Systemic lupus erythematosus is a chronic autoimmune disease that affects multiple organs and systems, and current treatment strategies can only result in clinical remission. In recent years, cell therapies have shown promising advancements in the treatment of autoimmune diseases, particularly chimeric antigen receptor technology has demonstrated potential as a transformative therapy for these diseases. This review summarizes the application and prospects of various cell therapies in systemic lupus erythematosus, including hematopoietic stem cell transplantation, mesenchymal stem cell therapy, chimeric antigen receptor-T cell therapy, natural killer cell therapy, and regulatory T cell therapy, aiming to provide insights for optimization and clinical implementation of cell therapies.

Tissue-resident memory T (TRM) cells are a recently defined subtype of non-recirculating memory T cells with longevity and protective functions in peripheral tissues. As an essential frontline defense against infections, TRM cells have been reported to robustly patrol the tissue microenvironment in malignancies. Accumulating evidence also implicates that TRM cells in the relapse of chronic inflammatory skin diseases such as psoriasis and vitiligo. In light of these developments, this review aims to synthesize these recent findings to enhance our understanding of TRM cell characteristics and actions. Therefore, after providing a brief overview of the general features of the TRM cells, including precursors, homing, retention, and maintenance, we discuss recent insights gained into their heterogeneous functions in skin diseases. Specifically, we explore their involvement in conditions such as psoriasis, vitiligo, fixed drug eruption - dermatological manifestations of drug reactions at the same spot, cutaneous T cell lymphoma, and melanoma. By integrating these diverse perspectives, this review develops a comprehensive model of TRM cell behavior in various skin-related pathologies. In conclusion, our review emphasizes that deciphering the characteristics and mechanisms of TRM cell actions holds potential not only for discovering methods to slow cancer growth but also for reducing the frequency of recurrent chronic inflammation in skin tissue.
Humans ; Skin Diseases/immunology* ; Memory T Cells/immunology* ; Animals ; Vitiligo/immunology* ; Psoriasis/immunology* ; Immunologic Memory

Systemic lupus erythematosus is a chronic autoimmune disease that affects multiple organs and systems, and current treatment strategies can only result in clinical remission. In recent years, cell therapies have shown promising advancements in the treatment of autoimmune diseases, particularly chimeric antigen receptor technology has demonstrated potential as a transformative therapy for these diseases. This review summarizes the application and prospects of various cell therapies in systemic lupus erythematosus, including hematopoietic stem cell transplantation, mesenchymal stem cell therapy, chimeric antigen receptor-T cell therapy, natural killer cell therapy, and regulatory T cell therapy, aiming to provide insights for optimization and clinical implementation of cell therapies.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Background::Percutaneous local tumor ablation (LTA) and stereotactic body radiotherapy (SBRT) have been regarded as viable treatments for early-stage lung cancer patients. The purpose of this study was to compare the efficacy and safety of LTA with SBRT for early-stage non-small cell lung cancer (NSCLC).Methods::PubMed, Embase, Cochrane library, Ovid, Google scholar, CNKI, and CBMdisc were searched to identify potential eligible studies comparing the efficacy and safety of LTA with SBRT for early-stage NSCLC published between January 1, 1991, and May 31, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were applied to estimate the effect size for overall survival (OS), progression-free survival (PFS), locoregional progression (LP), and adverse events.Results::Five studies with 22,231 patients were enrolled, including 1443 patients in the LTA group and 20,788 patients in the SBRT group. The results showed that SBRT was not superior to LTA for OS (HR = 1.03, 95% CI: 0.87-1.22, P = 0.71). Similar results were observed for PFS (HR = 1.09, 95% CI: 0.71-1.67, P = 0.71) and LP (HR = 0.66, 95% CI: 0.25-1.77, P = 0.70). Subgroup analysis showed that the pooled HR for OS favored SBRT in patients with tumors sized >2 cm (HR= 1.32, 95% CI: 1.14-1.53, P = 0.0003), whereas there was no significant difference in patients with tumors sized ≤2 cm (HR = 0.93, 95% CI: 0.64-1.35, P = 0.70). Moreover, no significant differences were observed for the incidence of severe adverse events (≥grade 3) (OR = 1.95, 95% CI: 0.63-6.07, P = 0.25) between the LTA group and SBRT group. Conclusions::Compared with SBRT, LTA appears to have similar OS, PFS, and LP. However, for tumors >2 cm, SBRT is superior to LTA in OS. Prospective randomized controlled trials are required to determine such findings.INPLASY Registration Number::INPLASY202160099

BACKGROUND:Previous studies on immunosuppression and anti-rejection after organ transplantation mainly focused on effects of T lymphocytes-mediated immune response and immunosuppressive agents on T lymphocytes. Effects of dendritic cel s were unclear. The manifestation and mechanism of immunosuppressive agent effects on dendritic cel s are not identical. OBJECTIVE:To compare the effects of different immunosuppressive agents on expression and function of costimulatory molecules of dendritic cel s, and to explore the mechanism of action of immunosuppressive agents. METHODS:20μg/L rapamycin, 0.04 mg/L mycophenolate, 10μg/L tacrolimus and 1 mg/L cyclosporine A were separately added during bone marrow cel s of C57BL/6 mice were differentiated into dendritic cel s. RESULTS AND CONCLUSION:Flow cytometry results revealed that CD40 expression in each group:rapamycin0.05). One-way mixed lymphocyte reaction results displayed dendritic cel costimulatory T cel proliferation in each group:rapamycin

OBJECTIVETo investigate the cause and related risk factors of an outbreak caused by Brucellosis.

