score at admission,proportion of poor collateral circulation,PIV and BAR in the progression group were significantly higher than those in the non-progression group(all P＜0.05).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.177,95％CI 1.001-1.384,P=0.049),poor collateral circulation(OR,3.107,95％CI 1.216-7.939,P=0.018),high PIV(OR,1.006,95％CI 1.003-1.009,P=0.001),and high BAR(OR,1.610 × 109,95％CI 5.769 × 104-4.494 × 1013,P＜0.01)were independent risk factors of disease progression in patients with APACI.ROC curve analysis results showed that the area under the curve(AUC)of combination of PIV,BAR,collateral circulation and NIHSS score at admission for predicting disease progression in patients with APACI was 0.914(95％ CI0.861-0.952,P＜0.01),which was greater than that of each indicator(all P＜0.05).No statistically significant differences were found in smoking,drinking,hypertension,hyperlipidemia,coronary heart disease,atrial fibrillation,lesion location,and BAR between the poor prognosis and the good prognosis group(all P＞0.05).Compared with the good prognosis group,the poor prognosis group had significantly older age and higher proportion of patients with diabetes,NIHSS score at admission,proportion of patients with poor collateral circulation,and PIV(all P＜0.05).Moreover,the proportion of men in the poor prognosis group was lower than that in the good prognosis group(P=0.039).There was a statistically significant difference between the good prognosis group and the poor prognosis group in the Fazekas classification of white matter lesions(P＜0.01).Multivariate Logistic regression analysis showed that high NIHSS score at admission(OR,1.345,95％CI 1.081-1.674,P=0.008),poor collateral circulation(OR,3.903,95％CI 1.061-14.355,P=0.040),and high PIV(OR,1.011,95％CI 1.005-1.017,P＜0.01)were independent risk factors of poor prognosis in patients with APACI.The AUC for predicting poor prognosis in patients with APACI through combining PIV,collateral circulation and NIHSS score at admission was 0.911(95％CI 0.857-0.950,P＜0.01),which is greater than using poor collateral circulation or NIHSS score at admission alone(both P＜0.05).However,there was no statistically significant difference in AUC between the PIV,collateral circulation and NIHSS score combined predictive model and the PIV(alone)predictive model(P＞0.05).Conclusions High PIV,high BAR,poor collateral circulation,and high NIHSS score at admission were independent risk factors of disease progression in patients with APACI.Combination of these four indices demonstrates relatively high predictive value for disease progression.In addition,high PIV,poor collateral circulation,and high NIHSS score at admission are independent risk factors of poor prognosis in patients with APACI.Joint detection of the three indices may assist in short-term prognosis evaluation of patients with APACI.

Objective To analyze the clinical features,therapeutic effects and relapse factors of anti-myelin oligodendrocyte glycoprotein-IgG antibody associated diseases(MOGAD)in adult patients.Methods The clinical data of 15 adult patients with MOGAD were retrospectively analyzed.The patients were divided into conventional treatment group and plasma exchange group according to the treatment.The efficacy was analyzed by comparing the scores of mRS and expanded disability status scale(EDSS)before and after treatment.And the patients were divided into single course group and relapse course group according to the course of disease,and the relapse-related factors were analyzed.Results There were 10 patients in the conventional treatment group and 5 patients in the plasma exchange treatment group,and the mRS and EDSS of the two groups were significantly lower after treatment than those before treatment(all P＜0.05).There were no significant differences in mRS and EDSS scores between the plasma exchange group and the conventional treatment group after treatment(all P＞0.05).There were 11 patients in the unidirectional course group and 4 patients in the relapsing course group.There were no significant differences between the two groups in gender,age,severity of disease,clinical phenotype,antibody titer,and treatment plan in the acute stage(all P＞0.05).The detection rate of OCB in CSF of patients with relapse course was significantly higher than that of patients with single course.The proportion of patients with maintenance oral hormone duration＜6 months in recurrent disease course group was significantly higher than that in single disease course group(all P＜0.05).Conclusions MOGAD patients respond effectively to glucocorticoid pulse therapy and double filtration plasmapheresis during the acute phase,with a favorable prognosis.MOGAD have a risk of recurrence,those who present with encephalitis at the onset,have positive OCB in CSF,and have a shorter duration of oral glucocorticoid maintenance treatment may be more prone to recurrence.Acute-phase treatment with double filtration plasmapheresis may reduce the recurrence rate.

Objective To understand the awareness and willingness of primary medical staff in Songjiang District, Shanghai towards human papillomavirus (HPV) and its vaccines, and to provide references for improving the vaccination willingness of HPV vaccine and primary prevention of cervical cancer. Methods From July to August 2023, a questionnaire survey was conducted among the in-service medical staff in 17 community health service centers in Songjiang District, Shanghai, using the random sampling method. Descriptive analysis, χ² test and logistic regression were used for statistical analysis. Results A total of 951 valid questionnaires were collected during the survey. The awareness rate of HPV among medical staff was 92.74%, and the awareness rate of HPV vaccine was 93.38%. The maximum score for HPV knowledge was 6 points, with an average score of (3.99±1.34) points. The maximum score for HPV vaccine knowledge was 10 points, with an average score of (5.63±1.61) points. 881 (92.64%) medical staff were willing to receive or recommend HPV vaccination. Multivariate analysis showed that concerns about being infected with HPV (OR=2.648, 95% CI: 1.459-4.806), qualified score on HPV vaccine knowledge (OR=1.717, 95% CI: 1.012-2.912), high price burden of HPV vaccine (OR=0.343, 95% CI: 0.157-0.746), and concerns about side effects of vaccination (OR=0.443, 95% CI: 0.243-0.805) were the influencing factors for medical staff's willingness to vaccinate. Conclusion There is insufficient knowledge of HPV and its vaccines among primary medical personnel in Songjiang District, Shanghai. It is necessary to strengthen the continuing education of medical personnel through multiple channels, supplement the HPV-related knowledge system, and eliminate their concerns about vaccines.