Phospholipase D regulates ferroptosis signal transduction in mouse spleen hypoxia response

High-altitude hypoxia exposure can lead to phospholipase D-mediated lipid metabolism disorder in spleen tissues and induce ferroptosis. Nonetheless, the key genes underlying hypoxia-induced splenic phospholipase D and the ferroptosis pathway remain unclear. This study aimed to establish a hypoxia animal model. Combined transcriptomic and proteomic analyses showed that 95 predicted target genes (proteins) were significantly differentially expressed under hypoxic conditions. Key genes in phospholipase D and ferroptosis pathways under hypoxic exposure were identified by combining Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis techniques. Gene set enrichment analysis (GSEA) showed that the differential gene sets of the phospholipase D and ferroptosis signaling pathways were upregulated in the high-altitude hypoxia group. The genes in the phospholipase D signalling pathway were verified, and the expression levels of KIT and DGKG were upregulated in spleen tissues under hypoxic exposure. Subsequently, the mRNA and protein expression levels of genes from the exogenous pathway such as TFRC, SLC40A1, SLC7A11, TRP53, and FTH1 and those from the endogenous pathway such as GPX4, HMOX1, and ALOX15 differentials in the ferroptosis signalling pathway were verified, and the results indicated significant differential expression. In summary, exposure to high-altitude hypoxia mediated phospholipid metabolism disturbance through the phospholipase D signalling pathway and further induced ferroptosis, leading to splenic injury.

Application value of bone cement containing rhbFGF and RHBMP-2 in PKP treatment of osteoporotic lumbar compression fracture / 中国骨伤

OBJECTIVE@#To investigate the effect of bone cement containing recombinant human basic fibroblast growth factor (rhbFGF) and recombinant human bone morphogenetic protein-2 (rhBMP-2) in percutaneous kyphoplasty(PKP)treatment of osteoporotic vertebral compression fracture(OVCF).@*METHODS@#A total of 103 OVCF patients who underwent PKP from January 2018 to January 2021 were retrospectively analyzed, including 40 males and 63 females, aged from 61 to 78 years old with an average of (65.72±3.29) years old. The injury mechanism included slipping 33 patients, falling 42 patients, and lifting injury 28 patients. The patients were divided into three groups according to the filling of bone cement. Calcium phosphate consisted of 34 patients, aged(65.1±3.3) years old, 14 males and 20 females, who were filled with calcium phosphate bone cement. rhBMP-2 consisted of 34 patients, aged (64.8±3.2) years old, 12 males and 22 females, who were filled with bone cement containing rhBMP-2. And rhbFGF+rhBMP-2 consisted of 35 patients, aged (65.1±3.6) years old, 14 males and 21 females, who were filled with bone cement containing rhbFGF and rhBMP-2. Oswestry disability index (ODI), bone mineral density, anterior edge loss height, anterior edge compression rate of injured vertebra, visual analog scale (VAS) of pain, and the incidence of refracture were compared between groups.@*RESULTS@#All patients were followed for 12 months. Postoperative ODI and VAS score of the three groups decreased (P<0.001), while bone mineral density increased (P<0.001), anterior edge loss height, anterior edge compression rate of injured vertebra decreased first and then slowly increased (P<0.001). ODI and VAS of group calcium phosphate after 1 months, 6 months, 12 months were lower than that of rhBMP-2 and group rhbFGF+rhBMP-2(P<0.05), bone mineral density after 6 months, 12 months was higher than that of rhBMP-2 and group calcium phosphate(P<0.05), and anterior edge loss height, anterior edge compression rate of injured vertebra of group rhbFGF+rhBMP-2 after 6 months and 12 months were lower than that of group rhBMP-2 and group calcium phosphate(P<0.05). There was no statistical difference in the incidence of re-fracture among the three groups (P>0.05).@*CONCLUSION@#Bone cement containing rhbFGF and rhBMP-2 could more effectively increase bone mineral density in patients with OVCF, obtain satisfactory clinical and radiological effects after operation, and significantly improve clinical symptoms.

