OBJECTIVE To investigate the effects of Mitoxantrone liposomes （Lipo-MIT） on the proliferation， migration and cancer stem cell （CSCs） stemness of ovarian cancer cells， as well as to explore its mechanism of action based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （AKT） pathway. METHODS The effects of Lipo-MIT on cell proliferation， migration and the stemness characteristics of CSCs were investigated through in vitro experiments. A human ovarian cancer A2780 cells xenograft tumor model of nude mouse was established to explore the effects of Lipo-MIT at doses of 2 and 5 mg/kg on the safety of tumor-bearing mice， as well as in vivo tumor growth and the pathological characteristics of tumor tissues. The influence of Lipo-MIT on the expression levels of PI3K/AKT pathway-related proteins， epithelial-mesenchymal transition related proteins， and stemness related proteins in both cells and tumor tissues was also investigated. RESULTS The half maximal inhibitory concentrations of Lipo-MIT against A2780， SK-OV3， and OV-CAR5 cells were 0.72， 5.41， and 2.77 μmol/L， respectively. Compared with solvent control （0.1% dimethyl sulfoxide）， 0.5-2.5 μmol/L Lipo-MIT significantly reduced the cell colony formation rate， shortened the cell migration distance， decreased the number of migrated cells， down-regulated the protein expression of N-cadherin， up-regulated the protein expression of E-cadherin （P＜0.05）， and also decreased the stem cell sphere formation frequency and down-regulated the protein expression of aldehyde dehydrogenase 1A1 （ALDH1A1） （P＜0.05）. Additionally， 1.0 and 2.5 μmol/L Lipo-MIT significantly reduced the stem cell sphere formation probability and down-regulated the protein expression of sex determining region Y box protein 2 in cells （P＜0.05）. In vivo experimental results demonstrated that 2， 5 mg/kg Lipo-MIT had no significant effects on the body weight， food intake， water intake， and organ （heart， liver， spleen， lung， and kidney） indices of tumor-bearing nude mice （P＞0.05）， but could significantly improve the pathological changes of tumor tissues and remarkably inhibit the protein expressions of N-cadherin， CD133 and ALDH1A1（ only at 5 mg/kg Lipo-MIT）， up-regulate the expression of E- cadherin （only at 5 mg/kg Lipo-MIT） in tumor tissues （P＜0.05）. Lipo-MIT at different concentrations/doses significantly reduced the phosphorylation levels of PI3K and AKT proteins in cells/tumor tissues （P＜0.05）. CONCLUSIONS Lipo-MIT can inhibit the proliferation and migration of ovarian cancer cells and the stemness by suppressing the activity of the PI3K/AKT pathway.

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.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.

Parkinson's disease （PD） is a chronic progressive neurodegenerative disorder primarily characterized by motor dysfunction. The main pathological features include the loss of dopaminergic neurons in the substantia nigra， abnormal aggregation of alpha-Synuclein （α-Syn）， and the formation of Lewy bodies. However， the exact mechanisms remain unclear. In recent years， the PD incidence has gradually increased， while current treatment methods are limited to symptom alleviation， incapable of halting disease progression， and prone to adverse effects， thus making it urgent to search for medicines effective for PD. Modern research indicates that the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway is closely related to oxidative stress， neuroinflammation， apoptosis， ferroptosis， and mitochondrial dysfunction， playing a crucial role in the pathophysiological development of PD. A large number of studies have further confirmed that traditional Chinese medicine （TCM） can regulate diseases through a holistic view of Syndrome differentiation and microscopic molecular pathways. With unique advantages， such as multiple targets， multiple pathways， and fewer adverse reactions， TCM provides a new strategy for PD treatment. This article elucidates the mechanism of the Keap1/Nrf2/ARE signaling pathway in the occurrence and development of PD， while summarizing the latest research on PD intervention by TCM monomers， active ingredients， and compounds， as well as acupuncture via the precise targeted regulation of the Keap1/Nrf2/ARE pathway， aiming to provide a reference for clinical medicine development to prevent and treat PD.

ObjectiveTo explore whether fluoroethylnormemantine （FENM）， an NMDA receptor antagonist， could improve compulsive-like behaviors and to investigate its underlying mechanisms in the RU24969-induced obsessive-compulsive disorder （OCD） mouse model. MethodsThirty-two mice were randomly assigned to four groups： Saline （n=8）， RU24969 （n=8）， RU+FENM （n=8）， and FENM （n=8）. Mice received FENM or an equivalent volume of saline for pre-treatment， followed by RU24969 or saline for model induction 30 minutes later. Behavioral tests were performed 1 hour after modeling， and serum samples were collected to measure the level of brain-derived neurotrophic factor （BDNF）. Evans Blue dye was intravenously injected to assess dye content in brain tissue， thereby evaluating potential blood-brain barrier damage. ResultsFENM treatment significantly improved repetitive stereotyped circling behavior （F=39.850， P＜0.001） and alleviated persistent motor activity （F=50.200， P＜0.001） in RU24969 model mice. Additionally， FENM treatment significantly increased serum BDNF level in RU24969-induced OCD mice （F=18.930， P＜0.001）. ConclusionsFENM ， an NMDA receptor antagonist， may alleviate compulsive behaviors in OCD mice by modulating BDNF levels ， thereby exerting anti-compulsive effects. Neither the RU24969 model nor FENM treatment significantly affectes blood-brain barrier integrity.

