Objective: To assess the impact of long-term antiretroviral therapy (ART) on human immunodeficiency virus (HIV) blood screening outcomes in post-exposure prophylaxis (PEP) failure cases through a longitudinal analysis of blood screening results over a 7-year period in a patient with HIV PEP failure. Methods: This study conducted 13 follow-up assessments for a high-risk individual who initiated ART shortly after exposure. The effectiveness of various blood screening methods, including immunological assays and nucleic acid testing (NAT), was analyzed. Blood samples were also tested with HIV RNA quantification testing, Western blot (WB) confirmation testing, chemiluminescence immunoassay (CLIA), and HIV rapid tests utilizing gold and selenium labels. A comprehensive analysis was performed to evaluate the changes in diagnostic capabilities of different testing methods for HIV biomarkers over an extended period following PEP failure. Results: The patient had two high-risk exposures: one day before ART initiation (BA1) and seven days preceding treatment (BA7). On the first day after the ART treatment (AA1), the HIV RNA concentration (viral load) was 9.07×10 copies/mL; by day five (AA5), the viral load decreased to 1.04×10 copies/mL. At day eleven (AA11), NAT and ELISA tests were both positive, with the WB result remaining indeterminate (gp160+). At day 48 (AA48), the S/CO value of the fourth generation ELISA reagent was 1.07, while results from a 6-sample pool and quantitative NAT were negative. However, a single sample NAT returned a positive result and WB tests indicated positivity for p17, p24, and gp160. At AA74, the quantitative NAT rebounded to 2.83×10 copies/mL, with positive NAT results for single and 6-sample pool NAT tests. The S/CO values of the imported and domestic ELISA reagents were 3.39 and 23.44, respectively. At AA201, 6-sample pool and quantitative NAT were negative again, while single sample NAT remained positive. From AA319 to AA2221, all NAT results have remained consistently below the minimum detection limit. At AA2221, S/CO values of the imported and domestic ELISA reagents were 3.47 and 23.44, respectively. Conclusion: The findings indicate that patients experiencing PEP failure after high-risk HIV exposure are at a higher risk of being missed by mixed-sample NAT pools and individual serological tests. Nonetheless, anti-HIV antibody levels are sustained at elevated values for an extended duration, underscoring antibody testing as an effective measure for blood screening.

Objective To investigate the effect and mechanism of emodin on focal cerebral ischemia in rats based on myeloid differentiation factor 88(MyD88)/extracellular signal-regulated kinase(ERK)pathway and nuclear factor-κB(NF-κB)nuclear translocation.Methods SD rats were randomly divided into sham operation group,model group and emodin group,with six rats in each group.The rat model of transient middle cerebral artery occlusion(tMCAO)was established by middle cerebral artery embolization.Rats in the emodin group were given 40 mg·kg-1 emodin by gavage for three times at 72,48 and 24 hours before modeling.At 24 hours after modeling,the neurological function of rats was scored.TTC staining was used to detect the area of cerebral infarction.HE staining was used to observe the morphological changes of brain tissue.The mRNA expression levels of MyD88 and tumor necrosis factor-α(TNF-α)in brain tissue were detected by RT-qPCR.The expression levels of MyD88,ERK,p-ERK and TNF-α in brain tissue were detected by Western Blot.The protein expression of NF-κB in brain tissue was detected by immunofluorescence.Results Compared with the sham operation group,the neurological function score of the model group was significantly increased(P＜0.01),and the cerebral infarction area was significantly increased(P＜0.01).In the cortical area of the ischemic penumbra,cell necrosis,abnormal cell morphology,nuclear fragmentation and atrophy,and the number of cells decreased significantly;the mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly increased(P＜0.01,P＜0.001),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the proportion of NF-κB into nuclear cells was significantly increased(P＜0.001).Compared with the model group,the neurological function score of rats in the emodin group was significantly decreased(P＜0.05),and the area of cerebral infarction was significantly reduced(P＜0.05).The number and morphology of neurons in the ischemic penumbra cortex were restored to a certain extent.The mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly decreased(P＜0.05,P＜0.01),the protein levels of MyD88,p-ERK/ERK and TNF-α were significantly decreased(P＜0.05),and the proportion of NF-κB into nuclear cells was significantly decreased(P＜0.001).Conclusion Emodin has a preventive and protective effect on rats with focal cerebral ischemia,which may be related to its inhibition of MyD88 activation,ERK phosphorylation and NF-κB nuclear translocation,and then down-regulation of inflammatory cascades and secretion of pro-inflammatory factors such as TNF-α,thereby exerting anti-inflammatory effects.

