Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To investigate the mechanism of tea polyphenols(TP)for regulating NLRP3 inflammasomes and alleviating acute lung injury in septic mice.Methods Sixty C57BL/6 mice were randomly assigned into sham-operated,cecal ligation and puncture(CLP)and CLP+TP treatment groups,and survival of the mice was recorded after modeling in each group.The lung wet/dry weight ratio and myeloperoxidase(MPO)activity were determined,and lung injury of the mice was evaluated using HE staining and acute lung injury score.The expressions of IL-1β,TNF-α,IL-6,NLRP3,caspase-1 p10,ASC,MPO,and caspase-8 in the lung tissue were detected using ELISA,Western blotting,or immunohistochemical staining.MDA and H2O2 levels in the lungs were detected to evaluate the level of oxidative stress.Immunofluorescence assay was used to investigate the co-localization of NLRP3 and NOX4.Results The postoperative mortality rate at 72 h,lung wet/dry weight ratio,MPO level and acute lung injury scores were significantly lower in CLP+TP group than in CLP group(P<0.05).Treatment with TP significantly reduced the expressions of NLRP3-related inflammatory factors(P<0.05)and lowered MDA and H2O2 levels in the lung tissue of the septic mice(P<0.05).Immunofluorescence co-staining showed a lower level of NOX4 and NLRP3 co-localization in CLP+TP group than in CLP group.Conclusion TP inhibits NLRP3 inflammasome-associated inflammation to alleviate CLP-induced acute lung injury in mice through a regulatory mechanism that inhibits NOX4 expression and reduces oxidative stress in the lung tissue.

Objective:To investigate the effects of bisphenol A(BPA)on the proliferation activity and stemness characteristics of endometrial mesenchymal stem/stromal cells(eMSCs),and to elucidate the improvement effect of human umbilical cord mesenchymal stem cell-derived supernatant(hUCMSC-Sup)on the cell injury.Methods:The eMSCs were cultured in vitro and treated with different concentrations of BPA(0,200,250,300,350,and 400 μmol·L-1).The eMSCs were divided into control group(only cultured with culture solution),BPA group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA),BPA+hUCMSC-Sup group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 50%volumetric ratio of hUCMSC-Sup),and BPA+CHIR-99021 group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 10 μmol·L-1 CHIR-99021).The survival rates of eMSCs in various groups were detected by methyl thiazolyl tetrazolium(MTT)assay.The numbers and diameters of the spheroids in various groups were detected by spheroids formation assay,the proliferation activities of the cells in eMSCs stem cell spheroids in various groups were detected by CCK-8 assay;the percentage of CD73+cells in eMSCs in various groups were detected by flow cytometry;the expression levels of sex determining region Y-box 2(Sox2),octamer-binding transcription factor 4(Oct4),and Nanog mRNA in the eMSCs in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method,the expression levels of β-catenin protein in the eMSCs in various groups were detected by Western blotting method.Results:The MTT results showed that after treated with BPA for 24 and 48 h,compared with 0 μmol·L-1 BPA group,the survival rates of eMSCs in 200,250,300,350,and 400 μmol·L-1 BPA groups were significantly decreased(P<0.01).At 24 and 48 h after treatment,compared with control group,the survival rate of the eMSCs in BPA group was significantly decreased(P<0.01);at 48 h after treatment,compared with BPA group,the survival rate of the eMSCs in BPA+hUCMSC-Sup group was significantly inereased(P<0.05).The spheroids formation assay results showed that compared with culture 3 d group,the numbers and diameters of stem cell spheroids of the eMSCs in culture 4 d group and culture 5 d group were significantly increased(P<0.05 or P<0.01);compared with control group,after 48 h of culture,the number and diameter of the cells in eMSCs stem cell spheroids in BPA group were significantly decreased(P<0.05 or P<0.01).The CCK-8 results showed that after 24 and 48 h of treatment,compared with control group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA group was significantly decreased(P<0.01);compared with BPA group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The flow cytometry results showed that compared with control group,the percentage of the CD73+cells in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the percentage of the CD73+cells in eMSCs in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The RT-qPCR results showed that compared with control group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA group were significantly decreased(P<0.01);compared with BPA group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression level of β-catenin protein in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the expression levels of β-catenin protein in the eMSCs in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were signifrcantly inereased(P<0.01).Conclusion:BPA can inhibit the stemness characteristics of the eMSCs,and injury the self-renewal and repair of endometrium;its mechanism may be related to down-regulating the activity of Wnt/β-catenin signal pathway in the cells.hUCMSC-Sup can promote the proliferation of injured eMSCs,and has improvement effect on the stemness injury induced by BPA.

