Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation / 药物分析学报

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Predictive Value of NLR,PLR and sPESI Score for 30-day Mortality in Patients with Acute Pulmonary Embolism / 医学研究杂志

Objective To investigate the predictive value of neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and the simplified pulmonary embolism index(sPESI)score for 30-day death in patients with acute pulmonary embolism(APE).Methods The clinical data of 291 APE patients admitted to Xuanwu Hospital of Capital Medical University from January 2017 to December 2021 were retrospectively analyzed.White blood cell count(WBC),NLR,PLR,sPESI score,and other indicators were calculated at admission.The patients were followed up within 30 days and were divided into the death group and the survival group accord-ing to the prognosis.The differences in the above indexes between the two groups were compared.Multivariate Logistic regression was used to analyze the independent risk factors for 30-day mortality in APE patients.The area under the receiver operating characteristic(ROC)curve of NLR,PLR,and combined sPESI scores in predicting mortality was compared.Results Among the APE patients,11 cases(3.78％)died and 280 cases(96.22％)survived within 30 days.The WBC,NLR,PLR,and sPESI score in the death group were sig-nificantly higher than those in the survival group(P＜0.05).Multivariate Logistic regression analysis showed that PLR,NLR,and sPESI score were independent risk factors for 30-day mortality in APE patients(P＜0.05).The area under ROC curve(AUC)of PLR in pre-dicting the 30-day death of APE patients was 0.799(P=0.001).The AUC of NLR was 0.827(P=0.001).The AUC of sPESI score was 0.874(P=0.001).There was no significant difference in the AUC of PLR,NLR,and sPESI score in predicting death(P=0.181,0.340);the AUC of NLR combined with sPESI score was 0.925(P=0.001),which was greater than that of NLR(P=0.004).The AUC of PLR combined with sPESI score was 0.901(P=0.001),which was greater than that of PLR(P=0.002).Conclusion NLR,PLR,and sPESI score are independent risk factors for 30-day mortality in APE patients,and all of them have certain prognostic values.The prognostic value of PLR and NLR combined with sPESI score was higher than that of PLR and NLR alone.

Current Research Status and Application Technical Progress of Small Molecule Drug Screening Technology / 医药导报

Small molecule drug screening technology is continuously evolving and expanding along with drug discovery,and the innovation in drug screening technology can improve the research and development efficiency and success rate,shorten the cycle time,and reduce the cost.From traditional screening technologies based on known active compounds and high-throughput screening(HTS)to new technologies such as structure-based drug discovery(SBDD),fragment-based drug discovery(FBDD),DNA encoded compound library(DEL)and proteolysis targeting chimeras(PROTAC),small molecule drug screening technologies are continuously broadening the market potential for small molecule drugs.This article will provide an overview of the current status of small molecule drug screening technology,systematically review each technique along with their advantages and disadvantages,and offer essential insights for the development of new small molecule drug screening technologies.

Effect of RhoC silencing on migration and invasion of oral squamous cell carcinoma / 中国病理生理杂志

AIM:To explore the expression of RhoC in oral squamous cell carcinoma(OSCC)and its effects on the malignant biological behavior of OSCC cells.METHODS:The UALCAN and K-M plotter databases,alongside tis-sue sample analyses,facilitated understanding RhoC expression in cancer and its links to clinicopathological traits.Two small interfering RNAs(RhoC-siRNA)were constructed according to the RhoC gene sequence.The mRNA and protein ex-pression levels of RhoC in OSCC cells were determined.The protein levels of FAK,p-FAK,MAPK,p-MAPK,matrix me-talloproteinase-2(MMP-2)and MMP-9 were also examined by Western blot.Furthermore,the invasion and migration of OSCC cells were analyzed by Transwell assay and scratch test.Finally,the pulmonary metastasis model of nude mice was established.RESULTS:The results of the databases showed that RhoC was highly expressed in OSCC tissues,which was closely related to pathological stage,pathological grade and lymph node metastasis,but not significantly related to the sur-vival rate of patients.Furthermore,compared with paracancer tissues,the mRNA and protein expression levels of RhoC were increased in OSCC tissues(P<0.01).Silencing of RhoC prominently reduced the migration and invasion of OSCC cells as well as the protein levels of p-FAK,p-MAPK,MMP2 and MMP9(P<0.05).The protein levels of MAPK and FAK were unchanged(P>0.05).The fluorescence intensity of the experimental group was significantly lower than that of the control group,and the results of HE staining showed that the number of lung nodules in the experimental group was sig-nificantly reduced(P<0.05).CONCLUSION:RhoC can effectively influence the migration and invasion of OSCC cells,and its potential mechanism may be related to FAK/MAPK/MMPs signaling pathway.

