Mechanisms of Guizhi Fuling Pills Treating Polycystic Ovary Syndrome and Endometriosis with Homotherapy for Heteropathy Based on Network Pharmacology and Molecular Docking / 广州中医药大学学报

Objective To investigate the mechanism of Guizhi Fuling Pills in the treatment of polycystic ovary syndrome(PCOS)and endometriosis(EMT).Methods TCMSP was utilized to obtain the active ingredients and related targets of the constituent Chinese medicines of Guizhi Fuling Pills.GeneCards,PharmGKB,and TTD databases were used to screen PCOS and EMT disease targets,respectively.The Venn R diagram was drawn after obtaining the intersecting targets of drugs and diseases using the Venn R package in R software,the drug-active ingredient-potential target interactions network diagram was made in Cytoscape,the intersecting target protein-protein interactions(PPI)network diagram was drawn in the STRING platform,and Cytoscape was used to optimize the PPI network and screen the core targets.R language was applied for Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and AutoDockTools was for molecular docking.Results A total of 85 active ingredients and 191 corresponding targets of Guizhi Fuling Pills were obtained,and 77 potential targets of Guizhi Fuling Pills for the treatment of PCOS and EMT.The core active ingredients of Guizhi Fuling Pills for PCOS and EMT were quercetin,β-sitosterol,kaempferol,hederagenin,baicalein,and the core targets were AKT1,EGFR,IL-6,TNF,and TP53.GO functional analysis yielded 2 020 biological process,34 cellular components,126 molecular functions,and KEGG enrichment analysis yielded 165 signaling pathways.Molecular docking showed that the core components in the formula docked well with the targets.Conclusion Guizhi Fuling Pills may regulate the signaling pathways of lipid and atherosclerosis,AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis,and chemical carcinogenesis-receptor activation through quercetin,β-sitosterol,kaempferol,hederagenin,and baicalein,and act on AKT1,EGFR,IL-6,TNF,and TP53,thus treating PCOS and EMT with homotherapy for heteropathy.

Chinese Medicines Combined with Hormones in the Treatment of Premature Ovarian Failure:A Network Meta-analysis / 广州中医药大学学报

Objective To screen the optimal regimen of Chinese medicine combined with hormones for the treatment of premature ovarian failure(POF)using network meta-analysis and to provide an evidence-based basis for the clinical treatment of POF.Methods The randomized controlled trials(RCTs)of Chinese medicine combined with hormones in the treatment of POF were retrieved from thhe domestic and oversea databases of CNKI,VIP,Wanfang,CBM,PubMed,Cochrane,Embase,and Web of Science.The quality of the literature was assessed using the tools for analysis of bias recommended by Cochrane Reviewer's Handbook and by Jadad scale scores.Rstudio and StataSE 15.1 statistical software were used to perform network meta-analysis and graphical presentation of the data.Results A total of 50 RCTs were included,covering 8 intervention methods.The overall risk of bias of the included studies was low,but the quality of the literature was generally low.The results of network meta-analysis showed that,in terms of the effective rate,the intervetion of 7 various Chinese medicines combined with hormone was superior to the conventional treatment(hormone replacement therapy,HRT)in the control group,and Nuangong Qiwei Powder+HRT was superior to the remaining 6 kinds of Chinese medicines combined with HRT;with reference to the values of the surface under the cumulative ranking curve(SUCRA),the efficiencies of the effective rate of the 8 intervention methods in descending order were Nuangong Qiwei Powder+ HRT(SUCRA=81.2),Zishen Yutai Pills + HRT(SUCRA=80.0),modified Zuogui Pills + HRT(SUCRA= 66.1),Ankun Zhongzi Pills + HRT(SUCRA=49.6),Kuntai Capsules + HRT(SUCRA=45.2),modified Erxian Decoction + HRT(SUCRA=39.5),Liuwei Dihuang Pills + HRT(SUCRA=37.4)and HRT(SUCRA=1.0).In terms of improving serum follicle-stimulating hormone(FSH)levels,modified Zuogui Pills + HRT was superior to the remaining 7 intervention methods;with reference to the values of the SUCRA,the efficiencies of the 8 intervention methods in descending order were modified Zuogui Pills + HRT(SUCRA=97.0),HRT(SUCRA= 77.9),Liuwei Dihuang Pills + HRT(SUCRA=76.6),Kuntai Capsules + HRT(SUCRA=46.5),Nuangong Qiwei Powder+HRT(SUCRA=38.9),Ankun Zhongzi Pills + HRT(SUCRA=29.9),modified Erxian Decoction + HRT(SUCRA=18.1),and Zishen Yutai Pills + HRT(SUCRA=15.1).Conclusion All kinds of Chinese medicines combined with HRT exert stronger effect on improving the primary outcome indicators than HRT alone for the treatment of POF.The intervention with Nuangong Qiwei Powder+HRT exerts the highest probability of the optimal regimen for enhancing the efficiency,and the intervention with Zuogui Pills + HRT exerts the highest probability of the optimal regimen for lowering the serum FSH level.However,due to the low quality of the included studies,more rigorously-designed,large sample-size,and high-quality randomized controlled trials need to be conducted in the future to provide conclusive evidence-based evidence.

