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.

Acute lung injury （ALI） is one of the most common and critical diseases in clinical practice， with extremely high morbidity and mortality， seriously threatening human life and health. The pathogenesis of ALI is complex， in which the inflammatory response is a key factor. Studies have shown that NOD-like receptor protein 3 （NLRP3） inflammasomes are involved in ALI through mechanisms such as inflammation induction， increased microvascular permeability， recruitment of neutrophils， oxidative stress， and pyroptosis， playing a key role in the occurrence and progression of ALI. Therefore， regulating NLRP3 inflammasomes and inhibiting the release of inflammatory factors can alleviate the damage in ALI. At present， ALI is mainly treated by mechanical ventilation and oxygen therapy， which have problems such as high costs and poor prognosis. In recent years， studies have shown that traditional Chinese medicine （TCM） can reduce the inflammatory response and the occurrence of oxidative stress and pyroptosis by regulating the NLRP3 inflammasome， thus alleviating the damage and decreasing the mortality of ALI. Based on the relevant literature in recent years， this article reviews the research progress in TCM treatment of ALI by regulating NLRP3 inflammasomes， discusses how NLRP3 inflammasomes participate in ALI， and summarizes the active ingredients， extracts， and compound prescriptions of TCM that regulate NLRP3 inflammasomes， aiming to provide new ideas for the clinical treatment of ALI and the development of relevant drugs.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

[Objective]To investigate the presence of SARS-CoV-2 RNA in semen after COVID-19 infection in vaccinated individuals and to evaluate the impact of different recovery stages on sperm quality.[Methods]From January to March 2023,vaccinated male patients with recent SARS-CoV-2 infections confirmed by throat swabs were recruited from the Reproductive Medicine Center at the First Affiliated Hospital of Anhui Medical University.Semen samples were analyzed with RT-qPCR to detect SARS-CoV-2 RNA.A retrospective analysis assessed sperm quality across recovery stages,comparing patients within 30 days of recovery to those with 30 days or more.Semen parameters evaluated included volume,total sperm count,forward motility percentage,abnormal morphology rate,and sperm DNA fragmentation index.In addition,a longitudinal self-comparison was performed to examine changes in semen quality before and after recovery(＜30 days and≥30 days).[Results]SARS-CoV-2 RNA was undetectable in the semen of all 205 patients.Neither cross-sectional comparisons nor longitudinal analyses showed significant differences in semen volume,sperm concentration,total sperm count,sperm morphology rate,sperm DNA fragmentation index,or high DNA stainability between recovery stages or compared to pre-infection values(P＞0.05).However,forward motility percentage markedly decreased during recovery,with statistical significant between groups(P＜0.05).[Conclusions]In vaccinated individuals who contracted COVID-19,SARS-CoV-2 was not transmitted through semen.Although the incidence of asthenozoospermia may increase within 30 days post-infection,this effect appears reversible in the short time.

Objective To evaluate the applicability and guideline concordance of the Chinese Society of Clinical Oncology(CSCO)arti-ficial intelligence(AI)system in clinical decision-making for colorectal cancer(CRC)patients,and to explore its feasibility in real-world clinical applications.Methods A total of 972 CRC patients diagnosed and treated at the Second Affiliated Hospital,Zhejiang University School of Medicine,from January 2010 to December 2021,were included.Patient data were analyzed by the CSCO AI system to gener-ate treatment decisions,and decision concordance was assessed by a blinded independent central review(BICR)panel.The applicability and guideline concordance rates of the CSCO AI system were calculated for different treatment stages,and a logistic regression model was used to analyze factors influencing the system's decision discrepancies with actual treatments.Results The overall applicability rate of the CSCO AI system was 96.2%,and the overall guideline concordance rate was 94.9%.In the adjuvant and palliative treatment stages,the system's applicability rates were 95.8%and 96.7%,respectively,and the guideline concordance rates were 95.0%and 94.9%,respective-ly.Multivariate logistic regression analysis showed that age≥65 years and high-risk stage Ⅱ treatment were significant factors affecting guideline concordance in the adjuvant treatment stage(both P<0.05).Conclusions The CSCO AI system demonstrated high applicability and guideline concordance in the adjuvant and palliative treatment stages for CRC.The system's clinical decision-making potential is sig-nificant,and it can be further optimized for specific clinical scenarios and promoted for use across various medical institutions.