Analysis of annual report data of Keshan disease in Jilin Province from 2017 to 2021 / 中华地方病学杂志

Objective:To investigate the scope and changes in the outcome of Keshan disease in Jilin Province, and provide scientific basis for adjusting the focus of Keshan disease prevention and control.Methods:A retrospective analysis was conducted on the annual report data of Keshan disease reported by 38 Keshan disease endemic counties (cities, districts) in Jilin Province from 2017 to 2021. Descriptive analysis was conducted on the scope of Keshan disease endemic areas, population, general situation and outcomes of current patients.Results:As of the end of 2021, there was no overall change in the scope of Keshan disease endemic areas in Jilin Province. The number of permanent residents in counties, townships, and villages in the endemic areas had decreased by 11.77%, 26.77%, and 35.55%, respectively, compared to 2017. There were a total of 1 092 current patients with Keshan disease, including 926 cases of latent Keshan disease and 166 cases of chronic Keshan disease. The male to female ratio was 0.38∶1.00 (303∶789), and 79.76% (871/1 092) of the patients were over 60 years old. Some patients also had other chronic diseases such as hypertension and coronary heart disease. In 2021, the number of patients with Keshan disease decreased by 1 020 compared to 2017. Death, migration (in), loss of follow-up, and re-diagnosis accounted for 34.29% (500/1 458), 27.85% (406/1 458), 25.51% (372/1 458), and 12.35% (180/1 458) of the total number of outcomes, respectively; 57 middle-aged and young patients under 60 years old accounted for 11.40% (57/500) of the total deaths. Over the past 5 years, 24 new patients were discovered, including 4 cases of latent Keshan disease and 20 cases of chronic Keshan disease. Additionally, 6 patients with chronic Keshan disease died within 2 years of diagnosis.Conclusions:The overall scope of Keshan disease endemic areas in Jilin Province has not changed, with a significant decrease in the number of permanent residents, an aging population of current patients, and some patients coexisting with chronic diseases. Death, migration (in), and loss of follow-up are the main outcomes of current patients.

Current status of maintenance hemodialysis-related infection in 124 medi-cal institutions in Guizhou Province / 中国感染控制杂志

