Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (A_e) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10^-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

Objective To observe the protective effect of modified Baishile Decoction on hippocampal neuronal cells cultured in vitro;To explore its mechanism of treating post-stroke depression.Methods Hippocampal neuronal cells from mammary rats were isolated and cultured in vitro,cell injury was induced by oxygen glucose deprivation combined with lipopolysaccharide.The cells were divided into normal group,model group,blank serum group(10%)and modified Baishile Decoction containing serum group(10%).Invertedmicroscope was used to observe cell morphological changes,CCK-8 method was used to detect cell survival rate,Hoechst33342 staining was used to observe apoptosis,ELISA was used to detect Glu,5-HT,TNF-α,IL-1β,and IL-6 contents in cell supernatant,the expressions of purinergic P2X7 receptor(P2X7R)and NOD-like receptor protein 3(NLRP3)were detected by immunofluorescence staining.Results Compared with the normal group,the hippocampal neurons in the model group showed significant changes in cell morphology,the cell survival rate significantly decreased(P<0.01),the cell apoptosis increased(P<0.01);Glu,TNF-α,IL-1β,IL-6 contents in cell supernatant significantly increased(P<0.05,P<0.01),5-HT content significantly decreased(P<0.01),P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly increased(P<0.01).Compared with the model group,the morphology of hippocampal neurons in modified Baishile Decoction containing serum group was significantly improved,the cell survival rate significantly increased(P<0.01),the cell apoptosis reduced(P<0.01);Glu,TNF-α and IL-1β content in cell supernatant significantly reduced(P<0.05,P<0.01),5-HT content significantly increased(P<0.01),and P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly decreased(P<0.01).Conclusion Modified Baishile Decoction may exert a protective effect on oxidative glucose deprivation combined with lipopolysaccharide induced hippocampal neuronal inflammation damage by inhibiting the P2X7R/NLRP3 signaling pathway,regulating neurotransmitter secretion,and inhibiting inflammatory factor release,thus treating post-stroke depression.

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

In infants with severe bronchopulmonary dysplasia(sBPD),severe pulmonary lobar emphysema may occur as a complication,contributing to significant impairment in ventilation.Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation.However,prior to the lobectomy,it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively.In addition,preoperative planning and perioperative management are also quite challenging in these patients.This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema.Since infants with sBPD already have poor lung development and significant lung injury,lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution.Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema.However,given the technical difficulty,successful application of this technique requires close collaboration of an experienced interdisciplinary team.

An innovative on-site real-time avian influenza virus(AIV)detection method was estab-lished by integratingrecombinase-aided amplification(RAA)with the clustered regularly inter-spaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)system.After analy-zing 120 sequences of the M gene of avian influenza viruses of different subtypes publicly available on NCBI,the RAA primers and crRNA were designed based on the identified highly conserved segment and used for RAA nucleic acid amplification.After the amplified products were transferred to a CRISPR/Cas13a detection system,the fluorescence values were monitored throughout the re-action process to indicate the results.The sensitivity and specificity of the RAA-CRISPR/Cas13a method were validated using gradient dilutions(106-100 copies/μL)of positive plasmids and sev-en other avian viruses.Fifty clinical samples were tested using this method and compared with the national standard fluorescence RT-PCR method.The results indicated that the detection limit for RAA-CRISPR/Cas13a method was 102 copies/μL,a two-fold improvement over the standard RAA.Specificity assay showed the established method only detected AIV with no cross-reactivity with other seven avian viruses.Compared to the national standard fluorescence RT-PCR method,this method exhibited 100％specificity,95.24％accuracy,and 98.00％consistency in detection of clinical samples.In conclusion,a universal and rapid RAA-CRISPR/Cas13a for detection of AIV was established with the capacity of achieving detection within 60 minutes at 37 ℃,which provides a rapid,sensitive,and specific on-site detection method for AIV.

Aim To explore the mechanism of Yanghe decoction-containing serum on the migration and inva-sion of MCF-7 breast cancer cells in a co-culture sys-tem with M2 tumor-associated macrophages(TAMs)based on the paracrine epidermal growth factor(EGF)/epidermal growth factor receptor(EGFR)sig-naling pathway.Methods The M2-type TAMs model was induced from THP-1 monocytic cell line through in vitro treatment with phorbol 12-myristate 13-acetate(PMA)and recombinant human macrophage colony-stimulating factor(M-CSF).The MCF-7 cells were co-cultured with M2-type TAMs using a Transwell non-contact co-culture system to evaluate their effects on migration and invasion.Subsequently,the cells were intervened with serum containing Yanghe decoction,and the proliferation of MCF-7 cells was detected using the CCK-8 assay,while their lateral migration ability was assessed through scratch assays.The invasion and vertical migration abilities of the cells were evaluated separately using Transwell assays,and the concentra-tion of EGF was measured using ELISA.Finally,the expression of EGFR,MCP-1,and MMP9 proteins was detected using Western blot.Results Compared to the control group,Yanghe decoction-containing serum in-hibited the proliferation of MCF-7 cells before and after co-culture.The serum reduced the scratch healing a-bility before and after co-culture and decreased their migration and invasion abilities.Additionally,Yanghe decoction-containing serum reduced the levels of EGF before and after co-culture and decreased the expres-sion of EGFR,MCP-1,and MMP9 proteins before and after+co-culture.Conclusion Yanghe decoction-containing serum can inhibit the migration and invasion of breast cancer MCF-7 cells before and after co-cul-ture with M2 TAMs.This effect may be related to the inhibition of the EGF-EGFR signaling pathway.

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.

Abstract: To explore the clinical characteristics, diagnosis and treatment of imported severe malaria and COVID-19 co-infection cases, and to provide scientific basis for epidemic prevention and control measures. The epidemiological characteristics, clinical manifestations, laboratory tests, treatment process and prognosis of 4 cases of severe malaria and COVID-19 co-infection with confirmed diagnosis were analyzed retrospectively. Four cases of severe malaria were African returnees of the same batch, male, aged 40-54 years old, with the same journey track. They all had African work and life history and acute onset. The main clinical manifestations were fever (4/4), chills (3/4), chills (3/4), nausea and vomiting (3/4), diarrhea (4/4), fatigue and anorexia (4/4). Two cases had headache and dizziness, confusion, muscle aches, two cases had cough, one cases had sputum, sore throat and runny urine. All 4 cases were confirmed by positive nucleic acid detection of the new coronavirus (2019-nCOV) in throat swabs. Plasmodium falciparum was found by microscopic examination of peripheral blood smears of all patients, and all of them were consistent with high altitude helminthiasis. All cases were accompanied by abnormal liver function and severe hypoproteinemia, two cases were hyperbilirubinemia, three cases were dyslipidemia, three cases were involved in abnormal tertiary hemogram with different degrees of elevation of procalcitonin, two cases were lactic acid poisoning, and one case was hypoglycemia. One case showed viral pneumonia on chest CT. All cases were treated individually according to the different conditions and were discharged after improvement, and were rechecked for 2019-nCOV nucleic acid and microscopic examination of blood smear negative for Plasmodium.During the global COVID-19 epidemic, the emergence of coinfection cases of con-infection of imported malaria parasites and severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) makes the clinical diagnosis and treatment more complicated. It is important to establish the awareness of simultaneous prevention and diagnosis of COVID-19 and malaria for local prevention and control and early warning of severe cases, and timely and effective formulation of treatment plan to improve the comprehensive treatment efficiency.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve