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

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

Aim To identify the molecular target of gabapentin in the treatment of postherpetic neuralgia(PHN). Methods The molecular target of gabapentin for PHN was analyzed by network pharmacology and molecular docking and confirmed by coprecipitation test. Rats were randomly divided into control group, model group, model+50 mg·kg-1 gabapentin group, model+100 mg·kg-1 gabapentin group, and model+200 mg·kg-1 gabapentin group, with nine rats in each group. The pain-related behaviors of the rats were measured at different time points. The mRNA and protein expressions of CACNA2D1, Bax, and Bcl-2 in rat spinal cord were determined by immunofluorescence, Western blot, and qPCR. Results CACNA2D1 was the target gene of gabapentin that determined via network pharmacology, molecular docking, and co-precipitation tests. After modeling, mechanical pain threshold and thermal pain threshold significantly decreased, and the number of apoptotic GABA cells significantly increased. However, after intraperitoneal injection of 50, 100, and 200 mg·kg-1 gabapentin, mechanical pain threshold and thermal pain threshold significantly increased(P<0.05), and the number of apoptotic GABA cells significantly decreased(P<0.01). Immunofluorescence and Western blot results showed that compared with the model group, with the increase of gabapentin concentration, the positive expression rate of Bax significantly decreased, and the positive expression rate of Bcl-2 and CACNA2D1 significantly increased. The mRNA expression levels of Bax, Bcl-2 and CACNA2D1 detected by qPCR were consistent with the results of immunofluorescence and Western blot. Conclusions Gabapentin up-regulates the expression of target protein CACNA2D1, inhibits the proapoptotic protein Bax, and promotes the expression of apoptotic inhibitor Bcl-2.

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities

Objective To explore the potential targets of triclosan in the treatment of nonalcoholic fatty liver disease(NAFLD) and to provide new clues for the future research on the application of triclosan. Methods The targets of triclosan and NAFLD were obtained via network pharmacology.The protein-protein interaction network was constructed with the common targets shared by triclosan and NAFLD.The affinity of triclosan to targets was verified through molecular docking.Gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out to analyze the key targets and the potential mechanism of action.NAFLD model was established by feeding male C57BL/6J mice with high-fat diet for 12 weeks.The mice were randomly assigned into a model group and a triclosan group [400 mg/(kg·d),gavage once a day for 8 weeks].The hematoxylin-eosin(HE) staining was used for observation of the pathological changes and oil red O staining for observation of fat deposition in mouse liver.Western blotting was employed to detect the protein level of peroxisome proliferator-activated receptor alpha(PPARα) in the liver tissue. Results Triclosan and NAFLD had 34 common targets,19 of which may be the potential targets for the treatment,including albumin(ALB),PPARα,mitogen-activated protein kinase 8(MAPK8),and fatty acid synthase.Molecular docking predicted that ALB,PPARα,and MAPK8 had good binding ability to triclosan.KEGG pathway enrichment showcased that the targets were mainly enriched in peroxisome proliferator-activated receptor signaling pathway,in which ALB and MAPK8 were not involved.Triclosan alleviated the balloon-like change and lipid droplet vacuole,decreased the lipid droplet area,and up-regulated the expression level of PPARα in mouse liver tissue. Conclusion PPARα is a key target of triclosan in the treatment of NAFLD,which may be involved in fatty acid oxidation through the peroxisome proliferator activated receptor signaling pathway.
Animals ; Liver/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Non-alcoholic Fatty Liver Disease/drug therapy* ; PPAR alpha/therapeutic use* ; Triclosan/therapeutic use*

Antibodies, Viral ; blood ; Betacoronavirus ; Coronavirus ; immunology ; Coronavirus Infections ; immunology ; Humans ; Immunoglobulin G ; blood ; Pandemics ; Pneumonia, Viral ; immunology

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
Child ; Factor VIII/therapeutic use* ; Hemarthrosis ; Hemophilia A/drug therapy* ; Hemorrhage ; Humans ; Retrospective Studies

OBJECTIVETo investigate the effects of rhubarb powder on serum complement 3 (C3), complement 4 (C4), and hypersensitive C-reactive protein (hs-CRP) levels in patients with hypertensive intracerebral hemorrhage (HICH) after operation.