Targeted induction of human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum into neural stem cells / 中国组织工程研究

BACKGROUND:There are many kinds of cell media with different components,which have a great influence on cell growth.Several studies in and outside China have used serum-free media containing fetal bovine serum for in vitro amplification culture,but the use of media containing human peripheral blood serum to directionally induce human umbilical cord mesenchymal stem cells to neural stem cells and human peripheral blood serum to promote neural stem cells to differentiate into other nerve cells,so far there are few relevant studies. OBJECTIVE:To observe the feasibility of inducing human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum into neural stem cells. METHODS:(1)Human umbilical cord mesenchymal stem cells were cultured in DMEM/F-12 culture medium containing 10%human peripheral blood serum by volume fraction.Flow cytometry analysis was performed at the third passage to identify surface markers and alizarin red staining was used to detect osteogenic differentiation function.(2)The third-generation human umbilical cord mesenchymal stem cells were induced into neural stem cells using DMEM/F-12 medium containing 0.5%N2,1.5%B27,20 ng/mL basic fibroblast growth factor,and 20 ng/mL epidermal growth factor,and their surface markers were identified.(3)Well-growing human umbilical cord mesenchymal stem cell-derived neural stem cells were taken to prepare a single cell suspension.They were evenly inoculated into 96-well plates and incubated with DMEM/F-12 culture medium containing 10%human peripheral blood serum for 8 days.Then,hematoxylin-eosin staining,microtubule-associated protein 2,and glial fibrillary acidic protein immunofluorescence staining were performed to detect the differentiation of neural stem cells into other neural cells. RESULTS AND CONCLUSION:(1)Human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum grew in a spiral-like pattern and were distributed in multiple layers,with directional arrangement.The surface of human umbilical cord mesenchymal stem cells highly expressed CD44,CD105,CD29,and CD73.Cells stained with alizarin red showed a color reaction.(2)Human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum could be induced to differentiate into neural stem cells,and the surface of neural stem cells was highly expressed with CD44,CD105,CD29,CD73,Nestin,NF-L,and GALC.(3)On day 8 of induced differentiation of neural stem cells,after staining with hematoxylin and eosin,it was found that the protruding protrusions were longer,with more branches and adjacent cells connected,presenting typical neural cell morphology.Immunofluorescence staining for microtubule-associated protein 2 and glial fibrillary acidic protein was positive.It is concluded that human umbilical cord mesenchymal stem cells cultured by human peripheral blood serum can be directly induced to differentiate into neural stem cells.Under the action of human peripheral blood serum,neural stem cells can differentiate into other neural cells as the culture time prolongs.

