简介：AbstractObjective:To analyze the proportion of peripheral regulatory T cells (Tregs) and the expression of the immune checkpoint molecules T-cell immunoglobulin and ITIM domain (TIGIT) and CD226 on Tregs in patients with recurrent spontaneous abortion (RSA).Methods:The proportion of CD3+CD4+CD25+Foxp3+ Tregs and the expression levels of CD226 and TIGIT on Tregs in 30 normal pregnant women and 28 patients with RSA were determined via flow cytometry.Results:The proportion of Tregs in the RSA group (4.41 % ± 1.54%) was significantly lower than that in the control group (5.27% ± 1.52%, P = 0.0374). Compared with the normal pregnant women, patients with RSA showed decreased TIGIT expression (54.75 ± 9.70% vs. 63.07 ± 12.48%, P = 0.0066) and increased CD226 expression on Tregs (25.59% ± 8.22% vs. 20.46% ± 6.97%, P = 0.0168). The ratio of CD226 to TIGIT in the RSA group (0.48 ± 0.19) was higher than that in the control group (0.34 ± 0.15, P = 0.0027). The proportion of TIGIT+CD226+ Tregs was significantly lower in patients with RSA (9.30% ± 4.95% vs. 13.43% ± 4.72%, P = 0.0020) than in the controls.Conclusions:Patients with RSA show a reduced proportion of Tregs and an imbalance in the expression of TIGIT and CD226 on Tregs.

简介：AbstractAdult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1. The skin is affected in approximately half of ATLL patients, and skin lesions may be the first manifestation of the disease. The skin lesions of ATLL are polymorphous, and depend on the type of skin eruption, which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions. In this review article, we describe the clinical manifestations and histopathological patterns of skin lesions in ATLL, focus on its diagnostic and prognostic significance, and also summarize the advances in the treatment of ATLL.

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简介：AbstractBackground:The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT.Methods:A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort (n = 16), HR chemotherapy cohort (n = 31), and HR transplant cohort (n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed.Results:Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5-year overall survival [OS]: 58.5% vs. 100%, P = 0.003; 5-year event-free survival [EFS]: 54.1% vs. 83.4%, P = 0.010; 5-year cumulative incidence of relapse [CIR]: 45.2% vs. 6.3%, P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1% vs. 54.1%, P = 0.041; 5-year CIR: 11.6% vs. 45.2%, P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0% vs. 58.5%, P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR; age ≥10 years was an independent risk factor for OS and EFS; and high white blood cell count was an independent risk factor for EFS and CIR.Conclusion:Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.

简介：AbstractLike antibody evaluation, using an effective antigen-specific T-cell immunity assessment method in coronavirus disease 2019 (COVID-19) patients, survivors and vaccinees is crucial for understanding the immune persistence, prognosis assessment, and vaccine development for COVID-19. This study evaluated an empirically adjusted enzyme-linked immunospot assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell immunity in 175 peripheral blood samples from COVID-19 convalescents and healthy individuals. Results of viral nucleic acid were used as the gold standard of infection confirmation. The SARS-CoV-2M peptide pool had higher sensitivity of 85% and specificity of 71% for the single peptide pool. For combined peptide pools, the parallel evaluation (at least one of the peptide pools is positive) of total peptide pools (S1&S2&M&N) had higher sensitivity (up to 93%), and the serial evaluation (all peptide pools are positive) of total peptide pools had higher specificity (up to 100%). The result of the serial evaluation was better than that of the parallel evaluation as a whole. The detection efficiency of M and N peptide pool serial evaluation appeared the highest, with a sensitivity of 80% and specificity of 93%. This T-cell immunity detection assay introduced in this report can achieve high operability and applicability. Therefore, it can be an effective SARS-CoV-2-specific cellular immune function evaluation method.

简介：AbstractCell-cell communication is the basis of physiological processes and cell signals. The disease occurs when the cells do not adequately communicate and the messages are blocked. With ligand-receptor interaction databases and single-cell RNA sequencing (scRNA-seq) databases, we can detect intercellular signaling and reconstruct the cell-cell communications among different cell types. This review summarized the computational approaches for analyzing the cell-cell communication based on scRNA-seq data and discussed its applications in carcinogenesis and COVID-19. We believe that this review will accelerate the scRNA-seq data deciphering and facilitate the cell-cell communication studies for complex physiological processes, such as carcinogenesis and SARS-CoV-2 infection.

