Search

Vaccination is the most cost-effective means of preventing and even eliminating infectious diseases. However, adverse reactions after vaccination are inevitable. In addition to common vaccine-related adverse reactions, some rare but serious adverse reactions have been reported, including secondary immune thrombocytopenia (ITP). The measles-mumps-rubella (MMR) vaccine is currently the only vaccine for which a cause-effect relationship with immune thrombocytopenia has been demonstrated with an incidence of approximately 0.087-4 per 100,000 doses, and the complication is mostly observed in children. In addition, thrombocytopenia can be induced by coronavirus disease 2019 (COVID-19) vaccines following COVID-19 vaccination primarily occurs within a few weeks post-vaccination. The condition mostly occurs in elderly individuals with no sex differences. Its incidence is approximately 0.80 to 11.3 per million doses. Some patients have previously suffered from chronic ITP likely to develop exacerbation of ITP after COVID-19 vaccines, especially those who have undergone splenectomy or are being treated with5 medications. Based on clinical practice, first-line treatments for vaccine-associated thrombocytopenia are essentially limited to those used for primary ITP, including glucocorticoids and intravenous immunoglobulin (IVIg).

Objective. To use the logistic regression model to evaluate the value of ultrasound characteristics in the Ovarian-Adnexal Reporting and Data System ultrasound lexicon in determining ovarian solid component-containing mass benignancy/malignancy. Methods. We retrospectively analyzed the data of 172 patients with adnexal masses discovered by ultrasound, and diagnosis was confirmed by postoperative pathological tests from January 2019 to December 2021. Thirteen ovarian tumor-related parameters in the benign and malignant ovarian tumor groups were selected for univariate analyses. Statistically significant parameters were included in multivariate logistic regression analyses to construct a logistic regression diagnosis model, and the diagnostic performance of the model in predicting ovarian malignancies was calculated. Results. Of the 172 adnexal tumors, 104 were benign, and 68 were malignant. There were differences in cancer antigen 125, maximum mass diameter, maximum solid component diameter, multilocular cyst with solid component, external contour, whether acoustic shadows were present in the solid component, number of papillae, vascularity, presence/absence of ascites, and presence/absence of peritoneal thickening or nodules between the benign ovarian tumor and malignancy groups ( p < 0.05 ). Logistic regression analyses showed that maximum solid component diameter, whether acoustic shadows were present in the solid component, number of papillae, and presence/absence of ascites were included in the logistic regression model, and the area under the receiver operating characteristic curve for this regression model in predicting ovarian malignancy was 0.962 (95% confidence interval: 0.933~0.990; p < 0.001 ). Logit p ≥ − 0.02 was used as the cutoff value, and the prediction accuracy, sensitivity, specificity, positive predictive value, and negative predictive values were 93.6%, 86.8%, 98.1%, 96.7%, and 91.9%, respectively. Conclusion. The logistic regression model containing the maximum solid component diameter, whether acoustic shadows were present in the solid component, number of papillae, and presence/absence of ascites can help in determining the benignancy/malignancy of solid component-containing masses.

Besides the traditional roles of HBA1 and HBB, recent findings suggest that hemoglobin genes may have roles in other contexts.In the present study, we aim to investigate a possible tumor-suppressor role of HBA1 and HBB in acute myeloid leukemia.Quantitative real-time PCR (RT-qPCR) was performed to detect the expression levels of HBA1 and HBB in acute myeloid leukemia patients and AML cell lines. The transfected cells were analyzed for Cell Counting Kit-8 (CCK-8), apoptosis, and cell cycle assay.HBA1 and HBB genes were significantly decreased in acute myeloid leukemia patients and AML cell lines. Furthermore,Our data indicated that HBA1 and HBB genes may be potential tumor-suppressor genes in acute myeloid leukemia.

Biosimilars provide the possibility to reduce the high expenditure on biologic drugs and expand access to effective but less expensive treatments. Biosimilars of trastuzumab showed significant cost savings from the payer's perspective in the USA and Europe. After 2020, with the first approval of a trastuzumab biosimilar in China, it became feasible for biosimilar switching for trastuzumab. However, the economic impact of switching to a trastuzumab biosimilar was not evaluated. A budget impact model was constructed from a payer's perspective of China to demonstrate the economic impact of the introduction of a biosimilar trastuzumab in the treatment of human epidermal growth factor receptor 2-positive breast cancer.This budget impact model was based on disease incidence to estimate the net budget impact using epidemiological data from the literature, financial reports from manufacturers on the market shares of originator trastuzumab (HerceptinAnalyses of the base-case and scenario results implied that adoption of a trastuzumab biosimilar would lead to an expenditure decrease. The average total cost savings over 5 years was estimated to be US$46,651,348, with a range from $10,306,611 in year 1 to $60,821,822 in year 5. The cost savings could benefit an additional 654-3858 patients with breast cancer. If utilizing costs from real-world practice, the introduction of a trastuzumab biosimilar could help an additional 2237-13,203 patients get access to human epidermal growth factor receptor 2-positive targeted therapy. When volume-based procurement was carried out after year 4, $672,366,180 could be saved annually.This budget impact analysis emphasized the positive effects of adopting a trastuzumab biosimilar in the healthcare system of China. However, cost savings still have a large potential to decrease by regulating pricing and by the procurement policy of biosimilars.

Refractory or recurrent immune thrombocytopenia (ITP) patients suffer from the dual threat of high mortality and drug toxicity in addition to a very poor quality of life. Previous studies have shown that high mobility group box 1 (HMGB1) can promote the development of rheumatoid arthritis, systemic lupus erythematosus, and other autoimmune diseases. However, there is still a lack of research on the role of HMGB1 in the pathogenesis of ITP and whether it can be used as a predictor of efficacy and prognosis.20 patients of adult ITP with splenectomy were chosen as the experimental group, while 19 adults underwent splenectomy for traumatic splenic rupture without other diseases as the control group. We measured the expression of HMGB1, RORγt and Foxp3 in spleen tissues by immunohistochemistry. Another 50 patients, of which 20 were newly diagnosed without treatment and 30 were refractory ITP, and 25 healthy controls were enrolled to analyse the expression levels and mRNA levels of HMGB1, RORγt and Foxp3 in peripheral blood by Western blot and RT-qPCR. The expression of HMGB1, IL-17 and IL-10 in serum was assayed by ELISA. PBMCs from newly diagnosed ITP patients were cultured in vitro which stimulated with recombinant humanHMGB1 (rHMGB1) and its inhibitors, in which the expressions of RORγt and Foxp3 were measured.The expression of HMGB1 in the spleen with refractory ITP was significantly higher, while Foxp3 was decreased. A significant negative correlation was found between HMGB1 and Foxp3, and the overexpression of HMGB1 was significantly correlated with poor efficacy after splenectomy. The expression of HMGB1 and IL-17 increased and showed a positive correlation in serum, while IL-10 decreased and was negatively correlated with HMGB1. In PBMCs, the expression of HMGB1 and RORγt increased, while Foxp3 decreased, and the differences were more obvious in the refractory chronic ITP group. In a coculture system with PBMCs of untreated ITP patients, rHMGB1 increased RORγt expression and decreased Foxp3 expression, while an antiHMGB1 antibody partially corrected the above changes.Our results suggest that HMGB1 is associated with the imbalance of Treg/Th17 cells and is involved in the pathogenesis of ITP.

