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Objectives Shaokwan is one of the inhabitant regions of Hakka population in Guangdong province of southern China. Previous survey has reported that a higher prevalence of abnormal hemoglobin (Hb) in this region. However, large-scale survey on the molecular characteristics of abnormal hemoglobin in this south-north junctional region has not been reported.In this study, we aim to investigate the molecular characteristics of abnormal hemoglobin in this area. Methods Blood samples from medical check-up center in one local hospital were selected for abnormal hemoglobin screening. Hemoglobin electrophoresis and routine blood tests were performed. Hemoglobin variants were further analyzed by PCR and DNA sequencing. Results Among the 9731 study subjects, 45 cases of hemoglobin variants were found by hemoglobin electrophoresis, which gave an incidence of 0.46% (45/9731) in Shaokwan region. 8 kinds of hemoglobin variants were identified by gene sequencing. Hb Q-Thailand (16/45) was the most common hemoglobin variants, followed by HbE (7/45), Hb NewYork (6/45) and Hb G-Chinese (6/45). Discussion and Conclusion Hemoglobin variants had obviously genetic polymorphisms in Chinese. Our study of hemoglobin disorders in this special Hakka Chinese population will contribute considerably to our understanding of the historical, emigrational, and genetic relationships among different ethnic group in this region.

To explore the association between phenotype and the gut microbiome following damage to the GRID2 gene.Ten wild-type (WT) mice and 11 GRID2 knockout heterozygous mice (GRID2(±)) of a similar age and weight were randomly selected. Fresh feces were collected from both groups of mice under specified pathogen-free (SPF) conditions. The bacterial genomes were extracted from the feces, the 16S rRNA genes were sequenced, and the data were analyzed to determine clustering, diversity, abundance, LEfSe, and functional differences. Differential expression and enrichment analyses of the RNA-seq and protein levels of the GRID2 gene were also performed using data in the GENE database and the new version of the Human Protein Atlas portal (www.proteinatlas.org).The diversity analysis showed differences in species composition between the two groups at different levels. At phylum level, compared with the WT group, the distribution was more bacteriophages but showed a lower content of Tenericutes in the GRID2(±) group. At the order level, compared with the WT group, a higher content of Actinomycetales and Bacteriophages were found in the GRID2(±) group. The species difference analysis showed that 17 species, including E. faecalis and Paracoccus spp., showed differences in content between the two groups. LEfSe analysis showed that the abundance of Clostridiaceae, Allobaculum, and other groups decreased in the GRID2(±) group compared with the WT group, while Mycoplasma, Sphingomonas, and Alphaproteobacteria increased in abundance. Functional analysis revealed eight differential functions between the WT and GRID2(±) group (P lt; 0.05). The most significantly disrupted were neuroactive ligand-receptor interactions (P lt; 9.99e-4). In addition, the differential expression and enrichment analyses performed at RNA-seq and protein levels revealed that the GRID2 gene showed organ-specific expression and was mainly enriched in the brain tissue.Compared with the WT group, the defective GRID2 gene affected the species richness and composition of gut microbes in the GRID2(±) mice, which in turn affected the function of gut microbes, leading to the disruption of neuroactive ligand-receptor interactions. Our findings indicate that the host gene, GRID2, can influence the abundance of a subset of gut microbes but the exact mechanisms still need further investigation.

Background: Gastric Cancer (GC) is the fifth most common malignancy tumor and the third cause of cancer-related death around the world. Immune checkpoint inhibitors (ICIs) such as programmed cell death-1 (PD-1) antibodies play an active role in tumor therapy. A recent study reveals that Wnt/β-catenin signaling pathway is negatively correlated with T-cell infiltration in tumor microenvironment (TME), thereby influencing the therapeutic efficacy of PD-1 antibody. Objective: In this study, we aimed to uncover the relationship of Wnt/β-catenin pathway to CD8+ T cell activity as well as its effect on anti-PD-1 therapeutic efficacy in GC. Methods and Results: We first collected clinical samples and went through an immunohistochemical analysis and found that a high β-catenin expression in GC tissues was often associated with a significant absence of CD8+ T-cell infiltration. In addition, our data further indicated that disruption of the Wnt/β-catenin pathway in GC cells inhibited their migratory and invasive ability. Meanwhile, enhanced sensitivity of GC cells to PD-1 blockade therapy was evident by decreased Jurkat cell apoptosis rate and increased GC cell apoptosis rate in a tumor and Jurkat cells co-culture system with the presence of Wnt/β-catenin pathway inhibition. Conclusion: Collectively, these findings indicated Wnt/β-catenin pathway may play a significant role in modulating the activity of Jurkat cells and downregulation of Wnt/β-catenin may enhance the sensitivity of GC cells to PD-1 antibody in vitro. This result further indicated that β-catenin and PD-1 targeted inhibition might become a potential and effective therapy for GC patients.

The aim of this study was to objective to investigate the effects of umbilical cord mesenchymal stem cells on the expression of CYR61, FSH and AMH in mice with premature ovarian failure. For this purpose, thirty SPF female SD mice were selected as the research object, 10 of which were control group, namely group α, and 20 mice with premature ovarian failure model were established by cyclophosphamide. The mice were divided into model group, namely β group and the umbilical cord mesenchymal stem cell transplantation group (γ group), with 10 mice in each group. ELSA method was used to determine the levels of follicle-stimulating hormone (FSH), Luteinizing hormone (LH), estradiol (Estradiol) in serum. The changes of E2, Antimullerian hormone (AMH) and cysteine-rich protein 61 in ovarian tissues were determined by the protein imprinting method. Connective tissue growth factor (CTGF) and caspase-3 protein expression. Results showed that in fertility rate, γ group > α group > β group, the difference was statistically significant (P γ group > β group, the difference was statistically significant (P γ group > β group, and the levels of serum FSH and LH in β group > γ group > α group were statistically significant (P γ group > β group, and the atresia follicles were β group > γ group > α group, and there was a statistical difference among all groups (P0.05). In terms of CYR61 and CTGF protein expression, α group > γ group > β group, and in terms of caspase-3, β group > γ group > α group had statistical significance (P

