Objective: To analyze the epidemiological characteristics and influencing factors of severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang Province from 2019 to 2023, so as to provide the reference for strengthening SFTS prevention and control. Methods: Data on laboratory-confirmed SFTS cases in Zhejiang Province from 2019 to 2023 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. Meteorological data, geographic environment and socioeconomic factors during the same period were collected from the fifth-generation European Centre for Medium-Range Weather Forecasts, Geospatial Data Cloud, and Zhejiang Statistical Yearbook, respectively. Descriptive epidemiological methods were used to analyze the epidemiological characteristics of SFTS from 2019 to 2023, and a Bayesian spatio-temporal model was constructed to analyze the influencing factors of SFTS incidence. Results: A total of 578 SFTS cases were reported in Zhejiang Province from 2019 to 2023, with an annual average incidence of 0.23/105. The peak period was from May to July, accounting for 52.60%. There were 309 males and 269 females, with a male-to-female ratio of 1.15∶1. The cases were mainly aged 50-<80 years, farmers, and in rural areas, accounting for 82.53%, 77.34%, and 75.43%, respectively. Taizhou City and Shaoxing City reported more SFTS cases, while Shaoxing City and Zhoushan City had higher annual average incidences of SFTS. The Bayesian spatio-temporal interaction model showed good goodness of fit. The results showed that mean temperature (RR=1.626, 95%CI: 1.111-2.378) and mean wind speed (RR=1.814, 95%CI: 1.321-2.492) were positively correlated with SFTS risk, while altitude (RR=0.432, 95%CI: 0.230-0.829) and population density (RR=0.443, 95%CI: 0.207-0.964) were negatively correlated with SFTS risk. Conclusions SFTS in Zhejiang Province peaks from May to July. Middle-aged and elderly people and farmers are high-risk populations. Taizhou City, Shaoxing City, and Zhoushan City are high-incidence areas. Mean temperature, mean wind speed, altitude, and population density can all affect the risk of SFTS incidence.

ObjectiveTo conduct a comparative quality analysis of Inulae Flos， fuzz of Inulae Flos and calyx of Inulae Flos， elucidating the scientific connotation of the "removing calyx" process in the traditional processing of Inulae Flos. MethodsInulae Flos decoction pieces were collected， and the fuzz and calyx of Inulae Flos were prepared according to the experiences of old medicine workers. Subsequently， according to the methods under the "Inulae Flos" item in the 2025 edition of the Pharmacopoeia of the People's Republic of China， the appearance characteristics and thin-layer chromatography（TLC） identification of these samples were tested， and the moisture content， total ash content， extract content were also measured. The characteristic fingerprint patterns of Inulae Flos and fuzz of Inulae Flos were established by high-performance liquid chromatography（HPLC）， followed by similarity evaluation， principal component analysis（PCA）， and partial least squares-discriminant analysis（PLS-DA）. The contents of cryptochlorogenic acid， caffeic acid， 1，3-O-dicaffeoylqunic acid， 1，5-O-dicaffeoylqunic acid， and 1-O-acetyl britannilactone were determined to compare the quality differences of Inulae Flos， fuzz of Inulae Flos， and calyx of Inulae Flos. ResultsThe moisture content of Inulae Flos， fuzz of Inulae Flos， and calyx of Inulae Flos was all<10%. The determination results of total ash content were as follows：Calyx of Inulae Flos>Inulae Flos>fuzz of Inulae Flos， and the determination results of alcohol-soluble extract content were as follows：Fuzz of Inulae Flos>Inulae Flos>calyx of Inulae Flos. HPLC fingerprint patterns of Inulae Flos and fuzz of Inulae Flos were established， and 22 common peaks were identified. The similarity analysis and PCA showed that the overall quality of Inulae Flos and fuzz of Inulae Flos was similar， while the overall quality of calyx of Inulae Flos differed significantly from that of Inulae Flos and fuzz of Inulae Flos. PLS-DA results showed that Inulae Flos， fuzz of Inulae Flos， and calyx of Inulae Flos clustered into distinct groups， indicating significant differences among them. Cryptochlorogenic acid and caffeic acid had relatively high contents in calyx of Inulae Flos， the contents of 1，3-O-dicaffeoylqunic acid and 1，5-O-dicaffeoylqunic acid in Inulae Flos and fuzz of Inulae Flos were higher than those in calyx of Inulae Flos. The order of 1-O-acetyl britannilactone content was determined as follows：fuzz of Inulae Flos>Inulae Flos>calyx of Inulae Flos. ConclusionThe scientific nature of "Removing Calyx" process in the cleansing of Inulae Flos by old medicine workers is demonstrated by the resulting fuzz of Inulae Flos decoction pieces exhibiting enhanced cleanliness and higher content of the index component 1-O-acetyl britannilactone. This study provides a reference basis for further improving and enhancing the processing method and quality control standards of Inulae Flos.

