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.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To explore the value of quantitative parameters of diffusion weighted imaging (DWI) combined with dynamic enhanced magnetic resonance imaging (DCE-MRI) in predicting the efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) .Methods:A total of 97 patients with LABC admitted to the hospital from Mar. 2020 to Mar. 2023 were studied and received neoadjuvant chemotherapy to evaluate the therapeutic effect, and DWI and DCE-MRI scans were performed before and after treatment. The difference of DWI and DCE-MRI quantitative parameters before treatment in patients with different therapeutic effects was compared, and the correlation between the difference of DWI and DCE-MRI quantitative parameters and therapeutic effect was analyzed. The predictive value of quantitative parameters of DWI and DCE-MRI before treatment was analyzed. The quantitative parameters of DWI and DCE-MRI in patients with different pathological reactions were compared before treatment, and the quantitative parameters of DWI and DCE-MRI were compared before and after treatment.Results:The apparent diffusion coefficient (ADC) of patients with effective chemotherapy before treatment was higher, but transport constant (Ktrans) , extracellular space volume percentage (Ve) and rate constant (Kep) were lower ( t=5.0, 3.27, 3.55, 3.89, P < 0.05) ; Spearman correlation analysis showed that ADC was positively correlated with chemotherapy efficacy before treatment (r=0.66; P < 0.05) , while Kep, Ve, Ktrans were negatively correlated with it (r=-0.58, -0.47, -0.60; P < 0.05) ; ROC curves showed that the area under the curve (AUC) values of ADC, Kep, Ve and Ktrans in predicting chemotherapy efficacy before treatment were 0.771, 0.797, 0.664 and 0.715, respectively, while the combined AUC value of each indicator was 0.832; Compared with patients with non-significant pathological response, ADC before treatment was higher in patients with significant pathological response, Kep, Ve and Ktrans were lower ( t=4.46, 3.32, 3.60, 3.95, P < 0.05) ; Compared with before treatment, ADC value increased after treatment, while Kep, Ve and Ktrans decreased ( t=8.77, 6.22, 9.34, 10.26, P < 0.05) . Conclusion:Quantitative parameters of DWI and DCE-MRI can reflect the changes in the condition of patients with locally advanced neoadjuvant chemotherapy, and the combination of the two can help to improve the predictive value of chemotherapy efficacy in patients.

Objective:To explore the predictive value of dual-energy CT lumbar quantitative measurement combined with serum bone alkaline phosphatase (BALP), osteocalcin (BGP), and β-type I collagen carboxy-terminal peptide ( β-CTx) for the risk of fractures in patients with osteoporosis. Methods:A total of 90 patients with osteoporosis who underwent dual-energy CT lumbar quantitative detection at the First People’s Hospital of Shangqiu from Jan. 2020 to Jan. 2023 were selected as the research subjects. According to the occurrence of fractures within one year of follow-up, the patients were divided into the fracture group ( n=36) and the non-fracture group ( n=54). The clinical data, dual-energy CT lumbar quantitative parameters, and serum BALP, BGP, and β-CTx levels of the two groups were compared. Logistic multivariate regression analysis was used to analyze the risk factors for fractures in patients with osteoporosis, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of dual-energy CT lumbar quantitative parameters combined with serum BALP, BGP, and β-CTx for fractures in patients with osteoporosis. Results:There were no statistically significant differences in gender, age, body mass index (BMI), smoking history, drinking history, or bone marrow CT value parameters between the fracture group and the non-fracture group ( χ2=0.66, t=1.86, t=1.59, χ2=0.19, χ2=0.98, t=0.40, all P > 0.05). However, there were statistically significant differences in the history of fragility fractures, regular calcium supplementation, lumbar bone mineral density (BMD), calcium CT value, mixed energy image CT value, calcium concentration, fat fraction, BALP, BGP, and β-CTx ( χ2=9.73, χ2=4.17, t=3.14, t=7.06, t=7.92, t=6.50, t=3.26, t=8.12, t=12.66, t=11.37, all P < 0.05). Logistic multivariate regression analysis showed that the history of fragility fractures ( OR=1.863, P=0.023), regular calcium supplementation ( OR=1.728, P=0.031), fat fraction ( OR=1.685, P=0.009), BALP ( OR=1.815, P=0.002), BGP ( OR=1.605, P=0.003), and β-CTx ( OR=1.636, P < 0.001) were risk factors for fractures in patients with osteoporosis, while lumbar bone BMD ( OR=0.456, P=0.025), calcium CT value ( OR=0.486, P=0.005), mixed energy image CT value ( OR=0.490, P < 0.001), and calcium concentration ( OR=0.509, P=0.010) were protective factors. The ROC curve showed that the sensitivity of dual-energy CT lumbar quantitative measurement parameters combined with serum BALP, BGP, and β-CTx in predicting fractures in patients with osteoporosis was 94.68%, the specificity was 92.16%, the Youden index was 0.868, the area under the curve (AUC) was 0.947, and the 95% confidence interval ( CI) was 0.905 to 0.982. Conclusion:Dual-energy CT lumbar quantitative parameters and serum BALP, BGP, and β-CTx levels have certain predictive value for the risk of fractures in patients with osteoporosis, and the combined prediction value is higher.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