Objective To understand the infection status of patients with maintenance hemodialysis(MHD)in Guizhou Province,and provide basis for the prevention and control of hemodialysis-related infection.Methods MHD patients in hemodialysis centers of 124 secondary and or higher grade medical institutions in Guizhou Province from July to December 2022 were surveyed.Survey content included the general conditions of patients,hemodialysis-related conditions,infection of pathogens of blood-borne diseases,and other infection-related conditions.Results A total of 15 114 MHD patients were surveyed,with age mainly ranging from 36 to＜60 years old(55.83％).Hemodialysis history ranged mainly from 1 year to＜5 years(59.37％),and the frequency of hemodi-alysis was mainly 3 times per week(73.91％).Autologous arteriovenous fistula(AVF)was the major vascular access for dialysis,with a total of 12 948 cases(85.77％).The main primary disease was chronic renal failure(99.89％).The infection rates of hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodeficiency vi-rus(HIV),and Treponema pallidum in MHD patients were 5.29％,0.64％,0.24％,and 1.70％,respectively.HBV infection rates among MHD patients of different ages,different numbers of dialysis hospitals,and dialysis in-stitutions of different scales showed statistically significant differences(all P＜0.05).HCV infection rates among MHD patients of different ages,with different dialysis times and from institutions of different scales were signifi-cantly different(all P＜0.05).TP infection rates among MHD patients of different ages and different numbers of dialysis hospitals were all significantly different(all P＜0.05).Infection rates of HBV and HCV in MHD patients aged from 36 to 60 years old(not included)were relatively higher(6.10％and 0.84％,respectively).Patients with dialysis time ≥10 years had a higher HCV infection rate(1.64％).Infection rates of HCV,HIV,and TP in pa-tients dialyzed in medical institutions with ≥90 dialysis beds were relatively higher(0.74％,0.28％,and 1.94％,respectively).Medical institutions with＜30 dialysis beds had the highest HBV infection rate(18.64％).There were 9 cases(0.06％)of vascular puncture infection,12 cases(0.08％)of bloodstream infection,7 cases(0.05％)of vascular access-related bloodstream infection,and 30 cases(0.20％)of pulmonary infection.Vascular access-re-lated bloodstream infection rate and pulmonary infection rate among MHD patients with different types of vascular access showed statistically significant difference(all P＜0.05).Vascular access-related bloodstream infection rate(0.37％)and pulmonary infection rate(1.10％)of patients with non-cuffed catheters vascular access were higher than those of other types.Conclusion MHD patients in Guizhou Province are mainly middle-aged and young peo-ple,with more males than females.The dialysis frequency is mostly 3 times per week,and AVF is the major vascu-lar access.MHD patients are prone to complications such as infections of HBV,HCV,HIV,and TP,as well as bloodstream infection and pulmonary infection.

Effect of recombinant human epidermal growth factor combined with sodium hyaluronate eye drops in patients with cataract after multifocal intraocular lens implantation / 中国基层医药

Objective:To investigate the clinical efficacy of recombinant human epidermal growth factor combined with sodium hyaluronate eye drops in the treatment of cataracts after multifocal intraocular lens implantation and its effect on inflammation factors in tears and tear film stability.Methods:A total of 86 patients with cataracts who underwent multifocal intraocular lens implantation at Jinan 2 nd People's Hospital from July 2020 to January 2023 were included in this randomized controlled study. These patients were randomly divided into a control group and a combined group, with 43 patients in each group. Patients in the control group were administered sodium hyaluronate eye drops postoperatively, while patients in the combined group received a combination of recombinant human epidermal growth factor and sodium hyaluronate eye drops. All patients were treated for 1 month. Before and after treatment, the levels of inflammatory factors in tears, tear film stability-related indicators, and corneal endothelial cells were measured and compared between the two groups. Additionally, any adverse reactions experienced by the patients were recorded throughout the treatment period. Results:After treatment, the levels of interleukin-6 and tumor necrosis factor-α in the tear fluid of the combined group were (17.91 ± 2.45) μg/L and (72.14 ± 8.43) μg/L, respectively. These values were significantly lower than those in the control group, which were (24.63 ± 3.05) μg/L and (86.97 ± 9.85) μg/L, respectively ( t = 11.26, 7.50, both P < 0.001). Additionally, the fluorescein staining score for corneal damage in the combined group was (2.34 ± 0.37) points. This was significantly lower than the score of (3.42 ± 0.48) points observed in the control group ( t = 11.69, P < 0.001). Tear break-up time and Schirmer I Test in the combined group were (8.68 ± 0.96) seconds and (9.31 ± 1.04) mm/5 minutes, respectively. These values were significantly higher than those in the control group, which were (7.81 ± 0.89) seconds and (7.14 ± 0.86) mm/5 minutes, respectively ( t = -4.36, -10.54, both P < 0.001). Furthermore, the corneal endothelial cell density and the proportion of hexagonal cells in the combined group were (2 514.09 ± 259.31) counts/mm 2 and (41.67 ± 5.05)%, respectively. These values were significantly higher than those in the control group, which were (2 244.82 ± 253.37) counts/mm 2 and (36.75 ± 4.96)% in the control group ( t = -4.87, -29.45, both P < 0.001). The incidence of adverse reactions in the combined group was 11.63% (5/43), which was significantly higher than 6.98% (3/43) in the control group ( χ2 = 0.55, P > 0.05). Conclusion:The combination of recombinant human epidermal growth factor with sodium hyaluronate eye drops following multifocal intraocular lens implantation in patients with cataracts effectively decreases the levels of inflammatory factors in tear fluid. This treatment regimen also enhances tear film stability, promotes the repair of injured corneal tissue, and is highly safe.