Biosafety risks and mitigation strategies for mosquito infection in Arthropod Containment Level-2 laboratory / 中国热带医学

@#Arthropods of medical importance such as mosquitoes, ticks and sandflies are one of the key drivers of arthropod-borne diseases outbreak, posing a great threat to global public health security. For further understanding the transmission mechanisms of arthropod-borne diseases and establishing the prevention and control measures, a series of experiments of arthropods infection need to be carried out under laboratory conditions. Besides the regular biosafety requirements, some specific considerations need to be taken into account when performing arthropod infection and the infected arthropod rearing. Except for the physical containment composed of biosafety facilities, a comprehensive assessment of the biosafety risks during operations and corresponding preventive measures are also critical to eliminate or mitigate the biosafety risks. In this paper, we introduce our practice in handling mosquito infection with Risk Group 2 pathogens in Arthropod Containment Level-2 (ACL-2) laboratory, with an aim to provide a reference for researchers in related fields.

Research progress on the mechanism of mesenchymal stem cells therapy for premature ovarian failure / 基础医学与临床

Premature ovarian failure(POF)is a gynecological endocrine disease caused by ovarian dysfunction.Mesenchymal stem cells(MSCs)can effectively treat premature ovarian failure,and play a role in repairing ovarian structure and improving ovarian function.The specific mechanism can be a direct differentiation into granulosa cells or inhibition of their apoptosis through the homing effect of MSCs or differentiate into primordial germ cells.Benefit of MSCs can also be attributed to ovarian angiogenesis promotion,immune regulation,reduce oxidative stress re-sponse and paracrine,all potentially promote recovery of ovarian function,and thus improve the fertility of women of childbearing age.

Effect of Rubus irritans Focke extract on differentiation of 3T3-L1 preadipocytes / 中国药理学通报

Aim To study the effect of Rubus irritans Focke extract on adipogenic differentiation of 3T3-L1 preadipocytes, and to further explore the potential mechanism of Rubus irritans Focke on adipocyte metabolism, so as to provide a new basis for the prevention and treatment of obesity. Methods Rubus irritans Focke extract was separated and prepared by MCI medium pressure chromatographic column. MTT method was used to detect cell proliferation, and oil red 0 staining and kit test was used to to detect the level of lipid accumulation. Western blot was employed to detect the expressions of peroxisome proliferator-activated receptor ¦y (PPAR7), CCAAT enhancer binding protein a (C/ EBPa), adenosine 5'-monophosphate activated protein kinase (AMPK) and phosphorylated AMPK (p-AMPK) protein. Results When the concentration of Rubus irritans Focke extract was less than 100 mg •L

Emerging and re-emerging zoonoses is a persistent challenges for human health / 中国热带医学

@#Zoonoses are a class of infectious diseases that are transmitted from animals to humans. More than 200 known types of zoonoses have been reported across the world until now. Among 1 400 pathogens of human infectious diseases, approximately 61% are zoonotic origin, and 75% human emerging infectious diseases are zoonoses. These zoonoses pose a great threat to human and animal health and decrease livestock production. To effectively tackle the persistent challenges resulting from zoonoses, WHO collaborates with member governments, academia, non-governmental and charitable organizations, and regional and international partners to prevent and manage zoonotic threats and their public health, social and economic impacts. Although great success has been achieved in the management of zoonoses, there are still multiple challenges for zoonoses control in China due to environmental, climate, socioeconomic factors and antimicrobial resistance. Based on the One Health concept, the integration of modern biological, information, artificial intelligent and big data tools through multidisciplinary and multi-sectorial collaborations may facilitate the containment and elimination of zoonoses.

