Objective:To analyze expression and models of CD39,CTLA-4,and PD-1 on T cells,to investigate effect of cyclic adenosine monophosphate(cAMP)on their expressions,and to analyze key pathways regulating their expressions.Methods:Small molecules such as adenylate cyclase(ACs)activators,phosphodiesterase(PDE)inhibitors,protein kinase A(PKA)inhibitors and PKA-CREB inhibitors were used to stimulate rhesus macaque peripheral blood mononuclear cells in vitro,and changes in ratios of CD39,CTLA-4,and PD-1 positive(CD39+,CTLA-4+,and PD-1+)T cells were detected by flow cytometry,and to analyze their expression patterns,and effects of small molecules on ratio of positively expressing/co-expressing cells were compared to clarify expres-sion patterns and molecules and pathways that regulated expression.Results:Normal macaque CD4+T and CD8+T cells had low ratios of CD39+,CTLA-4+,and PD-1+cells,and positive cells predominantly expressed only one of these molecules.Increasing intracellular cAMP levels did not affect CD39+T cell ratio,significantly increased CTLA-4+T cell ratio,and decreased PD-1+CD8+T cell ratio,involving cell populations with mono expression of CTLA-4 and PD-1.Inhibition of PKA activity reduced potentiation of CTLA-4 expression by broad-spectrum PDE inhibitor,3-isobutyl-1-methylxanthine(IBMX),but did not affect PD-1 expression.Exchange protein activated by cAMP did not affect CTLA-4 expression but downregulate PD-1+CD4+/CD8+T cells ratio.Upregulation of CTLA-4 by PDE4B selective inhibitors was similar to IBMX,while regulation of PDE3 and PDE5A selective inhibitors on PD-1 expression was similar to IBMX.Conclusion:CD39,CTLA-4 and PD-1 have different expression models on T cells but are differentially regulated by cAMP levels and have different cAMP downstream signal pathways involved in expression regulation.

Objective:To observe the inhibiting effects of manual acupuncture(MA)on bladder cell apoptosis in rats with diabetic neurogenic bladder(DNB)based on the protein and mRNA expression of B-cell lymphoma-leukemia(Bcl)-2,Bcl-2-associated X(Bax)protein,caspase-3,and the protein expression of α-smooth muscle actin(α-SMA),transforming growth factor(TGF)-β in the bladder tissue. Methods:A DNB rat model was established via intraperitoneal injection of streptozotocin(STZ).The rats were randomly divided into a control group,a model group,and an MA group,with 10 rats in each group.For the MA group,MA was applied after modeling.The body mass,fasting blood glucose(FBG),bladder wet weight,and bladder histomorphology were observed.Protein and mRNA expression levels of Bcl-2,Bax,and caspase-3 and the protein expression of α-SMA and TGF-β in the bladder tissue were determined.The apoptotic index of bladder cells was also evaluated. Results:After STZ injection,compared with the control group,the model group and the MA group both showed higher FBG from week 3 and lower body mass from week 9(P<0.05),and had a larger bladder wet weight(P<0.05).Compared with the model group,the MA group showed a smaller bladder wet weight(P<0.05).The histopathological evaluation indicated that MA improved muscle fiber alignment and detrusor cell compensatory hypertrophy in the bladder tissue.In addition,compared with the control group,the apoptotic index increased significantly in the model group and the MA group(P<0.05);the protein and mRNA expression levels of Bax and caspase-3 and the protein expression level of TGF-β in the bladder tissue in the model group and the MA group increased significantly(P<0.05),while the protein and mRNA expression levels of Bcl-2 and the protein expression level of α-SMA in the bladder tissue decreased significantly(P<0.05).Compared with the model group,the apoptotic index of the MA group decreased significantly(P<0.05);the protein and mRNA expression levels of Bax and caspase-3 and the protein expression level of TGF-β in the bladder tissue decreased significantly(P<0.05),while the protein and mRNA expression levels of Bcl-2 and the protein expression level of α-SMA in the bladder tissue increased significantly(P<0.05). Conclusion:MA can protect the bladder by inhibiting the excessive apoptosis of bladder cells,which may be related to the down-regulation of Bax and caspase-3 proteins and mRNAs and TGF-β protein expression,and the up-regulation of Bcl-2 protein and mRNA and α-SMA protein expression.

The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C₂₈-steroid with an unusual β- and γ-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC₅₀ value of 2.61 ± 0.05 μmol·L^-1. The β-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 μg·mL^-1. Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 μg·mL^-1, respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC₅₀ values of 9.2 ± 0.03 and 13.3 ± 0.01 μmol·L^-1, respectively.
Humans ; Acetylcholinesterase ; Molecular Docking Simulation ; Anti-Bacterial Agents ; Glycosides ; Lactones ; Pain

ObjectiveTo investigate the impact of posture and sports experience on distance perception in Paralympic athletes with lower limbs disabilities. MethodsFrom May to August, 2019, athletes were selected from the wheelchair racing team (n = 19) and the wheelchair fencing team (n = 16) in Shanghai, China. The athletes were tested the relative distance perception and absolute distance perception using the successive equal-appearing distance and blind walking tasks. ResultsThe interaction effects between sport and posture (F = 4.118, P < 0.05), sports events and distance judgment (F = 8.913, P < 0.01), and posture and distance judgment (F = 11.894, P < 0.01) were significant; while the main effects of sport (F = 7.467, P < 0.01) and posture (F = 11.918, P < 0.01) were significant; the relative distance judgment accuracy was better in the athletes of wheelchair fencing than in those of wheelchair racing, and in standing posture than those in sitting posture. ConclusionThe relative distance judgment accuracy is better for the Paralympic athletes standing and playing wheelchair fencers. There was no significant difference in the accuracy of absolute distance judgment between the different postures and the different sports.

