Objective　To understand the impact of early and timely treatment and initial antiviral treatment regimen on mortality and attrition of antiretroviral therapy. Methods A retrospective cohort study was conducted using download data on antiretroviral therapy for HIV-infected patients in Liuzhou City, Guangxi Province, from the database of the Basic Information System for AIDS Control and Prevention (BISAC) from 2010 to 2020. The Cox proportional risk regression model was used to analyze the influencing factors of mortality and attrition. Results A total of 15 713 infected patients were included, including 53.4% aged 18-<50 years, 69.4% male, 61.0% farmer, 75.1% CD4 count <350 cells /μL before initial antiviral treatment, the overall mortality rate was 4.30/100 person-years, and the overall attrition was 2.42/100 person-years. The results of Cox regression analysis showed that the influencing factors of mortality were pretreatment CD4 counts of 350-<500 cells/μL(AHR=0.72, 95%CI: 0.63-0.81) and ≥500 cells/μL (AHR= 0.64, 95%CI: 0.55-0.76); duration from diagnosis to initial antiviral treatment 91-180 days (AHR=1.25, 95%CI: 1.08-1.45), 181-365 days (AHR=1.26, 95%CI: 1.08-1.47), and ≥365 days (AHR=1.26, 95%CI: 1.11-1.44); initial antiviral treatment regimens of D4T+3TC+EFV/NVP (AHR=1.47, 95%CI: 1.32-1.63) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.73, 95%CI: 1.50-1.99). Factors affecting attrition were pretreatment CD4 counts of 350-499 cells/μL (AHR=1.32, 95%CI: 1.16-1.50) and ≥500 cells/μL (AHR=1.28, 95%CI: 1.10-1.50); interval from HIV positivity confirmation to initial dosing ≥365 days (AHR=1.21, 95%CI: 1.04-1.40), initial antiviral treatment regimens of TDF+3TC+NVP (AHR=1.32, 95%CI: 1.13-1.55), AZT+3TC+EFV/NVP (AHR=1.43, 95%CI: 1.26-1.62) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.33, 95CI%: 1.06-1.67). Conclusions　Early and timely treatment and the initial antiviral treatment regimen of TDF+3TC+EFV have good efficacy, but attention should be paid to the high risk of attrition of HIV-infected people with high CD4 count before treatment.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To observe the clinical efficacy and action mechanism of Jujing Decoction(JJD)in the treatment of as-thenoteratozoospermia(ATZ)by comparing JJD with combined administration of the antioxidant stress drug and sperm energy metabo-lism agent.Methods:According to the inclusion criteria,we enrolled 67 male patients with ATZ in this randomized controlled clini-cal study and treated them by oral administration of JJD(the JJD group,n=34)or natural vitamin E combined with L-carnitine solu-tion(the positive control group,n=33),both for 12 weeks.We collected the semen parameters,sperm DNA fragmentation index(DFI),sperm mitochondrial membrane potential(MMP),seminal plasma reactive oxygen species(ROS)and superoxide dismutase(SOD)levels from the patients,observed the ultrastructure of sperm mitochondria under the transmission electron microscope(TEM)before and after treatment,and analyzed the clinical efficacy and action mechanism of JJD by comparing the data obtained between the two groups.Results:Treatment and follow-up were completed in 60 of the cases,30 in the JJD and 30 in the positive control group.The total rate of clinical effectiveness was significantly higher in the JJD than in the positive control group(76.8％vs 43.3％,P＜0.05).Compared with the baseline,the percentages of progressively motile sperm(PMS)and morphologically normal sperm(MNS),DFI and MMP were significantly improved(P＜0.05),the level of seminal plasma ROS decreased(P＞0.05),and that of SOD re-markably increased(P＜0.05)after treatment with JJD;PMS,MNS,DFI and