The Endoplasmic Reticulum Stress Response Mediates Shikonin-Induced Apoptosis of 5-Fluorouracil–Resistant Colorectal Cancer Cells

Resistance to chemotherapeutic drugs is a significant problem in the treatment of colorectal cancer, resulting in low response rates and decreased survival. Recent studies have shown that shikonin, a naphthoquinone derivative, promotes apoptosis in colon cancer cells and cisplatin-resistant ovarian cells, raising the possibility that this compound may be effective in drug-resistant colorectal cancer. The aim of this study was to characterize the molecular mechanisms underpinning shikonin-induced apoptosis, with a focus on endoplasmic reticulum (ER) stress, in a 5-fluorouracil–resistant colorectal cancer cell line, SNU-C5/5-FUR. Our results showed that shikonin significantly increased the proportion of sub-G1 cells and DNA fragmentation and that shikonin-induced apoptosis is mediated by mitochondrial Ca 2+ accumulation. Shikonin treatment also increased the expression of ER-related proteins, such as glucose regulatory protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (PERK), phospho-eukaryotic initiation factor 2 (eIF2α), phospho-phosphoinositol-requiring protein-1 (IRE1), spliced X-box–binding protein-1 (XBP-1), cleaved caspase-12, and C/EBP-homologous protein (CHOP). In addition, siRNA-mediated knockdown of CHOP attenuated shikonininduced apoptosis, as did the ER stress inhibitor TUDCA. These data suggest that ER stress is a key factor mediating the cytotoxic effect of shikonin in SNU-C5/5-FUR cells. Our findings provide an evidence for a mechanism in which ER stress leads to apoptosis in shikonin-treated SNU-C5/5-FUR cells. Our study provides evidence to support further investigations on shikonin as a therapeutic option for 5-fluorouracil–resistant colorectal cancer.

Femoral head necrosis rate and risk factors after internal fixation of femoral neck fracture:a Meta-analysis / 中国骨伤

OBJECTIVE@#To study the incidence and risk factors of osteonecrosis of the femoral head (ONFH) after internal fixation in adult patients with femoral neck fracture (FNF) after 2000, and identify high-risk population of ONFH.@*METHODS@#PubMed, Medline, The Cochrane Library, CNKI, Wanfang and VIP Database were searched to collect all the literatures on ONFH and related risk factors after internal fixation of FNF from January 1th 2000 to July 1th 2020. Study extraction was performed according to inclusion and exclusion criteria. Endnote X9 and Excel 2019 were used for literatures extraction, management and data entry, and R Studio 3.6.5 software was used for Meta-analysis. Subgroup analysis, sensitivity analysis and publication bias detection were used to explore the sources of heterogeneity and the reliability of the evaluation results.@*RESULTS@#A total of 16 studies with 5521 patients were included. Meta-analysis showed that the incidence of ONFH after internal fixation for adult FNF was 14.5% [95% CI(0.126-0.165)]. Fracture displacement[OR=0.27, 95%CI(0.21-0.35)] and reduction quality [OR=0.15, 95%CI(0.09-0.27)] were related risk factors for ONFH. The results of subgroup rate analysis showed that the non-displaced fracture necrosis rate was 6.2%[95%CI(0.051-0.077)] and the displaced fracture necrosis rate was 20.4% [95%CI(0.166-0.249)];the good reduction fracture necrosis rate was 8.3%[95%CI(0.072-0.095)] and the poor reduction fracture necrosis rate was 35.5%[95%CI(0.233-0.500)]. The included literatures have good consistency and no publication bias.@*CONCLUSION@#After 2000, the total incidence of ONFH after internal fixation of adult FNF has decreased, while the necrosis rates of patients with displaced fracture and poor reduction are still at a high level. The interval between injury and surgery was not analyzed in this study because of the inconstant division in the original literature.

