Objective: To develop a comprehensive health economics evaluation model for HIV blood screening using Markov modeling, so as to evaluate the quality-of-life adjustment years (QALYs) gained by transfusion recipients after implementation of blood HIV screening. Methods: Shenzhen Blood Center was selected as the validation case for model development. Based on historical HIV screening data of Shenzhen Blood Center and published literature, the health economics evaluation of donor HIV screening was performed using cost-utility analysis. The single factor sensitivity analysis was performed on parameters in the model. Results: 3.09 QALYs were gained for each transfusion recipient prevented from HIV infection. During 2020-2023, donor HIV screening at Shenzhen Blood Center saved 506.76 QALYs, and each QALY saved 182 900 yuan. Conclusion: From the perspective of long-term benefit of transfusion recipients, HIV screening of blood donors demonstrates high health and economic value.

Objective: To develop a comprehensive health economics evaluation model for HIV blood screening using Markov modeling, so as to evaluate the quality-of-life adjustment years (QALYs) gained by transfusion recipients after implementation of blood HIV screening. Methods: Shenzhen Blood Center was selected as the validation case for model development. Based on historical HIV screening data of Shenzhen Blood Center and published literature, the health economics evaluation of donor HIV screening was performed using cost-utility analysis. The single factor sensitivity analysis was performed on parameters in the model. Results: 3.09 QALYs were gained for each transfusion recipient prevented from HIV infection. During 2020-2023, donor HIV screening at Shenzhen Blood Center saved 506.76 QALYs, and each QALY saved 182 900 yuan. Conclusion: From the perspective of long-term benefit of transfusion recipients, HIV screening of blood donors demonstrates high health and economic value.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

【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 prepare C-phycocyanin nanoparticles （CPC-NPs） and evaluate the in vitro mechanism of CPC- NPs on acute lung injury induced by lipopolysaccharide （LPS） combined with seawater. METHODS Ion crosslinking method was used to prepare CPC-NPs using CPC as the drug， carboxymethyl chitosan （CMCS） as the carrier， and CaCl2 as the crosslinking agent. The basic characterization of CPC-NPs was carried out. Mouse alveolar type Ⅱ epithelial cells MLE-12 and macrophages RAW264.7 were divided into 7 groups： normal group （Con group）， model group （Mod group）， blank NPs group， CPC-NPs 30， 60， 120 and 240 μg/mL groups. Except for the Con group， all other groups were treated with a combination of 10 μg/mL LPS and 25% seawater for 6 hours. After modeling， each treatment group was treated with corresponding drugs for 24 hours. The levels of malondialdehyde （MDA）， total antioxidant capacity （T-AOC）， superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） in MLE-12 cells， as well as the expression levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-3 protein and mRNA， CAT and glutathione S-transferase （GST） mRNA were determined. The levels of interleukin- 1β （IL-1β）， tumor necrosis factor-α （TNF-α） and IL-6 in RAW264.7 cells， as well as the expression levels of NOD-like receptor thermal protein domain associated protein 3 （NLRP3）， cleaved caspase-1 protein， and mRNA expressions of IL-1β，TNF-α， IL-6 and inducible nitric oxide synthase （iNOS） were all detected. RESULTS The prepared CPC-NPs had particle size of （675.69±64.58） nm， Zeta potential of （－20.11± E-mail：zhangleifang1986@163.com 0.98） mV， polydispersity coefficient of 0.455±0.010 （n＝3）；entrapment efficiency of 35.60%， and drug loading of 16.13%；CPC-NPs had regular spherical shapes， where the drug could be sustainably released for more than 30 hours. Compared with Mod group， the levels of T-AOC， SOD， CAT （excluding the 30 μg/mL group of CPC-NPs） and GSH-Px， mRNA expressions of CAT and GST， as well as the Bcl-2/Bax protein ratio and mRNA ratio were significantly increased in MLE-12 cells of different concentration groups of CPC-NPs， while MDA levels and caspase-3 protein and mRNA expression were significantly reduced （P＜0.01 or P＜0.05）. Compared with Mod group， the levels of IL-1β， TNF-α and IL-6， NLRP3 and cleaved-caspase-1 protein expressions， as well as the mRNA expressions of IL-1β， TNF-α， IL-6 and iNOS in RAW264.7 cells of different concentration groups of CPC-NPs were significantly reduced （P＜0.01 or P＜0.05）. CONCLUSIONS CPC-NPs with lung targeting and sustained release property were prepared successfully， which can alleviate acute lung injury induced by LPS combined with seawater through antioxidant stress， inhibiting cell apoptosis and inflammatory response.

