Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

IL-27 signalling promotes adipocyte thermogenesis and energy expenditure.

Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3-6. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.

High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma.

Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10-11) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10-8). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.

Proteomics-Based Identification of Potential Therapeutic Targets of Artesunate in a Lupus Nephritis MRL/lpr Mouse Model.

This study aimed to identify potential therapeutic targets of artesunate in an MRL/lpr lupus nephritis mouse model by quantitative proteomics. We detected serum autoimmune markers and proteinuria in 40 female mice that were divided into 4 groups (n = 10): normal C57BL/6 control group; untreated MRL/lpr lupus; 9 mg/kg/day prednisone positive control MRL/lpr lupus; and 15 mg/kg/day artesunate-treated MRL/lpr lupus groups. Renal pathology in the untreated MRL/lpr lupus and artesunate groups was examined by Periodic acid-Schiff (PAS) staining. Artesunate treatment in lupus mice decreased serum autoantibody levels and proteinuria while alleviating lupus nephritis pathology. Through tandem mass tag-tandem mass spectrometry (TMT-MS/MS) analyses, differentially expressed proteins were identified in the artesunate group, and subsequent functional prediction suggested associations with antigen presentation, apoptosis, and immune regulation. Data are available via ProteomeXchange with the identifier PXD046815. Parallel reaction monitoring (PRM) analysis of the top 19 selected proteins confirmed the TMT-MS/MS results. Immunohistochemistry, immunofluorescence, and Western blotting of an enriched protein from PRM analysis, cathepsin S, linked to antigen presentation, highlighted its upregulation in the untreated MRL/lpr lupus group and downregulation following artesunate treatment. This study suggests that artesunate holds potential as a therapeutic agent for lupus nephritis, with cathepsin S identified as a potential target.

Electroacupuncture attenuates middle cerebral artery occlusion-induced learning and memory impairment by regulating microglial polarization in hippocampus.

BACKGROUND: As a traditional medical therapy, electroacupuncture (EA) has been demonstrated to have beneficial effects on ischemic stroke-induced cognitive impairment. However, the underlying mechanism is largely unclear. METHODS: Adult rats received occlusion of the middle cerebral artery and reperfusion (MCAO/R) to establish the ischemic stroke model. Morris water maze test was performed following EA stimulation at the GV20, PC6, and KI1 acupoints in rats to test the learning and memory ability. Western blot, immunofluorescent staining, and enzyme-linked immunosorbent assay were conducted to assess the cellular and molecular mechanisms. RESULTS: EA stimulation attenuated neurological deficits. In the Morris water maze test, EA treatment ameliorated the MCAO/R-induced learning and memory impairment. Moreover, we observed that MCAO/R induced microglial activation and polarization in the ischemic hippocampus, whereas, EA treatment dampened microglial activation and inhibited M1 microglial polarization but enhanced M2 microglial polarization. EA treatment inhibited the increased expression of proinflammatory cytokines and enhanced the increased expression of anti-inflammatory cytokines. Finally, we found that EA treatment dampened microglial p38 mitogen-activated protein kinase (MAPK) phosphorylation. CONCLUSION: Collectively, our data suggested that EA treatment ameliorated cognitive impairment induced by MCAO/R and the underlying mechanism may be p38-mediated microglia polarization and neuroinflammation.

Clinical and genome-wide association analysis of chemoradiation-induced hearing loss in nasopharyngeal carcinoma.

Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors' long-term quality of life. However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC patients and identified rs1050851 (within the exon 2 of NFKBIA), a variant with a high deleteriousness score, to be significantly associated with hearing loss risk (HR = 5.46, 95% CI 2.93-10.18, P = 9.51 × 10-08). The risk genotype of rs1050851 was associated with higher NFKBIA expression, which was correlated with lower cellular tolerance to cisplatin. According to permutation-based enrichment analysis, the variants mapping to 149 hereditary deafness genes were significantly enriched among GWAS top signals, which indicated the genetic similarity between hereditary deafness and CRIHL. Pathway analysis suggested that synaptic signaling was involved in the development of CRIHL. Additionally, the risk score integrating genetic and clinical factors can predict the risk of hearing loss with a relatively good performance in the test set. Collectively, this study shed new light on the etiology of chemoradiation-induced hearing loss, which facilitates high-risk individuals' identification for personalized prevention and treatment.

Genomic Landscapes of Epstein-Barr Virus in Pulmonary Lymphoepithelioma-Like Carcinoma.

Epstein-Barr virus (EBV) infection is associated with multiple malignancies, including pulmonary lymphoepithelioma-like carcinoma (pLELC), a particular subtype of primary lung cancer. However, the genomic characteristics of EBV related to pLELC remain unclear. Here, we obtained the whole-genome data set of EBV isolated from 78 pLELC patients and 37 healthy controls using EBV-captured sequencing. Compared with the reference genome (NC_007605), a total of 3,995 variations were detected across pLELC-derived EBV sequences, with the mutational hot spots located in latent genes. Combined with 180 published EBV sequences derived from healthy people in Southern China, we performed a genome-wide association study and identified 32 variations significantly related to pLELC (P < 2.56 × 10-05, Bonferroni correction), with the top signal of single nucleotide polymorphism (SNP) coordinate T7327C (OR = 1.22, P = 2.39 × 10-15) locating in the origin of plasmid replication (OriP). The results of population structure analysis of EBV isolates in East Asian showed the EBV strains derived from pLELC were more similar to those from nasopharyngeal carcinoma (NPC) than other EBV-associated diseases. In addition, typical latency type-II infection were recognized for EBV of pLELC at both transcription and methylation levels. Taken together, we defined the global view of EBV genomic profiles in pLELC patients for the first time, providing new insights to deepening our understanding of this rare EBV-associated primary lung carcinoma. IMPORTANCE Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare, distinctive subtype of primary lung cancer closely associated with Epstein-Barr virus (EBV) infection. Here, we gave the first overview of pLELC-derived EBV at the level of genome, methylation and transcription. We obtained the EBV sequences data set from 78 primary pLELC patients, and revealed the sequences diversity across EBV genome and detected variability in known immune epitopes. Genome-wide association analysis combining 217 healthy controls identifies significant variations related to the risk of pLELC. Meanwhile, we characterized the integration landscapes of EBV at the genome-wide level. These results provided new insight for understanding EBV's role in pLELC tumorigenesis.

Peptidome-wide association analysis of Epstein-Barr virus identifies epitope repertoires associated with nasopharyngeal carcinoma.

Human leukocyte antigen (HLA) molecules are essential for presenting Epstein-Barr virus (EBV) antigens and are closely related to nasopharyngeal carcinoma (NPC). This study aims to systematically investigate the association between HLA-bound EBV peptides and NPC risk through in silico HLA-peptide binding prediction. A total of 455 NPC patients and 463 healthy individuals in NPC endemic areas were recruited, and HLA-target sequencing was performed. HLA-peptide binding prediction for EBV, followed by peptidome-wide logistic regression and motif analysis, was applied. Binding affinity changes for EBV peptides carrying high-risk mutations were analyzed. We found that NPC-associated EBV peptides were significantly enriched in immunogenic proteins and core linkage disequilibrium (LD) proteins related to evolution, especially those binding HLA-A alleles (p = 3.10 × 10-4 for immunogenic proteins and p = 8.10 × 10-5 for core LD proteins related to evolution). These peptides were clustered and showed binding motifs of HLA supertypes, among which supertype A02 presented an NPC-risk effect (padj = 3.77 × 10-4 ) and supertype A03 presented an NPC-protective effect (padj = 4.89 × 10-4 ). Moreover, a decreased binding affinity toward risk HLA supertype A02 was observed for the peptide carrying the NPC-risk mutation BNRF1 V1222I (p = 0.0078), and an increased binding affinity toward protective HLA supertype A03 was observed for the peptide carrying the NPC-risk mutation BALF2 I613V (p = 0.022). This study revealed the distinct preference of EBV peptides for binding HLA supertypes, which may contribute to shaping EBV population structure and be involved in NPC development.

The interaction and mediation effects between the host genetic factors and Epstein-Barr virus VCA-IgA in the risk of nasopharyngeal carcinoma.