Heart rate control and influencing factors of patients with coronary heart disease and arrhythmia in Qinghai in 2019 / 公共卫生与预防医学

Objective To investigate the heart rate control and related influencing factors of patients with coronary heart disease and arrhythmia in Qinghai in 2019. Methods Clinical data of 263 patients with coronary heart disease and arrhythmia in our hospital in 2019 were retrospectively analyzed. According to their resting heart rate control status at 6 months after discharge, the patients were divided into a well-controlled heart rate group (n=151) and a poorly controlled heart rate group (n=112). The clinical characteristics of patients with different heart rate control status were compared, and influencing factors of heart rate control were analyzed. Results Among patients with coronary heart disease and arrhythmia in Qinghai in 2019, atrial arrhythmia had a higher incidence rate (55.51%), and the main types of arrhythmia were atrial premature beat. The rate of good heart rate control of patients at 6 months after discharge was 57.41%. The heart rate control status was related to the resting heart rate at discharge, age, smoking status, treatment methods, type of coronary heart disease, CCS grade, NYHA classification, hypertension, diabetes mellitus, cardiac enlargement, use of beta blocker and awareness of heart rate control target at discharge (t=32.370, P2=26.300, P2=45.690, P2=15.161, P2=67.500, P2=18.788, P2=10.228, P=0.006; χ2=78.769, P2=66.374, P2=51.165, P2=43.360, P2=40.315, P<0.001), and the difference was statistically significant. Smoking, coronary artery bypass grafting, myocardial infarction, diabetes mellitus, non-use of beta blockers, and poor awareness of heart rate control were independent risk factors for poor heart rate control in patients with coronary heart disease and arrhythmia (P<0.05). Conclusion In 2019, the rate of good heart rate control in patients with coronary heart disease and arrhythmia in Qinghai is above the average level, and the health education on heart rate control relate knowledge for high-risk groups should be strengthened.

Effect of combined treatment with human umbilical cord blood mononuclear cells and human umbilical cord mesenchymal stem cells on liver function, inflammation grade, and immune function in patients with hepatitis B cirrhosis / 临床肝胆病杂志

ObjectiveTo retrospectively investigate the effect of combined treatment with human umbilical cord blood mononuclear cells (hUCB-MNCs) and human umbilical cord mesenchymal stem cells (hUC-MSCs) on liver function, inflammation grade, and immune function in patients with hepatitis B-related decompensated cirrhosis. Methods 11 patients with liver cirrhosis who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from November 2016 to June 2019 were enrolled in this clinical study and were given infusion of hUCB-MNCs (＞18×109/time) once in the first week and infusion of hUC-MSCs (1×106/kg) once a week in the second, third, and fourth weeks. Reexamination was performed at 4, 8, and 12 weeks after treatment to compare the changes in liver function, blood ammonia, blood coagulation factors, serum levels of cytokines, and lymphocyte subsets after treatment, and the changes in neurological and psychiatric symptoms were observed and recorded. A one-way repeated-measures analysis of variance was used for comparison of continuous data between groups. ResultsAfter the combined treatment with hUCB-MNCs and hUC-MSCs, all 11 patients achieved certain improvements in psychiatric and neurological symptoms after infusion, and liver function parameters and blood coagulation function basically returned to normal (all P＜0.05). At 12 weeks after the combined infusion of cells, blood ammonia level returned to the normal level (P＜0.05), and there were significant reductions in the levels of the inflammatory cytokines interleukin-6 and tumor necrosis factor (F=49497 and 37.071, both P＜0.05) and significant increases in the levels of the anti-inflammatory cytokines transforming growth factor-β and interleukin-10 (F=35.843 and 15.918, both P＜005). There were also significant reductions in the percentages of the cytotoxic cells CD3+CD8+ T and CD19+ B cells (F=52.242 and 89.097, both P＜0.05) and a significant increase in the regulatory T cells CD4+CD25+ (F=17.337, P＜0.05). ConclusionCombined treatment with hUCB-MNCs and hUC-MSCs for liver cirrhosis can optimize liver function, reduce the production of inflammatory cytokines, alleviate liver inflammation and liver cell destruction, and increase regulatory T cells, thereby affecting the body’s immune function.

