Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.

The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min^-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.

Combined radiation and burn injury (CRBI) is a severe syndrome, which is induced by the simultaneous or successive radiation and burn; but no appropriate clinical therapies are available. Loong oil (LO) is a traditional Chinese medicine oil composed of the oil extracts of cuttlebone, safflower, walnut oil, and rapeseed oil, which has been demonstrated to own anti-radiation and tissue healing functions. In this study, glyceryl monostearate (GMO) was used for the preparation of lyotropic liquid crystals that loaded LO to obtain Loong oil-lyotropic liquid crystals (LOL) for the treatment of skin CRBI. The hexagonal phase structure of LOL was proved by small X-ray scattering (SAXS) analysis with an approximate 7:9:11 ratio of peaks and under the polarizing microscope with the birefringence phenomenon. LOL had a high LO loading capacity (4%) and good bio-adhesive force, favoring skin administration. Animal experiments were approved by the Ethics Committee of the Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations (approval number: IACUC-DWZX-2022-834). Compared to triethanolamine creams, LOL had higher skin permeability with total skin penetration within 1 h, benefiting the treatment of deep CRBI. A deep II degree burn CRBI mouse model was established after whole-body irradiation with 5 Gy ⁶⁰Co γ-ray and the next 6-second 100 ℃ burn injury. LOL promoted LO skin penetration, improved epithermal cell proliferation and the formation of hair follicles, accelerated wound healing, and inhibited scarring, which benefitted the therapy of CRBI. In this study, LO application fields are expanded and LO is a promising medication for the treatment of CRBI.

Background and objective The incidence rate of lung cancer in Xuanwei has been continuously in-creasing in recent years,and it also features high incidence across all age groups and high mortality rates among female lung cancer patients.Therefore,the search for more stable biomarkers for the diagnosis of Xuanwei lung cancer holds tremendous clinical application prospects.This study aims to explore the clinical application value of these four microRNAs(miRNAs)in-dividually and in combination with traditional lung cancer tumor markers in the detection and diagnosis of Xuanwei lung can-cer.Methods By detecting the expression levels of four miRNAs and five traditional lung cancer tumor markers in the serum of 45 Xuanwei lung cancer patients and healthy physical examination participants,the Logistic regression model was employed to comprehensively evaluate the sensitivity,specificity,diagnostic efficacy,and other relevant statistical indicators of the four miR-NAs in the diagnosis of Xuanwei lung cancer.Results Among the individual miRNAs,miR-4646-5p and miR-3654 showed significant differences in expression levels between the Xuanwei lung cancer group and the control group(P＜0.05).miR-3654 demonstrated the best diagnostic performance with a sensitivity of 86.7％ ,specificity of 82.2％ ,and an area under the curve of 0.847.Combining miR-3654 with miR-4646-5p and carcinoembryonic antigen(CEA)resulted in the highest diagnostic ef-ficacy for Xuanwei lung cancer,with a sensitivity of 73.3％ ,specificity of 93.3％ ,area under the curve of 0.901,and a positive predictive value of 91.7％ .Conclusion Among the four miRNAs,serum miR-3654 exhibits the best diagnostic efficacy for Xuanwei lung cancer.Combined with miR-4646-5p and CEA,its diagnostic value for Xuanwei lung cancer can be effectively enhanced,making it a promising screening indicator for Xuanwei lung cancer.