Previous studies have demonstrated strong associations between host genetic factors and Epstein-Barr virus (EBV) VCA-IgA with the risk of nasopharyngeal carcinoma (NPC). However, the specific interplay between host genetics and EBV VCA-IgA on NPC risk is not well understood. In this two-stage case-control study (N = 4804), we utilized interaction and mediation analysis to investigate the interplay between host genetics (genome-wide association study-derived polygenic risk score [PRS]) and EBV VCA-IgA antibody level in the NPC risk. We employed a four-way decomposition analysis to assess the extent to which the genetic effect on NPC risk is mediated by or interacts with EBV VCA-IgA. We consistently found a significant interaction between the PRS and EBV VCA-IgA on NPC risk (discovery population: synergy index [SI] = 2.39, 95% confidence interval [CI] = 1.85-3.10; replication population: SI = 3.10, 95% CI = 2.17-4.44; all pinteraction < 0.001). Moreover, the genetic variants included in the PRS demonstrated similar interactions with EBV VCA-IgA antibody. We also observed an obvious dose-response relationship between the PRS and EBV VCA-IgA antibody on NPC risk (all ptrend < 0.001). Furthermore, our decomposition analysis revealed that a substantial proportion (approximately 90%) of the genetic effects on NPC risk could be attributed to host genetic-EBV interaction, while the risk effects mediated by EBV VCA-IgA antibody were weak and statistically insignificant. Our study provides compelling evidence for an interaction between host genetics and EBV VCA-IgA antibody in the development of NPC. These findings emphasize the importance of implementing measures to control EBV infection as a crucial strategy for effectively preventing NPC, particularly in individuals at high genetic risk.

Trending prevalence of healthcare-associated infections in a tertiary hospital in China during the COVID-19 pandemic.

BACKGROUND: The purpose of this study was to demonstrate both the four-year prevalence trend of healthcare-associated infections (HAIs) in a large tertiary hospital and the trend regarding the prevalence of HAIs following the outbreak of coronavirus disease 2019 (COVID-19) in order to provide evidence of hospital infection management during the COVID-19 pandemic. METHODS: Based on the hospital's electronic nosocomial infection databases related to HAIs, we retrospectively identified the HAI cases to assess the epidemiological characteristics of HAIs from January 1, 2018, to December 31, 2021, in a large tertiary hospital in China. Similarly, the trends of HAIs after the COVID-19 outbreak and the seasonal variation of HAIs were further analyzed. RESULTS: The HAI cases (n = 7833) were identified from the inpatients (n = 483,258) during the 4 years. The most frequently occurring underlying cause of HAIs was respiratory tract infections (44.47%), followed by bloodstream infections (11.59%), and urinary tract infections (8.69%). The annual prevalence of HAIs decreased from 2.39% in 2018 to 1.41% in 2021 (P = 0.032), with the overall prevalence of HAIs significantly decreasing since the outbreak of COVID-19 (2.20% in 2018-2019 vs. 1.44% in 2020-2021, P < 0.001). The prevalence of respiratory tract infections decreased most significantly; whereas, overall, the prevalence of HAIs was significantly greater during the winter compared with the rest of the year. CONCLUSIONS: Not only did the annual prevalence of HAIs decrease from 2018 to 2021, but it also significantly decreased since the start of the COVID-19 pandemic, particularly respiratory tract infections. These results provide evidence for the need to prevent HAIs, especially during the winter season.

Hemostatic Effects of Bio-Zeolite Gauze and QuikClot Combat Gauze on Major Bleeding in Rabbits Acutely Exposed to High Altitude.