Hepatocellular carcinoma (HCC) is a common malignancy in the world, with high mortality and poor prognosis. Hepatitis B virus (HBV) is one of the key factors implicated in the occurrence of HCC. Increasing evidence suggests that miRNAs play important roles in the development and metastasis of HBV-associated HCC (HBV-HCC). Here, we performed CCK8 (Cell count kit-8), EdU (5-ethynyl-2'-deoxyuridine) incorporation assay, wound-healing assay, transwell assay to study the changes in the cellular phenotype. Luciferase reporter assay, RNA pull-down experiment, RT-qPCR and western blotting were employed to study molecular mechanism. In addition, we also constructed a mouse HCC xenograft model to verify the functional role of HMMR-AS1/miR-627-3p/HMGA2 signal axis

The pro-inflammatory cytokine interleukin-17A (IL-17A) is a key driver of multiple inflammatory and immune disorders. Therapeutic antibodies targeting IL-17A have been proven effective in treating patients with these diseases; however, large variations in clinical outcomes have been observed with different antibodies. In this study, we developed HB0017, a novel monoclonal antibody that targets human IL-17A. HB0017 specifically and strongly bound to human, cynomolgus monkey, and mouse IL-17A at the physiological interface with the IL-17A receptor. In human and monkey cells, HB0017 potently antagonized the functions of IL-17A through competitive binding. HB0017 functioned equivalently to that of clinically approved antibodies in terms of therapeutic efficacy for inflammatory disorders and psoriasis in a mouse model. The results indicate that HB0017 may be an alternative biological therapy for treating patients with inflammation and autoimmune diseases.

To investigate the risk factors of perioperative in-hospital death in elderly patients with hip fracture and the applicability of risk assessment tools.Thirteen in-hospital death cases from 1878 geriatric hip fracture treated in Jishuitan Hospital, China from May 2015 to December 2017 were collected, each dead patient was compared with 4 normal discharged patients with a postoperative survival of more than 90 days at the same admission time (within 2 weeks), gender, age (±5 years), and fracture type. Binary logistic regression was used to analyze the risk factors of in-hospital death; Hosmer-lemeshow goodness of fit test was used to evaluate the goodness of fit of E-PASS (estimation of physical ability and surgical stress) and NHFS (Nottingham hip fracture score).Mortality in hospital was 0.7%; the number of comorbidities and the time from fracture to operation were the risk factors of in-hospital death. Nottingham hip fracture score system is more accurate to elderly hip fractures in China.Early operation is the key factor to reduce mortality in elderly patients with hip fracture, and the comorbidities in the basic state of the elderly are the independent risk factors of death; NHFS is recommended to estimate death risk in geriatric hip fractures.

Background Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune‐related adverse events (irAEs) remain poorly understood, especially in a real‐world setting. Methods A multicenter observational study was conducted. Medical records of lung cancer patients treated with ICIs at 26 hospitals from January 1, 2015, to February 28, 2021, were retrieved. Types of ICIs included antiprogrammed cell death 1 or antiprogrammed cell death ligand 1 (PD‐L1) monotherapy, anticytotoxic T‐lymphocyte antigen‐4 monotherapy, or combination therapy. Results In total, 1905 patients with advanced lung cancer were evaluated. The median age was 63 (range 28–87) years, and the male/female ratio was 3.1:1 (1442/463). The primary histological subtype was adenocarcinoma (915). A total of 26.9% (512/1905) of the patients developed 671 irAEs, and 5.8% (110/1905) developed 120 grade 3–5 irAEs. Median duration from ICI initiation to irAEs onset was 56 (range 0–1160) days. The most common irAEs were thyroid dysfunction (7.2%, 138/1905), pneumonitis (6.5%, 124/1905), and dermatological toxicities (6.0%, 115/1905). A total of 162 irAEs were treated with steroids and 11 irAEs led to death. Patients with positive PD‐L1 expression (≥1%) and who received first‐line ICI treatment developed more irAEs. Patients who developed irAEs had a better disease control rate (DCR, 71.3% [365/512] vs. 56.0% [780/1145]; p, This was a multicenter observational study of real‐world treatment status immune checkpoint inhibitors (ICIs) and incidence of immune‐related adverse events (irAEs). A total of 512 (26.9%) of 1905 patients developed 671 any grade irAEs and 110 (5.8%) patients developed 120 grades 3–5 irAEs. Positive programmed cell death‐ligand 1 expression, first‐line ICI treatment and sustained disease control were observed more in patients with irAEs.

Background Pretreatment and on‐treatment plasma cytokine levels in predicting clinical benefit in patients with advanced non‐small cell lung cancer (NSCLC) treated with anti‐programmed death‐1 (PD‐1)‐based chemotherapy is still a matter of debate. Methods We measured 12 kind of plasma cytokines in patients with stage III/IV NSCLC before and during treatment with anti‐PD‐1 based chemotherapy. Associations with best overall response, and survival including progression‐free survival (PFS) and overall survival (OS) were assessed using Chi‐square test and Kaplan–Meier plots with log‐rank test, respectively. Logistic regression and Cox regression were used to determine independent risk factors. Results Of a total of 60 patients, high‐level of pretreatment interleukin‐2 was associated with longer PFS (log rank p = 0.049), while high‐level of pretreatment interleukin‐8 was associated with shorter OS (log rank p = 0.006). Increased on‐treatment interleukin‐1β (IL‐1β) was associated with both better response (odds ratio [OR] 6.233, 95% confidential interval [CI]: 1.451–26.344, p = 0.013) and longer PFS (hazard ratio [HR] 0.305, 95% CI: 0.127–0.730, p = 0.008). On the contrary, increased on‐treatment interleukin‐6 (IL‐6) was associated with a worse response (OR 0.015, 95% CI: 0.001–0.400, p = 0.012), worse PFS (HR 2.639, 95% CI: 1.163–5.991, p = 0.020) and worse OS (HR 2.742, 95% CI: 1.063–7.074, p = 0.037). Increased interferon‐γ (IFN‐γ) was found to be associated with better PFS (HR 0.336, 95% CI: 0.153–0.745, p = 0.007). Conclusions In patients with advanced NSCLC who received chemoimmunotherapy, on‐treatment increased IL‐1β and IFN‐γ may serve as positive indicator of efficacy, while on‐treatment increased IL‐6 might play a predictive role of worse clinical outcome., We retrospectively measured 12 kind of plasma cytokines in patients with stage III/IV non‐small cell lung cancer before and during immune checkpoint inhibitor (ICI)‐based chemoimmunotherapy. Results showed that increased on‐treatment interleukin‐1β, interferon‐γ were related to longer progression‐free survival (PFS). Increased on‐treatment IL‐6 was related to shorter PFS. We suggest the indicative role played by circulating cytokines and efficacy of ICI‐based chemotherapy.

