BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

OBJECTIVES: To develop a risk prediction model for the transformation of chronic atrophic gastritis to high-grade intraepithelial neoplasia (HGIN) based on traditional Chinese medicine (TCM) syndrome patterns. METHODS: Clinical data of 201 chronic atrophic gastritis patients who visited the Second People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine and Dong'erhuan Branch between January 2022 and March 2023 were retrospectively analyzed, including 32 patients with HGIN (HGIN group) and 169 patients with moderate and severe chronic atrophic gastritis (non-HGIN group). The information of demographic characteristics, dietary habits, lifestyle factors, social and psychosocial factors, family history of tumors, medical history and comorbidities, long-term medication, endoscopic findings, histopathological examination results, as well as TCM syndrome types were collected. Potential HGIN risk factors were screened using LASSO regression, and the significant risk factors for establishing an HGIN risk prediction model were identified using logistic regression analysis. The final model was visually presented using a nomogram, and its diagnostic performance was evaluated through receiver operating characteristic curve analysis. RESULTS: Spleen-stomach Qi deficiency was the most common TCM syndrome in both HGIN and non-HGIN groups. LASSO-logistic regression model analysis showed that heavy alcohol consumption (X1), syndrome of static blood in stomach collaterals (X2), low-grade intraepithelial neoplasia (X3), high-salt diet (X4), and age (X5) were independent risk factors related to the occurrence of HGIN, and the predictive model was ln［P/(1－P)］=2.159X1+2.230X2+1.664X3+2.070X4+0.122X5- 11.096. The model demonstrated good discriminative ability, calibration, and goodness-of-fit, with area under the curve values of 0.940 and 0.891 in the training and validation sets, respectively. CONCLUSIONS The TCM syndrome of static blood in stomach collaterals shows correlation with the transformation from chronic atrophic gastritis to HGIN. The HGIN prediction model based on TCM syndrome patterns developed in the study demonstrates potential value in clinical application.
Humans ; Gastritis, Atrophic/diagnosis* ; Medicine, Chinese Traditional ; Retrospective Studies ; Female ; Male ; Middle Aged ; Stomach Neoplasms/diagnosis* ; Adult ; Risk Factors ; Carcinoma in Situ/diagnosis* ; Aged ; Nomograms ; Chronic Disease ; Logistic Models

Objective To investigate the effectiveness and safety of endoscopic mucosal resection with precutting(EMR-P)for the treatment of rectal neuroendocrine neoplasm(RNEN)smaller than 1 cm in diameter.Methods Clinical data of 177 patients with RNEN smaller than 1 cm in diameter from December 2016 to December 2021 were retrospectively analyzed.According to different treatment protocols,177 patients with RNEN were divided into endoscopic mucosal resection(EMR)group(n = 46),EMR-P group(n = 40)and endoscopic submucosal dissection(ESD)group(n = 91).The en bloc resection rate,complete resection rate,operation time,postoperative hospitalization time and incidence of operative complications among the three groups were compared.Results The complete resection rate in the EMR-P group(95.0%)and ESD group(97.8%)were significantly higher than that in the EMR group(87.0%)(P<0.05);The operation time in the EMR-P group(9.86±2.23)min was longer than that in the EMR group(4.12±0.88)min,EMR-P group and EMR group were shorter than that in the ESD group(19.55±3.67)min,the difference was statistically significant(P<0.05);Postoperative hospitalization time in the EMR group was(2.45±0.29)d and EMR-P group was(2.43±0.23)d,which were shorter than that in the ESD group(3.30±0.32)d,and the difference was statistically significant(P<0.05).There were no significant difference in the rates of en bloc resection and operative complications among the three groups(P>0.05).Conclusion EMR-P for the treatment of RNEN<1 cm in diameter has the advantages,such as simple operation,short operation time and hospitalization time,high histological complete resection rate and low complication rate,which is worthy of clinical application.

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Background::Endoscopic resection is increasingly used in the treatment for early gastric cancer (EGC); however, about 15% of endoscopic submucosal dissection (ESD) cases report non-curative resection. The efficacy of different remedial interventions after non-curative ESD for EGC remains controversial. This meta-analysis aimed to compare the long-term outcomes of additional surgery and non-gastrectomy treatment for EGC patients who underwent non-curative ESD.Methods::All relevant studies published up to October 2021 were systematically searched in the PubMed, Web of Science, and Embase databases. The medical subject headings terms "early gastric cancer," "gastrectomy," "endoscopic submucosal dissection," and their related free keywords were used to search relevant articles without restrictions on regions, publication types, or languages. The Newcastle–Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Odds ratios (ORs) with 95% confidence intervals (CIs) of 5-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and hazard ratios (HRs) with 95% CIs of OS were calculated using a random- or fixed-effects model.Results::This meta-analysis included 17 retrospective cohort studies with 5880 patients, of whom 3167 underwent additional surgery and 2713 underwent non-gastrectomy. We found that patients receiving additional gastrectomy had better 5-year OS (OR = 3.63, 95% CI = 3.05–4.31), DSS (OR = 3.22, 95% CI = 2.22–4.66), and DFS (OR = 4.39, 95% CI = 1.78–10.82) outcomes than those receiving non-gastrectomy treatments. The pooled HR also showed that gastrectomy following non-curative ESD significantly improved OS (HR = 0.40, 95% CI = 0.33–0.48). In addition, elderly patients benefited from additional surgery in consideration of the 5-year OS (HR = 0.54, 95% CI= 0.41–0.72).Conclusions::Compared with non-gastrectomy treatments, additional surgery offered better long-term survival outcomes for patients with EGC who underwent non-curative ESD.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Objective:To evaluate the diagnostic value of endoscopic ultrasonography (EUS) in colorectal submucosal lesions, and provide evidence for clinical diagnosis and treatment strategies.Methods:A retrospective analysis was performed on data of 229 patients with colorectal submucosal lesions discovered by electronic colonoscopy and EUS. The diagnosis was confirmed by pathology. The location, type, EUS features of lesions and the coincidence rate of EUS and histopathological diagnosis were analyzed.Results:Colorectal submucosal lesions were common in the rectum (44.98%, 103/229) and ascending colon (15.28%, 35/229). Lipoma was the most common pathological type of colorectal submucosal lesions (34.93%, 80/229), which was commonly located in transverse colon (22.50%, 18/80) and ascending colon (20.00%, 16/80). Neuroendocrine tumor was the second one, accounting for 33.63% (77/229), and was commonly located in rectum (96.10%, 74/77), followed by cyst (18.78%, 43/229). Under EUS, 229 cases of lesions originated from submucosa in 215 cases, muscularis mucosa in 11 cases, and muscularis propria in 3 cases. The overall coincidence rate of EUS and pathological diagnosis was 89.08% (204/229). The coincidence rate of EUS diagnosis was 100.00% (80/80) for lipoma, 5/5 for air-cyst, 3/3 for intestinal stromal tumor, 81.82% (72/88) for neuroendocrine tumor, 89.13% (41/46) for cyst, 1/4 for leiomyoma, 2/5 for lymphangioma, and granulosa cell tumor and neurofibroma were both 0.Conclusion:EUS has a more accurate diagnosis of the origin, echogenicity and pathological properties of colorectal submucosal lesions, but it has certain limitations for the diagnosis of rare tumors such as granulosa cell tumor and neurofibroma.

Objective To examine the prevalence of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS),and to evaluate the relationship of OSA with inflammatory biomarkers in ACS patients.Methods Patients with ACS treated at Beijing Anzhen Hopital from June 2015 to May 2017 were enrolled.Subjects were evaluated for OSA by sleep study,and were divided into a normal-mild OSA group (Apnea Hypopnea Index,AHI ＜ 15 times/h) and a moderate-severe OSA group (AHI ≥ 15 times/h).Laboratory examination and sleep study were monitored to analyze the effects of OSA on biomarkers by LSD-t test,Mann-whitney U test,or Chi-square test.Correlation analysis was performed to analyze the association of OSA with high sensitivity C-reactive protein (hs-CRP) by Spearman correlation anaylsis.Results A cohort of 836 patients with ACS were enrolled including 408 patients in the normal-mild OSA group and 428 patients in the moderate-severe OSA group.The levels of leukocyte(x 109L) [7.78 (6.33,9.86) vs 7.29 (6.01,9.16),P=0.006],neutrophils(× 109L) [5.05 (3.84,7.23)vs 4.80 (3.74,6.66),P=0.044],monocytes(x 109L) [0.42 (0.33,0.54) vs 0.39 (0.31,0.51),P=0.033],hsCRP(mg/L) [3.18 (1.10,11.52) vs 1.78 (0.65,6.46),P＜0.01],fibrinogen(g/L) [3.17 (2.87,3.74) vs 2.97 (2.59,3.50),P=0.002],and uric acid(μmol/L) [360 (302,422) vs 341(283,407),P=0.006] in the moderatesevere OSA group were significant higher than those in the normal-mild OSA group.AHI (correlation coefficient=0.171,R2=0.020,P＜0.01),ODI (correlation coefficient =0.201,R2=0.027,P＜0.01),and TSaO2 ＜ 90％ (correlation coefficient =0.105,R2=0.005,P＜0.01) were positively correlated with hs-CRP;minimal SaO2 (correlation coefficient=-0.100,R2=0.001,P=0.008) and mean SaO2 (correlation coefficient =-0.127,R2=0.006,P＜0.01) were negatively correlated with hs-CRP.Conclusions For patients with ACS,the level of inflammatory markers in the moderate-severe OSA group is significantly higher than that in the normal-mild OSA group.Hs-CRP is significantly associated with the severity of OSA.Diagnosis and monitoring of OSA should be considered in ACS management in the future.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Objective To investigate the clinical efficacy of Baduanjin combined with biofeedback on functional defecation disorders and the effect on serum brain-gut peptide.Methods From June, 2017 to February, 2018, 68 patients were randomly divided into control group (n=34) and observation group (n=34). Both groups received biofeedback therapy, and the observation group took the training of Baduanjin in addition, for twelve weeks. Then, their overall clinical efficacy, main syndrome score of constipation, the score of Patient Assessment of Constipation Quality of Life (PAC-QOL) and Brain-gut peptide level were compared before and after intervention.Results The total clinical efficacy was higher in the observation group than in the control group (Z=-2.065, P=0.039) without shedding cases. After treatment, the main symptoms of constipation significantly improved (t>2.162, P<0.05) in both groups, while the defecation inactivity, defecation time and abdominal distension score were significantly lower in the observation group than in the control group (t>2.837, P<0.01), as well as the defecation strain (t=-2.070, P<0.05); the score of PAC-QOL decreased (t>2.085, P<0.05) in both groups, and was lower (t=-2.243, P<0.05) in the observation group than in the control group; the level of serum 5-hydroxytryptamine (5-HT), nitric oxide (NO) and vasoactive intestinal peptide (VIP) decreased (t>2.420, P<0.05), while the level of serum substance P (SP) increased (t>6.780, P<0.001), the level of serum 5-HT, serum NO and serum VIP was lower (t>2.039, P<0.05), and the level of serum SP was higher (t=3.500, P<0.001) in the observation group than in the control group.Conclusion Baduanjin combined with biofeedback can improve the clinical efficacy of patients with functional defecation disorders, and its mechanism is closely related to the regulation of abnormal secretion and the expression of brain-gut peptide.