Objective:To understand the pathogen infection and epidemiological characteristics of children with diarrhea in Tianjin.Methods:Stool samples from 1 466 children with diarrhea in Tianjin Children's Hospital from August 2017 to July 2018 were collected, and all samples were tested for five intestinal-related pathogens (norovirus, rotavirus, Clostridium difficile toxin, adenovirus, and astrovirus). Results:Among the 1 466 samples, 627 samples were positive for nucleic acid detection of intestinal pathogens, with a positive rate of 42.8%. The detection rate of norovirus was the highest (26.3%), followed by rotavirus (15.3%), Clostridium difficile toxin (4.6%), adenovirus (4.1%), and astrovirus (1.84%). The infection has obvious seasonality. The positive detection rates of the five pathogens were similar among children of different sexes, and only the positive detection rates of norovirus and rotavirus were statistically significant among different ages ( P<0.05). There were 110 cases of mixed infection, and the mixed infection of norovirus and rotavirus was the most common, with a total of 37 cases. Conclusions:The pathogen spectrum of infant infectious diarrhea in Tianjin is complex and diverse, and the main pathogens are norovirus and rotavirus.

Adult-onset Still disease (AOSD) is a polygenic autoinflammatory disease with uncertain etiology.The clinical manifestations are complex,including high-spiking fever,rash,arthritis,arthralgia,lymphadenopathy,and leukocytosis.The pathogenesis of AOSD is still unclear,whereas it has been confirmed that many inflammatory cells and cytokines take part in the development of AOSD.The treatment of AOSD is mainly based on corticosteroids and immunosuppressive agents.Recently,with the research progress of autoinflammatory diseases and the emerging biological agents,we have new knowledge on the pathogenesis and therapeutic strategies of AOSD.This article reviews the current progress in pathogenesis and therapy of AOSD.

ObjectiveTo investigate the mechanism of Xuefu Zhuyu capsules against atherosclerosis via regulating polarization of macrophages based on Notch1/jagged canonical Notch ligand 1（Jagged1）/Hes family BHLH transcription factor 1（Hes1） signaling pathway. MethodThe mouse models with atherosclerosis were prepared by feeding the mice with an ApoE^-/- high-fat diet for four weeks， and they were randomly divided into the model group， Xuefu Zhuyu capsule group， and atorvastatin group. C57BL/6 mice were fed as a normal group. The Xuefu Zhuyu capsule group was intragastrically given Xuefu Zhuyu capsules （0.728 g·kg^-1·d^-1）， and the atorvastatin group was intragastrically given atorvastatin tablet （6.07 mg·kg^-1·d^-1）. The normal group and the model group were given equal volume of the deionized water by intragastric administration， and the intervention lasted for 12 weeks. Aortic plaque morphology was observed by hematoxylin-eosin （HE） staining， and aortic plaque area and lipid deposition were observed by oil red O staining. The positive expression levels of CD86 and CD206 in aortic tissue were detected by immunohistochemistry， and serum levels of tumor necrosis factor （TNF）-α， interleukin（IL）-1β， transforming growth factor （TGF）-β₁， and IL-10 were detected by enzyme-linked immunosorbent assay （ELISA）. The relative mRNA expressions of inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， Notch1， Jagged1， and Hes1 in aortic tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The relative protein expression of iNOS， Arg-1， Notch1， Jagged1， and Hes1 in aortic tissue was detected by Western blot. ResultCompared with the normal group， the model group had significant aortic plaque and lipid deposition， and the expression levels of pro-inflammatory cytokines TNF-α and IL-1β were increased （P<0.01）. The expression level of anti-inflammatory cytokine TGF-β₁ showed a downward trend， but the difference was not statistically significant. The mRNA and protein expressions of iNOS were increased （P<0.01）. The protein expression of Arg-1 was decreased （P<0.01）， and the mRNA expression of related pathway molecule Jagged1， as well as the protein expressions of Notch1， Jagged1， and Hes1 were increased in the model group （P<0.05， P<0.01）. Compared with those in the model group， the plaque area and lipid deposition had a decreasing trend in the Xuefu Zhuyu capsule group， and the expressions of TNF-α and IL-1β showed a downward trend. The expression of TGF-β₁ was increased （P<0.05）， and the expression of macrophage marker CD86 was decreased. The mRNA and protein expressions of iNOS were decreased （P<0.01）. The mRNA and protein expressions of Arg-1 were increased （P<0.05， P<0.01）. Furthermore， the mRNA and protein expressions of Notch1， Jagged1， and Hes1 were decreased （P<0.01）. ConclusionXuefu Zhuyu capsules can reduce aortic plaque area and lipid deposition in mice with atherosclerosis， alleviate inflammation， inhibit M1 macrophages， and promote the expression of M2 macrophages， and the mechanism may be related to the regulation of Notch1/Jagged1/Hes1 signaling pathway.