简介：AbstractIntroduction:Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy, and its pathogenesis might relate to ultraviolet light and Merkel cell polyomavirus infection. MCC in the Chinese population is uncommon.Here, we present a case of MCC that occurred based on widespread actinic keratosis (AK) in a Chinese female.Case report:An 82-year-old woman presented with two rapidly enlarging and rupture lesions on the face for 1 year. Biopsy was suggestive of squamous cell carcinoma (SCC) on the forehead and MCC on the left cheek. The patient had a history of generalized AK for 3 years. The lesion on the left cheek was also revealed as an AK by histopathological examination 1 year ago. Complete surgical resection was performed to remove the two malignancies.Discussion:The co-occurrence of AK, SCC, and MCC in a Chinese woman is unusual. Immunohistopathological examination is vital for correct diagnosis. The three tumors, in this case, may originate from two different precursor cells and are affected by the same carcinogen. Alternatively, they may come from the same pluripotent epidermal stem cells, and chronic exposure to ultraviolet light and Merkel cell polyomavirus lead to the formation of different types of tumors. The coexist of MCC with other cutaneous tumors provided a train of thought for exploring the origin of MCC.Conclusion:We reported a rare co-existence phenomenon of MCC associated with AK and SCC. Hence, long-term follow-up and early treatment are imperative for patients with premalignant lesions, such as widespread AK.

简介：AbstractGlucagon is a potent glucose-elevating hormone that is secreted by pancreatic α- cells. While well-controlled glucagon secretion plays an important role in maintaining systemic glucose homeostasis and preventing hypoglycaemia, it is increasingly apparent that defects in the regulation of glucagon secretion contribute to impaired counter-regulation and hyperglycaemia in diabetes. It has therefore been proposed that pharmacological interventions targeting glucagon secretion/signalling can have great potential in improving glycaemic control of patients with diabetes. However, despite decades of research, a consensus on the precise mechanisms of glucose regulation of glucagon secretion is yet to be reached. Second messengers are a group of small intracellular molecules that relay extracellular signals to the intracellular signalling cascade, modulating cellular functions. There is a growing body of evidence that second messengers, such as cAMP and Ca2+, play critical roles in α-cell glucose-sensing and glucagon secretion. In this review, we discuss the impact of second messengers on α-cell electrical activity, intracellular Ca2+ dynamics and cell exocytosis. We highlight the possibility that the interaction between different second messengers may play a key role in the glucose-regulation of glucagon secretion.

简介：AbstractIntroduction:Basal cell carcinoma (BCC) is the most common human malignancy commonly in white people, but in less than 1% of cases it may appear on unexposed areas, like the perineal and anal regions. Vulvar BCC is often diagnosed late because it grows slowly and tends to be asymptomatic, with no specific physical findings. Here, we present a rare Latin patient with a 10-year history of vulvar BCC with dermatoscopic and histopathologic findings.Case report:A 65-year-old Latin woman presented with a nodule on her left labium majus, which she first noted 10 years ago, and that had grown slowly but constantly. She also reported a 20-year history of pruritus and occasional pain. Physical examination showed a 3.5 cm × 3.0 cm erythematous lesion with a central rough without inguinal lymphadenopathy. Contact dermatoscopy (Dermalite DL3 Gen.) showed one blurred cluster of arborising vessels in a pinkish background with white homogeneous areas and lines radial converging. An incisional biopsy was realized, and histopathology diagnosed BCC.Discussion:Vulvar BCC is a rare malignancy that affects mainly Caucasian women over 70 years of age. The most common etiology for BCC is ultraviolet radiation, but as the vulva is unexposed its cause is unclear. Mutations in tumor suppressor and regulatory genes such as p53 are present in 50% of cases. Gorlin syndrome, chronic radiation, chronic arsenic exposure, xeroderma pigmentosum, and immunosuppression have been considered as risk factors.Conclusion:Vulvar BCC characteristics are the same as other cutaneous forms, featuring blue ovoid nests and arborizing telangiectasia, confused with inflammatory diseases, such as eczema, psoriasis, and chronic infection (especially if it is accompanied by pruritus), this makes diagnosis complex, with a delay of 5 to 6 years on average, with an average size of 2.1 cm. Diagnosis is enhanced with dermatoscopy, as the preferred treatment for most BCC cases is wide surgical excision.