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may manifest as neonatal hyperbilirubinemia, is the most prevalent erythrocytic enzyme-related disease in the world. Objective To investigate the association between neonatal hyperbilirubinemia and co-inheritance of G6PD deficiency and 211 G to A variation of UGT1A1 in Chaozhou city of eastern Guangdong province, the effects of G6PD deficiency and UGT1A1 gene variant on the bilirubin level were determined in neonates with hyperbilirubinemia. Method The activity of G6PD was assayed by an auto-bioanalyzer. PCR and flow-through hybridization were used to detect 14 common G6PD mutations in G6PD deficient neonates. 211 G to A variation of UGT1A1 was determined by PCR and sequencing. The data of neonatal bilirubin was collected and analyzed retrospectively. Results Seventy four cases of the 882 hyperbilirubinemia neonates were G6PD deficiency (8.39%) while 12 cases of the 585 non-hyperbilirubinemia neonates (control group) were G6PD deficiency (2.05%). The rate of G6PD deficiency in the hyperbilirubinemia group was higher than that of the control group. Moreover, the peak bilirubinin of the G6PD-deficient group of hyperbilirubinemia neonates was 334.43 ± 79.27 μmol/L, higher than that of the normal G6PD group of hyperbilirubinemia neonates (300.30 ± 68.62 μmol/L). The most common genotypes of G6PD deficiency were c.1376G > T and c.1388G > A, and the peak bilirubin of neonates with these two variants were 312.60 ± 71.81 μmol/L and 367.88 ± 75.79 μmol/L, respectively. The bilirubin level of c.1388G > A was significantly higher than that of c.1376G > T. Among the 74 hyperbilirubinemia neonates with G6PD deficiency, 6 cases were 211 G to A homozygous mutation (bilirubin levels 369.55 ± 84.51 μmol/L), 27 cases were 211 G to A heterozygous mutation (bilirubin levels 341.50 ± 63.21 μmol/L), and 41 cases were wild genotypes (bilirubin levels 324.63 ± 57.52 μmol/L). Conclusion The rate of G6PD deficiency in hyperbilirubinemia neonates was significantly higher than that of the non-hyperbilirubinemia neonates in Chaozhou. For the hyperbilirubinemia group, neonates with G6PD deficiency had a higher bilirubin level compared to those with normal G6PD. For hyperbilirubinemia neonates with G6PD deficiency, there was a declining trend of bilirubin levels among 211 G to A homozygous mutation, heterozygous mutation, and wild genotype, but there was no significance statistically among the three groups.

To verify the clinical value of the good outcome following attempted resuscitation (GO-FAR) score in predicting the neurological status of patients with in-hospital cardiac arrest (IHCA) in the Chinese population.The clinical data of patients with IHCA who were admitted to the Zigong Fourth People's Hospital from January 1 to December 31, 2020 were retrospectively analyzed. Used Glasgow-Pittsburgh cerebral performance category (CPC) score 1 point as the end point, the subjects were divided into 4 groups according to the score: ≤ 0 group, 1-8 group, 9-20 group and ≥ 21 group. Taken the group which GO-FAR score ≤ 0 as the reference group, the odds ratio (OR) of the other three groups compared with this group was calculated. The receiver operator characteristic curve (ROC curve) was performed to evaluate the predictive value of the GO-FAR score in favorable neurological outcome. A calibration curve was drawn for the Hosmer-Lemeshow test to analyze the degree of calibration of the GO-FAR score for predicting good neurological outcome.A total of 230 IHCA patients were enrolled in the study, including 130 males, aged 74 (65, 81) years old, and 23 case (10.0%) had good neurological prognosis. There were statistically significant differences in GO-FAR-related variables, including age, a normal neurological function on admitted, acute stroke, metastatic cancer, septicemia, medical noncardiac admission, hepatic insufficiency, hypotension, renal insufficiency or dialysis, respiratory insufficiency, pneumonia, etc (all P0.05). Taken the GO-FAR score ≤ 0 group as the reference group, the OR values of good neurological prognosis in the GO-FAR score 1-8 group were 0.54 [95% confidence interval (95%CI) was 0.17-1.53, P = 0.250], 9-20 group were 0.17 (95%CI was 0.02-0.67, P = 0.009) and ≥ 21 group were 0.25 (95%CI was 0.05-0.85, P = 0.025). The area under the ROC curve (AUC) of the GO-FAR score for predicting favorable neurological outcome in IHCA patients was 0.653 (95%CI was 0.529-0.777, P = 0.015) and there was no significant difference in Hosmer-Lemeshow test (P = 0.311). All these suggested that there was no significant difference between the predicted value and the actual value.GO-FAR score can be applied to predict neurological prognosis of IHCA patients in Chinese population. It can help clinicians to predict the prognosis of cardio-pulmonary resuscitation (CPR) and propose critical recommendations in treatment for these patients or their families.

Background Acute kidney injury (AKI) is a common and severe complication of cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to establish a model to predict the probability of postoperative AKI in patients undergoing cardiac surgery with CPB. Methods We conducted a retrospective, multicenter study to analyze 1082 patients undergoing cardiac surgery under CPB. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for the AKI model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the feature selected in the previously mentioned model. Finally, we used multiple methods to evaluate the accuracy and clinical applicability of the model. Results Age, gender, hypertension, CPB duration, intraoperative 5% bicarbonate solution and red blood cell transfusion, urine volume were identified as important factors. Then, these risk factors were created into nomogram to predict the incidence of AKI after cardiac surgery under CPB. Conclusion We developed a nomogram to predict the incidence of AKI after cardiac surgery. This model can be used as a reference tool for evaluating early medical intervention to prevent postoperative AKI.

Distal enhancers play critical roles in sustaining oncogenic gene-expression programs. We identify aberrant enhancer-like activation of GGAA tandem repeats as a characteristic feature of B-cell acute lymphoblastic leukemia (B-ALL) with genetic defects of the ETV6 transcriptional repressor, including ETV6–RUNX1+ and ETV6-null B-ALL. We show that GGAA repeat enhancers are direct activators of previously identified ETV6–RUNX1+/− like B-ALL “signature” genes, including the likely leukemogenic driver EPOR. When restored to ETV6-deficient B-ALL cells, ETV6 directly binds to GGAA repeat enhancers, represses their acetylation, downregulates adjacent genes, and inhibits B-ALL growth. In ETV6-deficient B-ALL cells, we find that the ETS transcription factor ERG directly binds to GGAA microsatellite enhancers and is required for sustained activation of repeat enhancer-activated genes. Together, our findings reveal an epigenetic gatekeeper function of the ETV6 tumor suppressor gene and establish microsatellite enhancers as a key mechanism underlying the unique gene-expression program of ETV6–RUNX1+/− like B-ALL. Significance: We find a unifying mechanism underlying a leukemia subtype-defining gene-expression signature that relies on repetitive elements with poor conservation between humans and rodents. The ability of ETV6 to antagonize promiscuous, nonphysiologic ERG activity may shed light on other roles of these key regulators in hematolymphoid development and human disease. See related commentary by Mercher, p. 2. This article is highlighted in the In This Issue feature, p. 1