Objective To investigate the mechanism of tea polyphenols(TP)for regulating NLRP3 inflammasomes and alleviating acute lung injury in septic mice.Methods Sixty C57BL/6 mice were randomly assigned into sham-operated,cecal ligation and puncture(CLP)and CLP+TP treatment groups,and survival of the mice was recorded after modeling in each group.The lung wet/dry weight ratio and myeloperoxidase(MPO)activity were determined,and lung injury of the mice was evaluated using HE staining and acute lung injury score.The expressions of IL-1β,TNF-α,IL-6,NLRP3,caspase-1 p10,ASC,MPO,and caspase-8 in the lung tissue were detected using ELISA,Western blotting,or immunohistochemical staining.MDA and H2O2 levels in the lungs were detected to evaluate the level of oxidative stress.Immunofluorescence assay was used to investigate the co-localization of NLRP3 and NOX4.Results The postoperative mortality rate at 72 h,lung wet/dry weight ratio,MPO level and acute lung injury scores were significantly lower in CLP+TP group than in CLP group(P<0.05).Treatment with TP significantly reduced the expressions of NLRP3-related inflammatory factors(P<0.05)and lowered MDA and H2O2 levels in the lung tissue of the septic mice(P<0.05).Immunofluorescence co-staining showed a lower level of NOX4 and NLRP3 co-localization in CLP+TP group than in CLP group.Conclusion TP inhibits NLRP3 inflammasome-associated inflammation to alleviate CLP-induced acute lung injury in mice through a regulatory mechanism that inhibits NOX4 expression and reduces oxidative stress in the lung tissue.

Objective:To investigate the epidemic characteristics and current situation of animal plague in Zhejiang Province, in order to provide data support for prevention and control of the plague in the whole province.Methods:A retrospective study was carried out to collect surveillance data of animal plague in Zhejiang Province from 2006 to 2020 from the "Pubonic Plague Control Management Information System". Descriptive epidemiological methods were used to analyze the density of domestic and wild rodents, the distribution of rodent species and flea species, and the serological and pathogenic test results of host animals.Results:From 2006 to 2020, the annual average density of domestic rodent in Zhejiang Province was 3.99%, which was lower than that in 2006, 2007, 2008, 2009, 2019 and 2020. The annual average density of wild rodents was 4.52%, which was lower than that in 2013, 2016, 2017, 2018, 2019 and 2020. From 2006 to 2020, a total of 173 432 rodents were captured, belonging to 3 orders, 5 families, 12 genera and 17 species; in the composition of rodent species, Rattus norvegicus was the most, accounting for 32.15% (55 765/173 432). A total of 107 736 rodents were examined, the number of flea-infected rodent was 3 885, and the flea-infested rate was 3.61%; the total number of flea collected was 9 039 and the total flea index was 0.083 9. A total of 172 235 serological samples were tested at various monitoring sites in Zhejiang Province, and 10 positive samples were detected, there were 7 copies of Apodemus agrarianus, 2 copies of Smelly Shrew and 1 copy of Rattus norvegicus, with titers ranging from 1 ∶ 40 - 1 ∶ 320; a total of 163 618 copies of rodent liver and spleen organs were cultured, and no Yersinia pestis was isolated. Conclusions:Positive host animals have been detected in Zhejiang Province for many years. It is necessary to further standardize plague surveillance and make emergency preparations to prevent relapse and import of the epidemics.