Background and Aims: HEV infection is the most common cause of liver inflammation, but the pathogenic mechanisms remain largely unclear. We aim to explore whether HEV infection activates inflammasomes, crosstalk with antiviral interferon response, and the potential of therapeutic targeting. Approach and Results: We measured IL-1β secretion, the hallmark of inflammasome activation, in serum of HEV-infected patients and rabbits, and in cultured macrophage cell lines and primary monocyte-derived macrophages. We found that genotypes 3 and 4 HEV infection in rabbits elevated IL-1β production. A profound increase of IL-1β secretion was further observed in HEV-infected patients (1,733 ± 1,234 pg/mL; n = 70) compared to healthy persons (731 ± 701 pg/mL; n = 70). Given that macrophages are the drivers of inflammatory response, we found that inoculation with infectious HEV particles robustly triggered NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in primary macrophages and macrophage cell lines. We further revealed that the ORF2 capsid protein and the formed integral viral particles are responsible for activating inflammasome response. We also identified NF-κB signaling activation as a key upstream event of HEV-induced NLRP3 inflammasome response. Interestingly, inflammasome activation antagonizes interferon response to facilitate viral replication in macrophages. Pharmacological inhibitors and clinically used steroids can effectively target inflammasome activation. Combining steroids with ribavirin simultaneously inhibits HEV and inflammasome response without cross-interference. Conclusions: HEV infection strongly activates NLRP3 inflammasome activation in macrophages, which regulates host innate defense and pathogenesis. Therapeutic targeting of NLRP3, in particular when combined with antiviral agents, represents a viable option for treating severe HEV infection.

The diagnosis of functional dyspepsia (FD) presently relies on the self-reported symptoms. This study aimed to determine the potential of functional brain network features as biomarkers for the identification of FD patients. Firstly, the functional brain Magnetic Resonance Imaging data were collected from 100 FD patients and 100 healthy subjects, and the functional brain network features were extracted by the independent component analysis. Then, a support vector machine classifier was established based on these functional brain network features to discriminate FD patients from healthy subjects. Features that contributed substantially to the classification were finally identified as the classifying features. The results demonstrated that the classifier performed pretty well in discriminating FD patients. Namely, the accuracy of classification was 0.84 ± 0.03 in cross-validation set and 0.80 ± 0.07 in independent test set, respectively. A total of 15 connections between the subcortical nucleus (the thalamus and caudate) and sensorimotor cortex, parahippocampus, orbitofrontal cortex were finally determined as the classifying features. Furthermore, the results of cross-brain atlas validation showed that these classifying features were quite robust in the identification of FD patients. In summary, the current findings suggested the potential of using machine learning method and functional brain network biomarkers to identify FD patients.

Background Breast cancer is the most common malignant tumor diagnosed in women. It is the second leading cause of cancer‐related death among women in the world. Aberrant expression of microRNAs (miRNAs) have been identified to be involved in the development and progression of breast cancer. The aim of this study was to investigate the function of miR‐223‐3p in breast cancer progression and metastasis. Methods qRT‐PCR was used to analyze the expression levels of miR‐223‐3p in breast cancer tissues and cell lines. Wound healing and Matrigel assays were used to examine cell motility and invasiveness. FBXW7 3′‐UTR construct and luciferase reporter assays were performed for the target gene. Results miR‐223‐3p was overexpressed in breast cancer tissue and cell lines. A high level of miR‐223‐3p was associated with poor prognosis in breast cancer patients. In addition, overexpressed miR‐223‐3p promoted the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, we found that tumor suppressor gene FBXW7 is a target of miR‐223‐3p. Luciferase activity reporter assay indicated miR‐223‐3p could directly bind with the 3′‐UTR of FBXW7. miR‐223‐3p exhibited its oncogenic role partly by decreasing FBXW7 expression, and consequently promoted the invasion and metastasis of breast cancer cells. Conclusions Our study revealed a physical and functional relationship among miR‐223‐3p and FBXW7. By negatively regulating FBXW7 expression, miR‐223‐3p exerts a tumor promotion role promoting cell invasion and metastasis in breast cancer., miR‐223‐3p is overexpressed in breast cancer. miR‐223‐3p promotes the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, we found that FBXW7 is a target of miR‐223‐3p. Our study uncovered a physical and functional relationship among miR‐223‐3p and FBXW7, which plays an important role in breast cancer progression and metastasis.

Thymoquinone (TQ) has been reported as an anti‐tumour drug widely studied in various tumours, and its mechanism and effect of which has become a focus of current research. However, previous studies from our laboratory and other groups found that TQ showed weak anti‐tumour effects in many cancer cell lines and animal models. Therefore, it is necessary to modify and optimize the structure of TQ to obtain new chemical entities with high efficiency and low toxicity as candidates for development of new drugs in treating cancer. Therefore, we designed and synthesized several TQ derivatives. Systematic analysis, including in vitro and in vivo, was conducted on a panel of triple‐negative breast cancer (TNBC) cells and mouse model to demonstrate whether TQFL12, a new TQ derivative, is more efficient than TQ. We found that the anti‐proliferative effect of TQFL12 against TNBC cells is significantly stronger than TQ. We also demonstrated TQFL12 affects different aspects in breast cancer development including cell proliferation, migration, invasion and apoptosis. Moreover, TQFL12 inhibited tumour growth and metastasis in cancer cell–derived xenograft mouse model, with less toxicity compared with TQ. Finally, mechanism research indicated that TQFL12 increased AMPK/ACC activity by stabilizing AMPKα, while molecular docking supported the direct interaction between TQFL12 and AMPKα. Taken together, our findings suggest that TQFL12, as a novel chemical entity, possesses a better inhibitory effect on TNBC cells and less toxicity in both in vitro and in vivo studies. As such, TQFL12 could serve as a potential therapeutic agent for breast cancer.

Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore the relationship between the active status and receptor assembly. Different activity dependency on the linker length for these bitopic ligands corroborates the various occurrences of SMO assembly. These results reveal a rigid "near" assembly for active SMO, which is in contrast to previous results. Conversely, inactive SMO adopts a free ECD, which would be remotely captured at "far" assembly by cholesterol. Altogether, we propose a mechanism of cholesterol flow-caused SMO activation involving an erection of ECD from far to near assembly.

ADAM17 is a member of the a disintegrin and metalloproteinase (ADAM) family of transmembrane proteases involved in the shedding of some cell membrane proteins and regulating various signaling pathways. More than 90 substrates are regulated by ADAM17, some of which are closely relevant to tumor formation and development. Besides, ADAM17 is also responsible for immune regulation and its substrate-mediated signal transduction. Recently, ADAM17 has been considered as a major target for the treatment of tumors and yet its immunomodulatory roles and mechanisms remain unclear. In this paper, we summarized the recent understanding of structure and several regulatory roles of ADAM17. Importantly, we highlighted the immunomodulatory roles of ADAM17 in tumor development, as well as small molecule inhibitors and monoclonal antibodies targeting ADAM17.

Objective: We sought to understand the status of promotion pressure among university teachers in China. This study explored the promotion duration and influencing factors among teachers in different disciplines of the social sciences. Methods: Using event history analysis, this study collected data regarding university teachers of China. The sample included 536 teachers who had been promoted from assistant to associate professor and 243 teachers promoted from associate to full professor. Our results revealed that the overall time required for promotion in the social sciences is relatively long. For those promoted from assistant to associate professor, the mean time for promotion was 14.155 years, with a median of 11 years, while for the transition from associate to full professor, the mean was 13.904 years with a median of nine years. Furthermore, in the survival function of the promotion duration, there is a stage pattern for both assistant to associate professor and associate to full professor. In addition, the Kaplan–Meier results showed that the mean promotion time in economics was the shortest. The Cox regression results indicated that males had a higher chance of promotion than females, and faculty members with doctoral degrees had a higher likelihood of promotion than those without. For those advancing from assistant to associate professor, the university of employment had significant positive effects on promotion. This paper provides empirical support for the current societal concerns regarding promotion pressure among university teachers.