简介：AbstractIntroduction:Basal cell carcinoma (BCC) is the most common skin cancer which mainly affects the population over 50 years of age. In addition to surgical treatment, nonsurgical treatment is also an attractive option for some patients.We herein report a case of an 82-year-old man with BCC successfully treated with acitretin.Case presentation:An 82-year-old man presented with BCC on his left nose wing more than 2 years ago. Due to his unwillingness to accept treatment that may lead to pain, discomfort, or trauma, the patient was prescribed oral acitretin 25 mg twice daily [0.8 mg/(kg·d)] and was instructed to apply 2% fusidic acid cream topically once daily for trauma protection. The lesion progressively shrank in size after 4 weeks of treatment, and was almost completely resolved after 28 weeks of follow-up. The patient reported mild adverse effects, such as mild skin fragility and cheilitis, and apparent scaling skin, which caused minor discomfort but did not affect the continuation of treatment.Discussion:The pathogenesis of BCC is still unclear, but it has been demonstrated to be linked to overactive hedgehog signaling and its crosstalk with other pathways such as phosphoinositide 3-kinase and mammalian target of rapamycin. Acitretin could obviously inhibit cell growth and proliferation and down-regulate AMP-dependent protein kinases that plays critical role in the blocking of malignant progression of several tumors including BCC.Conclusion:We provide an effective alternative for the patients with BCC who are unwilling to receive surgical therapy.

简介：AbstractHematopoietic stem cell transplantation (HSCT) is a highly effective and unique medical procedure for the treatment of most hematological malignancies. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then, the field has evolved and expanded worldwide. The first successful allogenic HSCT (allo-HSCT) in China was conducted in 1981. Although the development of allo-HSCT in China lagged, China has since made considerable contributions to the process of HSCT worldwide, with more than 10,000 HSCTs performed annually. In particular, haploid HSCT (haplo-HSCT) technology represented in the Beijing Protocol has demonstrated similar efficacy to human leukocyte antigen-matched HSCT and has gradually become the pre-dominant choice for allo-HSCT in China. Currently, the number of haplo-HSCT procedures exceeds 5000 per year, and the Beijing Protocol has been greatly improved by implementing updated individualized strategies for controlling complications, relapse, and infection management. In addition, innovative haplo-HSCT technologies developed by different medical transplantation centers, such as Soochow, Zhejiang, Fujian, Chongqing, and Anhui, have emerged, providing inspiration for the refinement of global practice. This review will focus on the current activity in this field and highlight important trends that are vital in China’s allo-HSCT process, examining the current viewpoint and future directions.

简介：AbstractBackground:Previous studies have shown that bufalin exerts antitumor effects through various mechanisms. This study aimed to determine the antineoplastic mechanism of bufalin, an extract of traditional Chinese medicine toad venom, in ovarian cancer.Methods:The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2′-deoxyuridine (EdU), and colony formation assays were used to investigate the antiproliferative effect of bufalin on the ovarian cancer cell line SK-OV-3. Molecular docking was used to investigate the combination of bufalin and epidermal growth factor receptor (EGFR) protein. Western blotting was performed to detect the expression of EGFR protein and its downstream targets.Results:Bufalin inhibited the proliferation of SK-OV-3 cells in a dose- and time-dependent manner. Bufalin was confirmed to combine with EGFR protein using molecular docking and downregulate expression of EGFR. Bufalin inhibited phosphorylation of EGFR, protein kinase B (AKT), and extracellular signal-regulated kinase (ERK).Conclusion:Bufalin suppresses the proliferation of ovarian cancer cells through the EGFR/AKT/ERK signaling pathway.

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简介：AbstractThe coronavirus disease 2019 (COVID-19) pandemic has been an unmitigated disaster for society and the economy worldwide. However, much remains unknown about the pathogenesis of, treatment methods for, and preventive measures against COVID-19. Single-cell sequencing is a novel sequencing technology whose use has recently become prevalent in various life-science fields. This high-resolution technology is being used to analyze the COVID-19 pandemic at a single-cell level. In this review, we summarize the application of single-cell sequencing technology to the field of COVID-19-related research, including the biology of severe acute respiratory syndrome coronavirus 2, clinical concerns associated with COVID-19, neutralizing antibody screening, and vaccine development. We also address challenges to, and improvements in, existing single-cell research related to COVID-19.

