OBJECTIVE: The objective of our study was to evaluate the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) among < 5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study. METHODS: Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis (AGE) cases tested for rotavirus (RV) infection. RV-positive cases were propensity score matched with RV-negative controls for age, visit month, and province. RESULTS: The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis; 7.98% (2,192) were RV-positive. The VE (95% confidence interval, CI) of 1-2 and 3 doses of RV5 against any medically attended RV infection (inpatient or outpatient) was 57.6% (39.8%, 70.2%) and 67.2% (60.3%, 72.9%), respectively. Among children who received the 3rd dose before turning 5 months of age, 3-dose VE decreased from 70.4% (53.9%, 81.1%) (< 5 months since the 3rd dose) to 63.0% (49.1%, 73.0%) (≥ 1 year since the 3rd dose). The three-dose VE rate was 69.4% (41.3%, 84.0%) for RVGE hospitalization and 57.5% (38.9%, 70.5%) for outpatient-only medically attended RVGE. CONCLUSION Three-dose RV5 VE against rotavirus gastroenteritis (RVGE) in children aged < 5 years was higher than 1-2-dose VE. Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age, but remained above 60% for at least one year. VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
Humans ; Rotavirus Vaccines/immunology* ; China/epidemiology* ; Case-Control Studies ; Child, Preschool ; Infant ; Rotavirus Infections/epidemiology* ; Male ; Propensity Score ; Female ; Vaccine Efficacy ; Gastroenteritis/virology* ; Vaccines, Attenuated ; Rotavirus

The aim of this study was to investigate the improvement effect of Wenpi Pills(WPP) on non-alcoholic fatty liver disease(NAFLD). The experiment was divided into two parts, using C57BL/6 mouse models induced by a high-fat diet(HFD) and a methionine and choline deficiency diet(MCD). The HFD-induced experiment lasted for 16 weeks, while the MCD-induced experiment lasted for 6 weeks. Mice in both parts were divided into four groups: control group, model group, low-dose WPP group(3.875 g·kg~(-1), WPP＿L), and high-dose WPP group(15.5 g·kg~(-1), WPP＿H). After sample collection from the HFD-induced mice, lipid content in the serum and liver, liver function indexes in the serum, and hepatic pathology were examined. Real-time fluorescent quantitative reverse transcription PCR(qRT-PCR) was used to detect the expression of lipid-related genes. After sample collection from the MCD-induced mice, serum liver function indexes and inflammatory factors were measured, and hepatic pathology and lipid changes were analyzed by hematoxylin-eosin(HE) staining and widely targeted lipidomic profiling, respectively. The results from the HFD-induced experiment showed that, compared with the HFD group, WPP administration significantly reduced the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), triglyceride(TG), and total cholesterol(TC) in the serum, with the WPP＿H group showing the most significant improvement. HE staining results indicated that, compared with the HFD group, WPP treatment improved the morphology of white adipocytes, reducing their size, and alleviated hepatic steatosis and lipid droplet accumulation. The qRT-PCR results suggested that WPP might increase the mRNA expression of liver cholesterol-converting genes, such as liver X receptor α(LXRα) and cytochrome P450 family 27 subfamily A member 1(CYP27A1), as well as lipid consumption genes like peroxisome proliferator-activated receptor α(PPARα) and adenosine mono-phosphate-activated protein kinase(AMPK). Meanwhile, WPP decreased the mRNA expression of lipid synthesis genes, including fatty acid synthetase(FAS), stearoyl-CoA desaturase 1(SCD1), and sterol regulatory element-binding protein 1c(SREBP-1c), thereby reducing liver lipid accumulation. The results from the MCD-induced experiment showed that, compared with the MCD group, WPP administration reduced the levels of ALT, AST, and inflammatory factors in the serum, thereby alleviating liver injury and the inflammatory response. HE staining of liver tissue indicated that WPP effectively improved hepatic steatosis. Non-targeted lipidomics analysis showed that WPP improved lipid metabolism disorders in the liver, mainly by affecting the metabolism of TG and cholesterol esters. In conclusion, WPP can improve hepatic lipid accumulation in NAFLD mice induced by both HFD and MCD. This beneficial effect is primarily achieved by alleviating liver injury and inflammation, as well as regulating lipid metabolism.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Lipid Metabolism/drug effects* ; Mice ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Diet, High-Fat/adverse effects* ; Liver/drug effects* ; Humans ; Disease Models, Animal ; Methionine