Objective:To explore the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain and its subtypes on the risk of preeclampsia.Methods:Pregnant women delivered in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016 were selected as the research subjects. According to the inclusion and exclusion criteria, 9 274 pregnant women were included. 901 preeclampsia pregnant women were selected as the case group, and 8 373 non-preeclampsia pregnant women were selected as the control group. General demographic characteristics, pre-pregnancy weight, height, lifestyle during pregnancy, reproductive history, and disease history of pregnant women were collected, and pre-pregnancy BMI and gestational weight gain were calculated. Unconditional logistic regression was used to analyze the relationship between pre-pregnancy BMI and weight gain during pregnancy and PE and its clinical subtypes.Results:Among the 901 preeclampsia after inclusion and exclusion, 401 cases were diagnosed as early-onset PE (EOPE), 500 cases were late-onset PE (LOPE), 178 cases were Mild PE (MPE), and 723 cases were severe PE (SPE). There were statistically significant differences between PE and non-PE pregnant women in terms of maternal age, residence, parity, family history of gestational diabetes and hypertension ( P<0.05). After adjusting for the above factors, the logistic regression analysis results showed that pre-pregnancy BMI<18.5 kg/m 2 and inadequate gestational weight gain were protective factors for PE ( OR=0.74, 95% CI: 0.56-0.98; OR=0.78, 95% CI: 0.62-0.99), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for PE ( OR=1.82, 95% CI: 1.54-2.14; OR=1.82, 95% CI: 1.54-2.15). After subtype analysis on PE, the results showed that pre-pregnancy BMI<18.5 kg/m 2 was a protective factor for EOPE and MPE ( OR=0.52, 95% CI: 0.32-0.83; OR=0.47, 95% CI: 0.23-0.97), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for clinical subtypes of PE. After stratification according to pre-pregnancy BMI, excessive gestational weight gain was the risk factor for PE ( OR=1.86, 95% CI: 1.51-2.30; OR=1.90, 95% CI: 1.39-2.60) in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 and ≥24.0 kg/m 2. Inadequate gestational weight gain ( OR=0.55, 95% CI: 0.34-0.89) was a protective factor for PE in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive gestational weight gain ( OR=4.05, 95% CI: 1.20-13.69) was a risk factor for EOPE in pregnant women with pre-pregnancy BMI<18.5 kg/m 2. Excessive gestational weight gain was a risk factor for the clinical subtype of PE in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 before pregnancy. Inadequate gestational weight gain was a protective factor for EOPE and MPE ( OR=0.39, 95% CI: 0.19-0.80; OR=0.29, 95% CI: 0.11-0.77) in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive weight gain was a risk factor for EOPE, LOPE and SPE ( OR=1.60, 95% CI: 1.06-2.42; OR=2.20, 95% CI: 1.44-3.37; OR=2.28, 95% CI: 1.58-3.29). Conclusions:Pre-pregnancy BMI and gestational weight gain affect the risk of preeclampsia and its clinical subtypes. In contrast, the influence of gestational weight gain on preeclampsia varies among different pre-pregnancy BMI groups. Therefore, it is recommended to pay attention to the changes in pre-pregnancy BMI and gestational weight gain simultaneously to reduce preeclampsia.

Objective:To investigate the molecular epidemiologic and clinical characteristics of norovirus (NoV) in hospitalized children with acute gastroenteritis (AGE) in Tianjin to provide theoretical basis for clinical diagnosis and treatment.Methods:Fecal specimens were collected from children with AGE in Tianjin Children′s Hospital from August 2017 to July 2020. NoV was detected by real-time fluorescence reverse transcription-polymerase chain reaction (RT-PCR). Partial sequence of the capsid protein VP1 of positive samples was amplified by conventional RT-PCR. The products were sent for sequencing and genotyping based on the sequence. As the same time, the clinical symptoms were compared among children infected with different NoV genotypes.Results:Among the 6 432 specimens, 1 703 (26.5%) were positive for NoV. Sequence analysis showed that 761 identified NoV strains could be divided into 7 genotypes. Genotypes GII.4, GII.3, GII.2, GII.17, GII.1, GII.13 and GII.6 accounted for 55.5% (422/761), 36.7% (279/761), 4.9% (37/761), 0.9% (7/761), 0.8% (6/761), 0.8% (6/761) and 0.5% (4/761), respectively. All of the GII.4 belonged to GII.4 Sydney 2012. There was also a significant difference in the seasonal distribution of children infected with GII.4 and other genotypes ( χ2=103.53, P<0.001). Children infected with GII.4 NoV were more likely to have diarrhea, vomiting and dehydration ( χ2=8.42, P=0.004; χ2=20.39, P<0.001; χ2=4.99, P=0.025). Conclusions:GII.4 and GII.3 were mainly genotypes of NoV infection in Tianjin from 2017 to 2020 and genotypes were diverse. In addition, children with GII.4 NoV were more likely to suffer from diarrhea, vomiting and dehydration.