Objective:To analyze the epidemiological characteristics and spatiotemporal distribution of hemorrhagic fever with renal syndrome (HFRS) in Zhejiang province from 2005 to 2020, and provide scientific information for the precise prevention and control of HFRS.Methods:Data on HFRS cases in Zhejiang province during 2005-2020 were collected from the China National Notifiable Infectious Disease Reporting Information System (NNDS) for a descriptive analysis, and software ArcGIS 10.2 was used for global autocorrelation and local autocorrelation analyses. Spatiotemporal clusters were scanned with SaTScan 9.4.4 and visualized with ArcGIS 10.2.Results:A total of 7 724 HFRS cases were reported in Zhejiang province from 2005 to 2020, including 25 deaths. There were two incidence peaks each year, in late spring and early summer (May-June) and in winter (November-January). The top three areas with high cumulative cases were Ningbo (1 875, 24.27%), Taizhou (1 642, 21.25%), and Shaoxing (1 123, 14.54%). Among the reported cases, with a male to female ratio of 2.73∶1(5 656∶2 068). The majority of HFRS cases were middle-aged and elderly people, with cases aged 41-70 years accounting for 60.95%. Most HFRS cases were farmers, accounting for 69.89% (5 398/7 724). The spatial distribution of HFRS in most years was correlated. SaTScan was used for retrospective spatiotemporal scanning and three clusters were detected: the first type clusters were in 21 counties in eastern Zhejiang province and central Zhejiang province, among which 4 were in Ningbo, Shaoxing and Jinhua, 8 were in Taizhou, and 1 was in Lishui ( RR=13.69, LLR=5 522.60, P<0.001); the second type clusters were in Longquan and Qingyuan counties ( RR=31.20, LLR=1 232.46, P<0.001); the third types of clusters were in Changxing and Anji counties of Huzhou in northern Zhejiang province ( RR=3.42, LLR=23.93, P<0.001). Conclusions:HFRS mainly occurred in middle-aged,elderly and male farmers in Zhejiang province. The incidence was high in late spring, early summer and winter in eastern Zhejiang province. Precise prevention and control measures are needed for populations at high risk before the epidemic season.

Objective To evaluate the application value of polarized light dermoscopy in the diagnosis of vitiligo and differential diagnosis between vitiligo and other common hypopigmented diseases.Methods Dermoscopic images of lesions of 235 patients with confirmed vitiligo (130 with active vitiligo and 105 with stable vitiligo) were collected from the database in the Department of Dermatology,Xijing Hospital from January 2018 to July 2018,and retrospectively analyzed.Meanwhile,dermoscopic images of amelanotic nevus (151 cases),pityriasis alba (113 cases) and idiopathic guttate hypomelanosis (54 cases) were compared with the dermoscopic images of vitiligo.Chi-square test was used for comparison of rates among groups.Results The prevalence of perifollicular pigmentation,reticular pigmentation,starburst,Tapioca sago and micro-Koebner phenomenon was significantly higher in the patients with active vitiligo than in those with stable vitiligo (x2 =36.5,151.2,13.0,14.9,8.4 respectively,all P ＜ 0.05).The prevalence of perifollicular pigmentation,perilesional hyperpigmentation,perifollicular telangiectasia,leukotrichia was significantly higher in patients with stable vitiligo than in those with active vitiligo (x2 =91.2,166.0,54.3,41.1 respectively,all P ＜ 0.05).The prevalence of residual perifollicular pigmentation was significantly higher in patients with active (89.2％,116/130) or stable vitiligo (54.3％,57/105) than in those with amelanotic nevus (20.5％,31/151,P ＜ 0.05),pityriasis alba (12.4％,15/113,P ＜ 0.05)or idiopathic guttate hypomelanosis (9.3％,5/54,P ＜ 0.05).Conclusion Residual perifollicular pigmentation could serve as an important feature for distinguishing vitiligo from achromic nevus,pityriasis alba and idiopathic guttate hypomelanosis,and polarized light dermoscopy shows good value in the differential diagnosis between vitiligo and some hypopigmented diseases.

OBJECTIVETo investigate the effect of losartan in regulating oxidative stress and the underlying mechanism in mice with ventilator-induced lung injury.

METHODSThirty-six male C57 mice were randomly divided into control group, losartan treatment group, mechanical ventilation model group, and ventilation plus losartan treatment group. After the corresponding treatments, the lung injuries in each group were examined and the expressions of caveolin-1 and NOX4 in the lung tissues were detected.