Anti-angiogenesis drugs are applicable in treating advanced non-small cell lung cancer (NSCLC); however, the related data regarding apatinib, a Chinese domestic anti-vascular endothelial growth factor receptor-2 (VEGFR-2) production, are limited. Therefore, this study explored the efficacy and safety of apatinib plus platinum doublet chemotherapy in treating patients with advanced NSCLC.Twenty-four patients with advanced NSCLC were retrospectively enrolled. All patients received platinum doublet chemotherapy combined with apatinib 250 mg daily. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed.Zero (0.0%), seven (29.2%), 11 (45.8%), and six (25.0%) patients had partial response (PR), stable disease (SD), and progressed disease (PD), respectively, resulting in an ORR of 29.2% and a DCR of 75.0%. The median PFS was 12.6 months (95% CI: 3.9-21.3 months) with a 1-year PFS of 56.1%, and the median OS was 18.3 months (95% CI: 13.0-23.5 months) with a 1-year OS of 73.9%. Age ≤60 years (P = 0.034), ECOG performance score 1 (vs. 2; P = 0.005), and first-line treatment (vs. second or higher line treatment; P = 0.043) correlated with longer PFS. The most common treatment-related adverse events included fatigue (83.3%), nausea (79.2%), myelosuppression (70.8), and vomiting (66.7%), while most of them were mild and manageable. Only four (16.6%) patients witnessed grade 3-4 myelosuppression.Apatinib plus platinum doublet chemotherapy is effective and well-tolerated in treating patients with advanced NSCLC; moreover, reduced ECOG PS and lower lines of treatment relate to its better efficacy.

Tuberous sclerosis complex (TSC) is a rare disease that threatens multiple organs in the human body. TSC‑associated renal angiomyolipoma (TSC‑RAML) has potentially life‑threatening complications and a generally poor prognosis. The present study aimed to find plasma proteomic diagnostics and disease‑associated markers, and explore the tumor microenvironment using multi‑omics. To achieve this goal, the plasma proteomics as well as tissue proteomics, bulk and single‑cell RNA transcriptome from patients with TSC‑RAML were examined and analyzed. The results suggested that plasma proteins such as MMP9 and C‑C motif chemokine ligand 5 were able to differentiate TSC‑RAML from sporadic angiomyolipoma and renal cyst. A correlation analysis revealed that plasma proteomics were associated with lymphangioleiomyomatosis, TSC‑RAML grading and whole‑body disease burden. Tissue proteomics of participants with TSC‑RAML revealed disturbed small molecule catabolic process, mitochondrial matrix component and actin binding function. Bulk and single‑cell RNA sequencing suggested a greater number of tumor‑like cells, fibroblasts and mononuclear macrophages within the tumor microenvironment. The above results indicated that TSC‑RAML exhibited a characteristic and disease‑associated plasma proteomic profile. The unique microenvironment, made up of fibroblasts and mono‑macrophages, may promote tumorigenesis and TSC‑RAML progression.

As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the

ISG20 inhibits viruses such as SARS-CoV-2 invasion; however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m62A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations; the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20−009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m62A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression.

Building a friendship with peers is an important developmental task. However, peer victimization and social anxiety are among the most disturbing problems and have impaired adolescents' adaptive development. A total of 942 adolescents completed the survey. The results showed that peer victimization was related to social anxiety and that this effect was mediated by cognitive flexibility and moderated by affect intensity. Specifically, the damage of peer victimization and social anxiety was aggrevated for those with high levels of affect intensity. The current study provides evidence for the association between peer victimization and social anxiety. It contributes to the literature by clarifying the equivocal findings and uncovering the underlying mechanisms of the relationship between peer victimization and social anxiety. In the future, researchers and teachers should pay attention to adolescents' peer social status as early as possible, especially for adolescents with higher levels of affect intensity.

In recent years, there is a growing incidence of granulomatous lobular mastitis (GLM), but studies about the coexistence of erythema nodosum (EN) and GLM are rare. In this study, we assess the clinical characteristics and predictive factors of EN in GLM.A total of 303 patients diagnosed with GLM were enrolled from January 2012 to October 2018 at the second affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, including 78 patients with EN. Follow-up data included: lesion site, lesion size, therapy approaches, course of GLM, course of EN, the recurrence of disease, possible causes. All patients had pathologic confirmation of GLM based on core needle biopsy (CNB) or surgical excision.Fever in the EN group was significantly more common compared to the non-EN group (44.87% vs 12.89%, P 0.001). The proportion of lesion range2 quadrants in the EN group was significantly higher than that in the non-EN group (42.31% vs 16.00%, P 0.001). The course of the disease was longer in the EN group compared to the non-EN group (10.32 moths vs 8.74 moths, P 0.001). Patients with EN had a trend towards a higher risk of recurrence (5.13% vs 1.33%, P = 0.055).EN is more likely to be found in GLM patients with breast lesion range2 quadrants. The presence of EN in GLM indicates that the condition becomes more severe and the course of GLM also becomes longer.

Many individuals may face traumatic events throughout their lives. For intimate relationship partners, early traumatic experiences can have a specific effect on their interpersonal communication. This study examined the moderating effect of traumatic experiences at early ages between perceived conflict and communication behavior among individuals in an intimate relationship. A total of 186 college students in intimate relationships reported their perceived conflict and communication behaviors with their partners three times a day for 14 days using ambulatory assessment. Findings from the multilevel model showed that a higher level of perceived conflict significantly positively associated with negative communication and negatively correlated with positive communication at the within-person level. Traumatic experiences at the between-person level moderated the within-person level associations between the dynamic perceived conflict and negative and positive communication behavior. However, the moderating effect of traumatic experiences on the association between perceived conflict and positive communication was contrary to the hypothesis. Daily perceived conflict was associated with daily communication behavior. For those with early traumatic experiences, the relationship between negative communication and conflict was stronger than for those who had not experienced such trauma.

Proteomics analysis of O-GalNAc glycosylation is important for the screening of biomarkers and the assessment of therapeutic responses. However, its analysis still faces challenges due to the poor performance of currently available enrichment methods. In this study, an enrichment method was established on the basis of Ti-IMAC(IV) materials, which could enrich the intact O-GalNAc glycopeptides via both the hydrophilic interaction and affinity interaction. This method enabled nearly 200 intact O-GalNAc glycopeptides identified from only 0.1 μL of human serum. This was nearly 2-fold different from that of the HILIC method. An in-depth analysis of the O-GalNAc glycosylation was performed, and 2093 intact glycopeptides were identified from 7.2 μL of human serum samples. This is the largest O-GalNAc glycosylation database of human serum from a trace amount of sample. Furthermore, 52 significantly changed intact O-GalNAc glycopeptides were determined by the quantitative analysis of hepatocellular carcinoma (HCC) and control serum samples, indicating the potential applications of this enrichment method in biomarker discovery.

