Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective:To observe any effect of dual-task training on abnormal gait and fall risk among hemiplegic stroke survivors.Methods:A total of 90 stroke survivors were randomly divided into a control group, a cognitive dual-task group, and a motor dual-task group, each of 30. All 3 groups received conventional post-stroke medication and rehabilitation training, but the cognitive and motor dual-task groups received cognitive or motor dual-task training as well. Before and after 4 weeks of the training, everyone′s balance, walking and lower limb motor functioning were assessed using the Berg Balance Scale (BBS), the Timed Up and Go test (TUGT) and the Fugl-Meyer lower extremity assessment (FMA-LE). Additionally, three-dimensional gait analysis was performed to document gait speed, bilateral spatial asymmetry, bilateral temporal asymmetry, and the dual-task cost (DTC) of gait speed.Results:Significant improvement was observed in the average BBS scores, TUGT times, FMA-LE scores, gait speed, DTC of gait speed, bilateral spatial asymmetry ratios, and bilateral temporal asymmetry ratios of all 3 groups after the experiment. The averages of the cognitive dual-task group were then significantly better than the control group′s averages. The motor dual-task group′s average BBS score (42.67±7.87), TUGT time [(22.30±8.53)s], gait speed (0.58±0.2m/s), DTC of gait speed (19.02±5.99%), and bilateral spatial asymmetry ratio (19.79±10.41%) were then significantly better than the control group′s averages but not significantly different from those of the cognitive dual-task group.Conclusions:Dual-task training can significantly improve the balance, walking and lower limb motor function of stroke survivors, correcting their abnormal gait patterns and consequently reducing their fall risks.

Objective:To investigate the efficacy and safety of high-frequency irreversible electroporation (H-FIRE) in treating benign prostatic hyperplasia (BPH).Methods:This randomized controlled open-label multicenter clinical trial enrolled patients from nine medical centers in China between August 2020 and July 2022. Inclusion criteria: age 50–80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Q max) >5 ml/min and ≤15 ml/min. Exclusion criteria: prostate malignancy, contraindications to surgery or anesthesia. Patients were randomized 1∶1 into the H-FIRE group (experimental) or the control group (daily oral 0.2 mg tamsulosin hydrochloride sustained-release capsules). Primary outcomes included Q max, IPSS, prostate volume, and International Index of Erectile Function-5 (IIEF-5) scores, measured at baseline, 1 and 3 months post-treatment. Results:A total of 160 cases were included in this study, including 80 cases in the experimental group and 80 cases in the control group, 30 cases in Renji Hospital, 7 cases in Qilu Hospital of Shandong University, 8 cases in Tongji Hospital, 3 cases in Hunan Provincial Hospital, 13 cases in Shanghai Pudong Hospital, 29 cases in Hwa Mei Hospital, 18 cases in Yiyuan County People's Hospital, and 38 cases in Shanghai East Hospital, and 14 cases in Sun Yat-sen Memorial Hospital. At 3 months of post-treatment, Q max in the experimental group increased by a median of 7.50 (3.55, 14.50) ml/s from the baseline value, whereas in the control group it increased by a median of 1.70 (-1.40, 6.00) ml/s, and the difference between the two groups was statistically significant ( P < 0.01, U = 1 083); and at 3 months of post-treatment, IPSS in the experimental group decreased by a median of 12.00 (7.00, 17.00) points in the test group and 6.00 (2.00, 11.00) points in the control group, and the magnitude of improvement in IPSS scores in the test group was significantly higher than that in the control group ( P < 0.01, U = 1 248); at 3 months of post-treatment, the prostate volume decreased by a median of 12.16 (5.69, 18.27) ml in the experimental group and 0 (-3.94, 6.89) ml in the control group, suggesting that H-FIRE significantly reduced prostate gland volume ( P<0.01, U=1 111). The difference in elevated IIEF-5 scores from baseline at 3 months of treatment between the experimental and control groups was not statistically significant[0(-2.00, 1.00) points vs. 0(-2.00, 1.50) points; P=0.54, U=2 338]. There were no serious adverse events in the two groups. Conclusions:H-FIRE could significantly improve both subjective and objective symptoms of BPH with a low risk of severe complications.

Objective To construct an XGBoost predictive model using clinical characteristic data from patients with chronic obstructive pulmonary disease(COPD)and evaluate the efficacy of the predictive model in early risk prediction of lung cancer occurrence in COPD patients.Methods In this retrospective cross-sectional study,cluster sampling was used.We selected clinically diagnosed COPD patients admitted to The Second Affiliated Hospital of Xi'an Jiaotong University from January 1,2018,to December 31,2022.A total of 4 008 patients with complete data were included.First,the baseline of each characteristic was analyzed,and then XGBoost was used to construct the lung cancer risk prediction model for COPD patients,and SHAP(SHapley Additive exPlanation)value was used to quantify and attribute the importance of each characteristic.DC A curve was used to evaluate the clinical application value.Results After constructing a lung cancer risk model for COPD patients using 28 variables,eight variables were selected according to the importance of the variables and clinical experience,and the prediction model was reconstructed.The model efficacy in the training set and the test set was 0.948(0.938,0.958)and 0.797(0.738,0.856),respectively.SHAP diagram showed that elevated CEA,CA125,FIB,eosinophils,PLT and D-dimer and reduced TT all contributed to an increased risk of lung cancer in COPD patients.DCA curve showed that the prediction model had clinical application value,which could help doctors make more accurate prognosis prediction and treatment decisions.Conclusion The successful establishment of an XGBoost predictive model,utilizing a subset of features,enables early prediction of lung cancer occurrence in COPD patients.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