Liver transplantation is a vital treatment for end-stage liver disease. However, the shortage of donor livers has limited the development of liver transplantation. How to expand the source of donor livers has become a challenge in the academic community. In recent years, the proportion of donors with non-alcoholic fatty liver disease (NAFLD) has been increased. Rational use of steatotic donor livers is a feasible approach to expand the donor pool. Cold ischemia injury during donor liver preservation before liver transplantation increases the risk of postoperative organ dysfunction. Therefore, it is of significance to unravel the mechanism and intervention measures of cold ischemia injury of steatotic donor livers. Cold ischemia injury of steatotic donor livers is characterized as the damage of mitochondria, lysosomes and endoplasmic reticulum at the organelle level, and up-regulated expression of adenosine monphosphate activated protein kinase (AMPK), aldehyde dehydrogenase 2 (ALDH2) and heme oxygenase (HO)-1 at the protein level. In this article, the research progresses on cold ischemia injury of steatotic donor livers and relevant intervention measures were reviewed.

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd

Background: Psoriasis vulgaris is a chronic inflammatory skin disease which occur at any age. It can be clinically classified into two age-onset subtypes: early-onset psoriasis (EOP;＜40 years) and late-onset psoriasis (LOP; ≥40 years). More evidence showed EOP and LOP have different genetic architecture, notably the risk allele human leukocyte antigen (HLA)-C*06:02 located within the major histocompatibility complex (MHC) region, which was reported to be the outstanding variant associated with EOP. However, genetic structure of EOP and LOP have not been fully elucidated. Objective: To investigated HLA genetic heterogeneity between EOP and LOP in China. Methods: We first calculated the MHC-based heritability of EOP and LOP respectively.Then, we conducted a large-scale, stratified analysis including 7,097 EOP, 1,337 LOP patients, and 9,906 healthy controls by using MHC target sequencing data from a previousstudy. Results: We observed that HLA alleles collectively explained a larger heritability of EOP (27.4%) than LOP (11.3%).Further association analysis identified three independent loci (HLA-C*01:02, p=6.70×10−8 ; HLA-A amino acid position 9, p=3.27×10−17 ; and HLA-A amino acid position 161, p=5.75×10−10 ) that confer specific susceptibility to EOP. Our data also confirmed HLA-C*06:02 as an independent psoriasis-associated variant, contributing a higher degree of risk to EOP than LOP. Moreover, case-case analysis confirmed that HLA-C*06:02-positive psoriasis patients have earlier onset. Conclusion Our analysis indicating that different genetic background underlie the EOP and LOP. We believe these findings will serve to predict psoriasis risk in the future and facilitate clinical decision.

Objective: To investigate the effect of gross motor skills on physical activity of children aged 3-6 years, and to provide basis for children’s health behavior intervention. Methods: A total of 332 young children in Shanghai Xiangyin kindergarten were selected as survey objects. The development of gross movements of young children was measured by TGMD-2. Caregivers reported children’s physical activity using the International Physical Activity Questionnaire (IPAQ-SF). Results: The development level of gross movements of children aged 3-6 in Shanghai was relatively low(54.76±13.86). The physical activity of children was mainly light-intensity physical activity, and the daily moderate-to-vigorous intensity physical activity time was (58.62±52.73) minutes every day. Locomotor skills had the greatest effect on children’s VPA (β=0.19) and TPA(β=0.12), with a contribution rate of 3.3% and 1.1%, respectively; Object control skills has the greatest effect on children’s MVPA (β=0.17) and MPA (β=0.12) had the largest effect(P<0.05), with contribution rates of 2.5% and 1.2%, respectively. The relationship between gross motor skills and physical activity had nothing to do with gender and age. Conclusion Children’s gross motor skills in the 3-6 year-old population should be improved and may be an effective way to promote physical activity.

OBJECTIVE:To investigate the role of clinical pharmacists on drug therapy for acute exacerbations of chronic ob-structive pulmonary disease(AECOPD)patients with benign prostatic hyperplasia(BPH). METHODS:Clinical pharmacists partici-pated in drug therapy for a AECOPD patient with BPH. According to clinical guideline and relevant literatures,based on the history of disease,the characteristics of bronchodilators and the symptoms of acute urinary retention,it was suggested to stop taking Ip-ratropium bromide solution for inhalation but receive Finasteride capsules 5 mg,po,qd,to reduce prostate volume and improve ob-struction+Terazosin hydrochloride tablets 2 mg,po,qd,to relax urethral smooth muscle;the occurrence of ADR was monitored closely. Salmeterol xinafoate and fluticasone propionate powder for inhalation was suggested and medication guidance for patients af-ter discharge was given by clinical pharmacists. RESULTS:Physicians adopted some suggestions of clinical pharmacists. The pa-tient was stable and had no dysuria. The patient was allowed to leave the hospital with drugs. CONCLUSIONS:Rational use of bronchodilators is directly related to the remission of clinical symptoms and prognosis in AECOPD patients. In view of patient's dis-ease history,drug characteristics and clinical symptoms,clinical pharmacists point to possible risks of anticholinergics use,and as-sist physicians to formulate and adjust therapy plan so as to guarantee the safety and effectiveness of drug use.