Low disease activity and remission status of systemic lupus erythematosus in a real-world study / 北京大学学报(医学版)

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Preparation and Application of Polypyrrole Conductive Hydrogels in Biomedical Field / 分析化学

Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.

Colorimetric Determination of Antioxidant Capacity by Peroxidase Mimics Based on Ruthenium Nanoparticles Supported on Carbon Nanosheets / 分析化学

Lattice strain ruthenium nanoparticles uniformly and stably supported on nitrogen-modified carbon nanosheets(RuNPs/NC)were prepared via simple wet-chemical and subsequent pyrolysis method.The nitrogen doped NC could effectively improve their uniform dispersion and lattice compression of RuNPs.Through changing the pyrolysis temperature,the nitrogen content,types and degree of lattice strain of RuNPs could be effectively tuned,which could be used to adjust and control their peroxidase-like activity.The as-prepared RuNPs/NC-900 exhibited highest peroxidase-like activity,and could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine(TMB)to produce a blue product with the maximum absorption at 652 nm in the presence of H2O2.The steady-state kinetic analysis indicated that the reaction catalyzed by RuNPs/NC followed the Michaelis-Menten kinetic model.Tannic acid(TA),gallic acid(GA)and ascorbic acid(AA)could effectively inhibit the RuNPs/NC-H2O2-triggered chromogenic reaction of TMB,resulting in color fading and decrease in absorbance.Based on this,a sensitive and accurate system was constructed for detection of TA,GA and AA.The detection limits(3σ/S)for TA,GA and AA were 0.014,0.014 and 0.29 μmol/L,respectively.This study not only developed a colorimetric sensing method based on RuNPs/NC nanozyme but also offered a new approach for the sensitive detection of antioxidants in food.

A Precise and Portable Detection System for Infectious Pathogens Based on CRISPR/Cas Technology / 分析化学

Nucleic acid-based molecular diagnostic methods are considered the gold standard for detecting infectious pathogens.However,when applied to portable or on-site rapid diagnostics,they still face various limitations and challenges,such as poor specificity,cumbersome operation,and portability difficulties.The CRISPR(Clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein(Cas)-fluorescence detection method holds the potential to significantly enhance the specificity and signal-to-noise ratio of nucleic acid detection.In this study,we developed a portable grayscale reader detection system based on loop-mediated isothermal amplification(LAMP)-CRISPR/Cas.On one hand,in the presence of CRISPR RNA(crRNA),the CRISPR/Cas12a system was employed to achieve precise fluorescent detection of self-designed LAMP amplification reactions for influenza A and influenza B viruses.This further validated the high selectivity and versatility of the CRISPR/Cas system.On the other hand,the accompanying independently developed portable grayscale reader allowed for low-cost collection of fluorescence signals and high-reliability visual interpretation.At the end of the detection process,it directly provided positive or negative results.Practical sample analyses using this detection system have verified its reliability and utility,demonstrating that this system can achieve highly sensitive and highly specific portable analysis of influenza viruses.

Research Progress on Biological Evidence Identification in Fire Scenes / 法医学杂志

Biological evidence is relatively common evidence in criminal cases,and it has strong pro-bative power because it carries DNA information for individual identification.At the scene of fire-related cases,the complex thermal environment,the escape of trapped people,the firefighting and res-cue operations,and the deliberate destruction of criminal suspects will all affect the biological evi-dence in the fire scene.Scholars at home and abroad have explored and studied the effectiveness of biological evidence identification in fire scenes,and found that the blood stains,semen stains,bones,etc.are the main biological evidence which can be easily recovered with DNA in fire scenes.In order to analyze the research status and development trend of biological evidence in fire scenes,this paper systematically sorts out the relevant research,mainly including the soot removal technology,appearance method of typical biological evidence,and possibility of identifying other biological evidence.This pa-per also prospects the next step of research direction,in order to provide reference for the identifica-tion of biological evidence and improve the value of biological evidence in fire scenes.