RESULTSThe mean Smith score of lung injury was significantly higher in mechanical ventilation model group (3.3) than in the control group (0.4), and losartan treatment group (0.3); the mean score was significantly lowered in ventilation plus losartan treatment group (2.3) compared with that in the model group (P<0.05). The expressions of caveolin-1 and NOX4 were significantly higher in the model group than in the control and losartan treatment groups (P<0.05) but was obviously lowered after losartan treatment (P<0.05). Co-expression of caveolin-1 and NOX4 in the lungs was observed in the model group, and was significantly decreased after losartan treatment.

CONCLUSIONLosartan can alleviate ventilator-induced lung injury in mice and inhibit the expression of caveolin-1 and NOX4 and their interaction in the lungs.

Animals ; Caveolin 1 ; metabolism ; Losartan ; pharmacology ; Lung ; metabolism ; physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase 4 ; NADPH Oxidases ; metabolism ; Oxidative Stress ; Respiration, Artificial ; Ventilator-Induced Lung Injury ; drug therapy ; metabolism

OBJECTIVETo explore the technique of temperature control on the abdomen in penetrating moxibustion through observing moxibustion time on the abdomen, abdominal skin temperature and effect after moxibustion so as to provide the safe, effective and easily applicable method for penetrating moxibustion.

METHODSThirty-two patients were selected in an observation group, 32 healthy persons in a control group. In the observation group, the penetrating moxibustion was applied to the corresponding acupoint locations according to different symptoms. In the control group, moxibustion was used on the abdomen around the umbilicus. The skin temperature was recorded once every minute. The skin temperature of known heat sensation, the time of known heat sensation, the known reduced temperature, the time of temperature reducing, the skin temperature difference, the duration of penetrating moxibustion and the reaction of moxibustion from participants were recorded.

RESULTSThe differences in the skin temperature of known heat sensation, the time of known heat sensation and the duration of penetrating moxibustion were significant statistically in comparison between the observation group and the control group (all P<0.01). The differences in the known reduced temperature, the time of temperature reducing and the skin tem- perature difference were not significant (all P>0.05). The differences were significant statistically in skin rashes and moxibustion reaction (gastrointestinal peristalsis, chills, ant climbing feeling and hunger, etc.) between the two groups (P<0.01). The differences were not significant statistically in flushing, sweating and blisters (all P>0.05).

CONCLUSION(1) The level of temperature sensitivity in the observation group is lower than that in the control group. During penetrating moxibustion, the sensations such as gastrointestinal peristalsis, chills, ant climbing feeling and hunger appear easily, suggesting the positive self-adjustment in the body. (2) During penetrating moxibustion, the warm feeling is penetrated not just from the epidermis to the abdominal cavity and lumbar region, but also up to thehead and down to the knee. (3) The flushing, sweating and skin rashes are the important indices for the effectiveness of penetrating moxibustion. (4) The temperature control is the core technique of penetrating moxibustion. The penetrating moxibustion in 28 min to 32 min and the temperature controlled in 43 degrees C to 45 degrees C can solve the moxibustion smoky impact to the environment, but also relieve pains of the patients.

Abdomen ; physiology ; Acupuncture Points ; Adult ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Skin Temperature ; Thermosensing ; Young Adult

Objective To investigate the effect of losartan in regulating oxidative stress and the underlying mechanism in mice with ventilator-induced lung injury. Methods Thirty-six male C57 mice were randomly divided into control group, losartan treatment group, mechanical ventilation model group, and ventilation plus losartan treatment group. After the corresponding treatments, the lung injuries in each group were examined and the expressions of caveolin-1 and NOX4 in the lung tissues were detected. Results The mean Smith score of lung injury was significantly higher in mechanical ventilation model group (3.3) than in the control group (0.4), and losartan treatment group (0.3); the mean score was significantly lowered in ventilation plus losartan treatment group (2.3) compared with that in the model group (P<0.05). The expressions of caveolin-1 and NOX4 were significantly higher in the model group than in the control and losartan treatment groups (P<0.05) but was obviously lowered after losartan treatment (P<0.05). Co-expression of caveolin-1 and NOX4 in the lungs was observed in the model group, and was significantly decreased after losartan treatment. Conclusions Losartan can alleviate ventilator-induced lung injury in mice and inhibit the expression of caveolin-1 and NOX4 and their interaction in the lungs.