Objective To investigate the impact of immobilization devices and treatment couches on the planned dose in stereotactic body radiation therapy(SBRT).Methods A retrospective study was conducted involving 23 SBRT patients,all of whom underwent CT simulation with foam padding or vacuum bag immobilization.For each patient,two sets of contours were outlined on CT images:one encompassing only the patient's skin(Body),and the other including the skin plus immobilization devices(BodyF).Initially,a reference plan(noFC)meeting clinical requirements was generated based on the Body contour.Without altering the plan(noFC)parameters and field setups,plan calculations were performed separately based on three different contours:BodyF(with immobi-lization devices only),Body+C(with treatment couch only),and BodyF+C(with both immobilization devices and treatment couch),yielding plan(F),plan(C),and plan(FC),respectively.By comparing the target and skin dose parameters across these four plans,the effects of immobilization devices and treatment couches on the planned dose were evaluated.Results Compared to plans based solely on the patient's skin contour,plans incorporating immobilization devices showed reduced high-dose,prescription dose coverage,and average dose in the target volume.Notably,the difference in the percentage of the planning target volume(PTV)receiving 105%of the prescribed dose(PTV/V105%p(%))between plan(FC)and plan(noFC)could reach 61.86%.Conversely,plans with immobilization devices increased both the maximum and average skin doses.Specifically,the dose to 10 cc of skin within 2 mm of the surface(body 2 mm/D 10 cc(Gy))showed a 21.36%difference between plan(FC)and plan(noFC).For all target and skin parameters,no statistically significant differences were observed between plan(C)and plan(noFC).Among plans with immobilization devices,the minimum distance from the target to the skin correlated inversely with skin dose,indicating greater impact on skin dose with closer proximity.Conclusions Immobilization devices in SBRT lead to beam attenuation and altered build-up effects,significantly reducing target dose parameters while increasing skin dose.The closer the target is to the skin,the greater the impact of immobiliza-tion devices on skin dose.It is recommended to incorporate immobilization devices into the contour design during radiotherapy planning.

Objective To investigate the effect of liquid-liquid phase separation(LLPS)of YTH domain family protein 2(YTHDF2)on the sodium arsenite-induced malignant transformation of skin cells,providing a new intervention target for the prevention and control of sodium arsenite-induced carcinogenesis.Methods The HaCaT cell model of malignant transformation was constructed by continuous treatment with 1 μmol/L sodium arsenite for 22 weeks,including cells with normal YTHDF2 LLPS(YTHDF2-wt)and cells with inhibited YTHDF2 LLPS(YTHDF2-mut).Confocal microscopy was employed to observe and characterize the LLPS droplets formed by YTHDF2 during sodium arsenite-induced malignant transformation of skin cells.Cell proliferation,scratch healing,and colony formation assays were performed to detect malignant phenotypes.Western blotting,quantitative reverse transcription PCR,and immunofluorescence experiments were conducted to examine the effects of YTHDF2 LLPS on the mRNA and protein levels of phosphatase and tensin homolog deleted on chromosome ten(PTEN)during sodium arsenite-induced malignant transformation of skin cells.Results After 4 weeks of sodium arsenite treatment,LLPS droplets of YTHDF2 appeared in YTHDF2-wt cells,and the number of droplets gradually increased as the treatment time was prolonged(F=35.252,P<0.001),while no phase-separated droplets were observed in YTHDF2-mut cells.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed enhanced proliferation at the time points of 48 h(t=3.654,P=0.006)and 72 h(t=5.458,P<0.001)after 22 weeks of sodium arsenite treatment.The scratch healing rate of YTHDF2-wt cells was increased at the 8th(t=12.137,P<0.001)and 22th(t=4.484,P=0.011)weeks of sodium arsenite treatment.The number of colonies formed by YTHDF2-wt cells was higher at the 4th(t=3.365,P=0.027),8th(t=5.580,P=0.005),and 22th(t=3.328,P=0.029)weeks of sodium arsenite treatment.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed down-regulated protein(t=-3.119,P=0.036)and mRNA(t=4.051,P=0.015) levels of PTEN after 22 weeks of sodium arsenite treatment.Immunofluorescence results showed that after 4 weeks of sodium arsenite treatment,YTHDF2 LLPS droplets in YTHDF2-wt cells were localized to stress granules,translation-related membrane-less organelles.Conclusions During sodium arsenite-induced malignant transformation of skin cells,YTHDF2 undergoes LLPS and localizes to stress granules,translation-related membrane-less organelles.YTHDF2 LLPS participates in sodium arsenite-induced malignant transformation of skin cells by down-regulating the mRNA level of the key tumor suppressor PTEN.
Arsenites/toxicity* ; Sodium Compounds/toxicity* ; Humans ; Cell Transformation, Neoplastic/drug effects* ; PTEN Phosphohydrolase/metabolism* ; Cell Proliferation ; Skin/cytology* ; RNA-Binding Proteins ; Skin Neoplasms/chemically induced* ; Cell Line

