BACKGROUND: Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China. METHODS: This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs). RESULTS: We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain. CONCLUSIONS In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.
Adult ; Humans ; Anti-HIV Agents/therapeutic use* ; China ; Emtricitabine/pharmacology* ; HIV Infections/drug therapy* ; HIV-1 ; Lamivudine/pharmacology* ; Lipids ; Retrospective Studies

Objective: To understand the public health emergency response capacity in primary and secondary schools, and to explore the problems and challenges in the prevention and control of public health emergency in primary and secondary schools for specific strategies. Methods: By using the stratified group sampling method, a questionnaire survey on general situation, knowledge, attitude and training, as well as public health emergencies response capacity among 2 988 teachers or leaders responsible for school emergency response in primary and secondary schools from Beijing, Chongqing and Yunnan. Results: Participants varied on their positions, titles, educational background and knowledge accuracy. Higher knowledge accuracy was associated with higher educational background ( χ 2=50.73-203.36, P < 0.05 ). The implementation of regular public health emergency related programs was poorly conducted in high schools (50.0%). Urban schools (42.0%) had higher proportion of qualified health care professionals than rural schools (18.2%), and private schools (48.5%) was higher than public schools (24.7%). The primary challenges included the shortage of guidance from professionals and the lack of related testing equipment (84.91%, 74.03%). Conclusion Although the ability of emergency handling of public health emergencies in schools in the three regions is advancing with the times, there are still many deficiencies, some omissions in the mastery of knowledge. It is suggested to inerease pre service and special training of school health work CDC should strengthen technical guidance and work supervision of infectious disease management in schools.

OBJECTIVE To investigate the potential developmental toxicity and delayed toxicity of Fuganline oral liquid(FGLOL)after long-term administration in juvenile SD rats via a three-stage juve-nile animal study(JAS).METHODS Stage 1:according to the proposed clinical dose for infants within one year of age,FGLOL 3.88,11.64,38.75 g·kg-1 was orally administered to rats of postnatal day 4(PND4)rats for 18 days,and the drug was stopped for 3 weeks.Stage 2:according to the proposed clinical dose for children ages 1 to 6,FGLOL 3.88,11.64,38.75 g·kg-1 was orally administered to PND15 rats for 31 d,and the drug was discontinued for 3 weeks.Stage 3:according to the proposed clinical dose for children aged 7 to 12,FGLOL 29.06,58.13,116.25 g·kg-1 was orally administered to PND40 rats for 66 d,and the drug was stopped for 4 weeks.The effects of FGLOL on health status,food intake,body mass,growth and development,nerve reflex development,learning and memory ability,physical development(body length),bone development(bone mineral density),hematology and coagulation(white blood cells,red blood cells and platelet count),blood biochemistry(glutamate dehydrogenase,urea nitrogen and triglycerides)and histopathology were investigated in young rats.RESULTS In the three-stage JAS test,long-term administration of FGLOL did not cause rat death,and no toxicological effects were observed on body mass,growth and development,nerve reflex development,physical development,bone development,hematology and coagulation,blood biochemistry and histopathology of juvenile rats compared with the vehicle control group.CONCLUSION The no observed adverse effect level(NOAEL)of FGLOL is 38.75 g·kg-1 for the JAS test corresponding to humans between 1 and 6 years old,while the NOAEL of FGLOL is 116.25 g·kg-1 for the JAS test and repeated drug toxicity test corresponding to humans aged 7 to 12.