Correlation between low bilirubin levels and hyperthyroidism in patients with type 2 diabetes mellitus / 中国糖尿病杂志

Objective To explore the relationship between low bilirubin(T-BIL)levels and hyper-thyroidism in patients with type 2 diabetes mellitus(T2DM).Methods A total of 186 patients with T2DM admitted to the Endocrinology Department of our hospital were enrolled in this study from January 2019 to August 2022.They were divided into simple T2DM group(n=107)and hyperthyroidism group(HT,n=79)according to whether they were complicated with hyperthyroidism.The influence factors for T2DM patients complicated with hyperthyroidism were evaluated by logistic regression analysis.Results Compared with T2DM group,DM duration,FPG,the proportion of patients with salty taste and nervous increased in HT group(P<0.05),while BMI,T-BIL decreased in HT group(P<0.05).Pearson correlation analysis showed that T-BIL was positively correlated with TSH levels(P<0.05),and negatively correlated with TT3,TT4,FT3 and FT4(P<0.05).Logistic regression analysis showed that DM duration,salty taste,FPG and T-BIL were the influencing factors of T2DM patients with hyperthyroidism.The receiver operating characteristic(ROC)Curve showed that the AUC of the model was 0.812(95%CI 0.748～0.839),with sensitivity and specificity 87.4%and 82.6%respectively.Conclusion T-BIL was significantly correlated with TSH and FT3.Low T-BIL level is an independent risk factor for T2DM patients with hyperthyroidism,which is of great significance for predicting whether T2DM patients complicated with hyperthyroidism.

Relationship among physical activity,mild depressive symptoms and frontal alpha power asymmetry in college students / 中国心理卫生杂志

Objective:To investigate the correlation among physical activity,mild depressive symptoms and frontal alpha power asymmetry in college students.Methods:Seventy college students with mild depressive symp-toms who conformed to the standard of the Self-Rating Scale for Depression(SDS)of 53-62 and 70 normal col-lege students were recruited.The frontal alpha power was measured under quiet and closed-eye state,and the total physical activity(PA)was assessed with the International Physical Activity Questionnaire.Results:The college students with mild depressive symptoms had lower Total PA scores,right frontal alpha power and frontal alpha a-symmetry(FAA)than the normal controls(P＜0.001).In college students with mild depressive symptoms,the to-tal PA scores(r=-0.29,P＜0.05)and FAA(r=-0.41,P＜0.001)were negatively correlated with SDS scores,and the total PA scores were positively correlated with FAA(r=0.34,P＜0.01).Conclusion:The college students with mild depressive symptoms may have reduced physical activity and asymmetric right lateralization of frontal alpha power.There is a correlation among depressive symptoms,physical activity and frontal alpha power a-symmetry in college students with mild depressive symptoms.

