Objective: To investigate the epidemiological characteristics of human brucellosis in Jiande City, Zhejiang Province from 2005 to 2024, so as to provide the evidence for strengthening the prevention and control of brucellosis. Methods: Data on brucellosis cases and surveillance in Jiande City from 2005 to 2024 were collected through the Chinese Disease Prevention and Control Information System, the annual brucellosis surveillance reports from the Jiande Center for Disease Control and Prevention, and the annual summaries of brucellosis prevention and control efforts. The epidemiological characteristics of human brucellosis were analyzed using a descriptive epidemiological method. Results: A total of 1 125 individuals were monitored in Jiande City from 2005 to 2024, with 18 seropositive cases identified and the seropositivity rate of 1.60%. The average annual seropositivity rate from 2015 to 2024 was 3.35%, which was significantly higher than that of 0.57% from 2005 to 2014 (P<0.05). There were 10 confirmed brucellosis cases and 8 asymptomatic infections, with no reported deaths. The peak incidence occurred between March and August. Among the 16 towns (streets) in Jiande City, 8 reported brucellosis cases. Of the brucellosis cases, 14 were male and 4 were female, with a male-to-female ratio of 3.5∶1. The majority of cases (13 cases) were aged between 40 and 60 years. Occupational exposure was identified in 16 cases, all of whom were infected through direct hand contact with the excreta, secretions, or animal products of infected sheep or cattle. The primary source of infection was sheep, followed by cattle. Five strains of Brucella were isolated and cultured, all identified as Brucella melitensis biovar 3. Conclusions The brucellosis epidemic in Jiande City remained at a sporadic and low prevalence level from 2005 to 2024, with an increasing trend observed from 2015 to 2024. Male occupational groups aged 40 to 60 years were the key population for brucellosis prevention and control, and sheep were the primary source of infection.

ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing. MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group， a model group， and a Danshen Tongluo formula （28 mg·kg^-1·d^-1） group. The efficacy was evaluated by examining the cardiac ultrasound， determination of the plasma level of N-terminal pro-brain natriuretic peptide， and pathological staining. After single-cell sequencing， SingleR package， public datasets， and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis， and scmetabolism was used for metabolic analysis of endothelial cells. ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide （ NT-proBNP ） level （P<0.05）， ameliorated myocardial cell damage and fibrosis， and increase left ventricular ejection fractions （LVEF） in the rat model of heart failure after myocardial infarction（P<0.05）. Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells， venous endothelial cells， and capillary-arterial endothelial cells， while reducing the proportion of capillary-venous endothelial cells. In addition， this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells， while downregulating Mif-（CD74⁺CXCR44） signaling in endothelium-M1 macrophages and Mif-（CD74⁺CD44） signaling in endothelium-M2 macrophages. It reduced the citric acid cycle， oxidative phosphorylation， and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells， venous endothelial cells， and venous capillary endothelial cells can all regulate oxidative phosphorylation， cell adhesion molecules， and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids. ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.

INTRODUCTION: Health literacy plays an essential role in one's ability to acquire and understand critical medical information in the coronavirus disease 2019 (COVID-19) infodemic and in other pandemics. We aimed to summarise the assessment, levels and determinants of pandemic-related health literacy and its associated clinical outcomes. METHODS: A systematic review was performed in Medline ® , Embase ® , PsycINFO ® , CINAHL ® and four major preprint servers. Observational and interventional studies that evaluated health literacy related to the novel COVID-19, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) were included. Items used in health literacy instruments were grouped under the themes of knowledge, attitudes and practices. Determinants of health literacy were grouped into five domains: sociodemographic, medical, psychological/psychiatric, health systems-related and others. RESULTS: Of the 2,065 articles screened, 70 articles were included. Of these, 21, 17 and 32 studies evaluated health literacy related to COVID-19, SARS and MERS, respectively. The rates of low pandemic health literacy ranged from 4.3% to 57.9% among medical-related populations and from 4.0% to 82.5% among nonmedical populations. Knowledge about the symptoms and transmission of infection, worry about infection, and practices related to mask usage and hand hygiene were most frequently evaluated. Sociodemographic determinants of health literacy were most frequently studied, among which higher education level, older age and female gender were found to be associated with better health literacy. No studies evaluated the outcomes associated with health literacy. CONCLUSION The level of pandemic-related health literacy is suboptimal. Healthcare administrators need to be aware of health literacy determinants when formulating policies in pandemics.
Humans ; Health Literacy ; COVID-19/epidemiology* ; Severe Acute Respiratory Syndrome/epidemiology* ; Health Knowledge, Attitudes, Practice ; Pandemics ; SARS-CoV-2 ; Coronavirus Infections/epidemiology* ; Middle East Respiratory Syndrome Coronavirus ; Female ; Male