This paper systematically elaborates on the key points of diagnosis and differential diagnosis of salivary gland tumors characterized by a substantial amount of extracellular mucus as a main or prominent feature, and clarifies the core differential features. The term "mucus-rich" specifically denotes that mucus is a major component of the tumor, rather than a focal or minor one. This phenomenon is associated with distinct histogenetic mechanisms: it may result from specific genetic mutations (e.g., AKT1 E17K in mucinous adenocarcinoma) that drive ductal epithelial differentiation into mucus-secreting cells, or from myoepithelial cells secreting glycosaminoglycans that form a myxoid stroma. Salivary gland tumors with abundant extracellular mucus include mucinous cystadenoma, sialadenoma papilliferum-like intraductal papillary tumors, mucinous myoepithelioma, pleomorphic adenoma with mucin-rich stroma, mucinous adenocarcinoma, low-grade mucoepidermoid carcinoma, mucin-rich salivary duct carcinoma and intestinal-type adenocarcinoma. The diagnosis of these tumors is complicated by the dual nature of extracellular mucus: while it is a defining feature of some entities, it can also obscure key diagnostic architectural features in others, leading to histological overlap and inconspicuous diagnostic areas. Given the frequent histological morphological overlap among these tumors, immunohistochemical findings and molecular characteristics have emerged as crucial differential diagnostic criteria. Core differential diagnostic points include the following: histologically, there must be meticulous identification of typical structures obscured by mucin (such as squamoid cells in mucoepidermoid carcinoma and apocrine features in salivary duct carcinoma); in immunohistochemical staining, CK20 is useful for distinguishing intestinal-type adenocarcinoma (positive) from mucinous adenocarcinoma (negative), while androgen receptor aids in differentiating salivary duct carcinoma (positive) from mucoepidermoid carcinoma (negative); and molecular testing plays a critical role in definitive diagnosis (e.g., the AKT1 E17K mutation for mucinous adenocarcinoma, MAML2 rearrangement for mucoepidermoid carcinoma, and MEF2C::SS18 fusion for microsecretory adenocarcinoma). This paper systematically summarizes the core pathological features and differential diagnostic points of mucin-rich salivary gland tumors, aiming to provide a practical reference for clinical pathological diagnosis.

ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.

BACKGROUND:Increasing evidence supports the association between different exercise intensities and the risk of osteoarthritis,but this may be affected by confounding and reverse causality,and the conclusions have not been unified. OBJECTIVE:To explore the causal association between different exercise intensities and osteoarthritis using Mendelian randomization method. METHODS:Data from genome-wide association studies associated with different exercise intensities were selected,and instrumental variables were screened with a threshold of P＜5×10-8.Causal associations between exposure and risk of outcome were assessed using five analysis methods of Mendelian randomization with inverse variance weighting as the primary analysis method.Selected instrumental variables were used to assess causal associations between different exercise intensities and osteoarthritis,and sensitivity analyses with inverse Mendelian randomization were performed. RESULTS AND CONCLUSION:In the analysis results of the inverse variance weighting method,low-intensity exercise showed a significant protective effect on knee osteoarthritis[odds ratio(OR)=0.14,95%confidence interval(CI):0.06-0.32,P＜0.001],while sedentary behavior without exercise intensity,such as watching TV,was confirmed to be a risk factor for knee osteoarthritis and hip osteoarthritis(OR=2.24,95%CI:1.74-2.88,P＜0.001;OR=1.34,95%CI:1.01-1.78,P=0.04).Through the reverse Mendelian randomization analysis of osteoarthritis to different exercise intensities,it was found that osteoarthritis was negatively correlated with low-intensity exercise and positively correlated with watching TV.The analysis results show that there is a two-way causal relationship between different exercise intensity and osteoarthritis risk.

Neurofibromas are benign peripheral nerve sheath tumors. It is more common in neurofibromatosis type Ⅰ. However, isolated vagal nerve neurofibroma（VNN） of the neck is extremely rare, and only a few case reports have been reported. Its etiology and pathogenesis are not clear. The diagnosis is mainly based on pathological examination and immunohistochemistry, and surgical resection is the main treatment. This study reports a rare case of giant solitary vagus neurofibroma in the neck. The patient was a 29-year-old female who was found to have a mass on the right side of the neck by physical examination, which was considered to be a vagus nerve tumor by neck ultrasound and imaging examination. The tumor was completely removed during the operation, with the size of about 10.0 cm×2.5 cm, and the patient had no special discomfort. Postoperative pathology and immunohistochemistry confirmed neurofibroma. After surgery, the patient had right vocal cord paralysis, hoarseness, choking and paroxysmal cough. After swallowing function training and voice rehabilitation treatment in the department, the patient recovered satisfactorily. There was no complication and recurrence during the follow-up of 1 year. This article reviews the literature to improve the diagnosis and treatment of solitary vagus neurofibroma in the neck by combining its medical history, imaging features, pathology and immunohistochemistry, and surgical treatment.
Humans ; Female ; Adult ; Neurofibroma ; Vagus Nerve/pathology* ; Neck ; Cranial Nerve Neoplasms

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC₅₀ = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC₅₀ = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.