Imaging diagnosis, pathological upgrade, and imaging technology progress of ductal carcinoma in situ of the breast / 国际肿瘤学杂志

Ductal carcinoma in situ of the breast (DCIS) most commonly manifests as asymptomatic calcifications at mammography. The most common manifestation of MRI is nonmass enhancement. The ultrasound mainly presents as a hypoechoic irregular hypervascular mass without posterior features. Core-needle biopsy is a commonly used method for preoperative diagnosis of DCIS. Due to differences in needle type and sample size, there is a certain degree of pathological upgrading of the lesion. In recent years, there has been controversy over the diagnosis and treatment of DCIS. With the development of breast disease diagnostic technology, advances in digital breast tomography, artificial intelligence, and radiomics are expected to help DCIS management and address issues such as overdiagnosis.

Effects of Jianpi Bushen Jiedu Prescription regulating JAK2/STAT3 pathway on proliferation and migration of hepatocellular carcinoma cells / 国际中医中药杂志

Objective:To explore the effects of Jianpi Bushen Jiedu Prescription on the proliferation and migration of hepatocellular carcinoma cells; To discuss its possible mechanism.Methods:Using human highly metastatic liver cancer cell line (HCCLM3) as the research object, they were randomly divided into control group and TCM group (100, 200, 400, 800, 1 600, 3 200 μg/ml Jianpi Bushen Jiedu Prescription) and Western medicine group (2.5, 5, 10, 20, 40 μmol/L sorafenib) using a random number table method. Cell viability was detected using cell counting reagent (CCK-8) method; HCCLM3 cells were divided into control group and TCM (Jianpi Bushen Jiedu Prescription 800 μg/ml) group and combined group (Jianpi Bushen Jiedu Prescription 800 μg/ml +sorafenib 20 μmol/L). Western blot method was used to detect the protein expressions of kinase/signaling transducer and transcriptional activator (JAK2/STAT3) pathway related proteins (p-JAK2, JAK2, p-STAT3, STAT3) in each group.Results:Compared with the control group, viability and mobility of HCCLM cell in TCM group and Western medicine group decreased ( P<0.01 or P<0.05); compared with the control group, the protein expressions of P-JAK2, JAK2, P-STAT3 and STAT3 in the TCM group and the combined group decreased ( P<0.05), and the JAK2 protein expression in the combined group was lower than that in the TCM group ( P<0.05). Conclusion:Jianpi Bushen Jiedu Prescription can inhibit the proliferation and migration of HCC cells by regulating JAK2/STAT3 pathway.

Regulatory Mechanism of Drug-Containing Serum of Jinghou Zengzhi Prescription on GDF9 Expression and Apoptosis of Ovarian Granulosa Cells in Rats with Controlled Ovarian Hyperstimulation / 广州中医药大学学报

Objective To observe the regulatory mechanism of drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method on the expression of growth and differentiation factor 9(GDF9)and apoptosis of ovarian granulosa cells in rats with controlled ovarian hyperstimulation(COH).Methods Serum of COH rats(blank serum)and serum of COH rats gavaged by the Jinghou Zengzhi Prescription were prepared.A COH rat model was established and ovarian granulosa cells were collected.The experiment was divided into 5 groups:blank serum group,drug-containing serum group,drug-containing serum+SB203580[p38 mitogen-activated protein kinase(p38MAPK)inhibitor]group,drug-containing serum + PDTC[nuclear transcription factor κB(NF-κB)inhibitor]group,drug-containing serum + SB203580 + PDTC group.The mRNA expression levels of p38MAPK,casein kinase 2(CK2),nuclear transcription factor κB inhibitor α(IκBα),NF-κB and GDF9 were detected by real-time quantitative polymerase chain reaction(qRT-PCR),and GDF9 protein expression level was detected by Western Blot,and ovarian granulosa cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).Results The drug-containing serum of Jinghou Zengzhi Prescription decreased the mRNA expressions of p38MAPK and NF-κB,elevated the mRNA expressions of CK2 and IκBα,increased the mRNA and protein expression levels of GDF9,and decreased the apoptosis rate of ovarian granulosa cells in COH rats.The addition of p38MAPK inhibitor SB203580 alone and the addition of NF-κB inhibitor PDTC alone both promoted the mRNA and protein expressions of GDF9 and reduced the apoptosis rate of granulosa cells.Conclusion The drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method can promote the expression of GDF9 and inhibit the apoptosis of ovarian granulosa cells in rats with COH,and its mechanism may be related to the regulation of the expression of genes of the dual signaling pathways of p38MAPK and NF-κB.

