BACKGROUND:Regulatory T cels (Treg) are classified into two subsets, nature Treg (nTreg) and induced Treg (iTreg). Although there is consensus that CD4+CD25+FoxP3+CD127-is the widely accepted phenotype of Treg, it remains unclear what is the difference in phenotypes including cytokine patterns of nTreg and iTreg. OBJECTIVE:To understand and compare the plasticity of nTreg and iTreg and to search the exact mechanism of cytokine secretion in Tregs. METHODS: We investigated the frequency and cytokine pattern of CD4+CD25+FoxP3+CD127-nTreg in freshly separated peripheral blood mononuclear cels of five healthy individuals using 8-color fluorescence flow cytometry (FACSCanto II). Subsequently, after 9 days of alostimulation in mixed lymphocytes, the frequency and cytokine pattern of CD4+CD25+FoxP3+CD127-iTreg were determined and analyzed. RESULTS AND CONCLUSION:In fresh cels, (1.5±0.70)% of CD4+ T cels were CD4+CD25+FoxP3+CD127- nTregs. Almost al these cels expressed interferon (IFN)-γ-, interleukin (IL)-2- or transforming growth factor-β+, and partial cels expressed IL-10+ or IL-10-. After 9-day alostimulation, the number of CD4+CD25+FoxP3+CD127- iTreg expressing IFN-γ+, IL-2-, IL-2+, IL-10+ or TGF-β+increased strongly. The main subsets of human nTregs were CD4+CD25+FoxP3+CD127-IFN-γ-IL-2-IL-10+TGF-β+and CD4+CD25+FoxP3+CD127-IFN-γ-IL-2-IL-10-TGF-β+ T cels. The proportion of each subset in CD4+ T cels was (1.1±0.59)% and (0.39±0.16)%, respectively. Whereas the main subsets of human iTregs were CD4+CD25+FoxP3+CD127-IFN-γ+IL-2-IL-10+TGF-β+ and CD4+CD25+FoxP3+CD127-IFN-γ+IL-2+IL-10+TGF-β+. Human nTregs were characterized as IFN-γ-IL-2- double negative, producing IL-10 and TGF-β or only TGF-β without IL-10, and not proliferatingin vitro. During the alostimulation in mixed lymphocytes, IFN-γ+ iTregs proliferated remarkably. One-third of IFN-γ+ iTreg expressed IL-2+, and two-thirds of IFN-γ+ iTregs expressed IL-2, both of which produce IL-2 and TGF-β. Our results imply that CD4+CD25+FoxP3+CD127- Treg are potentialy immunosuppressive probably because of their mandatory TGF-β and optional IL-10 production.

Objective:To systematically evaluate the effect of hydrocortisone combined with vitamin C and vitamin B1 on the efficacy of patients with sepsis or septic shock.Methods:Databases including CNKI, Sino Med, VIP, Wanfang, PubMed, the Cochrane Library, and Embase were searched from inception to January 2021 for the randomized controlled trial (RCT) about hydrocortisone combined with vitamin C and vitamin B1 to treat sepsis or septic shock. The experimental group was given intravenous injection of hydrocortisone, vitamin B1 and vitamin C based on conventional treatment; the control group was given conventional treatment or placebo/hydrocortisone/hydrocortisone+vitamin B1 based on conventional treatment. Outcome indicators included sequential organ failure assessment (SOFA), mortality, the duration of vasoactive drugs, new acute kidney injury (AKI) patients, length of stay in intensive care unit (ICU) and in hospital. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan 5.3 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 6 articles involving 816 patients were included, with 411 patients in the experimental group and 405 patients in the control group. The Meta-analysis results showed that the duration of vasoactive drugs in the experimental group was significantly shorter than that in the control group [mean difference ( MD) = -24.02, 95% confidence interval (95% CI) was -32.36 to -15.68, P < 0.000 01]. However, there were no significant differences in SOFA, mortality, new AKI patients, the length of ICU stay and hospital stay between the two groups [SOFA: MD = -0.14, 95% CI was -1.15 to 0.87, P = 0.79; mortality: relative risk ( RR) = 0.99, 95% CI was 0.81 to 1.21, P = 0.92; new AKI patients: RR = 1.10, 95% CI was 0.42 to 2.87, P = 0.84; length of ICU stay: MD = 1.33, 95% CI was -2.22 to 4.89, P = 0.46; length of hospital stay: MD = 1.02, 95% CI was -0.66 to 2.69, P = 0.23]. The funnel plot showed that most of the points were symmetrical and showed an inverted funnel shape, suggesting that the publication bias among the studies was small. There was no significant publication bias on this Meta-analysis. Conclusions:Hydrocortisone combined with vitamin C and vitamin B1 can shorten the duration of vasoactive drugs in patients with sepsis or septic shock, but it cannot effectively reduce the SOFA score, mortality, new AKI patients, length of stay in ICU and in hospital. Limited by the number and quality of the included studies, further large-scale, multi-center, blinded, RCT are still needed for verification.