Objective To summarize and analyze the clinicopathological characteristics,imaging manifestations,treatment and prognosis of anaplastic lymphoma kinase(ALK)-positive histiocytosis(APH)involving the central nervous system(CNS),so as to enhance understanding of this rare disease.Methods A retrospective analysis was conducted on 5 cases of CNS-involved APH diagnosed in Huashan Hospital,Fudan University between 2019 and 2023.Clinical,imaging and pathological data were collected,and supplemented by immunohistochemical staining(IHC),fluorescence in situ hybridization(FISH)and high-throughput sequencing for auxiliary diagnosis and molecular characterization.The findings were summarized and integrated with previous literature for a comprehensive analysis.Results All five patients were male,with a mean age of 27.6 years,in which 2 cases exhibited multi-system involvement,while 3 cases exhibited single system involvement.Imaging revealed multiple intracranial lesions in multi-system cases and solitary lesions in single system cases,with well-defined boundaries and homogeneous enhancement.Histologically,tumor cells were intermingled with lymphocytes,displaying an alternating"light and dark"pattern in 1 case.Granuloma-like structures were observed in 4 cases,along with frequent nuclear grooves,indentations and convolutions.Tumor cells usually infiltrated surrounding tissues.IHC demonstrated that tumors expressed histiocytic markers(CD68/CD163)and ALK predominantly expressed in the cytoplasm.FISH confirmed ALK gene rearrangements in all patients,while high-throughput sequencing identified KIF5B-ALK fusions in 2 cases.All single system CNS cases achieved complete remission after surgical resection with or without adjuvant chemotherapy/ALK inhibitors.Among multi-system cases,one achieved partial remission,and one experienced relapse and progression.Conclusion CNS APH is prone to preoperative misdiagnosis.Its histopathological features,ALK immunohistochemical expression,and ALK gene fusions are critical for diagnosis.Patients with single system involvement demonstrate overall superior outcomes compared to multi-system cases.Total resection is effective for localized disease,while multi-system cases require systemic therapy.Multidisciplinary collaboration is crucial for precise diagnosis and treatment.

Objective To observe the clinical efficacy of multi-target repetitive transcranial magnetic stimulation on freezing of gait in Parkinson's disease. Methods A total of 45 Parkinson's disease patients with freezing of gait in our hospital from January 2023 to January 2024 were selected and randomly divided into primary motor cortex(M1) treatment group (M1 group),dorsolateral prefrontal cortex (DLPFC) group (D group),and M1+DLPFC group (MD group),with 15 cases in each group. The stimulation site of patients in M1 group was bilateral M1 region lower limb innervation region,the stimulation site of patients in D group was bilateral DLPFC,and the left M1 region and DLPFC region of patients in MD group were stimulated on alternate days. The efficacy of Parkinson's disease patients with freezing of gait and the changes of mood scores were compared among the groups. Results One patient in D group and one in MD group were lost to follow-up,and 43 patients were eventually included. The freezing of gait questionnaire (FOGQ) scores,timed up and go test (TUGT) total time,modified standing-start 180° turn test (SS-180) time,unified Parkinson's disease rating scale part Ⅲ(UPDRS Ⅲ) scores,Hamilton depression scale (HAMD) scores and Hamilton anxiety scale (HAMA) scores of patients after treatment were improved compared with those before treatment in all three groups (P<0.05),and the improvement effect of MD group was significantly better than those of M1 group and D group (P<0.05). Conclusion High-frequency repetitive transcranial magnetic stimulation targeting bilateral M1 region and DLPFC region can improve freezing of gait,walking ability,and motor function,and alleviate symptoms of depression and anxiety of Parkinson's disease patients.