Invasion and metastasis are the main causes of colorectal cancer (CRC)‐related death. Accumulating evidence suggested that sphingosine kinase 1 (SphK1) promoted the metastasis of CRC and autophagy played an important role in SphK1 promoting the metastasis of malignancy. However, the mechanism by which SphK1‐driven autophagy promotes invasion and metastasis in CRC remains to be clarified. In the present study, immunohistochemical detection showed the expression of SphK1 and paxillin was higher in human CRC tissues than those of normal colorectal mucosal tissues, they were both associated with TNM staging, lymphatic, and distance metastasis. In addition, study of in situ tumor transplantation model in nude mice showed that the suppression of SphK1 inhibited the growth of colonic orthotopic implantation tumors and the expression of paxillin, p‐paxillin, LC3 in the tumor. So, SphK1 may promote CRC metastasis via inducing the expression of paxillin expression and its phosphorylation, in vivo. Furthermore, results of CCK8 assay, transwell and wound healing assays showed that SphK1 promoted the viability, invasion, and metastasis of CRC cells. Transmission electron microscopy detection showed that SphK1 is the key factor in autophagy induction in CRC cells. Moreover, western blot examination indicated that the expression of LC3Ⅱ/Ⅰ, paxillin, p‐paxillin, MMP‐2, and vimentin was enhanced in SphK1‐overexpressed CRC cells and suppressed in SphK1 knockdown CRC cells, meanwhile, the expression of E‐cadherin was suppressed in SphK1‐overexpressed CRC cells and enhanced in SphK1 knockdown CRC cells. Suppression of autophagy by 3MA reversed the expression of paxillin and its phosphorylation in SphK1‐overexpressed CRC cells, indicated that SphK1‐driven autophagy induced the expression of paxillin and its phosphorylation in CRC cells. Together, these findings reveal that SphK1‐driven autophagy may promote the invasion and metastasis of CRC via promoting the expression of focal adhesion paxillin and its phosphorylation., SphK1‐driven autophagy may promote the invasion and metastasis of CRC via promoting of the expression of focal adhesion paxillin and its phosphorylation.

To assess the association between serum vitamin D levels and heart rate variability in patients with type 2 diabetes mellitus (T2DM). This study included 469 patients who were retrospective assessed for eligibility from Changzhou Second People's Hospital, Affiliated Nanjing Medical University, between March 2013 and June 2020. A total of 191 T2DM patients were recruited and divided into 3 groups. A total of 191 patients were recruited. A significant difference was noted among groups for HbA1c (P.001), serum uric acid (P = .048), and urea nitrogen (P = .043). The Vitamin D level in deficiency, insufficiency, and sufficient was 23.17, 38.89, and 63.01 nmol/L, respectively. The insufficient group had lower levels of percentage of normal-to-normal intervals differing by more than 50 milliseconds, and the square root of the mean of the squares of the differences between adjacent normal-to-normal R peak-to-R-peak time intervals than the sufficient vitamin D group. Furthermore, patients in deficiency and insufficiency group were associated with high level of low frequency power/high frequency power as compared with sufficient vitamin D group. Finally, serum 25-hydroxyvitamin D (25(OH)D) levels were positively correlated with rMSSD (P = .002). This study found that low serum 25(OH)D levels were associated with reduced heart rate variability parameters in patients with T2DM.

Prevalence of drug resistance (DR) challenges the epidemic control of human immunodeficiency virus (HIV)-1. However, little is known about DR among patients with antiretroviral therapy (ART) failure in Guangxi province, China. This cross-sectional study was aimed to investigate the prevalence of DR and the characteristics of DR sequences in the genetic transmission network among HIV-1 patients with ART failure in Guangxi. We enrolled 358 eligible patients between 2012 and 2018. Blood samples were subjected to reverse transcription polymerase chain reaction, followed by sequencing of the HIV-1 polymerase (

Background As a key process in transcriptional regulatory mechanisms, alternative splicing (AS) plays a crucial role in maintaining the diversity of RNA and protein expression, and mediates the immune response in infectious diseases, especially for the COVID-19. Therefore, urgent data gathering and more research of AS profiles in microbe-infected human cells are needed to improve understanding of COVID-19 and related infectious diseases. Herein, we have created CASA, the COVID-19 Alternative Splicing Atlas to provide a convenient computing platform for studies of AS in COVID-19 and COVID-19-related infectious diseases. Methods In CASA, we reanalyzed thousands of RNA-seq datasets generated from 65 different tissues, organoids and cell lines to systematically obtain quantitative data on AS events under different conditions. A total of 262,994 AS events from various infectious diseases with differing severity were detected and visualized in this database. In order to explore the potential function of dynamics AS events, we performed analysis of functional annotations and drug-target interactions affected by AS in each dataset. RNA-binding proteins (RBPs), which may regulate these dynamic AS events are also provided for users in this database. Results CASA displays microbe-induced alterations of the host cell splicing landscape across different virus families and helps users identify condition-specific splicing patterns, as well as their potential regulators. CASA may greatly facilitate the exploration of AS profiles and novel mechanisms of host cell splicing by viral manipulation. CASA is freely available at http://www.splicedb.net/casa/.

BackgroundThere are huge differences in female breast cancer mortality between urban and rural China. In order to better prevent breast cancer equally in urban and rural areas, it is critical to trace the root causes of past inequities and predict how future differences will change. Moreover, carcinogenic factors from micro-individual to macro-environment also need to be analyzed in detail. However, there is no systematic research covering these two aspects in the current literature.MethodsBreast cancer mortality data in urban and rural China from 1994 to 2019 are collected, which from China Health Statistical Yearbook. The Age-Period-Cohort model is used to examine the effects of different age groups, periods, and birth cohorts on breast cancer mortality. Nordpred project is used to predict breast cancer mortality from 2020 to 2039.ResultsThe age effect gradually increases and changes from negative to positive at the age of 40–44. The period effect fluctuates very little and shows the largest difference between urban and rural areas in 2019. The birth cohort effect gradually decreases with urban-rural effects alternating between strong and weak. In the predicted results, the urban-rural mortality gap becomes first narrow and then wide and shows a trend of younger death.ConclusionsFrom the perspective of a temporal system, the changing trend of breast cancer mortality is highly consistent with the history of social and economic structural changes in China. From the perspective of the theory of social determinants of health, individuals, families, institutions and governments need to participate in the prevention of breast cancer.