Objective:To explore the correlation between gene mutations and clinical characteristics,prognosis of myelodysplastic syndromes(MDS).Methods:Clinical data of 131 patients with MDS were collected from the First Hospital of Lanzhou University from June 2015 to February 2023,which 19 of them developed into secondary acute myeloid leukemia(sAML)during follow-up time.Second generation sequencing technology was used to detect the mutation types of MDS disease-related genes,drawn gene maps,and analyzed their correlation and prognosis based on the clinical data of patients.Results:The median age of 131 MDS patients was 58(17-86)years old.The ratio of male to female was 1.3:1.A total of 148 gene mutations and 25 types were found in the center.U2AF1 and ASXL1 were often co-mutations with other genes,which were accompanied by 20q-and normal karyotype(NK)respectively.SETBP1 and SRSF2 were more common in patients over 60 years old,while NPM1 and WT1 under 60 years.Older patients had a higher the number of genetic mutations than younger patients.The incidence of SF3B1 and RUNX1 in males was higher than females and DNMT3A in females was higher than males.The number of gene mutations in sAML was higher than MDS(1.8 vs 1.0,P=0.006).The univariate and multivariate analysis showed that IPSS-R prognostic score≥ 3.5,TP53 were adverse factors for poor prognosis in MDS patients.Patients with monoallelic mutation(ma-TP53)and wild-type(wt-TP53)TP53 had OS better than biallelic mutation(bi-TP53)(P=0.003).The OS of MDS patients was better than sAML(P=0.01)and transplant patients was significantly better than non-transplant patients(P=0.036).Conclusion:Gene mutation is closely related to cytogenetic indexes and clinical features(peripheral blood cell count,sex,age).IPSS-R prognostic score and TP53 were risk factors affecting OS in MDS patients.

In the study of age estimation in living individuals,a lot of data needs to be analyzed by mathematical statistics,and reasonable medical statistical methods play an important role in data design and analysis.The selection of accurate and appropriate statistical methods is one of the key factors af-fecting the quality of research results.This paper reviews the principles and applicable principles of the commonly used medical statistical methods such as descriptive statistics,difference analysis,consistency test and multivariate statistical analysis,as well as machine learning methods such as shallow learning and deep learning in the age estimation research of living individuals,and summarizes the relevance and application prospects between medical statistical methods and machine learning methods.This paper aims to provide technical guidance for the age estimation research of living individuals to obtain more scientific and accurate results.

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.

【Objective】 To investigate the level of serum bone metabolism and biochemical markers and bone density of plasmapheresis donors, and to provide scientific basis for ensuring the health and safety of plasmapheresis donors in China. 【Methods】 A total of 437 plasmapheresis donors from Linwu plasmapheresis station in Hunan Province from July 1 to September 30, 2022 were recruited to determine the levels of total serum calcium, albumin, serum 25-hydroxyvitamin D (25OHD), serum type I procollagen N-terminal propeptide (P1NP), and collagen type 1 crosslinked carboxyl-terminal peptide (β-CTX). Dual-energy X-ray method was used to measure the bone density of the anteroposterior lumbar spine (L1-L4) and bilateral femoral neck bone density of plasmapheresis donors. Plasmapheresis donors were grouped according to the type of plasma donation (first-time and repeat plasmapheresis donors) and the total number of plasma donations to assess the differences in bone density and serum bone metabolism biochemical markers between groups. The dose-response relationship between the total number of plasmapheresis donations and biochemical indexes was analyzed by limiting cubic spline, and the influencing factors of different indexes were explored by multiple linear regression. 【Results】 A total of 437 plasmapheresis donors were included in this study, including 187 first-time plasmapheresis donors and 250 repeat plasmapheresis donors. There were no significant differences in bone density and prevalence of osteoporosis between first-time donors and repeat donors (P>0.05). There was also no significant difference in bone density levels between groups of total number of plasmapheresis donations. The levels of albumin and 25OHD decreased with the increase of the total number of plasma donations, while the serum P1NP level was positively correlated with the total number of plasma donations. The results of the restriction cubic spline showed that the total number of plasmapheresis donations had a nonlinear dose-response relationship with 25OH and P1NP (P<0.05). The results of multiple linear regression showed that the frequency of plasmapheresis donation was the influencing factor of 25OHD, and the total number of plasmapheresis donation was the influencing factor of P1NP. 【Conclusion】 Plasmapheresis donation does not affect the bone health of donors and increase the risk of osteoporosis due to the use of long-term anticoagulants, but it will increase the osteogenic activity of plasmapheresis donors. It is recommended that middle-aged and elderly plasmapheresis donors supplement vitamin D appropriately.

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.

Objective To evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90％confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90％CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.