Genome-wide development of polymorphic microsatellite markers and their application in peanut breeding program

BACKGROUND: Cultivated peanut (Arachis hypogaea. L) represents one of the most important oil crops in the world. Although much effort has been expended to characterize microsatellites or Simple Sequence Repeats (SSRs) in peanut, the quantity and quality of the markers in breeding applications remain limited. Here, genome-wide SSR characterization and marker development were performed using the recently assembled genome of the cultivar Tifrunner. RESULTS: In total, 512,900 microsatellites were identified from 2556.9-Mb genomic sequences. Based on the flanking sequences of the identified microsatellites, 7757 primer pairs (markers) were designed, and further evaluated in the assembled genomic sequences of the tetraploid Arachis cultivars, Tifrunner and Shitouqi, and the diploid ancestral species, A. duranensis and A. ipaensis. In silico PCR analysis showed that the SSR markers had high amplification efficiency and polymorphism in four Arachis genotypes. Notably, nearly 60% of these markers were single-locus SSRs in tetraploid Arachis species, indicating they are more specific in distinguishing the alleles of the A and B sub-genomes of peanut. In addition, two markers closely related with purple testa color and 27 markers near to FAD2 genes were identified, which could be used for breeding varieties with purple testa and high-oleic acid content, respectively. Moreover, the potential application of these SSR markers in tracking introgressions from Arachis wild relatives was discussed. CONCLUSIONS: This study reported the development of genomic SSRs from assembled genomic sequences of the tetraploid Arachis Tifrunner, which will be useful for diversity analysis, genetic mapping and functional genomics studies in peanut

Oral health status in elderly residents in Songjiang District of Shanghai / 上海预防医学

Objective To understand oral health of the elderly in nursing home in Songjiang District, Shanghai, and to provide references for improving their oral health. Methods A total of 375 elderly people in 15 nursing homes in Songjiang District were investigated by questionnaires and oral examination.Tooth loss, denture repair, periodontal condition and oral hygiene habit were analyzed. Results The rate of the tooth loss reached 94.13%.The tooth loss rate in females (96.09%) was significantly higher than that in males (91.03%) (P < 0.01).The rate of complete edentulous jaws was 28.27%.There was a significant difference between the rate of complete edentulous jaws in females (34.35%) and in males (18.62%)(P < 0.05).The rate of denture restoration was 91.51% (97/106).The number of existing teeth per capita was 11.54, and the number of teeth per capita in males (14.48 per person) was significantly higher than that in females (9.70 per person) (P < 0.05).Both the rate of the tooth loss of upper and lower posterior teeth were significantly higher than that of upper and lower anterior teeth (P < 0.01).Thirty-three percent (33.33%) of the elderly brushed their teeth more than twice a day, and almost 20.53% of them didn′t brush their teeth. Conclusion The oral health of the elderly in the nursing homes in Songjiang District is not satisfactory at present.It is necessary to strengthen the publicity and education of oral health care for the elderly in nursing homes in cooperation with multiple departments to improve their awareness of oral health care including appropriate tooth repair for the quality of life.

Literature review of the research on chronic prostatitis treated by traditional Chinese medicine / 国际中医中药杂志

This paper reviews the clinical research on the treatment of chronic prostatitis with traditional Chinese medicine in recent years. It is believed that the core of the etiology and pathogenesis of this disease lies in the deficiency of spleen and kidney, dampness heat, phlegm turbid and blood stasis toxin. If the disease lasts for a long time, the spleen and kidney become to the deficiency from excess. The internal treatment of traditional Chinese medicine includes syndrome differentiation, disease differentiation or single prescription, while the external treatment mainly includes herbal bathing, enema, anal administration and acupuncture. Traditional Chinese medicine has advantages in the treatment of this disease. We should continue to study the the mechanism of traditional Chinese medicine for this disease, standardize the syndrome differentiation and treatment and outocmes evaluation, and carry out research on famous prescriptions on prostatitis.