A review of early identification and conversion studies of event-related potentials in individuals with high risk of schizophrenia / 中国心理卫生杂志

There is a clinical high-risk period(CHR)before the onset of schizophrenia.Early detection and early treatment are crucial for the prognosis of the disease.Event-related potential(ERP)is a special brain evoked potential.Different ERP components can reflect the neuroelectrophysiological changes of the brain in different cog-nitive processes.Exploring the ERP components of CHR abnormalities may have an important role in the early rec-ognition of diseases and transformation risk.This review found that P300 and MMN have predictive effects on the risk of mental illness conversion,while other ERP components such as P50,Pl.and N400 require more research to verify their reliability as risk markers for mental illness conversion in high-risk populations.

Clinical application of non-invasive prenatal testing for twin pregnancies / 中华医学遗传学杂志

OBJECTIVE@#To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies.@*METHODS@#A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated.@*RESULTS@#Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction (P < 0.05).@*CONCLUSION@#It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.

Genetic diversity analysis and fingerprinting of 175 Chimonanthus praecox germplasm based on SSR molecular marker / 生物工程学报

The elucidation of resources pertaining to the Chimonanthus praecox varieties and the establishment of a fingerprint serve as crucial underpinnings for advancing scientific inquiry and industrial progress in relation to C. praecox. Employing the SSR molecular marker technology, an exploration of the genetic diversity of 175 C. praecox varieties (lines) in the Yanling region was conducted, and an analysis of the genetic diversity among these varieties was carried out using the UPDM clustering method in NTSYSpc 2.1 software. We analyzed the genetic structure of 175 germplasm using Structure v2.3.3 software based on a Bayesian model. General linear model (GLM) association was utilized to analyze traits and markers. The genetic diversity analysis revealed a mean number of alleles (Na) of 6.857, a mean expected heterozygosity (He) of 0.496 3, a mean observed heterozygosity (Ho) of 0.503 7, a mean genetic diversity index of Nei՚s of 0.494 9, and a mean Shannon information index of 0.995 8. These results suggest that the C. praecox population in Yanling exhibits a rich genetic diversity. Additionally, the population structure and the UPDM clustering were examined. In the GLM model, a total of fifteen marker loci exhibited significant (P < 0.05) association with eight phenotypic traits, with the explained phenotypic variation ranging from 14.90% to 36.03%. The construction of fingerprints for C. praecox varieties (lines) was accomplished by utilizing eleven primer pairs with the highest polymorphic information content, resulting in the analysis of 175 SSR markers. The present study offers a thorough examination of the genetic diversity and SSR molecular markers of C. praecox in Yanling, and establishes a fundamental germplasm repository of C. praecox, thereby furnishing theoretical underpinnings for the selection and cultivation of novel and superior C. praecox varieties, varietal identification, and resource preservation and exploitation.

Effect of group counseling integrating tea drinking on mental health improvement of college students / 中国学校卫生

Objective@#To explore the intervention effect of group counseling integrating teadrinking on depression, social avoidance and distress, coping styles and selfesteem among college students, so as to provide references for promoting the psychological health of students.@*Methods@#From March to June 2021, a convenience sampling method was used to recruit 46 college students from a university in Nanjing for intervention project. There were 23 students in intervention group and control group, respectively. The intervention was conducted for 2.5 hours per week across a 6 week period. The intervention group received two sessions of group counseling that incorporated teadrinking experience, and the sessions involved tea knowledge explanation, observation and learning, embodied experience, emotional expression, interpersonal assistance and emotional support, cultural customs and life integration. After the intervention was completed, the control group received onetime group counseling that integrated teadrinking. The Wilcoxon difference test and Mann-Whitney U test were performed to compare the scores of each scale within and between the groups, and the χ2 test was used to compare the detection rates.@*Results@#There were no statistically significant differences in the scores of positive coping, negative coping, selfesteem, social avoidance and distress between the intervention group and the control group (Z=-1.20, -0.33, -0.35, 1.31,P>0.05). There were statistically significant differences in positive coping styles, selfesteem, social avoidance and distress between the intervention group and the control group after the intervention(27.70±5.60，22.05±4.30；30.52±3.63，28.27±4.06；7.43±7.38，13.64±6.79) (Z=-3.31, -2.10, 3.22, P<0.05). The intervention group showed statistically significant differences in social avoidance and distress scores before and after the intervention(11.96±7.47,7.43±7.38) (Z=-2.88), and the depression detection rate decreased(60.9%，30.4%) (χ2=4.29) (P<0.05). There were no statistically significant differences in positive coping, negative coping, selfesteem, social avoidance and distress scores, and depression detection rate between the control group before and after the intervention (Z/χ2=-0.28, -0.42, -1.24, -1.25；1.39, P>0.05). The followup results 1year later showed that there was a statistically significant difference in social avoidance and distress(6.57±6.21,14.16±9.22), and in the detection rates of depression(21.7%,52.2%) between the intervention group and the control group (Z/χ2=2.70,4.57,P<0.05).@*Conclusions@#Group counseling integrating teadrinking could improve interpersonal relationships, emotional states, selfesteem levels and coping strategies among college students. Group psychological counseling that incorporates teadrinking can be adopted to improve the mental health status of college students.

