Objective:To evaluate the efficacy of multimodal prehabilitation in patients with refractory functional constipation undergoing Jinling procedure(modified Duhamel surgery).Methods:In this prospective randomized controlled trial,80 patients with refractory functional constipation scheduled for Jinling procedure at the Department of General Surgery,the General Hospital of Eastern Theater Command between January 2020 and December 2021 were enrolled.Participants were randomly assigned to either the observation group(n=40,multimodal prehabilitation)or control group(n=40,routine nursing care).Outcome measures included:time to first flatus,time to first ambulation,defecation volume on postoperative day 5,length of hospitalization,nutritional markers(hemoglobin,albumin,total protein at postoperative day 7),anxiety/depression scores(Hospital Anxiety and Depression Scale,HADS),and total complication rates.Results:Compared to controls,the first ventilation time(48.02±6.15)h,first ambulation time(49.92±5.58)h,defecation volume on the fifth day(234.50±51.03)mL,hospital stay(13.15±2.64)d,anxiety score(43.68±3.45)points,depression score(43.81±1.58)points,and the total incidence of postoperative complications(15%)were significantly lower in the observation group(all p values<0.05).By contrast,the serum levels of hemoglobin(115.60±11.60)g/l,albumin(41.19±5.79)g/L and total protein(61.64±4.94)g/L on day 7 post-operatively were significantly higher in the observation group than those in the control group(P<0.05).Conclusions:Multimodal prehabilitation enhances postoperative intestinal recovery,reduces complications,improves nutritional status,and shortens hospital stays in refractory functional constipation patients undergoing Jinling procedure,supporting its clinical adoption.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Breast cancer is one of the most common malignant tumors, and postoperative radiotherapy remains an essential component of its treatment. In recent years, hypofractionated radiotherapy has gradually become the recommended approach for postoperative breast cancer treatment. Compared with conventional fractionated radiotherapy, hypofractionated regimens shorten the overall treatment duration, enhance patient convenience, and reduce treatment costs, while achieving comparable long-term efficacy and maintaining good quality of life. Based on relevant domestic and international studies and clinical experience, this consensus establishes expert recommendations regarding indications, prescribed doses, dose constraints for organs at risk (OAR), implementation methods, and plan evaluation for hypofractionated radiotherapy after breast cancer surgery, with a particular focus on moderately hypofractionated (MHF) and ultrahypofractionated (UHF) regimens. MHF radiotherapy is applicable to whole-breast irradiation, chest wall irradiation, and regional nodal irradiation, and is suitable for most breast cancer patients. UHF radiotherapy, which employs a higher dose per fraction to further shorten the treatment course, is suitable for patients requiring rapid therapy or prioritizing treatment convenience. Although the short-term efficacy of UHF radiotherapyis similar to that of MHF radiotherapy, its long-term efficacy and safety require further clinical validation. Meanwhile, potential adverse effects of UHF, such as breast induration and atrophy, should be carefully assessed. Therefore, radiotherapy dose and fractionation regimen should be individualized according to patient-specific factors, particularly considering OAR dose constraints. Rational selection of radiotherapy regimens can minimize adverse effects while maintaining therapeutic efficacy, ultimately improving patient outcomes and quality of life. This consensus provides scientific guidance for the clinical and research application of hypofractionated radiotherapy in breast cancer.

G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

Breast cancer is one of the most common malignant tumors, and postoperative radiotherapy remains an essential component of its treatment. In recent years, hypofractionated radiotherapy has gradually become the recommended approach for postoperative breast cancer treatment. Compared with conventional fractionated radiotherapy, hypofractionated regimens shorten the overall treatment duration, enhance patient convenience, and reduce treatment costs, while achieving comparable long-term efficacy and maintaining good quality of life. Based on relevant domestic and international studies and clinical experience, this consensus establishes expert recommendations regarding indications, prescribed doses, dose constraints for organs at risk (OAR), implementation methods, and plan evaluation for hypofractionated radiotherapy after breast cancer surgery, with a particular focus on moderately hypofractionated (MHF) and ultrahypofractionated (UHF) regimens. MHF radiotherapy is applicable to whole-breast irradiation, chest wall irradiation, and regional nodal irradiation, and is suitable for most breast cancer patients. UHF radiotherapy, which employs a higher dose per fraction to further shorten the treatment course, is suitable for patients requiring rapid therapy or prioritizing treatment convenience. Although the short-term efficacy of UHF radiotherapyis similar to that of MHF radiotherapy, its long-term efficacy and safety require further clinical validation. Meanwhile, potential adverse effects of UHF, such as breast induration and atrophy, should be carefully assessed. Therefore, radiotherapy dose and fractionation regimen should be individualized according to patient-specific factors, particularly considering OAR dose constraints. Rational selection of radiotherapy regimens can minimize adverse effects while maintaining therapeutic efficacy, ultimately improving patient outcomes and quality of life. This consensus provides scientific guidance for the clinical and research application of hypofractionated radiotherapy in breast cancer.

Objective:To search,evaluate and summarize the best evidence about nasal mucosa pressure injury caused by nasal feeding tube at home and abroad,and provide evidence-based basis for clinical practice.Methods:According to the"6S"model of evidence resources,literatures related to nasal mucosal stress injury were systematically searched from UpToDate,Guidelines International Network,Joanna Briggs Institute Evidence-based Healthcare Center,Web of Science,Cochrane Library,CNKI,Wanfang database and other related nutrition professional websites.The search period was from the establishment of the database to February 2024.Four researchers independently evaluated the literature quality,and after consulting the opinions of evidence-based experts,evidence was extracted and summarized for literatures that met the quality standards.Results:A total of 12 studies were included,including 5 guidelines,4 expert consensus,1 clinical decision,1 systematic review and 1 evidence summary,covering 24 pieces of evidence on 5 topics,including team building,nasal mucosa evaluation,nasal mucosa care,placement and maintenance of nasal feeding tube,monitoring and education.Conclusions:The evidence of prevention and nursing of nasal mucosal pressure injury caused by nasal feeding tube can be applied to clinical practice,promote the standardized management of nasal feeding tube and improve the implementation effect of enteral nutrition.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens.GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.