Objective To investigate the role of H9c2-derived exosomes in regulating angiogenesis in rat cardiomyocytes under hypoxia.Methods The hypoxia model of H9c2 cells was prepared by mixed gas method(the hypoxia model group),and the normal cultured cells were used as the control group.The exosomes secreted by the two groups of cells were extracted respectively.The concentration and particle size of exosomes were detected by nanoparticle tracking analysis.The morphology and size of exosomes were detected by transmission electron microscopy.Western blot assay was used to verify the exosome marker proteins.The hypoxia model of human umbilical vein endothelial cells(HUVEC)was established.HUVECs were incubated with H9c2 exosomes and divided into the normoxia group,the hypoxia group,the hypoxia+normal H9c2 exosomes(EXO-C)group and the hypoxia+hypoxia H9c2 exosomes(EXO-M)group.The proliferation,migration and tube formation of HUVECs were detected by CCK-8 method,cell scratch test and Matrigel in vitro three-dimensional forming test.Results The results of exosome identification showed that the particle concentration of H9c2 exosome samples was 1×107-1×1012 particles/mL and the particle size was 40-160 nm in the normoxia group and the hypoxia group.The morphological characteristics were spherical or saucer-like structure,uniform in size and complete in shape.Exosome marker proteins TSG101,CD63 and CD9 were expressed,and there was no expression of negative protein Calnexin.Compared with the normoxic group,the proliferation ability,migration area and migration rate of HUVEC were significantly decreased in the hypoxic group,and the length of tube,the number of branches and the number of nodes were decreased(P＜0.01).Compared with the hypoxia group,the proliferation ability of HUVEC cells was decreased,the migration area was decreased,the migration rate was decreased and the length and number of branches involved in tube formation were further decreased in the EXO-M group(P＜0.05).Compared with the EXO-C group,the proliferation ability of the EXO-M group decreased,the cell migration area decreased and the migration rate decreased(P＜0.01).Conclusion Exosomes derived from hypoxic H9c2 can inhibit the proliferation,migration and tube formation of HUVEC.

Objective:To describe a series of systemic sclerosis (SSc) patients with the combination of scleroderma renal crisis (SRC) and pulmonary arterial hypertension (PAH).Methods:The medical records of 472 SSc patients in Peking Union Medical College Hospital between January 2012 and October 2020 were reviewed and a retrospective analysis of the characteristics of patients with SRC and PAH among SSc patients was conducted.Results:Thirteen patients suffered from SRC and PAH in the SSc patients, 1 case was limited cutaneous SSc, and 12 cases were diffuse cutaneous SSc. Five patients had renal crisis before pulmonary arterial hypertension, 4 patients had pulmonary arterial hypertension before the occurrence of renal crisis, and the remaining 4 patients were found at the same time. Among them, 11 patients had Raynaud's phenomenon, 7 had gastrointestinal bleeding, 6 had pulmonary edema and 3 had telangiectasias. Twelve cases were positive for anti-nuclear antibodies and 4 cases were positive for anti-Scl-70 antibodies. N-terminal pro-brain natriuretic peptide (NT-proBNP)>1 400 ng/L in 11 patients. Two patients had thrombotic microangiopathy (TMA). Among the 13 patients, 3 patients died during hospitalization, 2 patients were lost to follow-up, and 2 patients died within 5 years of follow-up. Six patients survived, and 1 of the 4 patients with regular dialysis were discharged from dialysis.Conclusion:In patients with scleroderma, SRC can occur earlier, later than, or at the same time with SSc-PAH. Patients may have a higher incidence of gastrointestinal bleeding and higher level of NT-proBNP. PDE5i or ERAs may be beneficial.

Natural killer (NK) cells are an important part of the body's innate immune system. As the first line of defense against pathogens, they need to be transformed into a mature state under the control of various cell signaling molecules and transcription factors to play cytotoxic and immune regulatory roles. Under the interaction of activated receptors and inhibitory receptors, NK cells are activated to perform a direct cell killing effect by secreting perforin and granzyme, or indirectly eliminate pathogenic microorganisms in the body by secreting various cytokines, such as type I and type II interferons. These functions of NK cells play a very important role in antiviral and anti-autoimmune diseases, especially in anti-tumor.
Humans ; Killer Cells, Natural ; Interferon-gamma ; Apoptosis ; Autoimmune Diseases ; Cytokines