MMP were also improved(P＞0.05),seminal plas-ma ROS decreased(P＞0.05)and SOD increased(P＜0.05)in the positive controls after medication.In comparison with the posi-tive controls,the patients treated with JJD showed even more significant improvement in PMS([29.37±14.56]％vs[42.68±15.86]％,P＜0.05),MNS([1.84±1.32]％vs[3.66±1.72％]％,P＜0.05),DFI([32.66±5.23]％vs[16.61±4.20]％,P＜0.05)and MMP([46.47±9.48]％vs[61.79±8.61]％,P＜0.05),ROS([7.08±0.51]vs[5.06±0.52]μmol/L,P＞0.05),and SOD([100.65±10.59]vs[139.05±14.71]U/ml,P＜0.05).TEM revealed significantly improved ultrastructure of sperm mitochondria after treatment with JJD.No serious adverse reactions were observed in either group dur-ing follow-up.Conclusion:JJD,superior to natural vitamin E and L-carnitine oral solution,can safely and effectively increase the percentages of PMS and MNS,MMP and the level of seminal plasma SOD,reduce sperm DFI and seminal plasma ROS,and improve the ultrastructure of sperm mitochondria in patients with ATZ.The underlying mechanism of action may be related to its ability of im-proving the structure and function of sperm mitochondria via antioxidant stress.

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Clostridioides difficile/genetics* ; Clostridioides ; Real-Time Polymerase Chain Reaction ; Feces ; Bacterial Proteins/genetics*

OBJECTIVES: To observe the effects on the glucose-lipid metabolism and the expression of zinc-α2-glycoprotein (ZAG) and glucose transporter 4 (GLUT4) in the femoral quadriceps and adipose tissue after electroacupuncture (EA) at "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) in the rats with diabetes mellitus type 2 (T2DM), so as to explore the effect mechanism of EA in treatment of T2DM. METHODS: Twelve ZDF male rats were fed with high-sugar and high-fat fodder, Purina #5008 for 4 weeks to induce T2DM model. After successfully modeled, the rats were randomly divided into a model group and an EA group, with 6 rats in each one. Additionally, 6 ZL male rats of the same months age were collected as the blank group. The rats in the EA group were treated with EA at bilateral "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), with continuous wave, 15 Hz in frequency, and 2 mA in intensity. The electric stimulation lasted 20 min each time. EA was delivered once daily, 6 times a week for 4 weeks. Separately, the levels of fasting blood glucose (FBG) was measured before modeling, before and after intervention, and the body mass of each rat was weighted before and after intervention. After intervention, the levels of the total cholesterol (TC), triacylglycerol (TG) and free fatty acid (FFA) in serum were detected using enzyme colorimetric method; and the levels of the serum insulin (INS) and ZAG were detected by ELISA. Besides, the insulin sensitivity index (HOMA-ISI) was calculated. With Western blot technique adopted, the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue were determined. RESULTS: After intervention, compared with the blank group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS increased (P<0.01), while HOMA-ISI decreased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue dropped (P<0.01) in the model group. In the EA group, compared with the model group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS were reduced (P<0.01), and HOMA-ISI increased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue increased (P<0.01, P<0.05). CONCLUSIONS Electroacupuncture can effectively regulate glucose-lipid metabolism, improve insulin resistance and sensitivity in the rats with T2DM, which is associated with the modulation of ZAG and GLUT4 expression in the skeletal muscle and adipose tissue.