Objective To investigate the impact of immobilization devices and treatment couches on the planned dose in stereotactic body radiation therapy(SBRT).Methods A retrospective study was conducted involving 23 SBRT patients,all of whom underwent CT simulation with foam padding or vacuum bag immobilization.For each patient,two sets of contours were outlined on CT images:one encompassing only the patient's skin(Body),and the other including the skin plus immobilization devices(BodyF).Initially,a reference plan(noFC)meeting clinical requirements was generated based on the Body contour.Without altering the plan(noFC)parameters and field setups,plan calculations were performed separately based on three different contours:BodyF(with immobi-lization devices only),Body+C(with treatment couch only),and BodyF+C(with both immobilization devices and treatment couch),yielding plan(F),plan(C),and plan(FC),respectively.By comparing the target and skin dose parameters across these four plans,the effects of immobilization devices and treatment couches on the planned dose were evaluated.Results Compared to plans based solely on the patient's skin contour,plans incorporating immobilization devices showed reduced high-dose,prescription dose coverage,and average dose in the target volume.Notably,the difference in the percentage of the planning target volume(PTV)receiving 105%of the prescribed dose(PTV/V105%p(%))between plan(FC)and plan(noFC)could reach 61.86%.Conversely,plans with immobilization devices increased both the maximum and average skin doses.Specifically,the dose to 10 cc of skin within 2 mm of the surface(body 2 mm/D 10 cc(Gy))showed a 21.36%difference between plan(FC)and plan(noFC).For all target and skin parameters,no statistically significant differences were observed between plan(C)and plan(noFC).Among plans with immobilization devices,the minimum distance from the target to the skin correlated inversely with skin dose,indicating greater impact on skin dose with closer proximity.Conclusions Immobilization devices in SBRT lead to beam attenuation and altered build-up effects,significantly reducing target dose parameters while increasing skin dose.The closer the target is to the skin,the greater the impact of immobiliza-tion devices on skin dose.It is recommended to incorporate immobilization devices into the contour design during radiotherapy planning.

Objective To summarize and analyze the clinicopathological characteristics,imaging manifestations,treatment and prognosis of anaplastic lymphoma kinase(ALK)-positive histiocytosis(APH)involving the central nervous system(CNS),so as to enhance understanding of this rare disease.Methods A retrospective analysis was conducted on 5 cases of CNS-involved APH diagnosed in Huashan Hospital,Fudan University between 2019 and 2023.Clinical,imaging and pathological data were collected,and supplemented by immunohistochemical staining(IHC),fluorescence in situ hybridization(FISH)and high-throughput sequencing for auxiliary diagnosis and molecular characterization.The findings were summarized and integrated with previous literature for a comprehensive analysis.Results All five patients were male,with a mean age of 27.6 years,in which 2 cases exhibited multi-system involvement,while 3 cases exhibited single system involvement.Imaging revealed multiple intracranial lesions in multi-system cases and solitary lesions in single system cases,with well-defined boundaries and homogeneous enhancement.Histologically,tumor cells were intermingled with lymphocytes,displaying an alternating"light and dark"pattern in 1 case.Granuloma-like structures were observed in 4 cases,along with frequent nuclear grooves,indentations and convolutions.Tumor cells usually infiltrated surrounding tissues.IHC demonstrated that tumors expressed histiocytic markers(CD68/CD163)and ALK predominantly expressed in the cytoplasm.FISH confirmed ALK gene rearrangements in all patients,while high-throughput sequencing identified KIF5B-ALK fusions in 2 cases.All single system CNS cases achieved complete remission after surgical resection with or without adjuvant chemotherapy/ALK inhibitors.Among multi-system cases,one achieved partial remission,and one experienced relapse and progression.Conclusion CNS APH is prone to preoperative misdiagnosis.Its histopathological features,ALK immunohistochemical expression,and ALK gene fusions are critical for diagnosis.Patients with single system involvement demonstrate overall superior outcomes compared to multi-system cases.Total resection is effective for localized disease,while multi-system cases require systemic therapy.Multidisciplinary collaboration is crucial for precise diagnosis and treatment.

Objective To observe the clinical efficacy of multi-target repetitive transcranial magnetic stimulation on freezing of gait in Parkinson's disease. Methods A total of 45 Parkinson's disease patients with freezing of gait in our hospital from January 2023 to January 2024 were selected and randomly divided into primary motor cortex(M1) treatment group (M1 group),dorsolateral prefrontal cortex (DLPFC) group (D group),and M1+DLPFC group (MD group),with 15 cases in each group. The stimulation site of patients in M1 group was bilateral M1 region lower limb innervation region,the stimulation site of patients in D group was bilateral DLPFC,and the left M1 region and DLPFC region of patients in MD group were stimulated on alternate days. The efficacy of Parkinson's disease patients with freezing of gait and the changes of mood scores were compared among the groups. Results One patient in D group and one in MD group were lost to follow-up,and 43 patients were eventually included. The freezing of gait questionnaire (FOGQ) scores,timed up and go test (TUGT) total time,modified standing-start 180° turn test (SS-180) time,unified Parkinson's disease rating scale part Ⅲ(UPDRS Ⅲ) scores,Hamilton depression scale (HAMD) scores and Hamilton anxiety scale (HAMA) scores of patients after treatment were improved compared with those before treatment in all three groups (P<0.05),and the improvement effect of MD group was significantly better than those of M1 group and D group (P<0.05). Conclusion High-frequency repetitive transcranial magnetic stimulation targeting bilateral M1 region and DLPFC region can improve freezing of gait,walking ability,and motor function,and alleviate symptoms of depression and anxiety of Parkinson's disease patients.