Objective: Hemostatic gauze application is an effective way to control major bleeding, which is the most common cause of death in trauma in both civilian and military settings. Coagulation derangement after acute exposure to high altitude might alter the effects of hemostatic gauzes. The present study aimed to observe the hemostatic effects of bio-zeolite gauze (BZG) and QuikClot Combat Gauze® (QCG) on major bleeding in rabbits acutely exposed to high altitude.Methods: Sixty rabbits were randomly and evenly divided into six groups. Animal models of simulated blast- and fragment-induced inguinal major bleeding were prepared in lower altitude and high-altitude areas, and BZG, QCG, and ordinary gauze without hemostatic material were used to control bleeding. The primary outcomes included immediate hemostasis rate, blood loss, and survival rate, while the secondary outcomes included hemodynamic parameters, laboratory examinations, and coagulation-relevant markers.Results: The overall effects of BZG and QCG were better than those of ordinary gauze, with a higher immediate hemostatic rate, less blood loss, and higher survival rate at 90 min after gauze application and higher red blood cell and platelet counts and lower creatinine level at 30 min after gauze application in lower altitude. The concentrations of coagulation factor XII and factor X in rabbits acutely exposed to high altitude were significantly lower than those in lower altitude. At high altitude, the hemostatic effects of BZG did not decrease significantly compared to those in the lower altitude, whereas those of ordinary gauze and QCG decreased significantly at high altitude compared to those in the lower altitude.Conclusions: Coagulation derangement after acute exposure to high altitude has negative effects on ordinary gauze and QCG but has no significant negative hemostatic effects on BZG.

Pregnancy in patients with systemic lupus erythematosus: a systematic review.

Systemic lupus erythematosus (SLE)-a most common disorder in women of reproductive age-has been described to be associated with adverse pregnancy outcomes. Despite the increased health risks for the mother (preeclampsia, lupus flare, arterial hypertension, gestational diabetes mellitus and thrombotic risk when antiphospholipid antibodies are present) and fetus (miscarriage, stillbirth, premature birth, intrauterine growth restriction and neonatal lupus), the majority of patients can deliver healthy neonates. With appropriate management by a multidisciplinary team, composing rheumatologists, obstetricians and neonatologists, women with SLE can achieve better pregnancy outcomes by monitoring associated predictive indicators, raising major concern for severe complications and somewhat early delivery if necessary. In this review, we summarize the latest advances in secondary infertility and pregnancy-related risk perception for lupus patients, with an emphasis on the safety of biological agents (mainly belimumab and rituximab) and traditional therapeutic regimens.

Animal model-based simulation training for three emergent and urgent operations of penetrating thoracic injuries.

PURPOSE: To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees' performance for emergent and urgent thoracic surgeries. METHODS: With a homemade machine, animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage, urgent sternotomy, and emergent thoracotomy. Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models. Five operation teams from basic-level hospitals (group A) and five operation teams from level III hospitals (group B) were included to be trained and tested. Testing standards for the operations were established after thorough literature review, and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Tests were carried out after the training. Pre- and post-training performances were compared. Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches. RESULTS: Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%. After literature review, testing standards were established, and expert questionnaire results showed that the scientific score was 7.30 ± 1.49, and the feasibility score was 7.50 ± 0.89. Post-training performance was significantly higher in both group A and group B than pre-training performance. Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury. CONCLUSIONS: Animal model-based simulation training established in the current study could improve the trainees' performance for emergent and urgent thoracic surgeries, especially of the surgical teams from basic-level hospitals.

Genomic landscape of Epstein-Barr virus in familial nasopharyngeal carcinoma.

To better understand the genomic characteristics of Epstein-Barr virus (EBV) in familial nasopharyngeal carcinoma (NPC), we sequenced the EBV genomes by whole-genome capture in 38 unrelated patients with NPC family history in first-degree relatives and 47 healthy controls, including 13 with family history and 34 without. Compared with type 1 reference genome, mutation hotspots were observed in the latent gene regions of EBV in familial NPC cases. Population structure analysis showed that one cluster has a higher frequency in familial cases than in controls (OR=5.33, 95 % CI 2.50-11.33, P=1.42×10-5), and similar population structure composition was observed among familial and sporadic NPC cases in high-endemic areas. By genome-wide association analysis, four variants were found to be significantly associated with familial NPC. Consistent results were observed in the meta-analysis integrating two published case-control EBV sequencing studies in NPC high-endemic areas. High-risk haplotypes of EBV composed of 34 variants were associated with familial NPC risk (OR=13.85, 95 % CI 4.13-46.44, P=2.06×10-5), and higher frequency was observed in healthy blood-relative controls with NPC family history (9/13, 69.23 %) than those without family history (16/34, 47.06%). This study suggested the potential contribution of EBV high-risk subtypes to familial aggregation of NPC.