Objective The aim of this study was to establish a preoperative prediction method for sparsely granulated (SG) growth hormone (GH) secreting pituitary adenoma, an aggressive tumor subtype with high recurrence risk, in acromegaly patients. Methods Eighty-three patients with GH-secreting pituitary adenomas were included in this study. GH measurements, cytokeratin immunostaining and electron microscopy were performed to detect granulation patterns. Preoperative factors, including general, radiological and endocrinological features and acute octreotide suppression test outcomes, were compared between SG and densely granulated (DG) groups. The predictive capabilities of these features were analyzed using a receiver operating characteristic (ROC) curve, and the most predictive features were combined to establish a grading scale. Results Thirty-nine of the 83 patients had SG GH-secreting pituitary adenomas; 44 had DG tumors. SG tumors tended to occur in younger patients and have larger diameters and volumes, higher Knosp grades, lower GH indexes and normalized insulin-like growth factor-1 (IGF-1) levels, and a lower ∆GH% after octreotide treatment. The tumor size, Knosp grade, GH index and ∆GH% after octreotide treatment had good predictive performance, with area under the curve (AUC) values ranging from 0.70 to 0.80. Combining four parameters, including diameter, Knosp grade, GH index and ∆GH% after octreotide treatment, we established a grading scale for predicting SG GH-secreting pituitary adenomas with an AUC of 0.84 and relatively high sensitivity and specificity. Conclusions We propose a predictive method for distinguishing SG and DG GH-secreting pituitary adenomas preoperatively. This method will help physicians identify candidates for presurgical medical treatment and neurosurgeons determine radical surgical strategies for high-risk tumors.

We herein develop a concentration gradient generator (CGG) on a microfluidic chip for diluting different nanoparticles. Specifically designed compact disk (CD)-shaped microchannels in the CGG module could thoroughly mix the flowing solutions and generate a linear concentration gradient of nanoparticles without aggregation. We combine the CGG with a single-cell trapper array (SCA) on microfluidics to evaluate the concentration-dependent bioeffects of the nanoparticles. The precise control of the spatiotemporal generation of nanoparticle concentration on the CGG module and the single-cell-level monitoring of the cell behaviors on the SCA module by a high-content system in real time, render the CGG-SCA system a highly precise platform, which can exclude the average effect of cell population and reflect the response of individual cells to the gradient concentrations accurately. In addition, the CGG-SCA system provides an automated platform for high-throughput screening of nanomedicines with high precision and low sample consumption.

Y-chromosome short tandem repeat (Y-STR) markers have been widely used in forensic applications and usually show monoallelic or diallelic genotypic patterns at certain double-copied loci. In this study, we have found 13 samples among 703 males with multi-alleles at the DYS385ab locus, including one with five mutant alleles, nine with four, and three with three. The frequency of abnormal DYS385ab genotypes was 1.85% (13/703), which is very high in the Han Chinese population. The percentage of samples with diallelic patterns at DYS385ab was higher than that of monoallelic patterns (80.23% vs. 17.92%). Additionally, the percentage of samples with tetra-allelic patterns at DYS385ab was higher than that of tri-allelic patterns (1.28% vs. 0.43%), suggesting that there are possibly two copies with duplicated events happening frequently on the Y chromosome. Interestingly, the peak height of allele 13 was two to three-folds higher than that of other alleles. The allele 18 peak height was also two-fold higher than others, which could potentially be explained by a duplication event mechanism. We also found that tri-allelic genotypes for alleles 13, 17, and 20, tetra-allelic genotypes for alleles 13, 14, 19, and 20, and tetra-allelic genotypes for alleles 12, 13, 19 and 21 were more common than others. Furthermore, all 13 samples had multi-alleles containing allele 13, implying a founder effect in this particular Chinese-specific ethnic group. Taken together, this study provides new information for this population and will be useful for paternal lineage identification, kinship analysis, and family relationship reconstruction using Y-STR forensic DNA analysis methods.

We retrospectively analysed the clinical features and prognostic factors of surgery in children with drug-resistant epilepsy involving the Rolandic area, and the relationship between the stable compound muscle action potentials (CMAPs) of intraoperative neurophysiological monitoring (IONM) and good motor function outcomes postoperatively. A study was conducted on the clinical data of 91 patients with epilepsy who underwent epilepsy surgery involving the Rolandic area and IONM from November 2015 to February 2019. In total, 91 patients were included in this study. The median age at seizure onset was 1.3 years old. The median age at surgery was 4.4 years old. Twenty-seven patients (29.7%), with age at onset below three years old, had epileptic spasms. The central operculum was the most common surgical region in 52 patients (57.1%). The most common pathology was focal cortical dysplasia (FCD) in 67 patients. At the last follow-up visit, 69 patients (75.8%) were seizure-free. Interictal epileptiform discharges in the Rolandic area were associated with good seizure outcome (p=0.016). Out of 91 patients, successful IONM was performed in 88 patients (96.7%). Stable CMAP was seen in 79 of 88 patients (89.8%), and irreversible disappearance of CMAP was seen in nine patients (10.2%). New permanent motor deficit was observed in 13 of 88 patients (14.8%). There was a significant correlation between stable CMAP and good motor function outcome (p

Medical institutions face a variety of challenges as they seek to enhance their reputation and increase the influence of their social media accounts. Becoming a social media influencer in the health field in today’s complex online environment requires integrated social and technical systems. However, rather than holistically investigating the mechanism of account influence, studies have focused on a narrow subset of social and technical conditions that drive online influence. We attribute this to the mismatch between complex causality problems and traditional symmetric regression methods. In this study, we adopted an asymmetric configurational perspective that allowed us to test a causally complex model of the conditions that create strong and not-strong account influence. We used fuzzy-set qualitative comparative analysis (fsQCA) to detect the effects of varying configurations of three social system characteristics (i.e., an oncology-related attribute, a public attribute, and comment interaction) and two technical system characteristics (i.e., telepresence and video collection) on the TikTok accounts of 63 elderly Chinese doctors (60 to 92 years old). Our results revealed two pathways associated with distinct sociotechnical configurations to strong account influence and three pathways associated with distinct sociotechnical configurations to not-strong account influence. Furthermore, the results confirmed that a single antecedent condition cannot, on its own, produce an outcome, i.e., account influence. Multiple inter-related conditions are required to produce an influential account. These results offer a more holistic picture of how health science communication accounts operate and reconcile the scattered results in the literature. We also demonstrate how configurational theory and methods can be used to analyze the complexities of social media platforms.

Background Melanoma is the most malignant skin tumor and is difficult to cure with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. Our previous study showed that triptolide (TP) exhibited powerful tumoricidal activity against melanoma. However, the clinical potential of TP is plagued by its poor aqueous solubility, short half-life, and biotoxicity. Therefore, developing an ideal vehicle to efficiently load TP and achieving targeted delivery to melanoma is a prospective approach for making full use of its antitumor efficacy. Results We applied exosome (Exo) derived from human umbilical cord mesenchymal stromal cells (hUCMSCs) and engineered them exogenously with a cyclic peptide, arginine-glycine-aspartate (cRGD), to encapsulate TP to establish a bionic-targeted drug delivery system (cRGD-Exo/TP), achieving synergism and toxicity reduction. The average size of cRGD-Exo/TP was 157.34 ± 6.21 nm, with a high drug loading of 10.76 ± 1.21%. The in vitro antitumor results showed that the designed Exo delivery platform could be effectively taken up by targeted cells and performed significantly in antiproliferation, anti-invasion, and proapoptotic activities in A375 cells via the caspase cascade and mitochondrial pathways and cell cycle alteration. Furthermore, the biodistribution and pharmacokinetics results demonstrated that cRGD-Exo/TP possessed superior tumor targetability and prolonged the half-life of TP. Notably, cRGD-Exo/TP significantly inhibited tumor growth and extended survival time with negligible systemic toxicity in tumor-bearing mice. Conclusion The results indicated that the functionalized Exo platform provides a promising strategy for targeted therapy of malignant melanoma. Graphical Abstract

Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies. .【中文题目：腺苷/A2AR信号通路阻断在肿瘤治疗中的应用】 【中文摘要：腺苷是一种在肿瘤微环境中高水平产生的代谢产物，主要通过在免疫细胞上表达的腺苷A2A受体（adenosine A2A receptor, A2AR）有效地抑制炎症组织中的免疫反应，抑制抗肿瘤免疫应答。因此阻断腺苷信号通路是促进抗肿瘤免疫的重要方向。在这篇文章中，我们将简介腺苷信号通路，总结腺苷/A2AR在抑制肿瘤免疫中的作用，并介绍腺苷/A2AR通路阻断在抗肿瘤治疗中的研究现状。临床前研究数据已揭示了抑制A2AR治疗肿瘤的潜在效力，A2AR拮抗剂从基础研究向临床应用的转化也正在进行当中。临床试验的初步结果显示，A2AR拮抗剂在肿瘤患者中安全性良好，无论单药还是联合其他疗法使用均有一定的疗效。未来仍需进一步探索如何选取生物标志物对潜在获益人群进行筛选，以及如何联用A2AR拮抗剂和其他治疗方案以实现最优的抗肿瘤策略。 】 【中文关键词：肿瘤微环境；腺苷；腺苷受体；A2A受体拮抗剂】.

Vagus nerve stimulation (VNS) is a neuromodulation therapy for children with drug-resistant epilepsy (DRE). The efficacy of VNS is heterogeneous. A prediction model is needed to predict the efficacy before implantation.We collected data from children with DRE who underwent VNS implantation and received regular programming for at least 1 year. Preoperative clinical information and scalp video electroencephalography (EEG) were available in 88 children. Synchronization features, including phase lag index (PLI), weighted phase lag index (wPLI), and phase-locking value (PLV), were compared between responders and non-responders. We further adapted a support vector machine (SVM) classifier selected from 25 clinical and 18 synchronization features to build a prediction model for efficacy in a discovery cohort (n = 70) and was tested in an independent validation cohort (n = 18).In the discovery cohort, the average interictal awake PLI in the high beta band was significantly higher in responders than non-responders (p 0.05). The SVM classifier generated from integrating both clinical and synchronization features had the best prediction efficacy, demonstrating an accuracy of 75.7%, precision of 80.8% and area under the receiver operating characteristic (AUC) of 0.766 on 10-fold cross-validation. In the validation cohort, the prediction model demonstrated an accuracy of 61.1%.This study established the first prediction model integrating clinical and baseline synchronization features for preoperative VNS responder screening among children with DRE. With further optimization of the model, we hope to provide an effective and convenient method for identifying responders before VNS implantation.

G protein-coupled receptors (GPCRs) are involved in a variety of human physiological processes and are attractive targets for treating various diseases. Yet, despite the importance as therapeutic targets, only 97 unique GPCR structures have been determined to date. A key challenge in their structural biology study is to obtain adequate protein samples because GPCRs usually have the low expression in native tissues. The in vitro recombinant expression provides the possibility to obtain large quantities of high-quality proteins suitable for three-dimensional structure determination by crystallography or single particle cryo-EM methods. For GPCR protein production, eukaryotic expression systems, such as baculovirus system and mammalian system, are the most widely used. In this chapter, we provide an overview of the methodological approaches on GPCRs expression and purification optimization using insect cells and mammalian cells, which is the prerequisite conditions for structural biology studies.

Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome associated with high short-term mortality and reversibility. This study aimed to compare the characteristics of survival and reversibility in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) patients with and without previous decompensation. Overall, 1044 patients who fulfilled the acute hepatic insult criteria of the APASL-ACLF Research Consortium (AARC) definition were enrolled from a prospectively established cohort of HBV-related liver failure patients. These patients were divided into the AARC ACLF group and the non-AARC ACLF group according to prior decompensation. Mortality, reversibility of ACLF syndrome, and predicted factors associated with reversibility were evaluated. Liver transplantation-free mortality of the AARC ACLF group was significantly lower than that of the non-AARC ACLF group (28 days: 28.2% vs. 40.3%, p = .012; 90 days: 41.7% vs. 65.4%, p lt; .001). The 5-year cumulative reversal rates of ACLF syndrome were 88.0% (374/425) and 66.0% (31/47) in the AARC and non-AARC ACLF groups, respectively, (p = .039). Following reversibility of ACLF syndrome, 340/374 (90.9%) and 21/31 (67.7%) patients in the AARC and non-AARC ACLF groups, respectively, maintained a stable status within 5 years. Although prior decompensation indicated poor reversibility of ACLF syndrome, HBV-infected patients with prior decompensation who fulfilled the acute hepatic insult criteria of the AARC definition showed favourable reversibility and maintained a stable status after receiving nucleoside analogues. The AARC ACLF definition identified HBV-ACLF as a distinct syndrome with good reversibility. HBV-infected patients with prior decompensation could be included in the AARC ACLF management.

The clinical anti-vascular endothelial growth factor (anti-VEGF) drugs and metronomic chemotherapy (MET) induced tumor vascular normalization treatment (TVNT) are easily antagonized by tumor microenvironment metabolic cross-talk between tumor cells and endothelial cells (ECs). To overcome this dilemma, nanodrug with the ability of ECs targeted glycolysis inhibition and nanodrug with the ability of tumor cell glycolysis inhibition, anti-VEGF, and MET are combined to prepare Nano-combination the pathways related to angiogenesis, tumor cell proliferation, and immunosuppression and breaking the negative sugar-lipid-protein metabolism balance in tumor microenvironment. Thus, stronger and more lasting normalized tumor vascular network and remarkable antitumor efficacy are obtained after treatment, constructing a positive feedback loop between TVNT and anti-tumor therapy. Above all, this study provides a new insight for solving the bottleneck of clinical TVNT.

Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease that threatens global health. During the pandemic period of COVID-19, the task for prevention in the general ward of cardiovascular surgery is fairly arduous. The present study intends to summarize our experience with infection control, including ward setting, admission procedures, personnel management, health education, and so on, to provide references for clinical management.

Reversible phosphorylation has emerged as an important mechanism for regulating 26S proteasome function in health and disease. Over 100 phospho-tyrosine (pTyr) sites of the human proteasome have been detected, and yet their function and regulation remain poorly understood. Here we show that the 19S subunit Rpt2 is phosphorylated at Tyr439, a strictly conserved residue within the C-terminal HbYX motif of Rpt2 that is essential for 26S proteasome assembly. Unexpectedly, we found that Y439 phosphorylation depends on Rpt2 membrane localization mediated by its N-myristoylation. Multiple receptor tyrosine kinases (RTKs) can trigger Rpt2-Y439 phosphorylation by activating Src, a N-myristoylated tyrosine kinase. Src directly phosphorylates Rpt2-Y439 in vitro and negatively regulates 26S proteasome integrity and activity at cellular membranes, which can be reversed by the membrane-associated isoform of protein tyrosine phosphatase non-receptor type 2 (PTPN2). In H1975 lung cancer cells with activated Src, blocking Rpt2-Y439 phosphorylation by the Y439F mutation conferred partial resistance to the Src inhibitor saracatinib both in vitro and in a mouse xenograft tumor model, and caused significant changes of cellular responses to saracatinib at the proteome level. Our study has defined a novel mechanism involved in the spatial regulation of proteasome function and provided new insights into tyrosine kinase inhibitor-based anti-cancer therapies.