【Objective】 To explore the the potential risks of antiretroviral therapy(ART) drugs on blood safety among blood donors in Shenzhen. 【Methods】 High pressure liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to measure ART drugs concentrations in the plasma of regular blood donors (negative control group, n=86) and anti-HIV positive individuals (experimental group, n=98, detected from approximately 440 000 blood donors during 2019—2023). The baseline plasma concentrations of ART drugs in the negative control group were clarified, and the impact of ART drugs on blood safety was analyzed. 【Results】 The baseline concentrations of ART drugs were not detected in 86 samples of negative control group. Four positive ART drugs samples were detected in 1∶2 pooled plasma samples of 98 anti-HIV positive blood donors plasma in the resolution test. The ART positive rate of anti-HIV positive donors was 4.08%, with tenofovir, lamivudine and efavirenz detected in three blood donors and lamivudine, lopinavir, ritonavir and zidovudine detected in one blood donor. 【Conclusion】 ART drugs were found among anti-HIV positive blood donors in Shenzhen. Additional research is needed to investigate the motivation of these specific donors, so as to ascertain the groups most susceptible to potential risks, and guarantee blood safety.

【Objective】 To establish a magnetic bead enrichment strategy for the detection of human immunodeficiency virus deoxyribonucleic acid (HIV DNA) in peripheral blood, and to verify the improvement of the sensitivity of this method for the detection of HIV DNA in HIV infected patients after early antiretrovital treatment (ART). 【Methods】 Peripheral whole blood was collected at 4 timepoints in one ART HIV window period (WP) patient. Peripheral blood mononuclear cells (PBMCs) were isolated on a Ficoll gradient. CD4⁺ T lymphocytes were enriched from total PBMCs by negative sorting. HIV DNA concentration in magnetic beads enriched group and whole blood group was detected by HIV DNA detection kit. 【Results】 CD4⁺ T cells were isolated by magnetic beads and identified by FCM for purity at (96.4 ± 2.6)%. The viability was (95.9 ± 2.9)%, as demonstrated by trypan blue staining. The person on continued ART treatment in this study had significantly greater reduction in HIV viral load and undetectable HIV plasma RNA at follow up timepoint 4. No HIV DNA was detected in the whole blood group at all 4 timepoints. The quantitative results of HIV DNA in the CD4⁺ T lymphocyte group of the magnetic bead enrichment group were 73.4, 429.3, 137.1, 449.9 copies/10⁶ CD4⁺ T cell′s respectively. 【Conclusion】 The magnetic bead enrichment method can be more sensitive in detecting the limit low copy HIV DNA in blood samples, and provide early confirmatory data for HIV WP infection and breakthrough infection after ART treatment.

OBJECTIVE: To explore the prognostic value of early multiple detection indicators in combination with sequential organ failure assessment (SOFA) in sepsis patients. METHODS: A retrospective analysis was conducted. Patients with sepsis admitted to the department of critical care medicine of Huanggang Central Hospital of Yangtze University from May 2020 to May 2022 were selected as the research subjects. Coagulation indicators, inflammatory factors, blood routine, liver and kidney function, and blood gas analysis were collected at admission. Organ dysfunction was assessed based on the SOFA score within 24 hours after admission. Patients were divided into a survival group and a death group according to the outcome of 28 days in ICU. Differences in the above indicators between the two groups were compared. Multifactorial Logistic regression analysis was used to analyze prognostic factors of 28-day mortality in sepsis patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive performance of various indicators, the SOFA score, and the combine model for the 28-day outcome in patients with sepsis. RESULTS: A total of 101 patients with sepsis were enrolled, 56 patients survived and 45 patients died. Compared to the survival group, patients in the death group were older, the proportion of patients with septic shock was larger, the SOFA score, and the proportion of pulmonary infection were higher, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged, the prothrombin activity (PTA) was significantly shortened, and antithrombin (AT) was significantly decreased, the levels of hypersensitivity C-reactive protein (hs-CRP), blood urea nitrogen (BUN), total bilirubin (TBil), and lactic acid (Lac) were significantly increased, while the platelet count (PLT) was significantly decreased. Multifactorial Logistic regression analysis showed that pulmonary infection [odds ratio (OR) = 0.010, 95% confidence interval (95%CI) was 0.001-0.164, P = 0.001], AT (OR = 0.944, 95%CI was 0.910-0.978, P = 0.002), hs-CRP (OR = 1.008, 95%CI was 1.001-1.015, P = 0.017), Lac (OR = 1.619, 95%CI was 1.195-2.193, P = 0.002), and SOFA score (OR = 1.363, 95%CI was 1.076-1.727, P = 0.010) were independent prognostic factors for 28-day mortality in patients. A combined model was constructed using pulmonary infection, AT, hs-CRP, Lac, and SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) for the combine model in predicting sepsis prognosis was 0.936 (95%CI was 0.869-0.975, P < 0.001), which was higher in value compared to single indicators (AUC of AT, hs-CRP, Lac, and SOFA score were 0.775, 0.666, 0.802, 0.796, respectively, all P < 0.05). CONCLUSIONS The predictive ability of the SOFA score for sepsis patient outcomes is limited. The combine model combining infection site, AT, hs-CRP, and Lac shows better predictive ability.
Humans ; Organ Dysfunction Scores ; Retrospective Studies ; C-Reactive Protein ; ROC Curve ; Sepsis/metabolism* ; Prognosis ; Anticoagulants ; Antithrombin III ; Intensive Care Units