OBJECTIVE To investigate the effects of Qinxiang Qingjie oral liquid(QXQJ)on growth and development after repeated administration of 18 d to postnatal day 4(PND4)rats.METHODS The number and sex of PND2 pups were adjusted using the cross-breeding method.These pups were ran-domly divided into the normal control,QXQJ 3.45,10.35 and 28.05 g·kg-1 groups.PND4,juvenile rats were ig given QXQJ every day,while the normal control group was given pure water,once a day,for 18 d,before observation of 3 weeks was resumed.During the experiment,the general condition,body mass,growth and development,physique,bone,hematology and coagulation of the rats in each group were detected.RESULTS 18 d after continuous administration of QXQJ,there was no obvious effect on the food intake,growth and development,nerve reflex,spontaneous behavior,hematology,coagula-tion,blood biochemistry,immunity,growth hormone,histopathology and other examination indexes of juve-nile rats.From PND5,juvenile rats in the QXQJ 10.35 and 28.05 g·kg-1groups developed yellow-brown soft or loose stools and abdominal distention,but the symptoms generally recovered at PND22.The body mass,top-rump length,tail length and limb length of the juvenile rats in the 28.05 g·kg-1 group were signifi-cantly lower at PND7(P<0.05),but recovered one week after drug withdrawal.The bone mineral specific gravity and bone mineral density of the 28.05 g·kg-1 group were significantly lower than those of the normal control group at PND22(P<0.05),but there was no significant difference at PND42.CONCLU-SION QXQJ can cause such indigestion symptoms as yellow brown soft stool or loose stool and abdominal enlargement in unweaned juvenile rats,thus affecting the physical development indicators of rats,but the symptoms can recover after withdrawal of medication or withdrawal from milk.The no observed adverse effect level(NOAEL)of QXQJ administered to 4-day-old rats for 18 d is 3.45 g·kg-1.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) that has become a major gastroenterologic problem during recent decades. Numerous complicating factors are involved in UC development such as oxidative stress, inflammation, and microbiota disorder. These factors exacerbate damage to the intestinal mucosal barrier. Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products. However, there have been few studies on the treatment of UC using S. platensis aqueous extracts (SP), and the underlying mechanism of action of SP against UC has not yet been elucidated. Herein, we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier. Dextran sulfate sodium (DSS) was used to establish a normal human colonic epithelial cell (NCM460) injury model and UC animal model. The mitochondrial membrane potential assay 3-‍‍(4,5-dimethylthiazol-2-yl)-2,‍5-diphenyltetrazolium bromide (MTT) and staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model. Moreover, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), western blot, and 16S ribosomal DNA (rDNA) sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice. In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury. SP also significantly reduced the excessive generation of intracellular reactive oxygen species (ROS) and prevented mitochondrial membrane potential reduction after DSS challenge. In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group. Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins (TJs) post-SP treatment. SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon. Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction, inhibition of DSS-induced ROS production, and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.
Animals ; Antioxidants/pharmacology* ; Colitis/prevention & control* ; Colitis, Ulcerative/metabolism* ; Colon/metabolism* ; Dextran Sulfate/toxicity* ; Disease Models, Animal ; Gastrointestinal Microbiome ; Inflammation/metabolism* ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Spirulina

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) that has become a major gastroenterologic problem during recent decades. Numerous complicating factors are involved in UC development such as oxidative stress, inflammation, and microbiota disorder. These factors exacerbate damage to the intestinal mucosal barrier. Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products. However, there have been few studies on the treatment of UC using S. platensis aqueous extracts (SP), and the underlying mechanism of action of SP against UC has not yet been elucidated. Herein, we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier. Dextran sulfate sodium (DSS) was used to establish a normal human colonic epithelial cell (NCM460) injury model and UC animal model. The mitochondrial membrane potential assay 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model. Moreover, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), western blot, and 16S ribosomal DNA (rDNA) sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice. In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury. SP also significantly reduced the excessive generation of intracellular reactive oxygen species (ROS) and prevented mitochondrial membrane potential reduction after DSS challenge. In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group. Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins (TJs) post-SP treatment. SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon. Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction, inhibition of DSS-induced ROS production, and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.

Objective:To analyze the clinical characteristics and prognosis of pregnant women with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 11 pregnant women with HFRS admitted to The Second Affiliated Hospital of Xi′an Jiaotong University (four cases), The Second Affiliated Hospital of Air Force Medical University (four cases), The First Affiliated Hospital of Xi′an Jiaotong University (one case) and Central Hospital of Xianyang City (two cases) between November 2009 and February 2019 were included as the study group, and 24 age-matched non-pregnant women with HFRS were selected as the control group. The age, complications, clinical classification and laboratory indexes of the two groups were analyzed retrospectively, and the clinical outcomes of pregnant women and their fetuses in the study group were followed up. The data between two groups were compared using Mann-Whitney U test or chi-square test. Results:Patients in the study and control groups were 29 (22, 33) and 32 (24, 37) years old, respectively. Seven of 11 patients in study group were severe and critical cases, which was significantly higher than that in the control group (16.7%(4/24), χ2=7.722, P=0.015). In the study group, 10 patients had hypervolemic syndrome, 10 patients had pulmonary edema and six patients had overlapping hypotension shock phase and oliguria phase, which were all higher than those in the control group ((2/24, 8.3%), (2/24, 8.3%) and (2/24, 8.3%), respectively; χ2=22.828, 22.828 and 9.135, respectively, all P<0.01). Compared with the control group, the pregnant patients in study group had a higher urea nitrogen maximum and serum creatinine maximum, and the differences were both statistically significant ( Z=-2.453 and -2.336, respectively, both P<0.05), while they had a lower serum albumin minimum, hemoglobin maximum and hemoglobin minimum, and the differences were all statistically significant ( Z=-3.742, -3.350 and -4.034, respectively, all P<0.01). All pregnant women with HFRS recovered. Nine pregnant women gave birth to nine healthy infants. All of them received breastfeeding and the feeding duration were more than six months. No abnormal growth and development were found during an average follow-up of three years. Conclusions:Pregnancy can aggravate the severity of HFRS, and pregnant women have higher risk of the multiple stages overlap and the complications such as hypervolemic syndrome and acute pulmonary edema. After recovery from HFRS, mother may carry to full-term pregnancy.