Burden, trends, and risk factors for breast cancer in China from 1990 to 2019 and its predictions until 2034: an up-to-date overview and comparison with those in Japan and South Korea.

BACKGROUND: The difference in epidemiological characteristics of breast cancer (BC) across countries is valuable for BC management and prevention. The study evaluated the up-to-date burden, trends, and risk factors of BC in China, Japan and South Korea during 1990-2019 and predicted the BC burden until 2034. METHODS: Data on incident cases, deaths, disability-adjusted life-years (DALYs) and age-standardized rate (ASR) of BC were extracted from the Global Burden of Disease Study 2019. Trend analysis and prediction until 2034 were conducted by estimated annual percentage change and a Bayesian age-period-cohort model, respectively. Besides, the attributable burden to BC risk factors was also estimated. RESULTS: In 2019, the number of BC incident cases, deaths and DALYs in China were 375,484, 96,306 and 2,957,453, respectively. The ASR of incidence increased, while that of death and DALYs decreased for Chinese females and Japanese and South Korean males during 1990-2019. High body-mass-index (BMI) was the largest contributor to Chinese female BC deaths and DALYs, while alcohol use was the greatest risk factor for Japanese and South Korean as well as Chinese males. The incident cases and deaths were expected to continue increase during 2020-2034 (except for Japanese female incident cases). CONCLUSIONS: China had the greatest burden of BC among the three countries. Incident cases and deaths of BC were projected to increase over the next 15 years in China, particularly among Chinese males. Effective prevention and management strategies are urgently necessary for BC control in China.

Calysepins I-VII, Hexasaccharide Resin Glycosides from Calystegia sepium and Their Cytotoxic Evaluation.

Seven new hexasaccharide resin glycosides, named calysepins I-VII (1-7), with 27-membered rings, were obtained from the aerial parts of Calystegia sepium. Their structures with absolute configuration were established on the basis of spectroscopic data interpretation analysis and the use of chemical methods. They were defined as hexasaccharides composed of one d-quinovose, four d-glucose, and one l-rhamnose unit, and their sugar moieties were partially acylated by (2S)-methylbutanoic acid in 1-7 and (2R,3R)-nilic acid in 1-5 and 7, which mainly differed at the positions of acylation. Additionally, calysepin IV (4) exhibited cytotoxicity against A549 cells with an IC50 value of 5.2 µM.

Anti-inflammatory sesquiterpene dimers and diterpenes from the aerial part of Inula japonica.

Phytochemical investigation on the 95% alcohol extract of the aerial part of Inula japonica led to the isolation of three new compounds, inulanolides F-G (1-2) and 17α-carboxaldehyde-ent-kaur-18-oic acid (3), together with four known compounds (4-7). The structures of new compounds were elucidated by using spectroscopic data. Most of the isolated compounds showed significant anti-inflammatory activities.

Establishment of a combat damage control surgery training platform for explosive combined thoraco-abdominal injuries.

PURPOSE: It is challenging to prepare military surgeons with the skills of combat damage control surgery (CDCS). The current study aimed to establish a damage control surgery (DCS) training platform for explosive combined thoraco-abdominal injuries. METHODS: The training platform established in this study consisted of 3 main components: (1) A 50 m × 50 m square yard was constructed as the explosion site. Safety was assessed through cameras. (2) Sixteen pigs were injured by an explosion of trinitrotoluene attached with steel balls and were randomly divided into the DCS group (accepted DCS) and the control group (have not accepted DCS). The mortality rate was observed. (3) The literature was reviewed to identify the key factors for assessing CDCS, and testing standards for CDCS were then established. Expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Then, a 5-day training course with incorporated tests was used to test the efficacy of the established platform. In total, 30 teams attended the first training course. The scores that the trainees received before and after the training were compared. SPSS 11.0 was employed to analyze the results. RESULTS: The high-speed video playback confirmed the safety of the explosion site as no explosion fragments projected beyond the wall. No pig died within 24 h when DCS was performed, while 7 pigs died in the control group. After a literature review, assessment criteria for CDCS were established that had a total score of 100 points and had 4 major parts: leadership and team cooperation, resuscitation, surgical procedure, and final outcome. Expert questionnaire results showed that the scientific score was 8.6 ± 1.25, and the feasibility score was 8.74 ± 1.19. When compared with the basic level, the trainees' score improved significantly after training. CONCLUSION: The platform established in this study was useful for CDCS training.