Rats ; Male ; Animals ; Glucose/metabolism* ; Electroacupuncture ; Rats, Sprague-Dawley ; Diabetes Mellitus, Type 2/therapy* ; Lipid Metabolism ; Triglycerides ; Adipose Tissue/metabolism* ; Acupuncture Points

Humans ; Mpox (monkeypox) ; China

Objective: To evaluate the mid-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using the Cai tube in the treatment of left colorectal cancer. Methods: A prospective randomized control trial (China Clinical Trials Registration Number: ChiCTR-OOR-15007060) was performed. Sixty patients with left colorectal cancer at Department of Gastrointestinal Surgery of Zhongshan Hospital from September 2015 to August 2017 were prospectively enrolled. Case inclusion criteria: (1) left colorectal adenocarcinoma (rectal cancer with distance ≥ 8 cm from tumor low margin to anal edge, sigmoid colon cancer, descending colon cancer and left transverse colon cancer) confirmed by preoperative pathology; (2) satisfactory conditions of conventional laparoscopic surgery; (3) maximum diameter of the tumor < 4.5 cm confirmed by preoperative abdominal and pelvic CT or MRI; (4) BMI < 30 kg/m². Case exclusion criteria: (1) benign lesions, mucinous adenocarcinoma, signet-ring cell carcinoma and other special pathological types of tumors confirmed by preoperative pathological examination; (2) multiple or recurrent cancers; (3) with a history of neoadjuvant chemoradiotherapy; (4) obvious regional infiltration or distant metastasis indicated by preoperative imaging examination; (5) intestinal obstruction, intestinal perforation, etc. Participants were randomly assigned to NOSES group (using the Cai tube) and conventional laparoscopy (CL) group by random number table method. Clinical data between two groups were compared and analyzed, including perioperative conditions, tumor exfoliation cell detection and bacterial culture results of intraperitoneal lavage fluid, postoperative complications (Clavien-Dindo grading), postoperative pain [visual simulation scoring (VAS) assessment], anal function (Kirwan anal function grading assessment), and postoperative 3-year disease-free survival (DFS), overall survival (OS), overall recurrence rate, and local recurrence rate. Results: A total of 60 patients were enrolled, with 30 in the NOSES group and 30 in the CL group. All the patients in the NOSES group successfully completed operation with Cai tube. Baseline data between the two groups were not significantly different (all P>0.05). There were no statistically significant differences between two groups in conversion rate to open surgery, number of lymph node harivested, proximal and distal resection margin of tumor, negative rate of circumferential margin, operation time, blood loss, inflammatory indexes, postoperative anal function, postoperative hospital stay, hospitalization cost, morbidity of postoperative complications (Clavien-Dindo grade II or above) (all P>0.05). Compared to the CL group, the NOSES group had lower maximum postoperative VAS score (2.5±0.3 vs. 5.1±0.4, t=3.187, P<0.01), and fewer use of additional postoperative analgesia [6.7% (2/30) vs. 33.3% (10/30),χ²=6.670, P=0.02]. The postoperative time to gas passage was shorter in the NOSES group [(2.2±1.4) days vs. (3.1±1.2) days,P=0.026]. No tumor cells and bacterial contamination were found in abdominal lavage fluid before and after operation in either group. The anal function at postoperative 3-month of all the patients in the NOSES group was Kirwan grade I to II, while in the CL group, anal function of 2 cases (6.7%) was Kirwan grade III, and of 28 cases was also Kirwan grade I to II, whose difference was not statistically significant (P>0.05). In the NOSES group and the CL group, 3-year DFS was 96.7% and 83.3% (P=0.090), OS was 100% and 90% (P=0.096), overall recurrence rate was 3.3% and 10.0% (P=0.166), and local recurrence rate was 3.3% and 3.3% (P=0.999), respectively, whose differences were not statistically significant (all P>0.05). Conclusions: In the treatment of left colorectal cancer, compared with conventional laparoscopic colectomy, NOSES colectomy using Cai tube exhibits less scar, less postoperative pain, shorter recovery of gastrointestinal function, and similar mid-term outcomes. Given proper surgical indications, the surgical procedure is safe and feasible.
Follow-Up Studies ; Humans ; Laparoscopy ; Pain, Postoperative ; Postoperative Complications/surgery* ; Prospective Studies ; Rectal Neoplasms/surgery* ; Retrospective Studies ; Sigmoid Neoplasms/surgery* ; Treatment Outcome