AIM:To explore the mechanism of Chonghe paste in regulating PTEN-induced kinase 1(PINK1)/parkin pathway-mediated mitophagy on diabetic ulcer wound healing.METHODS:Thirty-six rats were used to construct a diabetic ulcer model by high-sugar and high-fat feed,intraperitoneal injection of streptozotocin and skin defect method,and were randomly divided into model group,Chonghe paste group and growth factor group,with 12 rats in each group.Another 12 rats were taken to construct normal wound model as normal group.The rats in normal group and model group were treated with normal saline for debridement,while those in Chonghe paste group and growth factor group were treated with Chonghe paste and growth factors for wound coating,respectively.The changes in fasting blood glucose and wound healing were observed and recorded,and samples were collected on the 7th and 14th days after treatment.The expression levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),P62 and collagen type Ⅲ(COL3)in granulation tissues were detected by immunohistochemistry.The mitochondrial ultrastructure was observed under an electron microscope,and the number of autophagosomes was recorded.The expression of PINK1,parkin and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)in wound tissues was detected by immunofluorescence,Western blot and RT-qPCR.RE-SULTS:Compared with normal group,the blood glucose levels of the rats in model group,Chonghe paste group and growth factor group were higher than 16.67 mmol/L on the 7th,14th and 28th days,indicating successful modeling of dia-betes.Compared with normal group,the rats in model group had a lower wound healing rate,the mean absorbance of IL-6,TNF-α and P62 was increased,the mean absorbance of COL3 was decreased,the number of autophagosomes per unit area was increased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was decreased,and the mRNA and protein expres-sion levels of PINK1,parkin and LC3-Ⅱ were decreased.Compared with model group,the wound healing rate of the rats in Chonghe paste group and growth factor group was increased,the mean absorbance of IL-6,TNF-α and P62 was de-creased,the mean absorbance of COL3 was increased,the number of autophagosomes per unit area was decreased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was increased,and the mRNA and protein expression levels of PINK1,parkin and LC3-Ⅱ were elevated.CONCLUSIONS:Chonghe paste can alleviate local inflammatory response in diabetic ulcer wounds,reduce the levels of inflammatory factors IL-6 and TNF-α,promote COL3 expression,activate the PINK1/parkin signaling pathway,and promote mitophagy in wounds,thus accelerating wound healing.

Objective To evaluate the applicability and guideline concordance of the Chinese Society of Clinical Oncology(CSCO)arti-ficial intelligence(AI)system in clinical decision-making for colorectal cancer(CRC)patients,and to explore its feasibility in real-world clinical applications.Methods A total of 972 CRC patients diagnosed and treated at the Second Affiliated Hospital,Zhejiang University School of Medicine,from January 2010 to December 2021,were included.Patient data were analyzed by the CSCO AI system to gener-ate treatment decisions,and decision concordance was assessed by a blinded independent central review(BICR)panel.The applicability and guideline concordance rates of the CSCO AI system were calculated for different treatment stages,and a logistic regression model was used to analyze factors influencing the system's decision discrepancies with actual treatments.Results The overall applicability rate of the CSCO AI system was 96.2%,and the overall guideline concordance rate was 94.9%.In the adjuvant and palliative treatment stages,the system's applicability rates were 95.8%and 96.7%,respectively,and the guideline concordance rates were 95.0%and 94.9%,respective-ly.Multivariate logistic regression analysis showed that age≥65 years and high-risk stage Ⅱ treatment were significant factors affecting guideline concordance in the adjuvant treatment stage(both P<0.05).Conclusions The CSCO AI system demonstrated high applicability and guideline concordance in the adjuvant and palliative treatment stages for CRC.The system's clinical decision-making potential is sig-nificant,and it can be further optimized for specific clinical scenarios and promoted for use across various medical institutions.