Glioblastoma (GBM), as the immunologically cold tumor, respond poorly to programmed cell death 1 (PD-1) immune checkpoint inhibitors because of insufficient immune infiltration. Herein, through the analysis of The Cancer Genome Atlas data and clinical glioma samples, we found Wnt/β-catenin signal was activated in GBM and inversely related to the degree of immune cell (CD8+) infiltration and programmed cell death ligand 1 (PD-L1) expression. Blockade of Wnt/β-catenin signal could inhibit GBM U118 cells' growth and migration, and upregulate their PD-L1 expression which indicated the possible better response to anti-PD-1 immunotherapy. Besides, in a co-culture system comprising U118 cells and Jurkat cells, Wnt inhibition alleviated Jurkat cell's apoptosis and enhanced its cytotoxic function as evidenced by obviously increased effector cytokine IFNγ secretion and lactate dehydrogenase release. Moreover, the enhanced anti-GBM effect of PD-1 antibody triggered by Wnt inhibition was observed in GL261 homograft mouse model, and the upregulation of immune cell (CD4+/CD8+) infiltration and IFNγ secretion in tumor tissues suggested that Wnt/β-catenin inhibition could inflame cold tumor and then sensitize GBM to PD-1 blockade therapy. Taken together, our study verified the blockade of Wnt/β-catenin signal could augment the efficacy of PD-1 blockade therapy on GBM through directly inhibiting tumor proliferation and migration, as well as facilitating T-cell infiltration and PD-L1 expression in tumor microenvironment.

Objective This study investigated prevalence trends and identified the associated factors of HIV, syphilis and hepatitis C virus (HCV) among pregnant women in the Guangxi Zhuang Autonomous Region (Guangxi), Southwest China. Methods Serial cross-sectional surveys were performed annually among pregnant women in Guangxi from 2009 to 2018. Blood specimens were collected to test the prevalence of HIV, syphilis and HCV. Cochran–Armitage analysis was used to assess the trends of HIV, syphilis and HCV prevalence, as well as the sociodemographic and behavioural data. In this study, we used zero-inflated negative binomial (ZINB) regression models to identify factors associated with HIV, syphilis and HCV infection. Results A total of 23,879 pregnant women were included in the study. The prevalence of HIV, syphilis and HCV was 0.24%, 0.85% and 0.19%, respectively. There was a decrease in HIV prevalence from 0.54% to 0.10%, a decrease in HCV prevalence from 0.40% to 0.05% and a decrease in syphilis prevalence from 1.53% to 0.30%. The findings based on the ZINB model revealed that pregnant women who had a history of STI had significantly increased risks of HIV (OR 6.63; 95% CI 1.33–32.90) and syphilis (OR 9.06; 95% CI 3.85–21.30) infection, while pregnant women who were unmarried/widowed/divorced were more likely to have HIV (OR 2.81; 95% CI 1.20–6.54) and HCV (OR 58.12; 95% CI, 3.14–1076.99) infection. Furthermore, pregnant women whose husband had a history of STI (OR 5.62; 95% CI 1.24–25.38) or drug use (OR 7.36; 95% CI 1.25–43.43) showed an increased risk of HIV infection. Conclusions There was a relatively low prevalence of HIV, syphilis and HCV among pregnant women. Although decreasing trends in HIV, syphilis and HCV infections were observed, effort is needed to promote STI testing in both premarital medical check-ups and antenatal care, especially targeting couples with a history of STI or drug use.

Background HIV testing is a primary prevention strategy against the HIV epidemic and an entry point for HIV/AIDS-related care, prevention and treatment. This study aimed to estimate the uptake of HIV testing among Sino-Vietnam female sex workers (FSWs) in Guangxi, China, from 2016 to 2018, and to identify the factors influencing HIV testing uptake. Methods A cross-sectional survey was conducted among FSWs in two Sino-Vietnam border cities of Guangxi, China. The survey was conducted through face-to-face interview, the data were collected by a structured questionnaire, and HIV-1 infection was detected simultaneously. Logistic regression analysis was used to determine the factors associated with uptake of HIV testing. Results In total, 4565 Chinese local FSWs (CL-FSWs) and 636 cross-border migrant Vietnamese FSWs (CMV-FSWs) were recruited into this study. HIV-1 prevalence in CL-FSWs and CMV-FSWs was 0.70% and 3.14%, respectively. The rate of self-reported uptake of HIV testing in CL-FSWs and CMV-FSWs was 54.56% and 45.44%, respectively. The rates of self-reported uptake of HIV testing declined in both groups from 2016 to 2018. Logistic regression analysis indicated that a number of factors, including socio-demographic characteristics (age Conclusion In recent years, the rate of HIV testing uptake among Sino-Vietnam border FSWs in Guangxi, China was low, which may be an important reason for the high HIV-1 prevalence among FSWs in the region. A number of factors were identified to be associated with HIV-1 testing uptake, suggesting that HIV testing prevention strategies in this region could include accelerating AIDS education training, raising personal awareness of HIV testing, and improving accessibility of HIV testing.

Background Necroptosis is a new form of programmed cell death that is associated with cancer initiation, progression, immunity, and chemoresistance. However, the roles of necroptosis-related genes (NRGs) in colorectal cancer (CRC) have not been explored comprehensively. Methods In this study, we obtained NRGs and performed consensus molecular subtyping by “ConsensusClusterPlus” to determine necroptosis-related subtypes in CRC bulk transcriptomic data. The ssGSEA and CIBERSORT algorithms were used to evaluate the relative infiltration levels of different cell types in the tumor microenvironment (TME). Single-cell transcriptomic analysis was performed to confirm classification related to NRGs. NRG_score was developed to predict patients’ survival outcomes with low-throughput validation in a patients’ cohort from Fudan University Shanghai Cancer Center. Results We identified three distinct necroptosis-related classifications (NRCs) with discrepant clinical outcomes and biological functions. Characterization of TME revealed that there were two stable necroptosis-related phenotypes in CRC: a phenotype characterized by few TME cells infiltration but with EMT/TGF-pathways activation, and another phenotype recognized as immune-excluded. NRG_score for predicting survival outcomes was established and its predictive capability was verified. In addition, we found NRCs and NRG_score could be used for patient or drug selection when considering immunotherapy and chemotherapy. Conclusions Based on comprehensive analysis, we revealed the potential roles of NRGs in the TME, and their correlations with clinicopathological parameters and patients’ prognosis in CRC. These findings could enhance our understanding of the biological functions of necroptosis, which thus may aid in prognosis prediction, drug selection, and therapeutics development.