OBJECTIVE: To explore the optimal vertical traction weight, clinical efficacy, and safety of bidirectional cervical traction in the treatment of cervical kyphosis. METHODS: A total of 130 patients with neck pain and cervical kyphosis confirmed by cervical DR who visited the hospital from April 2023 to April 2024 were enrolled. They were divided into 4 groups according to the vertical traction weight accounting for 5%, 10%, 15%, and 20% of their body weight, respectively. The 5% body weight traction group included 33 cases (13 males and 20 females) with an average age of (34.00±10.58) years old;the 10% body weight traction group included 35 cases (17 males and 18 females) with an average age of (32.23±8.39) years old;the 15% body weight traction group included 32 cases (14 males and 18 females) with an average age of (33.88±10.09) years old;the 20% body weight traction group included 30 cases (11 males and 19 females) with an average age of (36.20±9.13) years old. Each group received treatment for 2 weeks. The visual analogue scale (VAS) score, neck disability index (NDI), and C₂-C₇ Cobb angle on cervical lateral X-ray films before and after treatment were recorded to evaluate the clinical efficacy of the 4 groups. RESULTS: When the traction weight was 10% and 15% of body weight, the pain VAS and NDI were significantly improved, and the C₂-C₇ Cobb angle increased, with statistically significant differences (P<0.05), and no adverse reactions occurred. However, in the 5% body weight group, the above indicators showed no significant changes, with no statistically significant differences (P>0.05). In the 20% body weight group, some patients could not tolerate the treatment, and adverse reactions such as dizziness, nausea, and aggravated neck pain occurred. CONCLUSION The optimal vertical traction weight of bidirectional cervical traction for cervical kyphosis is 10%-15% of body weight, which can effectively improve neck pain and cervical function, increase the C₂-C₇ Cobb angle of the cervical spine, with high safety, and is worthy of promotion and application.
Humans ; Male ; Female ; Traction/methods* ; Kyphosis/physiopathology* ; Adult ; Cervical Vertebrae/physiopathology* ; Middle Aged ; Neck Pain ; Young Adult

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

OBJECTIVE: This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease (NAFLD) in children with obesity. METHODS: We conducted a two-step case-control study. Ninety-three participants were subjected to whole-exome sequencing (exploratory set). Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing (validation set). RESULTS: In the exploratory set, 14 genes from the NAFLD-associated pathways were identified. In the validation set, after adjusting for sex, age, and body mass index, ECI2 rs2326408 (dominant model: OR = 1.33, 95% CI: 1.02-1.72; additive model: OR = 1.22, 95% CI: 1.01-1.47), C6orf201 rs659305 (dominant model: OR = 1.30, 95% CI: 1.01-1.69; additive model: OR = 1.21, 95% CI: 1.00-1.45), CALML5 rs10904516 (pre-ad dominant model: OR = 1.36, 95% CI: 1.01-1.83; adjusted dominant model: OR = 1.40, 95% CI: 1.03-1.91; and pre-ad additive model: OR = 1.26, 95% CI: 1.04-1.66) polymorphisms were significantly associated with NAFLD in children with obesity ( P < 0.05). Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516, COX11 rs17209882, and SCD5 rs3733228 was optional ( P < 0.05), demonstrating a negative interaction between the three genes. CONCLUSION In the Chinese population, the CALML5 rs10904516, C6orf201 rs659305, and ECI2 rs2326408 variants could be genetic markers for NAFLD susceptibility.
Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Child ; Male ; Female ; Genetic Predisposition to Disease ; Case-Control Studies ; Exome Sequencing ; Adolescent ; Polymorphism, Single Nucleotide ; Obesity/complications* ; Pediatric Obesity/complications* ; China

italic>Platycodon grandiflorum (Jacq.) A. DC is one of the most commonly used bulk medicinal herbs. It has important value in the fields of medicine, food and cosmetics, and its market demand is increasing year by year, and it has a good development prospect. In this study, based on 403 distribution records and 8 environmental variables, we used Maxent model to predict the potential distribution of P. grandiflorum under climate change. The results showed that the model simulation effect was the best when the Maxent parameter was FC (feature combination) = LQPH (L: linear features; Q: quadratic features; P: product features; H: hinge features) and RM (regularization multiplier) = 2.1, AUC (area under curve) = 0.901, and the model prediction showed that P. grandiflorum was widely distributed in 28 provinces of China under the current climate conditions, with a suitable area of 2 337 419.98 km². Under the influence of climate change in the future, the area of suitable habitat of P. grandiflorum showed a decreasing trend, and the distribution center as a whole showed a trend of northward and eastward shift. The distribution area of P. grandiflorum in the three main producing areas is affected by climate change, and the overall trend is that the future suitable distribution area of Chifeng in Inner Mongolia increases, while the future suitable distribution area of Zibo in Shandong and Taihe, Bozhou in Anhui decreases or even disappears under the SSP5-8.5 scenario (shared socioeconomic pathways). It is suggested to maintain and protect the ecological environment and germplasm resources of the reserved area suitable for the growth of P. grandiflorum, and increase the cultivation research in the expansion area of P. grandiflorum, so as to lay a foundation for the subsequent expansion of P. grandiflorum planting and to promote the protection and sustainable development of P. grandiflorum resources.

Objective: To establish an optimized method for isolation and purification of microglia from aged rat brain tissue, and the phenotype of microglia was detected by flow cytometry. Methods: With young rats(3 months old) as control, the brain tissues of aged rats were immediately processed into single cell suspensions by mechanical dissociation and enzymatic digestion using type IV collagenase. Microglia were isolated on Percoll gradients(30%-37%-70%). The cells were stained with fluorescence-labeled antibodies and the phenotype of microglia was detected by flow cytometry. Results: This study developed a method that enzymatic digestion and mechanical dissociation combined with density gradient centrifugation. More single cells could be obtained by using this method. And the survival rate of cells was more than 90%. The flow cytometric analysis showed that the expression of M1 microglia marker CD86 and MHC Ⅱ increased(P<0.01), and the expression of M2 microglia marker CD200R increased(P<0.01) in aged rats compared with that in young rats. Conclusion The use of type IV collagenase and mechanical digestion combined with density gradient centrifugation is good for isolating and purifying microglia from adult and aged rat brain tissue.