OBJECTIVE: Although dietary preferences influence chronic diseases, few studies have linked dietary preferences to mortality risk, particularly in large cohorts. To investigate the relationship between dietary preferences and mortality risk (all-cause, cancer, and cardiovascular disease [CVD]) in a large adult cohort. METHODS: A cohort of 1,160,312 adults (mean age 62.48 ± 9.55) from the Shenzhen Healthcare Big Data Cohort (SHBDC) was analyzed. Hazard ratios ( HRs) for mortality were estimated using the Cox proportional hazards model. RESULTS: The study identified 12,308 all-cause deaths, of which 3,865 (31.4%) were cancer-related and 3,576 (29.1%) were attributed to CVD. Compared with a mixed diet of meat and vegetables, a mainly meat-based diet (hazard ratio [ HR] = 1.13; 95% confidence interval [ CI]: 1.02, 1.27) associated with a higher risk of all-cause mortality, while mainly vegetarian ( HR = 0.87; 95% CI: 0.78, 0.97) was linked to a reduced risk. Furthermore, there was a stronger correlation between mortality risk and dietary preference in the > 65 age range. CONCLUSION A meat-based diet was associated with an increased risk of all-cause mortality, whereas a mainly vegetarian diet was linked to a reduced risk.
Humans ; China/epidemiology* ; Middle Aged ; Male ; Female ; Prospective Studies ; Aged ; Cardiovascular Diseases/mortality* ; Diet/statistics & numerical data* ; Neoplasms/mortality* ; Adult ; Cause of Death ; Food Preferences ; Proportional Hazards Models ; Mortality ; Cohort Studies

With reference to the Information and Documentation-Resource Description (GB/T 3792-2021) and Bibliographical Description for Ancient Chinese Books (GB/T 3792.7-2008) and other cataloging standards and rules, drawing on the practical experience of cataloging ancient TCM books, Bibliographical Cataloging for Ancient TCM Books was formulated. This standard specifies the entry items and their order of ancient TCM books, cataloging identifier, cataloging text, cataloging information source, and cataloging item details. The standard can provide standardized and unified guiding principles and methods for the work of ancient TCM books, and promote the sharing and utilization of ancient TCM books.

Objective To construct an XGBoost predictive model using clinical characteristic data from patients with chronic obstructive pulmonary disease(COPD)and evaluate the efficacy of the predictive model in early risk prediction of lung cancer occurrence in COPD patients.Methods In this retrospective cross-sectional study,cluster sampling was used.We selected clinically diagnosed COPD patients admitted to The Second Affiliated Hospital of Xi'an Jiaotong University from January 1,2018,to December 31,2022.A total of 4 008 patients with complete data were included.First,the baseline of each characteristic was analyzed,and then XGBoost was used to construct the lung cancer risk prediction model for COPD patients,and SHAP(SHapley Additive exPlanation)value was used to quantify and attribute the importance of each characteristic.DC A curve was used to evaluate the clinical application value.Results After constructing a lung cancer risk model for COPD patients using 28 variables,eight variables were selected according to the importance of the variables and clinical experience,and the prediction model was reconstructed.The model efficacy in the training set and the test set was 0.948(0.938,0.958)and 0.797(0.738,0.856),respectively.SHAP diagram showed that elevated CEA,CA125,FIB,eosinophils,PLT and D-dimer and reduced TT all contributed to an increased risk of lung cancer in COPD patients.DCA curve showed that the prediction model had clinical application value,which could help doctors make more accurate prognosis prediction and treatment decisions.Conclusion The successful establishment of an XGBoost predictive model,utilizing a subset of features,enables early prediction of lung cancer occurrence in COPD patients.

Objective:To observe any effect of dual-task training on abnormal gait and fall risk among hemiplegic stroke survivors.Methods:A total of 90 stroke survivors were randomly divided into a control group, a cognitive dual-task group, and a motor dual-task group, each of 30. All 3 groups received conventional post-stroke medication and rehabilitation training, but the cognitive and motor dual-task groups received cognitive or motor dual-task training as well. Before and after 4 weeks of the training, everyone′s balance, walking and lower limb motor functioning were assessed using the Berg Balance Scale (BBS), the Timed Up and Go test (TUGT) and the Fugl-Meyer lower extremity assessment (FMA-LE). Additionally, three-dimensional gait analysis was performed to document gait speed, bilateral spatial asymmetry, bilateral temporal asymmetry, and the dual-task cost (DTC) of gait speed.Results:Significant improvement was observed in the average BBS scores, TUGT times, FMA-LE scores, gait speed, DTC of gait speed, bilateral spatial asymmetry ratios, and bilateral temporal asymmetry ratios of all 3 groups after the experiment. The averages of the cognitive dual-task group were then significantly better than the control group′s averages. The motor dual-task group′s average BBS score (42.67±7.87), TUGT time [(22.30±8.53)s], gait speed (0.58±0.2m/s), DTC of gait speed (19.02±5.99%), and bilateral spatial asymmetry ratio (19.79±10.41%) were then significantly better than the control group′s averages but not significantly different from those of the cognitive dual-task group.Conclusions:Dual-task training can significantly improve the balance, walking and lower limb motor function of stroke survivors, correcting their abnormal gait patterns and consequently reducing their fall risks.