Discoidin domain receptor 1 (DDR1) has been demonstrated to be able to promote tumor invasion and metastasis and being closely related to tumor immune infiltration. However, DDR1 has rarely been studied in gastric cancer. Here, we primarily evaluated DDR1 expression in gastric cancer and its cell lines using multiple databases. Subsequently, the cancer prognosis was investigated in relation to DDR1 expression. After analysis, we discovered that DDR1 was highly expressed and significantly connected with poor prognosis in gastric cancer. To comprehensively understand the molecular mechanism of DDR1, we explored genes and proteins interacting with DDR1 in gastric cancer using databases. Additionally, we found that the expression level of DDR1 was inversely correlated with immune infiltration and significantly relative to various immune cell markers. Overall, DDR1 was implicated in invasion, metastasis, and immune infiltration of gastric cancer. Inhibition of DDR1 may have the potential to alleviate the strong invasiveness and metastasis of advanced gastric cancer. Meanwhile, immune exclusion by DDR1 may also provide a new strategy for improving the efficacy of immune checkpoints inhibitors (ICIs), such as programmed cell death protein 1 (PD-1) antibody.

The characteristic of glucose-6-phosphate dehydrogenase (G6PD) deficiency is red blood cell (RBC) destruction in response to oxidative stress. Patients requiring RBC transfusions may simultaneously receive oxidative medications or have concurrent infections, both of which can induce hemolysis in G6PD-deficient RBCs. We intend to investigate the incidence of G6PD deficiency in voluntary blood donors and to evaluate the transfusion risk associated with G6PD deficiency in Guangdong province.G6PD enzyme was analyzed in 3042 donors and gene mutations were genotyped in G6PD-deficient samples.The G6PD-deficient prevalence of voluntary blood donors was 6.97% (212/3042), 55.19% blood donors with G6PD deficiency donated blood more than twice. Eighty-five cases of G6PD deficiency were genotyped, and the common types of G6PD mutations were c.1376 G T, c.1388 G A, c.95 A G, c.1024 C T, and c.871 G A.Due to the high prevalence of G6PD deficiency in Foshan area, we recommended that the screening of G6PD deficiency should be carried out for the regular blood donors to ensure the safety of blood users.

Talaromyces marneffei (formerly Penicillium marneffei) is an important thermally dimorphic fungus endemic which is characterized by one of the most frequent opportunistic infections in HIV/AIDS patients, mainly prevalent in Southeast Asia, southern China, and northeastern India. Cotrimoxazole(CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi, thereby commonly used to prevent several opportunistic infections among HIV/AIDS patients. In addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis are considered to have the potential to prevent T. marneffei infection in HIV/AIDS patients receiving antiretroviral therapy (ART). However, the effect of cotrimoxazole towards T. marneffei fungus in vitro remains unclear.Human THP-1 macrophages were used as cell model in vitro to explore the effect and mechanism of cotrimoxazole resistance towards T. marneffei. Cell viability assay and drug sensitivity colony forming units (CFU) experiments were conducted to determine the minimum inhibitory concentration (MIC) of cotrimoxazole inside and outside THP-1 macrophages respectively. Enzyme-linked immunosorbent assay (Elisa) was used to measure the concentration of Dihydropteroic acid synthetase (DHPS), Dihydrofolate synthetase (DHFS) and Dihydrofolate reductase (DHFR) between T. marneffei adding TMP/SMX and without adding TMP/SMX group respectively. Real-time fluorescence quantitative PCR(qPCR) was performed to detect the mRNA expression levels in Dectin-1 mediated signaling pathway and downstream inflammatory cytokines including IL-6, IL-10, IL-23A, CXCL8 and TNF-α released by T. marneffei-infected macrophages between adding TMP/SMX and without adding TMP/SMX group respectively.Cotrimoxazole can inhibit the proliferation of T. marneffei within safe concentration inside and outside THP-1 macrophages. Drug susceptibility results showed the minimal inhibit concentration(MIC) of 1:5 TMP/SMX was ranging from 14/70 to 68/340 μg/ml. The MIC of SMX was ranging from 100 to 360 μg/ml. The MIC of TMP was ranging from 240 to 400 μg/ml outside macrophages. The MIC of TMP/SMX was ranging from 36/180 to 68/340 μg/ml. The MIC of SMX was ranging from 340 to 360 μg/ml. The MIC of TMP was ranging from 320 to 400 μg/ml inside macrophages. The synergistic interaction of 1:5 TMP/SMX was more effective in inhibiting T. marneffei than separate SMX and TMP. DHPS, DHFS and DHFR can be inhibited by cotrimoxazole within safe and effective concentration. Dectin-1 expression is increased following T. marneffei infection, leading to the increase of IL-6, IL-10, IL-23A and the decrease of CXCL8 and TNF-α. Conversely, cotrimoxazole decrease the levels of Dectin-1, IL-6, IL-10, IL-23A and increase the levels of CXCL8 and TNF-α, thereby enhancing the intracellular killing-T. marneffei capacity of macrophages.Our findings indicated that cotrimoxazole directly inhibited T. marneffei growth by blocking DHPS, DHFS and DHFR and indirectly inhibited T. marneffei growth perhaps by regulating the Dectin-1 signaling pathway, which may effectively interfere with the defense ability of the host against T. marneffei infection.

Purpose To explore the relevance of cytogenetic or molecular genetic abnormalities to clinical variables, including clinical and laboratory characteristics and prognosis in Chinese patients with myelodysplastic syndromes (MDS). Methods A total of 634 consecutive patients diagnosed with MDS at The First Affiliated Hospital, Zhejiang University School of Medicine from June 2008 to May 2018 were retrospectively included in this study. All patients had evaluable cytogenetic analysis, and 425 patients had MDS‐related mutations sequencing. Results 38.6% of patients displayed abnormal karyotypes. The most common cytogenetic abnormality was +8 (31%). Sole +8 was related to female (p = 0.002), hemoglobin >10 g/dL (p = 0.03), and, This study aimed to explore the relevance of cytogenetic or molecular genetic abnormalities to clinical variables, including clinical and laboratory characteristics and prognosis in patients with myelodysplastic syndromes (MDS) and showed that cytogenetic changes had a potential correlation with molecular genetic abnormalities and both had significant influence on the prognosis of MDS.