As one of the major diseases threatening human health,the early accurate diagnosis and localization of tumors are crucial for formulating effective treatment plans.In recent years,molecular probes(MPs)have made significant progress in the field of biological imaging.With advantages such as high sensitivity,high specificity,and non-invasiveness,they have become a research hotspot in the field of tumor diagnosis and treatment.This paper systematically reviews the applications of MPs in tumor diagnosis and treatment,covering their classifications(such as fluorescent,photoacoustic,chemiluminescent,bioluminescent,and multimodal probes),design strategies(including active/pas-sive targeting mechanisms and the synergistic construction of identification units,imaging units,signal conversion units and treatment units),as well as detection principles.It also focuses on elabo-rating the research progress of MPs based on enzymes,receptors,reactive substances,and tumor microenvironment.Meanwhile,this paper emphasizes the advantages of multifunctional integration and multimodal imaging,and analyzes the challenges faced by MPs in clinical translation(such as biocompatibility and optimization of supporting equipment).It aims to provide ideas for the develop-ment of high-performance MPs and promote the advancement of precise and personalized tumor di-agnosis and treatment.

Objective:To explore the value of quantitative parameters of diffusion weighted imaging (DWI) combined with dynamic enhanced magnetic resonance imaging (DCE-MRI) in predicting the efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) .Methods:A total of 97 patients with LABC admitted to the hospital from Mar. 2020 to Mar. 2023 were studied and received neoadjuvant chemotherapy to evaluate the therapeutic effect, and DWI and DCE-MRI scans were performed before and after treatment. The difference of DWI and DCE-MRI quantitative parameters before treatment in patients with different therapeutic effects was compared, and the correlation between the difference of DWI and DCE-MRI quantitative parameters and therapeutic effect was analyzed. The predictive value of quantitative parameters of DWI and DCE-MRI before treatment was analyzed. The quantitative parameters of DWI and DCE-MRI in patients with different pathological reactions were compared before treatment, and the quantitative parameters of DWI and DCE-MRI were compared before and after treatment.Results:The apparent diffusion coefficient (ADC) of patients with effective chemotherapy before treatment was higher, but transport constant (Ktrans) , extracellular space volume percentage (Ve) and rate constant (Kep) were lower ( t=5.0, 3.27, 3.55, 3.89, P < 0.05) ; Spearman correlation analysis showed that ADC was positively correlated with chemotherapy efficacy before treatment (r=0.66; P < 0.05) , while Kep, Ve, Ktrans were negatively correlated with it (r=-0.58, -0.47, -0.60; P < 0.05) ; ROC curves showed that the area under the curve (AUC) values of ADC, Kep, Ve and Ktrans in predicting chemotherapy efficacy before treatment were 0.771, 0.797, 0.664 and 0.715, respectively, while the combined AUC value of each indicator was 0.832; Compared with patients with non-significant pathological response, ADC before treatment was higher in patients with significant pathological response, Kep, Ve and Ktrans were lower ( t=4.46, 3.32, 3.60, 3.95, P < 0.05) ; Compared with before treatment, ADC value increased after treatment, while Kep, Ve and Ktrans decreased ( t=8.77, 6.22, 9.34, 10.26, P < 0.05) . Conclusion:Quantitative parameters of DWI and DCE-MRI can reflect the changes in the condition of patients with locally advanced neoadjuvant chemotherapy, and the combination of the two can help to improve the predictive value of chemotherapy efficacy in patients.