Esophageal cancer (ESCA), as a common cancer worldwide, is a main cause of cancer-related mortality. Comprehensive studies on molecular mechanism of ESCA have been carried out. Though numerous long noncoding RNAs (lncRNAs) was reported to participate in the occurrence and development of ESCA, the potential role of lncRNA potassium calcium-activated channel subfamily M regulatory beta subunit 2 (KCNMB2) antisense RNA 1 (KCNMB2-AS1) in ESCA remains to be discovered. This study intends to investigate the detailed function and molecular mechanism of KCNMB2-AS1 in ESCA. Gene expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was examined by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell invasion and migration were measured by wound healing assay and Transwell assay. Luciferase reporter assay was adopted to validate the interaction between KCNMB2-AS1 and miR-3194-3p. Western blotting was performed to assess protein levels. We discovered that KCNMB2-AS1 was significantly upregulated in ESCA. KCNMB2-AS1 downregulation suppressed the growth, invasion, migration and stemness of ESCA cells. KCNMB2-AS1 bound with miR-3194-3p, and glycogen phosphorylase L (PYGL) was a direct target of miR-3194-3p. KCNMB2-AS1 upregulated PYGL expression by directly binding with miR-3194-3p. Additionally, PYGL overexpression abolished the inhibitory influence of KCNMB2-AS1 depletion on ESCA cell behaviors. Collectively, lncRNA KCNMB2-AS1 promotes ESCA development through targeting the miR-3194-3p/ PYGL axis, which might provide theoretical basis to explore novel biomarkers for ESCA treatment.

In recent years, the number of women who are pregnant again with the history of cesarean section, has increased year by year in China. Scarred uterine attracts much attention due to its particularity. This study aimed to understand the knowledge domain and development trends of scarred uterus after cesarean section.Data were obtained from the Web of Science Core Collection databases (WoSCCd) including SSCI and SCI-Expanded. We carried out a comprehensive literature retrieval using index words as follows: "TI=((((prior) OR (previous) OR (after) OR (post)) AND ((cesarean) OR (caesarean))) OR (scarred uterus) OR ((uterine) AND ((scar) OR (scarring) OR (wound))))". The time interval for the search was from 1999 to 2018, totally 20 years. A document type was only article and the language of article was English. All electronic searches were performed on 15 May 2019. CiteSpace, HistCite, and VOSviewer software were used to facilitate the analysis.The analysis included 1938 bibliographic records. The annual number of publications exhibited the solid increase. A total of 84 countries contributed to the overall published output during the study period. USA published the highest number of publications (This bibliometrics provides a comprehensive analysis that delineates the scientific productivity, collaboration, and research hotspots about scarred uterus after cesarean section, which is very helpful to focus on the future research direction.

Background: Early-Onset Familial Alzheimer’s Disease (EOFAD) has been reported to be associated with Presenilin 1 (PSEN1), Presenilin 2 (PSEN2), and Amyloid Precursor Protein (APP) genes. The spectrum of mutations in Chinese patients with EOFAD was rarely investigated. Objective: To investigate the spectrum of mutations in patients with EOFAD in Chinese population. Methods: We performed whole-exome sequencing and described relevant clinical features in a total of 67 subjects from 3 families with EOFAD. Results: A splice mutation (p.S290C) in PSEN1 and a missense mutation (p.V717I) in APP were identified. Conclusion: The variant p. S290C (c.869-2>G) in PSEN1 in Chinese EOAD family revealed different clinical phenotypes when compared with that of Europeans.

Urinary metabolomics is a useful non-invasive tool for large-scale screening of disease-related metabolites. However, no comprehensive urinary metabolomic analysis of vitiligo is presently available. To investigate the urine metabolic pattern of vitiligo patients, we conducted a combined cross-sectional and prospective self-control cohort study and an untargeted urinary metabolomic analysis. In the cross-sectional study, 295 vitiligo patients and 192 age‐ and sex‐matched controls were enrolled, and 71 differential metabolites between two groups were identified. Pathway enrichment analysis revealed that drug metabolism-cytochrome P450, biopterin metabolism, vitamin B9 (folate) metabolism, selenoamino acid metabolism, and methionine and cysteine metabolism showed significant enrichment in vitiligo patients compared with the status in healthy controls. In the self-control cohort, 46 active vitiligo patients were recruited to analyse the urinary metabolic signatures after treatment. All of these patients were asked to undertake follow-up visits every 2 months three times after first consulting and the disease stage was evaluated compared with that at the last visit. Folate metabolism, linoleate metabolism, leukotriene metabolism, alkaloid biosynthesis, and tyrosine metabolism were predicted to be involved in vitiligo activity. Our study is the first attempt to reveal urinary metabolic signatures of vitiligo patients and provides new insights into the metabolic mechanisms of vitiligo.

Background and objectives Systemic sclerosis (SSc) is a connective tissue disorder (CTD) associated with an increased risk of malignancy including lung cancer (LC). Our objective was to provide a description of demographics and clinicopathological characteristics of LC patients with SSc. Methods Lung cancer patients with SSc admitted to Peking Union Medical College Hospital from January 2000 to August 2017 were reviewed. Demographic and clinicopathologic data were collected. Results Of the 12 cases included in our study, all were female. No patients had a history of smoking. The most common histological type was adenocarcinoma, followed by squamous cell carcinoma and small‐cell carcinoma. No driver mutation was identified in the five patients undergoing genetic testing. Eight patients had interstitial lung disease (ILD). Six were manifested as nonspecific interstitial pneumonia (NSIP) and two as usual interstitial pneumonia (UIP). Four (33.3%) patients underwent surgical resection. Among them, two had ILD with a normal preoperative pulmonary function tests (PFT). Eight (66.7%) patients received chemotherapy. Radiotherapy was administered in only one (8.3%) patient. No grade 3/4 adverse events were documented. Conclusion The predominance of female patients in our study is different from that reported in general lung cancer patients. A high proportion of patients has SSc‐ILD, including NSIP and UIP. Surgery or radiotherapy could still be considered in carefully selected patients with ILD.

Necroptosis is mediated by signaling complexes called necrosomes, which contain receptor-interacting protein 3 (RIP3) and upstream effectors, such as RIP1. In necrosomes, the RIP homotypic interaction motif (RHIM) of RIP3 and RIP1 forms amyloidal complex. But how the amyloidal necrosomes control RIP3 activation and cell necroptosis has not been determined. Here, we showed that RIP3 amyloid fibrils could further assemble into large fibrillar networks which presents as cellular puncta during necroptosis. A viral RHIM-containing necroptosis inhibitor M45 could form heteroamyloid with RIP3 in cells and prevent RIP3 puncta formation and cell necroptosis. We characterized mutual antagonism between RIP3–RHIM and M45–RHIM in necroptosis regulation, which was caused by distinct inter-filament interactions in RIP3, M45 amyloids revealed with atomic force microscopy. Moreover, double mutations Asn464 and Met468 in RIP3–RHIM to Asp disrupted RIP3 kinase-dependent necroptosis. While the mutant RIP3(N464D/M468D) could form amyloid as wild type upon necroptosis induction. Based on these results, we propose that RIP3 amyloid formation is required but not sufficient in necroptosis signaling, the ordered inter-filament assembly of RIP3 is critical in RIP3 amyloid mediated kinase activation and cell necroptosis.