Chronic myelomonocytic leukemia (CMML) is a rare disease of elderly people characterized by the presence of sustained peripheral blood monocytosis, overlapping features of myeloproliferation, and myelodysplasia. We present a large retrospective study of 156 CMML patients in China. Mean age at diagnosis was 68 years old (range 23‐91). According to the CMML‐specific prognostic scoring system (CPSS), 10 patients (8.3%) were low risk, 27 patients (22.5%) were intermediate‐1 risk, 72 patients (60%) were intermediate‐2 risk, and 11 patients (9.2%) were high risk. A total of 90 patients (57.7%) received hypomethylating agents (HMAs) treatment, 19 patients (12.2%) received chemotherapy and 47 patients (30.1%) received the best supportive care. Seventeen patients (10.9%) underwent allogeneic hematopoietic stem cell transplantation (allo‐SCT) after HMAs treatment or chemotherapy. With a median follow‐up of 35.3 months, overall response rate (ORR) was 69.5% in the HMAs ± chemotherapy group, 79.5% in the HMAs monotherapy group, 60.0% in the HMAs + chemotherapy group, and 37.5% in the chemotherapy group. HMAs monotherapy group had prolonged OS compared with the chemotherapy group (23.57 months vs. 11.73 months; p = 0.035). Patients who achieved ORR had prolonged OS (25.83 months vs. 8.00 months; p, Our retrospective study showed an advantage of HMAs therapy in CMML with an overall response rate of 65.9%‐79.5% compared with chemotherapy. The patients who respond to HMAs treatment have increased survival benefit compared to those who did not respond to HMAs treatment. HMAs monotherapy group had prolonged OS than the chemotherapy group.

OBJECTIVE: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

The SIRPαFc fusion protein can block the immunosuppressive CD47-SIRPα signal between macrophages and tumor cells as a decoy receptor and has demonstrated its immunotherapeutic efficacy in various tumors. However, its clinical application was limited because of the potential hematologic toxicity. The heptapeptide “TKKTLRT” is a collagen-binding domain (CBD) which can bind collagen specifically. Herein, we aim to improve the tumor targeting of SIRPαFc and therefore avoid its unnecessary exposure to normal cells through synthesizing a TKKTLRT–SIRPαFc conjugate. Experiments at molecular and cellular levels indicate that the TKKTLRT–SIRPαFc conjugate-derived collagen-binding affinity and the introduction of CBD did not impact the CD47-binding affinity as well as its phagocytosis-promoting effect on NSCLC cells. In vivo distribution experiments showed that CBD–SIRPαFc accumulated in tumor tissue more effectively compared to unmodified SIRPαFc, probably due to the exposed collagen in the tumor vascular endothelium and stroma resulting from the abnormal vessel structure. On an A549 NSCLC nude mouse xenograft model, CBD–SIRPαFc presented more stable and effective antitumor efficacy than SIRPαFc, along with significantly increased CD11b+F4/80+ macrophages especially MHC II+ M1 macrophages within tumors. All of these results revealed that CBD brought a tumor-targeting ability to the SIRPαFc fusion protein, which contributed to the enhanced antitumor immune response. Altogether, the CBD–SIRPαFc conjugate may have the potential to be an effective tumor immunotherapy with improved antitumor efficacy but less non-tumor-targeted side effect.

Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity. Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation. Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents. Guanxinning tablet (GXNT) is an oral Chinese patent medicine used for the treatment of angina pectoris, which contains phenolic acid active ingredients, such as salvianolic acids, ferulic acid, chlorogenic acid, caffeic acid, rosmarinic acid, tanshinol, and protocatechualdehyde. Our previous studies demonstrated that GXN exhibited significant antithrombotic effects, and clinical studies suggested that it did not increase bleeding risk. In addition, GXN exerted a significantly regulatory effect on immune inflammation. In the current study, we intended to evaluate the effects of GXN on bleeding events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction. First, we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred, but also had a certain promoting effect on the healing of gastric ulcer. Second, in vitroexperiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate (PMA), the adhesion and aggregation of leukocytes with human platelets were reduced. It was also found that GXN reduced the expression and activation of Mac-1 in leucocytes, and inhibited platelet activation due to leukocyte engagement via Mac-1. Overall, the results suggest that GXN may be a safe antithrombotic agent, and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.

Background: Epidermal function is associated with diabetes and renal disease. Whether obesity can reflect the changes in epidermal function is not clear yet. Objective: We assessed here the correlation of epidermal functions with body mass index (BMI) in a large Chinese cohort. Methods and Subjects: A total of 1,405 Chinese aged 21–98 years old were enrolled in this study. Epidermal functions, including transepidermal water loss (TEWL), stratum corneum hydration, and skin surface pH, were measured on the flexor forearm and the shin. Subjects’ height and body weight were also measured. Results: Age positively correlated with both TEWL and skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin of females. Similarly, age positively correlated with skin surface pH, while negatively correlating with stratum corneum hydration on both the forearm and the shin of males. In females, BMI positively correlated with skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin. However, BMI correlated neither with skin surface pH on both the forearm and the shin nor with stratum corneum hydration on the shin of males. Conclusion: These results demonstrate that correlations of BMI with age and epidermal functions vary with gender.

In China, the incidence of arrhythmia has also increased to approximately 20% of all cardiovascular diseases. The incidence of cardiovascular diseases in China has certain characteristics, which are generally low in the south and high in the north, and they tend to be younger and growing. Permanent pacemaker implantation is currently the most effective means of treating arrhythmia and preventing sudden death. To explore the clinical application value of metoprolol in patients after permanent pacemaker implantation. Ninety patients with permanent dual-chamber pacemaker implantation in our hospital are selected and divided into a metoprolol group and a control group according to whether metoprolol is used one week after the operation and 45 patients in each group. After one postoperative week, the LVEF%, LVEDd, LAD, and E/A of the metoprolol and the control groups had no statistically significant differences p > 0.05 . Twelve months postoperatively, the E/A of the metoprolol group is higher than that of the control group p < 0.05 , and LVEDd and LAD are lower than those of the control group (P p > 0.05 in the values recorded immediately postoperatively. The NT-proBNP of the metoprolol group is lower than that of the control group p < 0.05 at 12 months following pacemaker implantation. At one week after surgery, QTd, Pd, and Tp-Te are not significantly different (P > 0.05) between the metoprolol group and the control group, whereas the QTd and Pd times in the metoprolol group are lower than those in the control group p < 0.05 at the 12-month follow-up. At one week postoperatively, the SDNN, SDANN, and RMSSD between the metoprolol and control groups did not show any statistically significant differences p > 0.05 . The SDANN of the metoprolol group is higher than that in the control group p < 0.05 in the 12-month evaluation. One week after the operation, the serum IL-6 and TNF-α levels are not significantly different between the metoprolol and control groups p > 0.05 . At 12 months after surgery, the serum IL-6 and TNF-α levels in the metoprolol group are lower than those in the control group p < 0.05 . The incidence of adverse events in the metoprolol group is 9.30% lower than 26.83% in the control group within 12 months after the operation p < 0.05 . The use of metoprolol in patients with permanent pacemaker implantation after surgery can reduce the expansionary remodeling of the left atrium and have less impact on the QT-dispersion and Pd time.