Construction and operation of whole-process quality control of clinical research in research hospitals / 中国医学伦理学

More and more clinical research projects are carried out in research hospitals.Through the multi-angle and whole-process quality control of the clinical research conducted by the research hospitals， including pre-project establishment， implementation， and post-completion， it can timely identify risks or potential risk factors in the clinical research， evaluate and solve quality problems in real-time， and avoid the possibility of major clinical research problems.Through whole-process quality control， research hospitals identify problems timely and proactively， establish coordination mechanisms， optimize the communication process， reduce the occurrence of research project quality problems， continuously improve the quality management systems of clinical research， ensure that research is compliant， data is complete and accurate， as well as improve the reliability of research conclusions.

Research progress on mesenchymal stem cell products and their exosomes in the treatment of inflammatory bowel disease / 中国药科大学学报

@#Abstract: Inflammatory bowel disease (IBD), whose pathogenesis remains elusive, is a group of autoimmune diseases characterized by chronic, progressive, and lifelong inflammation of the digestive tract. The pathogenesis of IBD remains elusive. Although a number of drugs have been developed to treat IBD, their effects are merely anti-inflammatory. In addition, current treatments for IBD are easily susceptible to resistance in clinical practice. Mesenchymal stem cells (MSCs) have been reported to have the ability to migrate to the site of inflammation, with potent immunoregulatory effects, and to rebalance the immune microenvironment and restore the integrity of the epithelial barrier with significant value of application, particularly for patients who are refractory to classic medicines. In this paper, we reviewed the clinical applications, mechanisms and engineerable properties of MSC products and their exosomes to provide some reference for the use of MSCs and their exosomes in the treatment of IBD.

Expression relationship and significance of NEAT1 and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer disease / 北京大学学报(医学版)

