Central memory T (Tcm) cells are a crucial subset in T cell development, playing an important role in long-term immune responses. Tcm cells exhibit strong proliferative capacity, long-term survival characteristics, and re-activation potential, enabling them to rapidly differentiate into effector T cells (Teff) upon antigen re-exposure, thus providing robust immune protection. The function of Tcm cells is regulated by various factors, including antigen exposure, cytokines, and metabolic conditions. A deeper understanding of their metabolic and epigenetic mechanisms under different pathological conditions will contribute to the development of more precise and effective immunotherapeutic strategies. This review elaborates on the origin and characteristics of Tcm cells, as well as their roles in antiviral responses, tumor immunity, and immunotherapy.
Humans ; Memory T Cells/cytology* ; Animals ; Immunologic Memory ; Neoplasms/therapy* ; Immunotherapy

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To establish interferon-induced transmembrane protein 3(Ifitm3)knockout mice and to explore the effects of Ifitm3 on the proliferation and differentiation of adult neural stem cells of mice(aNSCs).Methods IFITM3 knockout mice were established by the CRISPR/Cas9 method and identified by genotype identification and Western Blot.The differences between Ifitm3-knockout mice and wild-type mice were analyzed by hematoxylin-eosin(HE)staining and flow cytometry.The aNSCs of wild-type mice and Ifitm3-knockout mice were isolated and cultured,the number and size of neurospheres were detected,The ability of aNSCs to proliferate and differentiate were detected by quantitative reverse-transcription polymerase chain reaction,Western Blot,and immunofluorescence.Results Ifitm3-knockout mice were successfully established.The mice developed normally,and there were no obvious abnormalities either histopathologically or the immune system.In vitro experiments showed that Ifitm3 knockout inhibited the self-renewal potential of aNSCs,led to a decrease in the proliferation ability of aNSCs,and inhibited the differentiation of aNSCs into immature neurons and astrocytes.Conclusions This study finds that a lack of IFITM3 result in the ability of aNSCs to proliferate and differentiate decreased,IFITM3 may regulate the function of aNSCs.

BACKGROUND:Traditional scoliosis orthosis has some disadvantages,such as complex manufacturing process,long processing cycle,poor fit and so on.Three-dimensional printed scoliosis orthosis has the advantages of high manufacturing precision and personalization. OBJECTIVE:To evaluate the efficacy of three-dimensional printed scoliosis orthosis for scoliosis based on multi-criteria decision model. METHODS:Clinical data of 72 patients with scoliosis admitted to Chen Xinghai Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to October 2022 were retrospectively collected and divided into two groups according to the treatment of orthosis.Study group(n=23)received three-dimensional printed scoliosis orthosis.Traditional group(n=49)received the traditional polypropylene spine brace treatment.The clinical efficacy and complications were compared between the two groups.A multi-criteria decision model for the treatment of scoliosis with three-dimensional printed scoliosis orthosis was established,and the stability of the benefit value,risk value and decision model of the two groups were evaluated. RESULTS AND CONCLUSION:(1)Compared with the traditional group,there were significant differences in the top vertebral offset distance,Cobb angle,top vertebral rotation,Functional Movement Screen score,visual analog scale score and total effective rate in the study group at 6 months after surgery(P<0.05).(2)Among the benefit indexes,Cobb angle had the greatest impact on the condition of patients,while the risk indexes had the greatest impact on dyspnea.(3)The benefit values of the study group and the traditional group for scoliosis were 79 and 64,and the risk values were 74 and 57,respectively.The combined benefit and risk values found that the benefit-risk value of the study group was 16 higher than that of the traditional group.(4)In the range of 0-100%relative risk weight,the benefit-risk value of the study group was always higher than that of the traditional group,which proved that the multi-criteria decision-making model had good stability.(5)It is indicated that three-dimensional printed scoliosis orthosis can better restore the physiological curvature of scoliosis and improve the efficiency of treatment.