Our study aimed to investigate the epidemiological and molecular characteristics of isolates collected from Group A Streptococcus (GAS) infections in children in Beijing China during the year 2019. Emm typing, superantigens, and erythromycin resistance genotypes were determined by PCR. Antimicrobial susceptibility testing was performed as recommended by Clinical Laboratory Standards Institute (CLSI). A total of 271 GAS isolates were collected. Thirteen different emm types, including 31 subtypes, were identified. The most prevalent emm types were emm12 (52.77%), emm1 (36.9%), emm3.1 (2.95%), and emm75.0 (2.95%). Two variant subtypes, STC36.0 and STG840.2, were identified. There was no difference in the portion of emm12 and emm1 isolates in scarlet fever, impetigo, and psoriasis. The majority of superantigens detected were smeZ (94.46%), speC (91.14%), and ssa (74.91%), followed by speH (56.46%), speI (45.76%), speJ (36.9%), and speA (34.32%). More scarlet fever isolates harbored speA (35.6%) and speJ (38.4%), more psoriasis isolates harbored speI (57.9%), and more impetigo isolates harbored ssa (89.7%). Isolates were universally susceptible to penicillin and resistant to erythromycin (94.83%). Moreover, 89.67% erythromycin resistance isolates harbored the ermB gene. The erythromycin resistance rate of the isolates from the three diseases was different. Scarlet fever is the common streptococcal infectious disease in dermatology. Emm12 and emm1 were the most prevalent emm types. The most prevalent superantigens detected were smeZ, spec, and ssa. There is association between diversity of superantigens and disease manifestation. Hence, continuous surveillance of GAS molecular epidemiological characterizations in different diseases is needed.

Membrane trafficking process is significant for the complex and precise regulatory of the nervous system. Rab11, as a small GTPase of the Rab superfamily, controls endocytic vesicular trafficking to the cell surface after sorting in recycling endosome (RE), coordinating with its receptors to maintain neurological function.This article reviewed the literature of Rab11 in nervous system.Rab11-positive vesicles targeted transport growth-related molecules, such as integrins, protrudin, tropomyosin receptor kinase (Trk) A/B receptor and AMPA receptor (AMPAR) to membrane surface to promote the regeneration capacity of axon and dendrites and maintain synaptic plasticity. In addition, many studies have shown that the expression of Rab11 is decreased in multiple neurodegenerative diseases, which is highly correlated with the process of production, transport and clearance of disease-related pathological proteins. And overexpression or increased activity of Rab11 can greatly improve the defect of membrane trafficking and slow down the disease process.With increasing research efforts on Rab11-dependent membrane trafficking mechanisms, a potential target for nerve regeneration and neurodegenerative diseases will be provided.

Breast cancer (BC) patients report complex negative emotions, including symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD). What’s more, being diagnosed with cancer also has a negative impact on the patient’s family such as additional financial burden and care needs, leading to higher levels of caregiver burden. This study aimed to explore whether dispositional mindfulness could alleviate multiple negative emotions of BC patients and to investigate the mediating effect of caregiver burden on the relationship between the patients’ dispositional mindfulness and negative emotions. A sample of 230 Chinese BC patients receiving chemotherapy and their caregivers voluntarily participated in the study by completing a set of questionnaires including the Mindfulness Attention Awareness Scale, the Caregiver Self-assessment Questionnaires, the General Anxiety Symptoms Scale, the Patient Health Questionnaire, and the PTSD Symptom Scale. Structural equation modeling was used to test the relationship between dispositional mindfulness, negative emotions, and caregiver burden. Dispositional mindfulness was significantly and negatively correlated with negative emotions, including anxiety, depression, and PTSD among the BC patients. Structural equation modeling showed that caregiver burden mediated the relation between patients’ dispositional mindfulness and negative emotions. BC patients with higher levels of dispositional mindfulness showed less negative emotions. The results of the mediation analysis suggested that higher levels of dispositional mindfulness of breast cancer patients could decrease the caregivers’ perceived burden and, in turn, relieve patients’ negative emotions. Dispositional mindfulness was beneficial to breast cancer patients as well as their caregivers, indicating that mindfulness-based interventions targeting distress in patient-caregiver dyads would be more effective than what interventions for patients alone.

Background Abnormalities in the KEPA1-NRF2 pathway have a role in cancer progression, metastasis, and resistance to chemo- and radiotherapies. Persistent activation of NRF2 associates with poor prognosis across different cancer types. However, the beneficial therapeutic strategy to harness this pathway in cancer remains unclear. This study aimed to investigate the clinical outcome with immunotherapy in NFE2L2/KEAP1 mutant population. Materials and Methods We investigated the correlation between NFE2L2/KEAP1 mutations and tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1) expression status to identify the therapeutic vulnerability. For this purpose, relevance analysis with TMB value was performed in 9,040 patients with cancer, and relevance analysis with PD-L1 expression was performed in 3,457 patients. The Memorial Sloan Kettering Cancer Center (MSKCC) database and real-world evidence were used to assess the immunotherapy response in NFE2L2/KEAP1 mutant subsets. Results NFE2L2/KEAP1 mutations occurred in various cancers, and the highest mutation incidences occurred in lung squamous cell carcinoma (LUSC) at 19.16% (NFE2L2) and 10.31% (KEAP1). We confirmed that higher TMB value and PD-L1 expression were associated with NFE2L2/KEAP1 mutations compared with wild-type, especially in non-small lung cancer. MSKCC database analysis showed the improved survival of patients with NFE2L2/KEAP1 mutant with immunotherapy compared with other treatments (median overall survival 22.52 VS 12.89, p = .0034). Real-world evidence further confirmed the efficacy of immunotherapy in the mutant population. Conclusion Our study revealed that patients with NFE2L2/KEAP1 mutant could achieve improved outcomes from immunotherapy than the other treatments. These findings may broaden the application of immune checkpoint blockade to patients harboring NFE2L2/KEAP1 mutations. Implications for Practice NFE2L2/KEAP1 alterations occur frequently in multiple cancer types and are associated with poor prognosis; however, the efficacious strategy to inhibit this pathway in cancer is poorly understood. This study was designed to analyze the mutational characteristics of NFE2L2/KEAP1 alterations in 9,243 Chinese patients. The highest mutation incidences occurred in lung squamous cell carcinoma at 19.16% (NFE2L2) and 10.31% (KEAP1). Relevance analysis showed the NFE2L2/KEAP1 mutant subsets were associated with higher tumor mutational burden value and programmed death-ligand 1 expression. Clinical data further confirmed NFE2L2/KEAP1 mutations correlate with improved outcome with immunotherapy. These findings suggest the clinical application of immunotherapy in the NFE2L2/KEAP1 mutant population.

As the innate immune cells that permanently reside in the central nervous system (CNS), microglia play an increasingly important role in maintaining brain function. Normally, microglia act as resting phenotype, which can be activated by various types of stimuli and release a variety of inflammatory mediators. Melatonin is an endogenous rhythmic hormone secreted principally by the pineal gland. Increasing evidence suggests that melatonin can detoxify reactive oxygen species (ROS) and prevent microglia from over-activation. This review summarizes the mechanisms of melatonin in inhibiting excessive activation of microglia and demonstrates the feasibility of melatonin in the treatment of diseases related to microglial over-activation.