Clinical Study on LUO's Nephropathy Recipe Ⅲ Combined with Conventional Western Medicine in Treating Stage 3-5 Non-dialysis Chronic Kidney Disease of Spleen-Kidney Deficiency with Turbidity-Toxin-Stasis Obstruction Type / 广州中医药大学学报

Objective To investigate the clinical effect of LUO's Nephropathy Recipe Ⅲ(composed of Sargassum,Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Rehmanniae Radix Praeparata,calcined Ostreae Concha,Houttuyniae Herba,Schizonepetae Spica,etc.)combined with conventional western medicine in treating stage 3-5 non-dialysis chronic kidney disease(CKD)of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type.Methods A total of 180 patients with stage 3-5 non-dialysis CKD of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type were randomly divided into observation group and control group,with 90 cases in each group.The control group was given conventional western medicine for symptomatic treatment,and the observation group was treated with LUO's Nephropathy RecipeⅢon the basis of treatment for the control group.The course of treatment for the two groups covered one month.Before and after treatment,the levels of serum inflammatory factors,renal function indicators and urine protein parameters in the two groups were observed.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After one month of treatment,the total effective rate in the observation group was 95.56%(86/90)and that in the control group was 81.11%(73/90).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the serum levels of inflammatory factors of transforming growth factor β1(TGF-β1),monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of renal function indicators of blood urea nitrogen(BUN),serum creatinine(Scr),blood uric acid(UA),and cystatin C(Cys-C)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of 24-hour urine protein quantification and urine microalbumin in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 4.44%(4/90),which was significantly lower than that of 15.56%(14/90)in the control group,and the difference was statistically significant between the two groups(P＜0.05).Conclusion LUO's Nephropathy Recipe Ⅲ combined with conventional western medicine exerts satisfactory efficacy in treating stage 3-5 non-dialysis CKD patients with spleen-kidney deficiency with turbidity-toxin-stasis obstruction syndrome type,and the therapy can significantly alleviate the inflammatory response,improve the renal function,decrease the urinary protein excretion of the patients,with high safety profile.

Clinical Observation on the Effect of Postmenstrual Proliferative Prescription Through Replenishing Qiand Blood on Ovulation Induction in Patients with Polycystic Ovarian Syndrome / 广州中医药大学学报