Objective:To investigate the efficacy of neostigmine combined with raw rhubarb enema on severe acute pancreatitis (SAP) patients with intra-abdominal hypertension (IAH).Methods:The clinical data of 89 SAP patients, who were admitted and underwent continuous renal replacement treatment (CRRT) in intensive care unit (ICU) department of the First Affiliated Hospital of Hebei North University from January 2018 to June 2022, were retrospectively analyzed. Patients were divided into control group ( n=44) and experimental group ( n=45) according to the treatment mode. Raw rhubarb enema plus sodium sulfate topical application were administrated twice a day for 7 days in control group; besides the treatment above, intramuscular injection of neostigmine 0.5 mg twice a day for 7 days was given in experimental group. Intra-abdominal pressure was monitored, acute physiology and chronic health evaluation (APACHE)Ⅱ, kidney disease: improving global outcome stage (KDIGO), lung injury score (LIS) were recorded, and serum leukocyte, CRP, procalcitonin (PCT), IL-6, IL-8 and tumor necrosis factor (TNF)-ɑ level were examined before and after treatment in both groups. The primary endpoint was the amount change of intra-abdominal pressure within 24 hours, and secondary endpoints included increased fecal volume within 7 days after treatment, new abdominal compartment syndrome (ACS), new organ dysfunction, vascular complications, length of ICU stay, total length of stay, survival rate and treatment intervention and occurrence of complications within 6 months after the end of treatment. Results:Intra-abdominal pressure began to decrease at 9 hours after treatment both in control group and experimental group. Compared with that before treatment, the intra-abdominal pressure of the two groups decreased significantly after 7 days of treatment, and the decrease rate of the experimental group within 7 days was obviously higher than that of the control group, with statistical significance (all P values <0.05). Compared with those before treatment, APACHEⅡ, KDIGO and LIS in both groups were significantly decreased, but the decreases in experimental group were more remarkable than those in control group (all P values <0.05). After treatment, the serum WBC count and the levels of inflammatory factors CRP, PCT, IL-6, IL-8, TNF-ɑ in experimental group were obviously lower than those in control group with statistical significance (all P values <0.05). Compared with control group, the change of intra-abdominal pressure in experimental group was significantly increased after 24-hour treatment, and the fecal volume was also obviously increased on day 1, 2, 3, 5 and 7 after treatment (all P values <0.05). However, there were no significantly statistical differences on the severity of intra-abdominal pressure, new occurrence of ACS and organ failure, vascular complication, ICU hospitalization and total length of stay and survival rate between two groups. After 6-month follow-up, the recurrence of pancreatitis and its treatment intervention between two groups were not statistically significant. Conclusions:The adjuvant treatment of neostigmine could reduce intra-abdominal pressure, increase defecation volume in SAP patients and alleviate SAP condition, which might be related to reducing the release of inflammatory cytokines.