Objective To find out the prevalence of antiretroviral therapy(ART)drugs among treponema pallidum(TP)antibody(anti-TP)positive blood donors in Shenzhen,and to assess the blood safety risks brought about by the new trends of human immunodeficiency virus(HIV)diagnosis and treatment.Methods A stratified random sampling method was used to select 60 repeat blood donors(negative control group)who passed blood screening in Shenzhen from March 2019 to January 2023,and 3 people who regularly took known ART drugs were named positive control group,358 anti-TP positive/anti-HIV negative blood do-nors were named experimental group 1,20 anti-TP positive/anti-HIV positive blood donors were named ex-perimental group 2.The liquid chromatography-mass spectrometry(HPLC-MS/MS)was applied to detect the concentration of 8 ART drugs in plasma samples of each group,and the use of ART drugs was analyzed.Re-sults After the positive control group's plasma was diluted with a 1:6 dilution mixture,the ART drugs could still be detected.The positive mixed plasma samples of 1:6 people in Group 1 and Group 2 were split and validation,one ART drug positive sample was detected in Group 2,which was positive for anti-HIV,pro-tein immunoblotting,and HIV RNA.The detection rate of ART drugs in anti-TP positive blood donors was 0.26％,0.00％in Group 1 and 4.00％in Group 2.Conclusion The use of ART drugs has been found among anti-TP positive blood donors in Shenzhen,and people with HIV infection and high-risk sexual behavior are more likely to use antiretroviral drugs.

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 results of different methods for reactive samples screened by the enzyme linked immunosorbent assay (ELISA) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in blood donors. 【Methods】 From March to April 2020, a total of 8 632 blood samples in Shenzhen were screened for SARS-CoV-2 total antibodies (TAb, including IgG, IgM, IgA) in plasma using ELISA(PC group), the antibody reactivity samples and their follow up plasma samples (FC group), and samples of disease control group(DC group) from January to April 2020 were detected using the following methods: 1) ELISA method for detecting IgG, IgM, and (or without detection) TAb; 2) pseudovirus neutralizing antibody test(pVNT); 3) western blot (WB) of SARS-CoV-2 antibody. The negative control group(NC group) from February to April 2020 performed ELISA and WB testing. 【Results】 Among the 34 total antibody positive samples, 2 were positive for pVNT test, and the total antibody, IgG and WB in the initial screening and tracking testing were positive. Thereafter, it was determined to be confirmed positive. The other 2 cases were positive for pVNT test, while the samples with positive WB results were in the follow-up stage. The TAb, IgG, and pVNT results did not conform to the dynamic evolution of antibodies, and cannot be determined as confirmed positive. 【Conclusion】 The infection status of antibody reactivity samples screened by SARS-CoV-2 ELISA can be judged by the logic of pVNT, WB and the dynamic change of antibody.

【Objective】 To analyze the SARS-CoV-2 detection results among blood donors in different periods of COVID-19 pandemic control in Shenzhen and assess the antibody levels and infection status of blood donors in different periods, so as to provide reference for subsequent blood testing strategies. 【Methods】 A total of 4 768 plasma samples of blood donors were subjected to pooled testing by nucleic acid testing(NAT) with 8 samples per pool. Additionally, these samples were subjected to a 1000-fold dilution, and the detection of SARS-CoV-2 total antibody was performed by enzyme-linked immunosorbent assay (ELISA). The 4 768 plasma samples were collected from blood donors at different time points in Shenzhen, with inquiries made to determine whether donors during the COVID-19 pandemic were in the convalescence. The antibody positive rates in blood screening samples during different periods of the pandemic and samples from individuals in the convalescence of COVID-19 infection were analyzed. Furthermore, the antibody levels were examined for differences based on gender, age, and blood type. 【Results】 All 4 768 plasma samples from blood donors were negative by NAT, while 2 342 samples were detected positive by the SARS-CoV-2 total antibody detection, with a positive rate of 49.1%. These samples from four periods (September 30 to October 3, 2022; November 3 to 6, 2022; December 27 to 31, 2022; January 6 to 18, 2023) were subjected to a 1 000-fold dilution for COVID-19 antibody detection, and the positive rates were 21.3%, 15.8%, 65.9%, and 93.9%, respectively. 【Conclusion】 The prevalence of COVID-19 antibodies among blood donors in Shenzhen during different periods of the pandemic varied significantly. There was no difference in antibody prevalence among different genders and blood types, while younger individuals exhibited a higher prevalence of antibodies. The risk of COVID-19 transmission through blood transfusion was found to be extremely low.

【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.