Objective To observe the effects of Postmenstrual Proliferative Prescription(mainly composed of Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Poria,Rehmanniae Radix Praeparata,Paeoniae Radix Alba,Angelicae Sinensis Radix,Chuanxiong Rhizoma,Cervi Cornu Degelatinatum,Corni Fructus,Cuscutae Semen,and Eucommiae Cortex)through replenishing qi and blood on the ovulation rate and pregnancy rate in patients with ovulatory dysfunction infertility caused by polycystic ovarian syndrome(PCOS)during ovulation-induction treatment,and to explore the therapeutic effects and possible therapeutic mechanism.Methods Sixty patients with ovulatory dysfunction infertility due to PCOS were randomly divided into a treatment group and a control group,with 30 patients in each group.The control group was given Clomifene Citrate Capsules to promote ovulation,and the treatment group was given Postmenstrual Proliferative Prescription on the basis of the ovulation-induction program of the control group starting from the fifth day of menstruation or progesterone withdrawal bleeding.The two groups were treated for one menstrual cycle as a course of treatment.The changes in the serum sex hormones of estradiol(E2),follicle-stimulating hormone(FSH),luteinizing hormone(LH),and progesterone(P)on the 2nd to 5th day of menstruation,as well as the changes in serum growth differentiation factor 9(GDF9)and bone morphogenetic protein 15(BMP15)levels on the 2nd to 5th day of menstruation and on the day of human chorionic gonadotropin(HCG)injection were observed in the two groups.Moreover,the ovulation rate,pregnancy rate and clinical efficacy of the patients in the two groups were analyzed.Results(1)No statistically significant differences in serum levels of sex hormones E2,FSH,LH and P on the 2nd to 5th day of menstruation were shown between the two groups of patients(P＞0.05).(2)On the 2nd to 5th day of menstruation and on the day of HCG injection,there were no significant differences in the serum GDF9 and BMP15 levels between the two groups(P＞0.05).(3)The ovulation rate and pregnancy rate in the treatment group were 93.33%(28/30)and 26.67%(8/30)respectively,which were significantly higher than 70.00%(21/30)and 13.33%(4/30)in the control group.And the differences tested by chi-square test were statistically significant between the two groups(P＜0.05).(4)The total effective rate of the treatment group was 93.33%(28/30),and that of the control group was 70.00%(21/30).The intergroup comparison(tested by rank sum test)showed that the therapeutic efficacy of the treatment group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Postmenstrual Proliferative Prescription through replenishing qi and blood can improve the ovulation rate and pregnancy rate during ovulation-induction treatment in the patients with ovulatory dysfunction infertility due to PCOS.It is indicated that Postmenstrual Proliferative Prescription can enhance the quality of the oocytes and the potential of embryo implantation during the ovulation-induction treatment.

Clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis / 解放军医学杂志

Objective To identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis(RCLM).Methods The clinical data of young RCLM patients at 45 years or under(n=40,as younger patient group)in Peking University First Hospital from January 2016 to January 2021 were reviewed,meanwhile,elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio.Proportions of categorical variables were compared between young patients and old patients.The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy.Results One hundred and twenty-two RCLM patients were identified,the 1-,3-and 5-year survival rates of young patient group were 97.5%,47.5%,15.0%,those of elder patient group were 84.1%,26.8%,9.8%,respectively.The differences in BMI(P=0.008),primary tumor with obstruction and bleeding(P=0.006),synchronous rectal cancer liver metastases(P=0.005),the maximum diameter of liver metastasis>3 cm(P=0.019)were statistically significant between the two groups.And univariate and multivariate analyses showed that age(P=0.003),N stage(P=0.007),local therapy for liver metastases(P=0.047)and the maximum diameter of liver metastasis(P=0.030)were independent risk factors for influencing the prognosis of RCLM patients;curative resection or not of primary tumor(P=0.035)and the maximum diameter of liver metastasis(P=0.041)were independent risk factors for influencing the prognosis of young RCLM patients.Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients(log-rank P=0.000).Conclusions Although with later staging of initial tumor station,young RCLM patients may obtain better survival benefit compared with old patients.Higher degree of lymph node metastasis,local therapy for liver metastases and the maximum diameter of liver metastasis>3 cm indicates poor prognosis in RCLM patients,and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients.Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.

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.