Context.— The pandemic of a novel coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an unprecedented global health burden. Objective.— To investigate the effect of the SARS-CoV-2 infection on maternal, fetal, and neonatal morbidity and other poor obstetrical outcomes. Design.— All suspected cases of pregnant women with coronavirus disease 2019 (COVID-19) admitted into one center in Wuhan from January 20 to March 19, 2020, were included. Detailed clinical data of those pregnancies with COVID-19 were retrospectively collected and analyzed. Results.— Twenty-seven pregnant women (4 early pregnancies included) with laboratory or clinically confirmed SARS-CoV-2 infection and 24 neonates born to the 23 women in late pregnancy were analyzed. On admission, 46.2% (13 of 27) of the patients had symptoms, including fever (11 of 27), cough (9 of 27), and vomiting (1 of 27). Decreased total lymphocytes count was observed in 81.5% (22 of 27) of patients. Twenty-six patients showed typical viral pneumonia by chest computed tomography scan, whereas 1 patient confirmed with COVID-19 infection showed no abnormality on chest computed tomography. One mother developed severe pneumonia 3 days after her delivery. No maternal or perinatal death occurred. Moreover, 1 early preterm newborn born to a mother with the complication of premature rupture of fetal membranes, highly suspected to have SARS-CoV-2 infection, was SARS-CoV-2 negative after repeated real-time reverse transcriptase polymerase chain reaction testing. Statistical differences were observed between the groups of women in early and late pregnancy with COVID-19 in the occurrence of lymphopenia and thrombocytopenia. Conclusions.— No major complications were reported among the studied cohort, though 1 serious case and 1 perinatal infection were observed. Much effort should be made to reduce the pathogenic effect of COVID-19 infection in pregnancies.

Dynamic recombination is the driving force in the genetic diversity of human immunodeficiency virus type 1 (HIV-1). When multiple subtypes are circulating in the same area of a population, new HIV-1 strains are likely to be generated through recombination. In this study, we report a novel recombinant strain (2018GXQZLSHET001) of HIV-1, isolated from a HIV-1-positive heterosexual individual infected in Guangdong province, who recently lived in Guangxi province, China. Phylogenetic analysis of the near full-length genome suggested that 2018GXQZLSHET001 was a recombinant of strains CRF55_01B and subtype B. Similarity plotting and bootscaning showed that a subtype B segment was inserted into the CRF55_01B genome with one breakpoint in the nef and 3' long terminal repeat regions. Further subregion phylogenetic analysis demonstrated that the CRF55_01B segment originated from Guangdong. The subtype B segment was similar to a Thai B lineage. This indicated that the strain might be a novel recombinant, comprising sequences of both CRF55_01B and B. The emergence of this unique recombinant strain illustrated the complexity of the HIV-1 epidemic, and the need to strengthen molecular epidemiological surveillance and measures to reduce its spread.

The prevalence of HIV in Guangxi was very high, and there were many children living with HIV (CLHIV) because of larger baseline of pregnant women infected by HIV. It is necessary for children to explore the status of antiretroviral therapy (ART) on different initial CD4 counts in children with HIV infected by mother-to-child transmission (MTCT) in Guangxi and to evaluate the progress towards the 90-90-90 targets proposed by UNAIDS/WHO. Based on a retrospective observational cohort of children with HIV infected from the Guangxi Center for Disease Prevention and Control (CDC), the variables of all patients included viral loads, CD4 counts, laboratory results and WHO clinical staging of HIV/AIDS were collected. Several indicators were defined before analyzed: (1) diagnosis of MTCT: infants born to HIV-positive mothers who tested positive for HIV twice before 18 months; (2) ART initiation: the children who were enrolled in the treatment cohort and were still having HIV monitoring as of 6 months before date censored and (3) viral suppression: a recently viral load measurement that was less than 1000 copies per milliliter. The number of CLHIV in Guangxi was projected by using the estimates of the national HIV/AIDS prevalence from China CDC. An Autoregressive Integrated Moving Average (ARIMA) model and the Holt Exponential Smoothing (ES) model were used to predict the number of CLHIV, the diagnosed CLHIV, the diagnosed CLHIV receiving ART and the number of them achieving viral suppression, in 2019 and 2021, respectively. In this 14-year HIV/AIDS treatment cohort, 807 children who were HIV infected by MTCT were enrolled. The ARIMA and Holt ES models showed that by the end of 2019, 82.71% of all CLHIV in Guangxi knew their HIV status, 84.50% of those diagnosed had initiated ART, and 85.68% of those on ART had durable viral suppression. By the end of 2021, 93.51% of all CLHIV in Guangxi will know their HIV status, 84.28% of those diagnosed will have initiated antiretroviral therapy, and 85.83% of those on ART will have durable viral suppression. Therefore, in 2021, Guangxi fails to achieve the WHO/UNAIDS 90-90-90 targets for CLHIV, and there is still a wide time interval between the first HIV-positive diagnosis and ART initiation. National free antiretroviral treatment program (NFATP) requires strong enforcement to reduce the prevalence of later chronic diseases and complications.

Recently, an increasing number of circulating recombinant forms (CRFs) and unique recombinant forms of HIV-1 have been identified in China, contributing substantially to the genetic variability of this virus. This study reports a novel second-generation recombinant form of HIV-1 (GX2015QZLS204), composed of segments from the CRF07_BC and CRF01_AE strains, which was isolated from an HIV-positive male individual infected through heterosexual contact, while residing in the Guangxi province of southwest China. Analysis of the near full-length genome sequence showed that one segment of the CRF01_AE virus subtype was inserted into the CRF07_BC subtype backbone. Recombination analysis demonstrated that the genome of GX2015QZLS204 was separated into seven segments with six breakpoints. Subregion trees constructed by the neighbor-joining method confirmed that the CRF01_AE segment was from the previously identified CRF01_AE cluster 2, and the CRF07_BC segment correlated with the CRF07_BC strain originating from the Jiangxi and Xinjiang provinces of China. The emergence of GX2015QZLS204 highlights the frequent generation of novel recombinant forms and the increasing complications of the HIV-1 epidemic among heterosexual transmission (HET) groups in China. This highlights the importance of monitoring HIV-1 molecular epidemiological characteristics and the urgent need for reduction of the HIV-1 epidemic among HET groups in China.