Staphylococcus aureus(S.aureus) secretes a variety of pathogenic toxins and one of the most prominent toxins is α-hemolysin,which is considered as the main virulence factor in skin necrosis and severe infections caused by S.aureus infection. α-hemolysin is so named because of its ability to dissolve red blood cells. However,it has a wide range of effects on various cells and may cause different pathogenic re-sponses in different host cells. This review summarizes recent studies on the structure of α-hemolysin and its interaction with different cells in order to better understand the role of α-hemolysin in the process of S.aureus infection,which may provide a reference for developing new approaches to the prophylaxis and treatment of S.aureus infection.

Objective To explore the effects of arm venous port new technology standard operating procedure (SOP) in breast cancer with chemotherapy.Methods The arm venous port SOP was established from infusing to drawing.It was completed by doctor and nurse from infusing to venous port drawing.Patients received bed nursing by nurses in individual case during hospital,and then they were treated with "arm venous port group" management of department post discharge.The SOP was carried out in 100 female breast cancer patients with chemotherapy of the First Affiliated Hospital of Nanjing Medical University from May 2016 to February 2017.The arm venous port was infused one day before chemotherapy.It was used for infusing chemotherapy agents and other ancillary drugs.The overall recheck was conducted three months after the completion of chemotherapy.The arm venous port was drawn after being confirmed it had no further use.Results A total of 100 patients successfully completed 8 times of chemotherapy and the arm venous port was drawn successfully.During being with port,there were two patients with bad healing of surgical wound around port along with sewing up again;there were one patient with capsular bag infection after the fourth chemotherapy along with anti-infective therapy.The satisfaction of patients and their family members for operative technique and tracking service by doctors and nurses was 100％.Conclusions The application of SOP in arm venous port new technology can ensure high satisfaction of patients and reduce complications.It is suitable for clinical generalization.

OBJECTIVETo study the genetic polymorphisms and mutations of 20 frequently used autosomal microsatellites among ethnic Hans from Henan.

METHODSPeripheral blood samples of 2604 individuals were collected. DNA was amplified and genotyped using a PowerPlex(TM) 21 system. The frequencies, forensic parameters and mutation rates of the 20 short tandem repeat (STR) loci were analyzed.

RESULTSA total of 323 alleles were found in this population and the allelic frequencies have ranged from 0.0003 to 0.5144. Except for D3S1358, TH01 and TPOX, mutations have been found in all of the remaining 17 STR loci, which totaled 47, with mutation rates ranging from 0 to 3.46 × 10.

CONCLUSIONThe 20 STR loci selected by the PowerPlex(TM) 21 system are highly polymorphic among ethnic Hans from Henan, and may be of great value in forensic and human population studies. As no similar study has been carried out previously, above results may be of great value for individual discrimination and paternal testing.