Level of Coagulation Function Indexes and Its Clinical Significance in Patients with Lymphoplasmacytic Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the level of coagulation function indexes in patients with lymphoplasmacytic lymphoma (LPL) and its clinical significance.@*METHODS@#The clinical data of 32 patients with initial LPL (LPL group) and physical examination data of 25 healthy persons (control group) who underwent physical examination in our hospital during the same period were collected. The differences of platelet (Plt), D-Dimer (D-D), fibrinogen (Fib), thrombin time (TT), prothrombin time (PT) and activated partial thrombin time (APTT) between the two groups were compared.@*RESULTS@#The Plt count in LPL group [ (137.06±40.14)×10/L] was significantly lower than that in control group [ (215.07±33.25)×10/L], D-D [ (1.01±0.16) mg/L, PT [ (13.01±1.37) s] and APTT [ (40.96±7.24) s] in LPL group were significantly higher than those in control group [ (0.37±0.09) mg/L, (11.96±0.87) s, (25.07±5.13) s] (P＜0.01); there was no significant difference in TT and Fib levels between the two groups (P＞0.05). There was no significant difference in Plt, D-D, Fib, AP, TT and APTT among LPL patients secreting different types of immunoglobulin (Ig) (P＞0.05). After treatment, the coagulation function of LPL patients returned to normal, and no death cases occurred due to hemorrhage or thrombosis.@*CONCLUSION@#LPL patients have hypercoagulable state blood and abnormal coagulation function, but which not closely relates to with the type of Ig secreted by patients.

Expression Level and Target Gene Prediction of miR-181b in Patients with Chronic Lymphocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the diagnostic value of multiple reverse transcription-polymerase chain reaction (RT-PCR) for detecting different fusion genes in children with primary acute lymphoblastic leukemia (ALL).@*METHODS@#The clinical data of 80 children with ALL treated in the 2 affiliated hospital of Xi'an Medical College from September 2012 to September 2017 were collected and retrospectively analyzed. Immunophenotype, chromosome karyotype and fusion gene were analyzed.@*RESULTS@#Immunophenotyping showed that there were 2 cases of mixed expression of myeloid + B system, 2 cases with pre- B expression, 58 cases with former B expression, 11 cases with CD13 combined with pre- B expression, 4 cases with CD5 combined with pre- B expression, and 3 cases with CD2 combined with pre- B expression. The results of chromosome karyotype analysis showed that among 72 cases of karyotype analysts 5 cases could not be analyzed, 27 cases were determined to be normal karyotype, 11 cases with abnormal karyotype and 29 cases without mitotic phase. Six fusion genes were expressed in 30 cases (37.50%) of 80 ALL children, including MLL/AF9, CBF/MYH 11, BCR/ABL, TLS/ERG, MLL/ENL and TEL/AML1. Among the 3 cases with MLL/AF9 fusion gene expression [t(9;11)], 2 cases showed a poor response to early treatment, but achieved complete remission after intensive chemotherapy, and 1 case accepted bone marrow transplantation; in 1 case with CBF/MYH 11 fusion gene expression, treatment was abandoned by family members, and 4 cases with BCR/ABL fusion gene expression [t (9;22) (q34; q11)] were all showed poor response to early treatment, and achieved complete remission after intensive chemotherapy. All the fusion genes were positive during remission, including 2 cases of bone marrow transplantation; 1 case with TLS/ERG fusion gene expression [t (16;21)] displayed poor response to early treatment, and completely remitted after intensive chemotherapy; 2 cases with MLL/ENL fusion gene expression [t (11;19)] recurred during chemotherapy; 19 cases with TEL/AML1 fusion gene expression [t (12;21)] also achieved complete remission. 4 cases achieved a partial remission.@*CONCLUSION@#Genotyping can make up for the insufficiency of MICM typing, and multiplex RT-PCR can be used to rapidly detect the fusion genes caused by chromosomal aberration in children with ALL.