Objective:To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1(LncRNA NEAT1)and miR-27a-3p in serum and cerebro-spinal fluid of patients with Alzheimer disease(AD).Methods:Sixty-six AD patients received by the department of neurology of our hospital from October 2019 to September 2021 were gathered,according to the clinical dementia rating scale score,they were grouped into mild group(≤ 1 point,n=41)and moderate-to-severe group(＞1 point,n=25).Another 66 cases of serum and cerebrospinal fluid sam-ples from outpatient physical examination personnel were regarded as the control group.The general infor-mation on all subjects was recorded and cognition was assessed;real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid;enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1(BACE1),β-amyloid(Aβ)40 and Aβ42 in cerebrospinal fluid;Spearman's method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with mini-mental state examination(MMSE)and montreal cognitive assessment(MoCA)scores;Pearson method was per-formed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio(SUVR)and cerebrospinal fluid miR-27a-3p,NEAT1,BACE1,Aβ42 and Aβ40 levels.Results:The MMSE score[21(17,25),9(7,11)vs.27(21,34)],MoCA score[17(12,21),10(7,13)vs.27(21,31)],serum miR-27a-3p level(0.55±0.13,0.46±0.06 vs.0.97± 0.22),cerebrospinal fluid miR-27a-3p(0.48±0.10,0.35±0.10 vs.1.03±0.31),Aβ42 levels[(303.55±36.77)ng/L,(231.45±34.14)ng/L vs.(499.99±53.63)ng/L]and Aβ42/Aβ40 ra-tio(0.030±0.008,0.022±0.007 vs.0.048±0.010)of AD patients in mild group and moderate-to-severe group were all lower than those in the control group,and the moderate-to-severe group were lower than the mild group(all P＜0.05);the serum NEAT1 level(2.31±0.64,3.13±0.76 vs.1.05± 0.20),SUVR(1.50±0.29,1.76±0.52 vs.0.74±0.15),and cerebrospinal fluid NEAT1(3.51± 1.24,4.30±1.65 vs.1.01±0.23)and B ACE 1 levels[(55.78±5.98)μg/L,(72.32±16.08)μg/L vs.(21.39±3.73)μg/L]were higher than those in the control group,and the moderate-to-se-vere group were higher than the mild group(all P＜0.05).Serum NEAT1 level in AD patients was posi-tively correlated with SUVR,cerebrospinal fluid NEAT1 and BACE1(r=0.350,0.606,0.341,P＜0.05),and negatively correlated with MMSE score and MoCA score(r=-0.473,-0.482,all P＜0.05);serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level,MMSE score and MoCA score(r=0.695,0.424,0.412,all P＜0.05),and negatively correlated with SUVR and cerebrospinal fluid BACE1 level(r=-0.521,-0.447,all P＜0.05).Conclusion:The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are con-sistent,the level of NEAT1 is increased,and the level of miR-27a-3p is decreased.The levels of the two are negatively correlated,which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD.

Exploration of prognostic factors and nomogram construction for advanced non-small cell lung cancer treated with immunotherapy based on hematologic indexes / 国际肿瘤学杂志

Objective:To explore influencing factors affecting the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy based on hematologic indexes, thus to construct and evaluate a nomogram prediction model.Methods:The clinical data of 80 patients with advanced NSCLC treated with programmed death-1 inhibitor monotherapy or combination regimen from January 2018 to June 2020 at the Affiliated Hospital of North China University of Science and Technology and Tangshan People's Hospital were retrospectively analyzed. Hematologic indexes at the baseline, the optimal remission and the progressive disease (PD) were collected separately, and independent influencing factors for patient prognosis were analyzed using Cox proportional hazards regression model. A nomogram prediction model was constructed based on the results of the multifactorial analysis, and the predictive performance of the model was evaluated by receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curves.Results:As of the follow-up cut-off date, of the 80 patients, 63 had PD, with a median overall survival (OS) of 16.9 months. Univariate analysis showed that, age ( HR=2.09, 95% CI: 1.17-3.74, P=0.013) , number of treatment lines ( HR=2.23, 95% CI: 1.21-4.12, P=0.010) , lymphocyte to monocyte ratio (LMR) at the baseline ( HR=0.75, 95% CI: 0.57-0.97, P=0.028) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) and lactate dehydrogenase (LDH) ( HR=1.01, 95% CI: 1.00-1.01, P=0.006) at the optimal remission, haemoglobin ( HR=0.97, 95% CI: 0.96-0.99, P<0.001) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) , C-reactive protein ( HR=1.01, 95% CI: 1.00-1.01, P=0.011) , albumin (ALB) ( HR=0.91, 95% CI: 0.87-0.96, P=0.001) , neutrophil to lymphocyte ratio (NLR) ( HR=1.16, 95% CI: 1.05-1.27, P=0.002) and LMR ( HR=0.62, 95% CI: 0.42-0.90, P=0.012) at the PD were all influencing factors for the prognosis of advanced NSCLC patients receiving immunotherapy. Least absolute shrinkage and selection operator regression were used to screen the variables for P<0.10 in the univariate analysis, and nine possible influencing factors were obtained, which were age, fibrinogen and LDH at the optimal remission, haemoglobin, D-dimer, C-reactive protein, LDH, ALB and LMR at the PD. Multivariate analysis of the above variables showed that, age ( HR=0.91, 95% CI: 0.86-0.97, P=0.004) , LDH ( HR=1.01, 95% CI: 1.00-1.01, P=0.013) and ALB ( HR=0.82, 95% CI: 0.67-0.99, P=0.041) at the PD were independent influencing factors for the prognosis of patients with advanced NSCLC who received immunotherapy. The area under curve of the nomogram predicting model based on the above indexes, 1- and 2-year OS rates of patients were 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.66-0.88) , respectively, and C-index was 0.71 (95% CI: 0.64-0.78) , the calibration curves showed good consistency between predicted and actual probability of occurrence. Patients in the low-risk group ( n=40) had a median OS of 29.9 months (95% CI: 22.5 months-NA) , which was significantly better than that of the high-risk group ( n=40) [13.4 months (95% CI: 11.4-23.5 months) , χ2=11.30, P<0.001]. Conclusion:Age, LDH and ALB at the PD are independent influencing factors affecting the prognosis of patients with advanced NSCLC receiving immunotherapy, and the nomogram model constructed based on the above indexes has good differentiation and calibration for predicting 1- and 2-year OS rates in advanced NSCLC patients receiving immunotherapy.