Association between HLA alleles and Epstein-Barr virus Zta-IgA serological status in healthy males from southern China.

BACKGROUND: Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV) associated cancer, exhibits an extremely high incidence in southern Chinese. Given that human leukocyte antigen (HLA) plays critical roles in antigen presentation and relates to NPC susceptibility, it is speculated that certain HLA variants may affect EBV reactivation, which is a key pathogenic factor of NPC. Therefore, we attempted to identify HLA alleles associated with the indicator of EBV reactivation, Zta-IgA, in healthy males from NPC endemic area. METHODS: HLA alleles of 1078 healthy males in southern China from the 21-RCCP study were imputed using genome-wide single nucleotide polymorphism data. EBV Zta-IgA in blood samples were measured using an enzyme-linked immunosorbent assay. Multiple logistic regression analysis was used to evaluate the effect of HLA allele on Zta-IgA serological status and its potential joint association with smoking. The binding affinity for Zta-peptide was predicted using NetMHCIIpan 4.0. RESULTS: HLA-DRB1*09:01 was found to be associated with a higher risk of Zta-IgA seropositivity (odds ratio = 1.80, 95% confidence interval = 1.32-2.45; p = 1.82 × 10-4 ). Compared with non-smokers without HLA-DRB1*09:01, the effect size increased to 2.19- and 3.70-fold for the light and heavy smokers carrying HLA-DRB1*09:01, respectively. Furthermore, HLA-DRB1*09:01 showed a stronger binding affinity to Zta peptide than other HLA-DRB1 alleles. CONCLUSIONS: Our study highlighted the pivotal role of genetic HLA variants in EBV reactivation and the etiology of NPC. Smokers with HLA-DRB1*09:01 have a significantly higher risk of being Zta-IgA seropositive, which indicates the necessity of smoking cessation in certain high-risk populations and also provide clues for further research on the etiology of NPC.

A fecal-based test for the detection of advanced adenoma and colorectal cancer: a case-control and screening cohort study.

BACKGROUND: Colorectal cancer (CRC) is the leading cause of cancer death worldwide. Screening is a confirmed way to reduce the incidence and mortality rates of CRC. This study aimed to identify a fecal-based, noninvasive, and accurate method for detection of colorectal cancer (CRC) and advanced adenoma (AA). METHODS: Through detection in tissue (n = 96) and fecal samples (n = 88) and tested in an independent group of fecal samples (n = 294), the methylated DNA marker ITGA4 and bacterial markers Fusobacterium nucleatum (Fn) and Pepetostreptococcusanaerobius (Pa) were identified from the candidate biomarkers for CRC and AA detection. A prediction score (pd-score) was constructed using the selected markers and fecal immunochemical test (FIT) for distinguishing AA and CRC from healthy subjects by logistic regression method. The diagnostic performance of the pd-score was compared with FIT and validated in the external validation cohort (n = 117) and in a large CRC screening cohort. RESULTS: The pd-score accurately identified AA and CRC from healthy subjects with an area under the curve (AUC) of 0.958, at a specificity of 91.37%; the pd-score showed sensitivities of 95.38% for CRC and 70.83% for AA, respectively. In the external validation cohort, the sensitivities of the pd-score for CRC and AA detection were 94.03% and 80.00%, respectively. When applied in screening, the pd-score identified 100% (11/11) of CRC and 70.83% (17/24) of AA in participants with both colonoscopy results and qualified fecal samples, showing an improvement by 41.19% compared to FIT. CONCLUSIONS: The current study developed a noninvasive and well-validated approach for AA and CRC detection, which could be applied widely as a diagnostic and screening test.