Critical hubs of renal ischemia-reperfusion injury: endoplasmic reticulum-mitochondria tethering complexes / 中华医学杂志(英文版)

Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.

MiR-182-5p Knockdown Targeting PTEN Inhibits Cell Proliferation and Invasion of Breast Cancer Cells

PURPOSE: Breast cancer (BC) is one of the most common malignant tumors, affecting a significant number of women worldwide. MicroRNAs (miRNAs) have been reported to play important roles in tumorigenesis. The aim of this study was to determine the roles of miR-182-5p in BC progression. MATERIALS AND METHODS: The expressions of miR-182-5p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) were measured in BC tissues and cells by quantitative real-time polymerase chain reaction or Western blot. Cell proliferation and invasion were detected by cell counting kit-8 assay and trans-well assay, respectively. The interaction between miR-182-5p and PTEN was probed by bioinformatics analysis, luciferase activity, and RNA immunoprecipitation. A murine xenograft model was established to investigate the role of miR-182-5p in BC progression in vivo. RESULTS: An abundance of miR-182-5p was noted in BC tissues and cells. High expression of miR-182-5p was associated with poor survival. Abrogation of miR-182-5p inhibited cell proliferation and invasion in BC cells. Interestingly, PTEN was indicated as a target of miR-182-5p, and its restoration reversed miR-182-5p-mediated promotion of proliferation and invasion of BC cells. Moreover, depletion of miR-182-5p suppressed tumor growth via up-regulating PTEN expression in the murine xenograft model. CONCLUSION: MiR-182-5p exhaustion blocked cell proliferation and invasion by regulating PTEN expression, providing a novel therapeutic avenue for treatment of BC.

A non-invasive diagnostic model of immunoglobulin A nephropathy and serological markers for evaluating disease severity / 中华医学杂志(英文版)

BACKGROUND@#Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN.@*METHODS@#A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was used to establish the diagnostic model.@*RESULTS@#There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P < 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of I, II, III, IV, and V accounted for 2.21%, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade III being the most prevalent. The levels of urea nitrogen (UN) (13.57 ± 5.95 vs. 6.06 ± 3.63, 5.92 ± 2.97, 5.41 ± 1.73, and 8.41 ± 3.72 mmol/L, respectively) and creatinine (Cr) (292.19 ± 162.21 vs. 80.42 ± 24.75, 103.79 ± 72.72, 96.41 ± 33.79, and 163.04 ± 47.51 μmol/L, respectively) were significantly higher in grade V than in the other grades, and the levels of TP (64.45 ± 7.56, 67.16 ± 6.94, 63.22 ± 8.56, and 61.41 ± 10.86 vs. 37.47 ± 5.6 mg/d, respectively), direct bilirubin (DB) (2.34 ± 1.23, 2.58 ± 1.40, 1.91 ± 0.97, and 1.81 ± 1.44 vs. 0.74 ± 0.57 μmol/L, respectively), and IgA (310.35 ± 103.78, 318.48 ± 107.54, 292.58 ± 81.85, and 323.29 ± 181.67 vs. 227.17 ± 68.12 g/L, respectively) were significantly increased in grades II-V compared with grade I (all P < 0.05).@*CONCLUSIONS@#The established diagnostic model that combined multiple factors (TC, FIB, D2, IgA, and age) might be used for IgAN non-invasive diagnosis. TP, DB, IgA, Cr, and UN have the potential to be used to evaluate IgAN disease severity.

Analysis of chronic kidney disease staging with different estimated glomerular filtration rate equations in Chinese centenarians / 中华医学杂志(英文版)

BACKGROUND@#Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy.@*METHODS@#A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis.@*RESULTS@#The κ values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P < 0.001).@*CONCLUSIONS@#The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS1 equations and the CKD-EPI and BIS1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.