Adolescent ; Adult ; Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Child ; Child, Preschool ; China ; ethnology ; Female ; Genotype ; Humans ; Male ; Microsatellite Repeats ; Mutation ; Pedigree ; Polymorphism, Genetic ; Young Adult

OBJECTIVE To investigate clinical efficacy and safety of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis （KOA） in the early and mid-term stage. METHODS Totally 100 KOA patients were randomly divided into control group and trial group， with 50 cases in each group. Control group received Diacerein capsules orally， 50 mg every time， bid. Trial group additionally received Jipei dilong ointment， once a day， on the basis of control group. Both groups had a treatment course of 4 weeks， and were followed up for 3 months after treatment. The clinical efficacy of 2 groups， visual analogue scale （VAS）， Western Ontario and McMaster University osteoarthritis index （WOMAC） score， Lysholm scores before and after treatment， at 3-month follow-up after treatment were all observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin 1β （IL-1β）， IL-6， superoxide dismutase （SOD）， malondialdehyde （MDA）， nitric oxide （NO）， cartilage oligomeric matrix protein （COMP）， matrix metalloproteinase-13 （MMP-13） and C-telopeptide of type Ⅱ collagen （CTX-Ⅱ） were detected in knee joint fluid. The incidence of adverse drug reactions was recorded. RESULTS After 4 weeks of treatment， total effective rate was 96.0% in trial group and 90.0% in control group， without statistical significance between 2 groups （P＞0.05）. At 3- 2019YFC1712500） month follow-up after treatment， total effective rate of trial group was 94.0%， and was higher than 62.0% of control group（P＜0.05）. After 4 weeks of treatment and at 3-month follow-up after treatment， VAS score， WOMAC score，the contents ofTNF-α， IL-1β， IL-6， MDA， NO， COMP， MMP-13 and CTX-Ⅱ in knee joint fluid of two groups were significantly lower than before； Lysholm score and SOD activity of knee joint fluid were significantly higher than before， and the trial group was significantly better than the control group during the same period （P＜0.05）. And there was no statistical significance in the incidence of adverse drug reactions between two groups（P＞0.05）. CONCLUSION For the treatment of KOA in early and mid- term stage， Jipei dilong ointment combined with diacerein relieve pain， improve knee function by inhibiting inflammatory reaction， reducing oxidative stress and inhibiting chondrocyte and matrix degradation， and have low incidence of adverse drug reactions.

Objective To evaluate the effect ofmicroRNA-143 (miR-143) on interleukin (IL)-13-induced expression of kallikrein 7 (KLK7) in primary normal human epidermal keratinocytes (NHEKs).Methods Some NHEKs at exponential growth phase were divided into 4 groups to be treated with recombinant human IL-13 at different concentrations of 0,2,10 and 50 μg/L respectively for 24 hours,and some NHEKs were treated with 50 μg/L IL-13 for 0,6,12,24 and 48 hours separately.After the treatment,NHEKs were collected,and total RNA was extracted.Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of KLK7.Some other NHEKs were divided into another 4 groups:NHEK group (blank control group) receiving no treatment,IL-13 group treated with 50 μg/L IL-13,miR-NC group transfected with miRNA mimics negative control followed by the treatment with 50 μg/L IL-13,and miR-143 group transfected with miR-143 mimics followed by the treatment with 50 μg/L IL-13.After 24-hour treatment with IL-13,real-time fluorescence-based quantitative PCR and Western blot analysis were conducted to determine the mRNA and protein expression of KLK7 respectively in the above groups.Results After 24-hour treatment with IL-13 at concentrations of 0,2,10 and 50 μg/L,the mRNA expression of KLK7 in NHEKs was 1.00 ± 0.12,0.89 ± 0.04,1.15 ± 0.09 and 1.70 ± 0.10 respectively,and significantly increased along with the increase of IL-13 concentrations (F =92.48,P ＜ 0.05).After 0-,6-,12-,24-and 48-hour treatment with 50 μg/L IL-13,the mRNA expression of KLK7 in NHEKs was 1.00 ± 0.05,1.05 ± 0.12,1.71 ± 0.20,1.97 ± 0.19 and 2.48 ± 0.13 respectively,and significantly increased over time (F =206.44,P ＜ 0.05).Compared with the miR-NC group,the miR-143 group showed significantly decreased mRNA and protein expression of KLK7 (t =6.76,4.23 respectively,both P ＜ 0.05).Conclusion In NHEKs,IL-13 can up-regulate the expression of KLK7,likely by the regulation of miR-143.