METHODSEpidemiological investigation and laboratory test were carried out among occupationally invloved population including sheep slaughters and sellers in the village.

RESULTS18 people were serology positive among the 129 occupationally involved persons under survey. Seven of them were confirmed cases, 11 were latent infection, to make the overall attack rate as 14%. 90% of the sheep were from high-risk areas of Brucella. Among the occupationally involved persons, 89% of them never wore face masks, 84% never wear overalls and 70% never wear gloves. Factors as:work but wearing no gloves (RR = 7.4, 95%CI:1.1-53.0), with hand wound (RR = 3.4, 95%CI:1.1-11.0) could increase the risk of Brucella infection.

CONCLUSIONThe cause of this outbreak was due to the plentiful influx of unchecked sheep from the northern part of China and the employees in the process of sheep slaughtering or trading were lack of effective prevention programs.

Abattoirs ; Animals ; Brucella ; isolation & purification ; Brucellosis ; epidemiology ; China ; epidemiology ; Commerce ; Disease Outbreaks ; Humans ; Incidence ; Occupational Diseases ; epidemiology ; Risk Factors ; Sheep ; microbiology

Objective To investigate the cause and related risk factors of an outbreak caused by Brucellosis. Methods Epidemiological investigation and laboratory test were carried out among occupationally invloved population including sheep slaughters and sellers in the village. Results 18 people were serology positive among the 129 occupationally involved persons under survey. Seven of them were confirmed cases,11 were latent infection,to make the overall attack rate as 14%. 90%of the sheep were from high-risk areas of Brucella. Among the occupationally involved persons,89%of them never wore face masks,84%never wear overalls and 70%never wear gloves. Factors as:work but wearing no gloves(RR=7.4,95%CI:1.1-53.0),with hand wound(RR=3.4,95%CI:1.1-11.0) could increase the risk of Brucella infection. Conclusion The cause of this outbreak was due to the plentiful influx of unchecked sheep from the northern part of China and the employees in the process of sheep slaughtering or trading were lack of effective prevention programs.

Objective To investigate the expression and significance of keratin 17 (K17) in proliferative skin diseases,including psoriasis,basal cell carcinoma (BCC),squamous cell carcinoma (SCC) and malignant melanoma.Methods Tissue specimens were collected from the lesions of 14 patients with severe plaque-type psoriasis,16 patients with BCC,16 patients with SCC,8 patients with malignant melanoma,as well as from the normal skin of 17 patients with trauma.Immunohistochemistry was conducted to detect the expression of K17 in these tissue samples.Results K17 was absent in the cytoplasm of keratinocytes in the basal layer,prickle cell layer or granular layer of the normal skin.There was a strong expression of K17 in the prickle cell layer,but a weak or negative expression of K17 in the basal layer of psoriatic skin,and parakeratotic cells did not express K17.In BCC tissues,K17 was absent in carcinoma cells,but visible in peritumoral cells in the prickle cell layer and granular layer.In SCC tissues,K17 was localized in highly differentiated carcinoma cells,but not in lowly differentiated carcinoma cells.There was a strong expression of K17 throughout the epidermis above the melanoma,but a negative expression in the melanoma cells or melanocytes.Conclusion K17 may serve as a molecular marker for the differential diagnosis of some proliferative skin diseases.

Objective To measure the expression of activin receptor-like kinases 1(ALK1)in dermal fibroblasts from patients with systemic scleroderma(SSc)and to estimate its role in the production of fibronectin and plasminogen activator inhibitor-1(PAI-1).Methods Dermal fibroblasts were isolated from the lesions of 12 patients with SSc as well as the normal skin of 14 healthy controls,and subjected to a primary culture.The third-passage fibroblasts were used in the next experiment.Western blot and indirect immunofluorescence technique were utilized to quantify the expression of ALK1.A specific siRNA targeting ALK1 was designed,constructed,and transiently transfected into the control dermal fibroblasts,which were then classified into 2 groups to be cultured with or without the presence of transforming growth factor(TGF)-β1 for 72 hours followed by the detection of fibronectin and PAI-1 expression with Western blot.Results As Western blot and direct immunofluorescence technique showed,both control and SSc fibroblasts showed an expression of ALK1 in the cytoplasm and membrane,and the expression intensity of ALK1 in SSc fibroblasts was significantly higher than that in the control fibroblasts(1.97 ± 0.05 vs.1.12 ± 0.03,t =50.96,P ＜ 0.05).The expression of ALK1,fibronectin and PAI-1 was decreased by 90％,58％ and 31％ respectively in specific siRNA-transfected SSc fibroblasts compared with the control siRNA-transfected fibroblasts.TGFβ1 significantly increased the expression of ALK1,fibronectin and PAI-1 in the control siRNA-transfected fibroblasts,but the increase was markedly inhibited by the siRNA-targeting ALK1.Conlusion TGFβ1 can promote the production of fibronectin and PAI-1 via ALK1 in fibroblasts,and ALK1 may be involved in the development of sclerosis in SSc.