Analysis of effect of Epimedium on cells endogenous metabolites before and after the processing based on UPLC-Q-Exactive Orbitrap-MS / 国际中医中药杂志

Objective:To analyze the effects of processed Epimedii Folium on endogenous metabolites of mouse melanoma cells (B16 cells) before and after processing based on cell metabolomics; To investigate the changes of processed Epimedii Folium before and after processing.Methods:Ultra performance liquid chromatography tandem four-stage orbital trap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) technology was used, and the endogenous small molecules of B16 cells treated with Epimedii Folium and processed Epimedii Folium were analyzed by metabolomics. The differential metabolites between groups were obtained, and relevant metabolic pathways were analyzed based on the MetaboAnalyst 5.0 database.Results:Significant changes were observed in 13 kinds of endogenous metabolites, including alanine, carnitine C3∶0, glutamic acid-1, lactic acid, isoleucine, choline, phosphatidylcholine (34∶2, 36∶2), free fatty acids, citric acid, carnitine C4∶0, lysophosphatidylcholine 16∶0 and malic acid after the intervention of Epimedii Folium and processed Epimedii Folium. And the impact of processed products on differential metabolites was stronger than that of raw products. The main pathways involved were Warburg effect, pyruvate metabolism, malate-aspartic acid shuttle, pyruvaldehyde degradation and so on.Conclusions:Epimedii Folium and processed Epimedii Folium would have certain effects on cellular metabolic pathways. The results may be related to the pharmacological effects and changes in cold and hot properties of Epimedii Folium before and after processing.

Advances on reprogramming of fatty acid metabolism in pulmonary fibrosis / 基础医学与临床

Pulmonary fibrosis is a progressive interstitial fibrotic lung disease with high mortality.Its pathogenesis is complex and involves the reprogramming of fatty acid metabolism.This reprogramming includes changes in de novo fatty acid synthesis,uptake,oxidation,and derivatives.It crucially influences alveolar epithelial cell survival,macrophage polarization,and fibroblast activation,thereby playing a significant role in either exacerbating or miti-gating the disease.Understanding and intervening in the reprogramming of fatty acid metabolism offers potential strategies for prevention,diagnosing and treatment of pulmonary fibrosis.

Characteristics of T cell immune responses in adults inoculated with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months / 解放军医学杂志

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.