【Objective】 To investigate the protective effect and mechanism of platelet-rich plasma (PRP) on lipopolysaccharide (LPS) -induced inflammatory response in BV2 cells. 【Methods】 BV2 microglia were divided into normal control group, 10%PRP control group, LPS group (LPS induction), 3%PRP+ LPS group (LPS induction, 3%PRP pretreatment), 5%PRP+ LPS group (LPS induction, 5%PRP pretreatment), 10%PRP+ LPS group (LPS induction, 10%PRP pretreatment), and the proliferation of BV2 cells was measured by CCK-8. The mitochondrial membrane potential of BV2 cells was measured by confocal microscopy, ROS was measured by fluorescence method, and NO was measured by Griess method. The protein expressions of IL-6, TNF-α, BACH1, GPX4, NRF2 and HO-1 were detected by Western blot. In addition, BV2 microglia were treated with HO-1 inhibitor and divided into normal control group, LPS group, ZnPP+ LPS group, 10%PRP+ LPS group, ZnPP+ LPS+ 10%PRP group, and the protein expressions of HO-1, IL-6 and TNF-α were detected by Western blot. 【Results】 Compared with normal control group, PRP promoted the proliferation of BV2 cells (P<0.01). The mitochondrial membrane potential decreased, ROS production increased, the levels of NO, IL-6, TNF-α and BACH1 increased (P<0.01). However, the expression levels of GPX4, NRF2 and HO-1 decreased (P<0.01) in LPS group. Compared with LPS group, the proliferation activity and mitochondrial membrane potential of BV2 cells in 3%PRP+ LPS, 5%PRP+ LPS and 10%PRP+ LPS groups significantly increased. The levels of ROS, NO, IL-6, TNF-α and BACH1 significantly decreased (P<0.01). The expressions of GPX4, NRF2 and HO-1 in different concentrations of PRP (3%, 5% and 10%) increased (P<0.01). Moreover, the expression of IL-6 and TNF-α in ZnPP+ LPS group was significantly higher than that in LPS group after HO-1 inhibitor treatment. Compared with 10%PRP+ LPS+ ZnPP group, HO-1 inhibitor could reverse the effect of PRP on the expression of IL-6 and TNF-α in LPS-induced BV2 cells (P<0.01). 【Conclusion】 PRP inhibits the inflammatory response of BV2 microglia induced by LPS by activating the NRF2/HO-1 signaling pathway.

Objective This paper introduces the research progress on the pathogenesis of depression related to gut microbiota and provides the resources for the subsequent development of antidepressant drugs targeting gut microbiota. Methods 33 literatures on gut microbiota and depression in recent years were reviewed. The changes of gut microbiota diversity under depression were discussed from the perspectives of phylum, family and genus. The relationship between gut microbiota and the pathogenesis of depression was expounded at the molecular level, and the existing relevant studies were summarized. The feasibility of drug development targeting gut microbiota was explored. Results There is a relationship between gut microbiota disorder and depression. Existing biological agents such as probiotics can alleviate depression by adjusting the disorder of gut microbiota. Conclusion The imbalance of gut microbiota is closely related to the occurrence of depression, and the development of drugs targeting gut microbiota may become a new way to treat depression.

Objective    To summarize the individualized selection of surgical treatment strategies and the key points of perioperative management for patients with heart valve disease complicated with severe chronic heart failure. Methods    The clinical characteristics of 5 male patients with valvular heart disease complicated with severe chronic heart failure (CHF) were analyzed retrospectively from June 2017 to October 2018 in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, with an average age of 60.21 years. Results    Five patients were given angiotensin receptor and neprilysin inhibitor (ARNI)-based anti-heart failure treatment after admission. The operation mode of these patients was decided to be valve replacement under cardiopulmonary bypass after individualized evaluation of patients’ improving symptoms. Three patients were treated with intra-aortic balloon pump (IABP) and continuous renal replacement therapy (CRRT) early after operation to assist patients in improving cardiac function. Five patients recovered oral anti-heart failure after awakening. All patients were discharged smoothly 2 weeks after operation. Conclusion    Individualized evaluation is needed for the choice of operation timing and mode, standardized preoperative treatment for heart failure, shortening the aortic blocking time during cardiopulmonary bypass, and early application of left ventricular adjuvant drugs or instruments are all important measures to help patients recover smoothly.