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简介：AbstractObjective:The treatments and prognoses of high-risk and low-risk basal cell carcinomas are quite different. This study aimed to examine the dermoscopic features of basal cell carcinomas and assess the association between the features and basal cell carcinomas recurrence risks in a Chinese population.Methods:Patients with histopathologically confirmed basal cell carcinomas examined from March 2016 to April 2020 were enrolled. The dermoscopic features were evaluated, and the correlations between these features and the histological types and recurrence risks were assessed.Results:The study cohort comprised 119 Chinese patients with a total of 119 skin lesions. The most common dermoscopic feature of basal cell carcinomas was the absence of a pigment network (119/119, 100%), followed by shiny white streaks (105/119, 88.24%), blue-gray ovoid nests (99/119, 83.19%), multiple blue globules (78/119, 65.55%), and arborizing vessels (78/119, 65.55%); yellow-white structures were present in 29/119 lesions (24.37%). Leaf-like and spoke-wheel areas were significantly associated with superficial basal cell carcinomas (P < 0.001), while arborizing vessels (P < 0.001), blue-gray ovoid nests (P < 0.001), and ulceration (P < 0.05) were significantly associated with nonsuperficial basal cell carcinomas subtypes. The dermoscopic features of the high-risk and low-risk groups exhibited considerable overlap; however, the respective independent predictive factors for a high and low risk of basal cell carcinomas recurrence were short fine telangiectases (P < 0.05) and blue-gray ovoid nests (P < 0.05).Conclusion:Dermoscopy provides important information about basal cell carcinomas and is helpful in differentiating superficial basal cell carcinomas from other subtypes. The dermoscopic vascular structures and blue-gray ovoid nests play a crucial role in evaluating the basal cell carcinomas risks preoperatively.

简介：AbstractObjective:The majority of non-small cell lung cancer (NSCLC) cases remain undiagnosed until advanced stages of the disease. Accumulating studies have highlighted the utility of palliative care as an effective treatment option, which relieves patients’ suffering by activating placebo effect in the body. To evaluate the clinical significance of palliative care, data from NSCLC drug-randomized controlled trials (RCTs) were collected and the effects of placebo treatment examined.Methods:PubMed (MEDLINE), Scopus, Web of Science, and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020. Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included. The quality of included studies was assessed using the Jadad method. Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo, that is, the primary and secondary outcome measures, were subsequently performed using either Bayesian or conventional models.Results:Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study. Low risk of bias was observed for all five included studies using the Cochrane method. Following placebo treatment, controlled disease rate of 24.1% (95% credible interval [CrI], -0.126-0.609) and dropout rate of 2.1% (95% CrI, 0.007-0.039) were calculated, with a dose reduction rate of 3.0% (95% CrI, 0.017-0.045). Compared with active drug treatment, the placebo treatment group had a risk ratio of 0.81 (95% confidence interval, 0.68-0.97) and 0.85 (95% confidence interval, 0.76-0.96) for the achievement of progression-free survival and overall survival, respectively.Conclusion:In NSCLC drug RCTs, placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events, although the therapeutic responses could not be precisely determined. The results suggest that under specific circumstances, palliative care which can activate placebo effect may have similar effects as active drugs (such as erlotinib, vandetanib, or pemetrexed) in terms of prolonging survival time.

简介：AbstractPreimplantation genetic testing (PGT) is a widely adopted screening method that can be performed to identify and select embryos with normal ploidy; however, PGT relies on embryo biopsy, that is, polar body, embryo cells, or trophectoderm biopsy, to obtain embryonic DNA, increase its technical limitations. Studies have indicated that biopsy may have an influence on the quality and development of embryos, and increase the chance of abnormal epigenetic modifications. Therefore, non-invasive PGT (niPGT) detection of cell-free DNA (cfDNA) has gradually become a hot research topic in the field of assisted reproduction. Studies showed cfDNA could be detected in blastocyst fluid and spent culture medium (SCM) in vitro cultured embryos. The cfDNA collection requires less skill and makes lower risk to embryos. Some studies have been conducted to evaluate the feasibility of SCM-based niPGT approaches. When comparing the ploidy consistency of cfDNA in SCM, its consistency to the conventional PGT for aneuploidies results fluctuated widely, it is critical to recognize the factors influencing accuracy. These contradictory results may be related to factors such as the difference in SCM sampling methods and sampling time, and the definition of consistency. In this review, we aimed to comprehensively summarize how researchers use embryonic cfDNA to conduct niPGT detection. It also systematically reviews the factors affecting the accuracy of the test and its underlying issues, as well as prospective applications. We hope to provide a basis for future niPGT research and a useful reference for the standardized operation of niPGT that can be widely applied in clinical practice.

简介：AbstractImmune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.