Analysis of recognition sites and application for commercial and homemade antibodies to aquaporin 9 / 解剖学报

Objective To analyze the antigen recognition sites of commercial and homemade antibodies against aquaporin(AQP)9,and to identify the application effect.Methods Western blotting was used to compare the efficacy of three commercial antibodies and self-made antibody in identifying AQP9 genotypes.The antigen recognition sites of four antibodies and their specificities in practical applications were analyzed.Results Western blotting showed that protein bands of three commercial antibodies were detected in both WT and Aqp9-/-mice.The keyhole limpet hemocyanin(KLH)conjugated synthetic peptides corresponding to the three commercial antibodies were derived from rat,human and human,respectively.And The sequences of these three synthetic peptides were different from those of mice.AQP3/7 and AQP9 have similar molecular weight and were expressed in the liver with high homology.An obvious band of self-made antibody was observed at the 27 kD position in WT mice,but no band was observed at the corresponding position in Aqp9-/-mice.Conclusion Commercial antibodies 1 and 3 can be used to assist in the identification of genotypes in Aqp9-/-mice.Homemade antibodies can accurately identify genotypes at the protein level.

Predictive Modeling of Chronic Kidney Disease with Hypertension or Diabetes Based on Machine Learning Algorithms / 昆明医科大学学报

Objective To build the early predictive model for chronic kidney disease(CKD)in hypertension and diabetes patients in the community.Methods The CKD patients were recruited from 4 health care centers in 4 urban areas in Kunming.The control group was residents without hypertension and diabetes(n = 1267).The disease group was residents with hypertension and/or diabetes(n = 566).The questionnaire survey,physical examination,laboratory testing,and 5 SNPs gene types in the PVT1 gene.The risk factors,which were filtered with logistics regression,were used to build predictive models.Four machine learning algorithms were built:support vector machine(SVM),random forest(RF),Na?ve Bayes(NB),and artificial neural network(ANN)models.Results Thirteen indicators included in the final diagnostic model:age,disease type,ethnicity,blood urea nitrogen,creatinine,eGFR from MDRD,ACR,eGFR from EPI2009,PAM13 score,sleep quality survey,staying-up late,PVT1 SNP rs11993333 and rs2720659.The accuracy,specificity,Kappa value,AUC of ROC,and PRC of ANN are greater than those of the other 3 models.The sensitivity of RF is the highest among 4 types of machine learning.Conclusions The ANN predictive model has a good ability of efficiency and classification to predict CKD with hypertension and/or diabetes patients in the community.

Impact of circadian rhythm of blood pressure and blood pressure variability on cerebral small vessel disease / 临床神经病学杂志

Nowadays,with the improvement of people's living standards and the acceleration of the aging process of population,cerebral small vessel disease has seriously endangered the life health and quality of life of the elderly.Hypertension has been paid more and more attention as an important risk factor of cerebral small vessel disease.However,in the management of hypertension,people generally concentrate on the influence of mean arterial pressure,ignoring the role of variability and circadian rhythm of blood pressure nowadays.By expounding the pathogenesis of cerebral small vessel disease and the recent studies on blood pressure variability and circadian rhythm of blood pressure,this review discusses a series of scientific problems such as the effects of blood pressure variability and circadian rhythm of blood pressure on the occurrence and development of cerebral small vessel disease.

Pathological characteristics of angioimmunoblastic T cell lymphoma with bone marrow involvement / 临床与实验病理学杂志