BackgroundNon-suicidal self-injury （NSSI） behaviors are prevalent among adolescents， significantly affecting their physical and mental well-being. Understanding the risk factors associated with adolescent NSSI is crucial for prevention. Previous studies have identified mobile phone dependence as a risk factor for NSSI in adolescents. However， as a key form of mobile phone dependence， the evidence regarding the impact of mobile phone social media dependence on adolescent NSSI behavior remains insufficient. ObjectiveTo explore the impact of mobile phone social media dependence and its associated factors on adolescent NSSI behavior， so as to provide references for intervention strategies targeting NSSI in adolescents. MethodsA total of 100 adolescents diagnosed with NSSI according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， and receiving treatment at Tongde Hospital of Zhejiang Province from January 2022 to December 2023 were included in the study group. Concurrently， 100 age- and sex-matched students from Hangzhou were recruited as the control group. Assessments were conducted using Ottawa Self-injury Inventory（OSI） Function Subscale and Addiction Features Subscale， Adolescents Self-Harm Scale（ASHS）， and Mobile Phone Social Media Dependence Questionnaire. Multiple linear regression was used to analyze the factors influencing NSSI behaviors. ResultsThe research group had a total of 99 patients （99.00%） who completed the study， while the control group consisted of 97 （97.00%） adolescents who finished this research.The study group had statistically significantly higher total scores on the Mobile Phone Social Media Dependence Questionnaire， as well as higher scores on the conflict and withdrawal dimensions， compared with control group（t=-3.061， -2.874， -2.368， P<0.05 or 0.01）. The study group also scored significantly higher on the OSI Function Subscale for internal emotion regulation， social influence， external emotion regulation， and sensation-seeking factors， as well as on the OSI Addiction Features Subscale scores， compared to the control group（t=-22.249， -8.854， -17.968， -10.591， -20.157， P<0.01）. OSI Function Subscale scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores （r=0.321， P<0.01）， and OSI Addiction Features Subscale scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores （r=0.282， P<0.01）. ASHS scores were positively correlated with Mobile Phone Social Media Dependence Questionnaire scores （r=0.145， P<0.05）. Multiple linear regression analysis showed that compulsivity （β=0.416， P<0.01） and conflict （β=0.256， P<0.05） were significant predictors for adolescent NSSI behaviors. ConclusionAdolescent NSSI behaviors are associated with mobile phone social media dependence. The compulsivity and conflict dimension of mobile phone social media dependence are influencing factors for adolescent NSSI behaviors. The higher level of the compulsivity and conflict are associated with an increased risk of the NSSI behaviors in adolescents. ［Funde by Zhejiang Medical and Health Science and Technology Plan Project in 2022 （number， 2022KY704］

Objective: To evaluate the clinical efficacy of digitally guided precision crown lengthening in secondary aesthetic rehabilitation cases, and to provide a clinical reference for digitally guided crown lengthening procedures and secondary aesthetic restorations. Methods: We present a case of a patient with tetracycline-stained teeth, partial detachment of anterior resin veneers, and gingival margin discrepancies. The patient underwent digitally guided precision crown lengthening followed by secondary aesthetic rehabilitation. Multimodal data, including intraoral, facial, and CBCT scans, were integrated to construct a four-dimensional virtual patient model (incorporating teeth, face, bone, and occlusion) for surgical planning and 3D-printed guide fabrication. Secondary aesthetic restoration was performed after achieving stable post-surgical outcomes. Based on this case, we conducted a detailed analysis and reviewed relevant literature on crown lengthening in secondary aesthetic rehabilitation. Results: The gingival contour of the anterior teeth exhibited significant improvement, with enhanced symmetry and stable gingival margin positioning that closely matched the preoperative design. The crown lengthening procedure demonstrated high precision, and the final outcome was aesthetic and functional. Literature review indicated that secondary restorations frequently present challenges such as gingival contour discrepancies and inflammation. Aesthetic crown lengthening in the anterior region should optimize both soft and hard tissue morphology to meet aesthetic standards, with digital technology improving procedural accuracy. Conclusion Precision crown lengthening effectively addresses gingival margin discrepancies in secondary aesthetic rehabilitation, ensuring stable gingival positioning and superior aesthetic outcomes. This approach is particularly suitable for cases with high aesthetic demands.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.