METHODSForty inpatients with HICH after operation were recruited from Department of Cerebral Surgery, Affiliated Hospital of Shaanxi College of Traditional Chinese Medicine from July 2009 to March 2010. They were randomly assigned to the treatment group (20 cases) and the control group (20 cases). From the 4th day after surgery, all patients received routine Western medical treatment. The rhubarb powder, 5-10 g dissolving in 40 mL warm water, was administered or nasally fed to those in the treatment group, 2 -3 times daily for 10 successive days. The contents of serum C3, C4, and hs-CRP were detected in the two groups on the 7th day and the 14th day after operation. The serum hs-CRP content was detected using latex particle enhanced immunoturbidimetric assay. The Scandinavia Stroke Scale (SSS) scores were recorded in the two groups.

RESULTSCompared with the same group on the 4th day after operation, the levels of serum C3 and C4 increased on the 7th day after operation, and SSS score increased on the 14th day after operation in the control group (P < 0.05). The contents of C4 and hs-CRP decreased, and the SSS score increased on the 14th day after operation in the treatment group (P < 0.05). Compared with the same group on the 7th day after operation, the contents of C4 and hs-CRP decreased and the SSS score increased on the 14th day after operation in the treatment group (P < 0.05). Compared with the control group at the same time points, the contents of C4 and C3 decreased on the 7th day after operation; the contents of C3, C4, and hs-CRP decreased, and SSS score increased in the treatment group on the 14th day after operation (P < 0.05).

CONCLUSIONThe rhubarb powder could significantly decrease the serum levels of C3, C4, and hs-CRP, and improve the curative effect in patients with HICH after operation.

Adult ; C-Reactive Protein ; metabolism ; Cerebral Hemorrhage ; blood ; Complement C3 ; metabolism ; Complement C4 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Male ; Middle Aged ; Postoperative Period ; Rheum ; chemistry

OBJECTIVETo evaluate the diagnostic value and safety of percutaneous lung biopsy in hematologic patients with lung infection.

METHODS28 cases hematologic patients received CT-guided percutaneous lung biopsy when they developed a fever associated with pulmonary nodules or lumps in CT scan whose clinical diagnosis were unclear during or after chemotherapy. Sample of each lesion were drawn twice. The lung tissue was re-scanned after lung biopsy to check up in order to discover bleeding and pneumothorax. Biopsy tissue was examined by bacteria culture, acid-fast staining and pathology. Pathological examination contained HE staining, acid-fast stain, PAS stain, TB-DNA, methenamine silver and others.

RESULTS28 cases contain 24 males and 4 females. Median age was 40 15 - 77 years old. Blood tests were as follows: 3 cases with HGB > 110 g/L, 9 with HGB 90 - 110 g/L, 12 with HGB 60 - 89 g/L, 4 with HGB < 60 g/L. 8 with WBC > 10×10(9)/L, 6 with WBC (4 - 10)×10(9)/L, 13 with WBC < 4×10(9)/L, 1 with WBC < 2×10(9)/L; 14 with PLT > 100×10(9)/L, 5 with PLT (50 - 100)×10(9)/L, 5 with PLT < 50×10(9)/L, 4 with PLT < 30×10(9)/L. 4 cases had mild extended PT, 3 mild extended APTT, 3 FIB lower than normal. Lung CT scans were as follows: 4 cases with simply lesion in right lung, 4 with simply lesion in left lung, 20 with lesions in bilateral lung. 8 cases were diagnosed as fungal infection, 3 as tuberculosis infection, 1 as lung cancer, 1 as pulmonary infiltration of lymphoma, 1 as pulmonary infiltration of leukemia, and 14 as inflammatory changes with no specific diagnosis. 4 cases came with pneumothorax during lung biopsy, mild to moderate in 3 cases and severe in 1 case. Severe patient turned better after CT-guided suction. 3 cases with mild hemoptysis turned better after treatment.

CONCLUSIONWhen hematopathy patients are with pulmonary nodules or lumps in CT scan whose clinical diagnosis is unclear, CT-guided percutaneous lung biopsy is safe and conducive to early diagnosis and conducive to early rehabilitation of patients if the coagulation function is basically normal and platelet count is not too low.

Adolescent ; Adult ; Aged ; Biopsy ; Female ; Hematologic Diseases ; microbiology ; pathology ; Humans ; Lung ; pathology ; Male ; Middle Aged ; Pneumonia ; diagnosis ; Young Adult