[Objective]To investigate the presence of SARS-CoV-2 RNA in semen after COVID-19 infection in vaccinated individuals and to evaluate the impact of different recovery stages on sperm quality.[Methods]From January to March 2023,vaccinated male patients with recent SARS-CoV-2 infections confirmed by throat swabs were recruited from the Reproductive Medicine Center at the First Affiliated Hospital of Anhui Medical University.Semen samples were analyzed with RT-qPCR to detect SARS-CoV-2 RNA.A retrospective analysis assessed sperm quality across recovery stages,comparing patients within 30 days of recovery to those with 30 days or more.Semen parameters evaluated included volume,total sperm count,forward motility percentage,abnormal morphology rate,and sperm DNA fragmentation index.In addition,a longitudinal self-comparison was performed to examine changes in semen quality before and after recovery(＜30 days and≥30 days).[Results]SARS-CoV-2 RNA was undetectable in the semen of all 205 patients.Neither cross-sectional comparisons nor longitudinal analyses showed significant differences in semen volume,sperm concentration,total sperm count,sperm morphology rate,sperm DNA fragmentation index,or high DNA stainability between recovery stages or compared to pre-infection values(P＞0.05).However,forward motility percentage markedly decreased during recovery,with statistical significant between groups(P＜0.05).[Conclusions]In vaccinated individuals who contracted COVID-19,SARS-CoV-2 was not transmitted through semen.Although the incidence of asthenozoospermia may increase within 30 days post-infection,this effect appears reversible in the short time.

AIM:To explore the mechanism of Chonghe paste in regulating PTEN-induced kinase 1(PINK1)/parkin pathway-mediated mitophagy on diabetic ulcer wound healing.METHODS:Thirty-six rats were used to construct a diabetic ulcer model by high-sugar and high-fat feed,intraperitoneal injection of streptozotocin and skin defect method,and were randomly divided into model group,Chonghe paste group and growth factor group,with 12 rats in each group.Another 12 rats were taken to construct normal wound model as normal group.The rats in normal group and model group were treated with normal saline for debridement,while those in Chonghe paste group and growth factor group were treated with Chonghe paste and growth factors for wound coating,respectively.The changes in fasting blood glucose and wound healing were observed and recorded,and samples were collected on the 7th and 14th days after treatment.The expression levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),P62 and collagen type Ⅲ(COL3)in granulation tissues were detected by immunohistochemistry.The mitochondrial ultrastructure was observed under an electron microscope,and the number of autophagosomes was recorded.The expression of PINK1,parkin and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)in wound tissues was detected by immunofluorescence,Western blot and RT-qPCR.RE-SULTS:Compared with normal group,the blood glucose levels of the rats in model group,Chonghe paste group and growth factor group were higher than 16.67 mmol/L on the 7th,14th and 28th days,indicating successful modeling of dia-betes.Compared with normal group,the rats in model group had a lower wound healing rate,the mean absorbance of IL-6,TNF-α and P62 was increased,the mean absorbance of COL3 was decreased,the number of autophagosomes per unit area was increased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was decreased,and the mRNA and protein expres-sion levels of PINK1,parkin and LC3-Ⅱ were decreased.Compared with model group,the wound healing rate of the rats in Chonghe paste group and growth factor group was increased,the mean absorbance of IL-6,TNF-α and P62 was de-creased,the mean absorbance of COL3 was increased,the number of autophagosomes per unit area was decreased,the mean absorbance of PINK1,parkin and LC3-Ⅱ was increased,and the mRNA and protein expression levels of PINK1,parkin and LC3-Ⅱ were elevated.CONCLUSIONS:Chonghe paste can alleviate local inflammatory response in diabetic ulcer wounds,reduce the levels of inflammatory factors IL-6 and TNF-α,promote COL3 expression,activate the PINK1/parkin signaling pathway,and promote mitophagy in wounds,thus accelerating wound healing.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.