OBJECTIVE: To observe the therapeutic effect of different doses of dihydroartemisinin (DHA) on atopic dermatitis (AD) in mice and explore the mechanism. METHODS: Forty-two C57BL/6 mice were randomly divided into 7 groups ( RESULTS: Treatment with 25, 75, and 125 mg/kg DHA and dexamethasone all alleviated AD symptoms of mice, reduced the severity scores of skin lesions, and ameliorated pathological changes of the skin tissue. DHA at 125 mg/kg produced the most obvious therapeutic effect and significantly alleviated mast cell infiltration in the lesions as compared with the other treatment groups ( CONCLUSIONS DHA is effective for the treatment of AD in mice with an optimal dose of 125 mg/kg. The therapeutic effect of DHA is achieved probably through regulation of local immunity by inhibiting mast cell infiltration in the lesions.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Artemisinins ; Cytokines ; Dermatitis, Atopic/drug therapy* ; Immunoglobulin E ; Mast Cells ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Skin

Objective:To explore the value of a radiomics nomogram based on T 1WI for prediction of the relapse of osteosarcoma after surgery within 1 year from multicenter data. Methods:The imaging and clinical data of 107 patients with pathologica1ly confirmed osteosarcoma who received neoadjuvant chemotherapy before surgery from 6 hospitals from January 2009 to October 2017 were retrospectively analyzed. A training cohort consisted of 75 patients from firstly enrolled 4 hospitals and an independent validation cohort of 32 patients from other 2 hospitals. Pretreatment T 1WI was used to extract radiomics features. Least absolute shrinkage and selection operator (LASSO) regression was applied to reduce the dimension and then the radiomics signature was constructed to predict the relapse of osteosarcoma after surgery within 1 year in training cohort. Independent clinical risk factors were screened using one-way logistic regression, and then a radiomics nomogram incorporated the radiomics signature and MRI characteristics was developed by multivariate logistic regression. The predictive nomogram was evaluated using receiver operating characteristic (ROC) curve in the training cohort, and validated in the independent validation cohort. The calibration curve was used to evaluate the agreement between prediction and actual observation and the decision curve was used to demonstrate the clinical usefulness. Results:Based on T 1WI from multicenter institutions, the radiomics signature was built using 2 valuable selected features that were significantly associated with relapse within 1 year. Two selected features included 1 gray-level co-occurrence matrices (GLCM) feature (L_G_1.0_GLCM_homogeneity1, LASSO coefficient 3.122) and 1 gray-level run length matrix (GLRLM) feature (GLRLM_RP, LASSO coefficient -2.474). The prediction nomogram including radiomics signature and MRI characteristics (joint invasion and perivascular involvement) showed good discrimination with the area under the ROC curve of 0.884 and 0.821 in the training and validation cohorts, respectively. The calibration curve showed that the nomogram achieved good agreement between prediction and actual observation. Decision curve analysis demonstrated that the radiomics nomogram was clinically useful when the threshold probability was greater than 21%. Conclusion:The radiomics nomogram based on T 1WI can be used as a non-invasive quantitative tool to predict relapse of osteosarcoma within 1 year before treatment, which provides support for clinical decision-making in osteosarcoma.

The infectious disease outpatient service as a frontier is an important fulcrum of public health service. Its standardized construction is an important support for ensuring medical safety, reducing nosocomial infections, and controlling the epidemic of infectious diseases. The sub-specialty outpatient service of infection diseases includes fever outpatient service, intestinal outpatient service, tuberculosis outpatient service, AIDS outpatient service, liver disease outpatient service, etc. According to the characteristics of each subspecialty outpatient service and combining with clinical practice, we elaborated the setting norms of subspecialty outpatient service for common infectious diseases from the perspective of planning and design, building layout, equipment and facilities configuration, staffing, daily management and demonstration.