Objective To evaluate the effect of extracorporeal membrane oxygenation (ECMO) on early allograft dysfunction (EAD) after heart transplantation. Methods Clinical data of 614 heart transplant recipients were retrospectively analyzed. All recipients were divided into the ECMO group (n=43) and non-ECMO group (n=571) according to postoperative application of ECMO. In the ECMO group, the conditions of recipients undergoing ECMO after heart transplantation were summarized. Perioperative status and long-term prognosis of recipients were compared between two groups. Results Among 43 recipients undergoing ECMO, 17 cases underwent thoracotomy due to bleeding, 10 cases of infection, 4 cases of venous thrombosis of the lower limbs, and 1 case of stroke, respectively. Twenty-six recipients were recovered and discharged after successful weaning from ECMO, six died during ECMO support, six died after weaning from ECMO, five received retransplantation due to unsuccessful weaning from ECMO, and only one survived after retransplantation. Compared with the non-ECMO group, intraoperative cardiopulmonary bypass duration was significantly longer, the proportion of recipients requiring postoperative intra-aortic balloon pump (IABP), dialysis due to renal insufficiency, reoperation for hemostasis, infection, mechanical ventilation time≥96 h and tracheotomy was significantly higher, and the length of postoperative intensive care unit (ICU) stay was significantly longer in the ECMO group (all P < 0.05). The survival rate after discharge and 90-d survival rate in the ECMO group were 63% and 96%, significantly lower than 97% and 100% in the non-ECMO group (both P < 0.05). Survival analysis showed that the long-term survival rate in the ECMO group was significantly lower than that in the non-ECMO group (P < 0.05). After excluding the recipients who died within 90 d after heart transplantation, no significant difference was observed in the long-term survival rate (P > 0.05). Conclusions ECMO is an effective treatment of EAD after heart transplantation. The short-term survival rate of recipients using ECMO after heart transplantation is lower than that of those who do not use ECMO, and there is no significant difference in long-term survival of recipients surviving 90 d after heart transplantation.

Anti-virulence strategy has been considered as one of the most promising approaches to combat drug-resistant bacterial infections. Pore-forming toxins (PFTs) are the largest class of bacterial toxins, inflicting their virulence effect through creating pores on the cell membrane. However, current solutions for eliminating PFTs are mostly designed based on their molecular structure, requiring customized design for different interactions. In the present study, we employed erythroliposome (denoted as RM-PL), a biomimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes, to neutralize different hemolytic PFTs regardless of their molecular structure. When tested with model PFTs, including α-hemolysin, listeriolysin O, and streptolysin O, RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals' lives without causing damage to organs or tissues. In addition, we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes. In summary, the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mechanism of lysosome-mediated toxin degradation.

Objective To analyze the early outcomes of heart transplantation in critical patients and its significance in donor allocation decision. Methods Clinical data of 449 recipients undergoing heart transplantation were retrospectively analyzed. According to preoperative status, all patients were divided into the critical status group (n=64) and general status group (n=385). The incidence of critical status was summarized. Clinical data of recipients were statistically compared between two groups. Postoperative survival and causes of death in recipients between two groups were analyzed. Perioperative results of critical recipients undergoing different mechanical circulation support as a bridge to heart transplantation were compared. Results Critical patients accounted for 14.3% of the total number of transplant recipients. The proportion of critical patients gradually increased in recent 5 years. Compared with the general status group, the recipients in critical status group had a lower proportion of smoking history, a higher proportion of cardiac surgery history, a higher serum level of creatinine, and a higher proportion of primary diseases of heart failure before heart transplantation(all P≤0.01). The proportion of undergoing mechanical circulation support was higher, the incidence of complications was higher, the stay time in intensive care unit (ICU) was longer and the in-hospital fatality was higher after heart transplantation in the critical status group (all P≤0.01). The 1-year survival rate of recipients in critical status group was significantly lower than that in general status group (83% vs. 95%, P < 0.01). The fatality of recipients due to infection and multiple organ failure in critical status group was higher than that in general status group. Among 64 critical recipients, 1 recipient received ventilator alone, and 63 recipients underwent mechanical circulation support devices as a bridge to heart transplantation. Among them, intra-aortic balloon pump (IABP) alone was applied in 49 cases (77%), 8 cases (13%) of extracorporeal membrane oxygenation (ECMO) combined with IABP, 4 cases (6%) of ECMO alone, and 2 cases (3%) of left ventricular assist device (LVAD) alone. Critical patients who received preoperative ECMO and ECMO combined with IABP bridging to heart transplantation have a higher proportion of postoperative complications, a longer ICU stay time, a longer mechanical ventilation time, and a higher proportion of hospital deaths. Conclusions The overall prognosis of critical patients undergoing heart transplantation is relatively poor. Effective preoperative management may reverse the high-risk status of critical patients in a certain extent. The limited quantity of donor heart should be allocated to the most urgent patients who can obtain the greatest benefit from heart transplantation.