Objectives For migrant female sex workers (FSWs) at the Sino-Vietnamese border, the impact of work time in their current location on the spread of HIV/AIDS is not clear. Methods Data were collected from the Sino-Vietnamese border cities of Guangxi, China. Migrant FSWs working in these cities were studied. FSWs who worked less than 6 months in their current location were assigned to the short-term work group (ST FSWs), and FSWs who worked equal to or longer than 6 months in their current location were assigned to the long-term work group (LT FSWs). Logistic regression was performed to examine the impact of work time in the current location and factors associated with HIV infection. Results Among the 1667 migrant FSWs, 586 (35.2%) and 1081 (64.9%) were assigned to the ST FSW and LT FSW groups, respectively. Compared to LT FSWs, ST FSWs were more likely to be of Vietnamese nationality, be less than 18 years old when they first engaged in commercial sex work, and have a low-level of HIV-related knowledge and had higher odds of using condoms inconsistently, having more male clients, having no regular male clients, and having a history of male clients who used aphrodisiacs but lower odds of receiving free condoms distribution and education/HIV counselling and testing programme. The analysis of factors associated with HIV infection revealed that Vietnamese FSWs, less than 18 years old when they first engaged in commercial sex work, having no regular male clients, and having lower average charge per sex transaction were correlated with HIV infection. Conclusion FSWs with short-term work at the Sino-Vietnamese border had a higher risk of risky sex and were correlated with HIV risk factors. Vietnamese FSWs were at higher risk of HIV infection, and they were more likely to have short-term work. More targeted HIV prevention should be designed for new FSWs who recently began working in a locality to further control the spread of HIV, particularly cross-border FSWs.

Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.

In vivo regeneration of lost or dysfunctional islet β cells can fulfill the promise of improved therapy for diabetic patients. To achieve this, many mitogenic factors have been attempted, including gamma-aminobutyric acid (GABA). GABA remarkably affects pancreatic islet cells' (α cells and β cells) function through paracrine and/or autocrine binding to its membrane receptors on these cells. GABA has also been studied for promoting the transformation of α cells to β cells. Nonetheless, the gimmickry of GABA-induced α-cell transformation to β cells has two different perspectives. On the one hand, GABA was found to induce α-cell transformation to β cells in vivo and insulin-secreting β-like cells in vitro. On the other hand, GABA treatment showed that it has no α- to β-cell transformation response. Here, we will summarize the physiological effects of GABA on pancreatic islet β cells with an emphasis on its regenerative effects for transdifferentiation of islet α cells to β cells. We will also critically discuss the controversial results about GABA-mediated transdifferentiation of α cells to β cells.

Although a compromised epidermal permeability barrier can contribute to the development of contact dermatitis, whether subjects with hand eczema display abnormalities in baseline epidermal permeability barrier function in their uninvolved skin remains unknown. The aim of the present study was to assess epidermal permeability barrier function in subjects with and without hand eczema in clothing manufacturers. Upon approval by the institutional review board, volunteers were recruited from clothing manufacturers in Guangzhou City, China. An 11-item questionnaire was used to collect general data from the volunteers. The diagnoses of self-proclaimed hand eczema were further confirmed by a dermatologist. Epidermal biophysical properties, including transepidermal water loss (TEWL) rates, stratum corneum hydration and skin surface pH were measured on the flexural surface of the left forearm in all volunteers. Epidermal biophysical properties were compared among cohorts of subjects with active hand eczema, a prior history of hand eczema and without any history of hand eczema. A total of 650 questionnaires were collected from 462 females and 188 males, with a mean age of 36.7 ± 0.46 years (range 16–69 years; 95% CI 35.8–37.59). Thirty-five subjects (5.4%) currently had hand eczema, while 28 subjects (4.3%) reported a prior history of hand eczema that was inactive currently. The prevalence of hand eczema did not differ significantly between genders. Neither a prior personal nor a family history of allergies was associated with the prevalence of hand eczema, but certain occupations and frequent contact with disinfectants were independently associated with the prevalence of hand eczema. In the overall cohort, males displayed higher TEWL rates and stratum corneum hydration levels than did females. Both skin surface pH and TEWL rates differed significantly among normal controls and subjects with active hand eczema or a prior history of hand eczema (p < 0.05). In conclusion, the uninvolved skin site of subjects with hand eczema exhibits abnormalities in epidermal perme­ability barrier, supporting a pathogenic role of epidermal dysfunction in hand eczema. Whether subjects with hand eczema in other occupations also display altered epidermal function on uninvolved skin remains to be explored.

Patients with lower‐risk myelodysplastic syndromes (LR‐MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter‐individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS‐relevant genes in 159 patients with LR‐MDS using next‐generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF, Shorter OS was associated with mutation status of ASXL1, EZH2 and JAK2, as well as TET2 VAF ≥18%. A novel prognostic scoring system based on the IPSS and the presence/absence of the four independent mutational factors further stratified LR‐MDS patients into three prognostically different groups. Integration of IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment.

Although poly (ADP-ribose) polymerase (PARP) inhibitors, as anti-tumor drugs targeting the DNA damage response (DDR), have been used for the therapy of various tumors, few researches reported their effect on laryngeal squamous cell carcinoma (LSCC). Here, we first discovered that the PARP-1/2 inhibitor Niraparib could simultaneously induce cell growth inhibition and autophagy in LSCC TU212 and TU686 cells. Niraparib decelerated cell cycle of LSCC by arresting G1 phase and preventing the cells from entering S phase. DNA lesions were also observed upon Niraparib treatment as evidenced by the accumulation of γH2AX and abatement of pRB expression. In addition, autophagy generation was confirmed by the observation of autophagosomes, LC3-positive autophagy-like vacuoles, and obvious conversion of LC3-I to LC3-II. Moreover, blocking autophagy enhanced Niraparib-induced growth inhibition and DNA lesions. Further studies suggested that autophagy suppression could obstruct the activation of checkpoint kinase 1 (Chk1) through elevating proteasomal activity and then impair the capacity of homologous recombination (HR), thereby improving the anti-LSCC efficiency of Niraparib. Collectively, these findings suggested that simultaneous targeting of Niraparib and autophagy might be a promising therapeutic schedule for LSCC in clinic.