Purpose To explore the pathological features of angioimmunoblastic T-cell lymphoma(AITL)with bone marrow involvement and to improve awareness of bone marrow infiltration in AITL.Methods The tissue morphology of 32 cases of AITL with bone marrow involvement was retrospectively analyzed.Im-munohistochemistry using the EnVision method and ten-color flow cytometry were conducted to detect AITL-related immune markers.T cell clonality was analyzed through T cell receptor(TCR)gene rearrangement.Results The predominant pat-terns of tumor cell infiltration were nodular(20/32,62.5％)and interstitial or small clusters(10/32,31.3％).The nodules showed a mixture of cellular components.In some cases,the fo-ci contained a mixture of cells with characteristic"granuloma-toid"changes.The tumor cells were mainly small to medium-sized lymphocytes with inconspicuous atypia.Some cases showed plasma cell proliferation.19 cases were subject to immunohisto-chemical staining,which revealed a low count of CD4-positive T cells,with an average of 8.4％.The positive rates of T follic-ular helper cells(TFH)markers were as follows:CD10(7/14,50.0％),BCL6(6/19,31.6％),PD-1(13/19,68.4％),and CXCL13(13/19,68.4％).In most cases,tumor cells showed co-expression of PD-1 and CXCL13,but the number of positive cells was less than 1％.Flow cytometry analysis was performed in 24 cases,among which 22 cases all consistently expressed cytoplasmic CD3(cCD3),CD5,CD4,and CD2,with varying degrees of CD10 expression.In some cases,there was a lack of expression of surface CD3(sCD3)(12/22,54.5％),while there was a lack of expression of CD7(8/22,36.4％).and no abnormal T cells were found in 2 cases.TCR gene rearrangement analysis was performed in 7 cases,with 3 cases showing TCR clonality.Conclusion AITL with bone marrow involvement exhibits a lower proportion of tumor cells and less atypia,making it prone to misdiagnosis.The presence of lymphocytic foci with mixed cellular components in the bone marrow can indicate bone marrow involvement in AITL.Flow cy-tometry detection of abnormal T cells(double positive for CD4 and CD10)strongly suggests bone marrow infiltration in AITL.A comprehensive diagnosis of bone marrow involvement in AITL re-quires consideration of bone marrow biopsy,flow cytometry,and TCR gene rearrangement analysis.

Autosomal recessive axonal neuropathy with neuromyotonia in a Tibetan family caused by HINT1 gene variation and literature review / 中华实用儿科临床杂志

Objective:To summarize the characteristics of autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1 gene mutation. Methods:Retrospective case summary.Clinical data of 2 Tibetan siblings diagnosed with ARAN-NM in the Department of Pediatrics of Peking University First Hospital in August 2023 were retrospectively analyzed.A review of literature reporting relevant Chinese patients was conducted.Results:The proband and her elder brother were aged 13 and 19, respectively.Both developed abnormal gait at the age of 11, followed by varus, claudication, and weak thumb strength.The proband also had neuromyotonia.Physical examinations showed that the proband and her elder brother had decreased muscle strength of the extremities, mainly in the thumbs and distal ends of lower limbs.The distal muscles of the proband′s lower extremities and the muscles of both hands of the proband′s elder brother were atrophied.Both feet showed talipes equinovarus in the proband and her elder brother.The proband′s electromyography (EMG) showed peripheral nerve injuries (motor and sensory axonal involvement, especially in distal ends) and myotonic potentials.The trio-whole exon sequencing detected homozygous pathogenic variation in HINT1 gene in both the proband and her elder brother, who were diagnosed as ARAN-NM based on c. 169A>G (p.K57E). After the Carbamazepine treatment, the proband′s neuromyotonia, numbness and weakness were relieved.Both the proband and her elder brother underwent orthopaedic surgery and rehabilitation.Their foot deformities and gait were significantly improved.Two Chinese literatures (2 patients) and four English literatures (8 patients) were retrieved.Including the proband and her elder brother in this study, there were 12 ARAN-NM patients, 10 of whom had clinical data.The ages of onset and diagnosis were 2-16 (1 case unknown) and 13-33 years old, respectively.Myasthenia was present in 9 patients, especially in distal ends.Eight patients were complicated with neuromyotonia, nine patients with muscle atrophy, seven patients with foot deformity, and two patients with sensory disturbance.Creatine kinase(CK) was elevated in all 9 patients tested or CK.EMG showed neurogenic injuries in all patients and neuromyotonia discharge in six patients.Three patients were treated with Carbamazepine, and some symptoms were relieved.Missense/nonsense mutations were found in the 12 patients, and the high-frequency variation was c. 112T>C (p.C38R). Conclusions:ARAN-NM is a rare autosomal recessive neuromuscular disease caused by HINT1 gene mutation.There is no ethnic difference in clinical manifestations, mainly distal limb weakness with neuromyotonia.Carbamazepine can alleviate some symptoms, and orthopaedic surgery can improve foot deformity and gait.