【Objective】 To analyze the viability of 2 different blood screening strategies against SARS-CoV-2 in low risk populations, so as to provide references for the formulation of blood screening strategy. 【Methods】 Two screening strategies for antibodies against SARS-CoV-2 were adopted: 1) the total antibody were initially screened for all samples, and the antibody IgG and IgM were retested in those primary positive samples; 2) only antibody test of IgG and IgM for all samples. And SARS-CoV-2 nucleic acid was detected in parallel. Reactive samples was confirmed by neutralization test. The sensitivity, specificity and true positive rate of two strategies were calculated. 【Results】 None was positive for SARS-CoV-2 nucleic acid among 880 samples. Four truly positive samples were implicated in 9 (1.02%, 9/880) initially reactive samples in total antibody test; 3 in 26 (2.95%, 26/880) initially IgG or IgM reactive samples. 【Conclusion】 The first strategy is superior to the second strategy in the sensitivity and specificity, and is recommended for the detection of SARS-CoV-2 antibody in low risk populations.

Along with the develoipment of high-throughput sequencing technologies, both sample size and SNP number are increasing rapidly in genome-wide association studies (GWAS), and the associated computation is more challenging than ever. Here, we present a memory-efficient, visualization-enhanced, and parallel-accelerated R package called"rMVP"to address the need for improved GWAS computation. rMVP can 1) effectively process large GWAS data, 2) rapidly evaluate population structure, 3) efficiently estimate variance components by Efficient Mixed-Model Association eX-pedited (EMMAX), Factored Spectrally Transformed Linear Mixed Models (FaST-LMM), and Haseman-Elston (HE) regression algorithms, 4) implement parallel-accelerated association tests of markers using general linear model (GLM), mixed linear model (MLM), and fixed and random model circulating probability unification (FarmCPU) methods, 5) compute fast with a globally efficient design in the GWAS processes, and 6) generate various visualizations of GWAS-related information. Accelerated by block matrix multiplication strategy and multiple threads, the association test methods embedded in rMVP are significantly faster than PLINK, GEMMA, and FarmCPU_pkg. rMVP is freely available at https://github.com/xiaolei-lab/rMVP.

Objective To investigate the infectious rates of 9 common pathogens and epidemiology in children with acute respira‐tory tract infections(ARI) in Maoming district .Methods The serum were collected from 6 241 children with acute respiratory in‐fection .IgM of 9 common pathogen including Mycoplasma pneumoniae (MP) ,Legionella pneumophila (LP) ,Coxiella burnetii (C .burnetii) ,Chlamydophila pneumoniae(CP) ,adenovirus(ADV) ,respiratory syncytial virus(RSV) ,type A and type B influenza virus(INFA and INFB) ,and parainfluenza virus(PIVS) ,were detected using immunofluorescence assay .Results Among 6 241 ca‐ses ,1 320 showed atypical pathogens infection ,and infection rate was 21% .The positive rate of MP was 15 .12% ,the highest infec‐tious pathogen;followed by the positive rate of INFB ,LP ,ADV and PIVS were 3 .03% ,1 .92% ,0 .54% and 0 .22% respectively . The pathogens with the lowest positive rate were RSV ,COX ,INFA and CP ,their infectious rates were 0 .14% ,0 .11% ,0 .048%and 0 .016% respectively .Conclusion The infection rate of atypical pathogen among children is high in this area ,which should be taken seriously .MP is the most common pathogen in children with ARI in Maoming district .The pathogen positive rate has rela‐tionship with season .

Objective To study the clinical value of esophageal stent placement with radiation therapy for the middle-late pa-tients with esophageal cancer.Methods To perform esophageal stent placement and radiation therapy for the middle-late 35 pa-tients,and to perform radiation therapy for the middle-late 37 patients,then observe the clinical curative effects.Results The treat-ment group were significantly alleviated with dysphagia symptom after operation,which 32 cases sticked the entire radiation,ac-counting for 91.4%,no one can′t complete the treatment because of nutritional status reason.Survival time of one month after ra-diotherapy was up to 100.0%,and survival time of six months was 85.7% (30/35).But the contrast group with dysphagia symp-tom were aggravated or no relief,and needed parenteral nutrition.There were 23 cases to complete the entire radiation,accounting for 62.2%,and 5 cases happened esophageal tracheal fistula.Survival time of one month after radiotherapy was 83.8%(31/37),and survival time of six months was 62.2% (23/37).Two groups of cases in radiotherapy resistance difference was statistically signifi-cant,one month and six months of survival time were statistically significant (all P <0.05 ).Conclusion Esophageal stent place-ment with radiotherapy is more efficient than only radiation therapy to the middle-late patients with esophageal cancer.