[Objective]To explore the effect of HSYA on pro/anti-inflammatory cytokine′s levels and mRNA expression in peripheral blood of mice.with sepsis.[Methods]Dividing NIH mice into four groups,as normal group,sham group,CLP group and HSYA group,24 mice in each group. The CLP sepsis mouse model was established. HSYA(120 mg/kg)were injected intravenously at 12 h before the operation ,and 0 h and 12 h following CLP ,and other groups were given normal saline. observed the animals behavior changes,measured the levels WBC,PLT,ALT,AST,BUN in serum,detected the levels and mRNA expression of IL-6, IL-10 ,TNF-α in peripheral blood. cultured of peripheral blood bacteria loads.[Results]24 h after surgery ,mice in CLP group appeared furring,feces residues on anus etc. compared to normal group,sham group and HSYA group,WBC,PLT,ALT,AST, BUN,levels and mRNA expression of IL-6,IL-10,TNF-αshowed significant increases,it was also found that bacterial load was significant increased in model group.[Conclusions]HSYA has a therapeutic effect in mice with sepsis ,can reduce bacteria into the blood,and inhibit inflammatory mediators which caused tissue damage.

Objective To probe into the effect of sitagliptin on blood glucose fluctuation of the patients with type 2 diabetes mellitus(T2DM) and poor control by insulin aspart 30.Methods Ninety cases of T2DM and poor control by insulin aspart 30 in affiliated Zhongshan hospital from January 1,2014 to December 31,2014 were selected and randomly divided into three groups:simply continuous subcutaneous insulin injection(CSII),acarbose combined CSII group(CSII + Aca) and sitagliptincombined CSII group (CSII + Sig),30 cases in each group.Three groups received the intensive treatment for 2 weeks,and72-h continuous glucose monitoring was performed on last 3 d.The 24 h mean blood glucose(24 hMBG),largest amplitude of glycemic fluctuation(LAGE),mean amplitude of glycemic excursion(MAGE) within 1 d,postprandial blood glucose spike(PGS),postprandial glucose peak time(△t),postprandial glucose excursion(PPGE) and total T were observed within 24 h.The difference of insulin dose(△ insulin),hypoglycemia incidence,glucose-target rate,blood glucose profiles were compared at the end of treatment.Results After two-week treatment,intraday blood glucose variation indicators(24 hMBG,LAGE and MAGE) and postprandial blood glucose variation indicators (PGS,△t,PPGE and total T) in the CSII+Sig and CSII+-Aca groups were significantly lower than those in the CSII group(P＜ 0.05),while the differences in blood glucose variation indicators between the CSII+Sig group and CSII+-Aca group were not statistical significant(P＞ 0.05).In the comparison after treatment,△ insulin,hypoglycemia incidence and glucose-target rate in the CSI + Sig group were lower(P＜0.05).Conclusion The combined application of short-term CSII and sitagliptin will achieve a better effect than the combination with acarbose,can smoothly and steadily reduces the blood glucose level,relieves the whole day glucose fluctuations,effectively reduces △ insulin,and has lower hypoglycemia occurrence rate.

Objective To investigate the clinical effectiveness of foam sclerotherapy for lower extremity varicose vein with deep venous valve incompetence.Methods A retrospective study was carried out in 124 patients (185 limbs) receiving foam sclerotherapy in our department.Sixty-one limbs diagnosed as deep venous valve incompetence were categorized as the observation group,while 124 limbs without that were the control group.The main outcome were success rate,remission rate of various symptoms and signs,the scores of CEAP and CIVIQ.Results The follow up rate was 69.3％,and the follow-up period ranged from one to nine months.There was no statistical difference in the success rate between the observation group (93.4％) and control group (94.4％)(P＞0.05).However,the symptom of heaviness and oedema and the CIVIQ scores in observation group be inferior to the control group,and the difference of them were statistically significant (P＜0.05).Conclusion Deep venous valve incompetence could not decrease the success rate of foam sclerotherapy,but may influence the remission of some symptoms.It should be supplemented with medical elastic stockings or ringing of femoral veins.