Objective:To explore the predictive value of dual-energy CT lumbar quantitative measurement combined with serum bone alkaline phosphatase (BALP), osteocalcin (BGP), and β-type I collagen carboxy-terminal peptide ( β-CTx) for the risk of fractures in patients with osteoporosis. Methods:A total of 90 patients with osteoporosis who underwent dual-energy CT lumbar quantitative detection at the First People’s Hospital of Shangqiu from Jan. 2020 to Jan. 2023 were selected as the research subjects. According to the occurrence of fractures within one year of follow-up, the patients were divided into the fracture group ( n=36) and the non-fracture group ( n=54). The clinical data, dual-energy CT lumbar quantitative parameters, and serum BALP, BGP, and β-CTx levels of the two groups were compared. Logistic multivariate regression analysis was used to analyze the risk factors for fractures in patients with osteoporosis, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of dual-energy CT lumbar quantitative parameters combined with serum BALP, BGP, and β-CTx for fractures in patients with osteoporosis. Results:There were no statistically significant differences in gender, age, body mass index (BMI), smoking history, drinking history, or bone marrow CT value parameters between the fracture group and the non-fracture group ( χ2=0.66, t=1.86, t=1.59, χ2=0.19, χ2=0.98, t=0.40, all P > 0.05). However, there were statistically significant differences in the history of fragility fractures, regular calcium supplementation, lumbar bone mineral density (BMD), calcium CT value, mixed energy image CT value, calcium concentration, fat fraction, BALP, BGP, and β-CTx ( χ2=9.73, χ2=4.17, t=3.14, t=7.06, t=7.92, t=6.50, t=3.26, t=8.12, t=12.66, t=11.37, all P < 0.05). Logistic multivariate regression analysis showed that the history of fragility fractures ( OR=1.863, P=0.023), regular calcium supplementation ( OR=1.728, P=0.031), fat fraction ( OR=1.685, P=0.009), BALP ( OR=1.815, P=0.002), BGP ( OR=1.605, P=0.003), and β-CTx ( OR=1.636, P < 0.001) were risk factors for fractures in patients with osteoporosis, while lumbar bone BMD ( OR=0.456, P=0.025), calcium CT value ( OR=0.486, P=0.005), mixed energy image CT value ( OR=0.490, P < 0.001), and calcium concentration ( OR=0.509, P=0.010) were protective factors. The ROC curve showed that the sensitivity of dual-energy CT lumbar quantitative measurement parameters combined with serum BALP, BGP, and β-CTx in predicting fractures in patients with osteoporosis was 94.68%, the specificity was 92.16%, the Youden index was 0.868, the area under the curve (AUC) was 0.947, and the 95% confidence interval ( CI) was 0.905 to 0.982. Conclusion:Dual-energy CT lumbar quantitative parameters and serum BALP, BGP, and β-CTx levels have certain predictive value for the risk of fractures in patients with osteoporosis, and the combined prediction value is higher.

As one of the major diseases threatening human health,the early accurate diagnosis and localization of tumors are crucial for formulating effective treatment plans.In recent years,molecular probes(MPs)have made significant progress in the field of biological imaging.With advantages such as high sensitivity,high specificity,and non-invasiveness,they have become a research hotspot in the field of tumor diagnosis and treatment.This paper systematically reviews the applications of MPs in tumor diagnosis and treatment,covering their classifications(such as fluorescent,photoacoustic,chemiluminescent,bioluminescent,and multimodal probes),design strategies(including active/pas-sive targeting mechanisms and the synergistic construction of identification units,imaging units,signal conversion units and treatment units),as well as detection principles.It also focuses on elabo-rating the research progress of MPs based on enzymes,receptors,reactive substances,and tumor microenvironment.Meanwhile,this paper emphasizes the advantages of multifunctional integration and multimodal imaging,and analyzes the challenges faced by MPs in clinical translation(such as biocompatibility and optimization of supporting equipment).It aims to provide ideas for the develop-ment of high-performance MPs and promote the advancement of precise and personalized tumor di-agnosis and treatment.