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.

Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

OBJECTIVE To investigate the synergistic effect and mechanism of curcumin （CUR） combined with zerumbone （ZER） on the biological behavior of non-small cell lung cancer （NSCLC） A549 cells. METHODS CCK-8 method and Gin’s formula were used to screen the optimal concentration combination for synergistic effect after the combination of CUR and ZER. The cells were divided into blank group， CUR group， ZER group， and CUR+ZER group. Flow cytometry was used to evaluate cell apoptosis， and clone formation experiment was used to evaluate cell proliferation ability， scratch experiment and Transwell migration experiment were used to evaluate cell migration ability， and Transwell invasion experiment was used to evaluate cell invasion ability. Western blot assay was used to detect the protein expressions of phosphorylated phosphatidylinositol-3-kinase （p- PI3K）， phosphorylated protein kinase B （p-Akt）， and vascular endothelial growth factor A （VEGF-A）. RESULTS The half inhibitory concentrations of CUR and ZER on A549 cells were approximately 16 and 12 μmol/L， respectively； the drug combination of CUR 8 μmol/L+ZER 6 μmol/L had the highest efficiency enhancement index， with the cell proliferation inhibition rate of （77.41±4.16）%， indicating the most significant synergistic effect. Compared with the CUR and ZER groups， the cell apoptosis rate in the CUR+ZER group was significantly increased （P＜0.01）， while the cell clone formation rate， cell migration rate， the number of migrating cells， the number of invading cells， and relative expression levels of p-PI3K， p-Akt， and VEGF-A proteins in the cells were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS The combination of CUR and ZER has a synergistic effect， significantly promoting the apoptosis of NSCLC cells， and inhibiting cell proliferation， migration， and invasion. Its potential mechanism may be closely related to the inhibition of the PI3K/Akt signaling pathway， thereby down-regulating the protein expression of VEGF-A.

The traditional experimental teaching mode of forensic science and biological evidence is mostly confined to experimental operation, which is not capable of cultivating students' comprehensive quality and post competency. Therefore, it is urgent to seek an innovative teaching and training mode. At present, the experimental teaching of forensic science and biological evidence is dominated by teachers. There are some problems, such as insufficient training of students' scientific thinking and innovation ability, single teaching and evaluation model, and disconnection from the practical application. This paper proposes an experimental teaching design scheme of forensic science and biological evidence based on post competency training. The course is implanted in the framework of simulated cases, and the virtual simulation experiment platform and group discussion learning method are used to achieve a training model oriented by social needs and centered on students. In the preliminary study on the students who were trained in this mode of selected sections, we found that, compared with traditional teaching, the time for students to complete the prescribed experimental operation in this teaching mode was shortened by 4 minutes on average, and the average score of theoretical course test case analysis questions was increased by 1.5 points. In conclusion, the instructional design of the experiment teaching forensic science and biological evidence can effectively improve students' post-competency, and it deserves further exploration and application.

Sodium hypochlorite(NaClO)overflow through apical foramen or damaged root canal wall and enter into soft tissue is rare during root canal treatment.This article reports a case of NaClO overflow during root canal treatment.Through literatures review,the symptoms,treatment methods and preventive measures of such cases are analyzed and discussed to provide reference for clinical diagnosis and treatment.

With the progress of society and the continuous improvement of people′s living standards in China, the public′s demand for medical services is becoming increasingly diversified. How to move hospital services forward and improve medical services centered on patients has become a key consideration for hospitals to enhance patients′ sense of medical satisfaction. A certain hospital has established a one-stop patient service hotline, integrating functions such as number inquiry, medical consultation, appointment registration, appointment examination, praise and suggestions, complaint follow-up, etc., injecting a complaint handling management mode, and responding to and solving patient feedback problems in a timely manner. Since the launch of the patient service hotline, it has effectively solved the problems that patients encountered during their visits, effectively reduced the hospital′s complaint rate, and initially formed a service closed-loop management. From March to October 2023, the demand ratio of the 12345 hotline in the hospital has continuously decreased, and was significantly lower than the average level of 22 municipal hospitals in Beijing. In the future, we should further improve the communication skills between doctors and patients, focus on managing appeals and services, and continue to strengthen proactive governance.

Objective To evaluate the effectiveness of internet-based decision aids(DA)in colorectal cancer screening.Methods Randomized controlled trials of efficacy of internet-based DA in colorectal cancer screening were searched by computer from CNKI,Wanfang Data,VIP,CBM,PubMed,the Cochrane Library,Embase and Web of Science.The retrieval period was from the establishment of the database to June 2023.Descriptive analysis was used to analyze the main contents and summarize their clinical application effects.Results A total of 12 literatures were included,including 6038 subjects,of which 3089 were in experimental group and 2949 were in control group.The results showed that the contents of internet-based DA mainly included basic information support,benefits and risks of colorectal cancer screening,and clarification of patients'personal values.It could help patients enhance screening willingness,improve informed decision-making ability,reduce decision-making conflicts,and promote the positive role of patients in decision-making.Patients have higher satisfaction with internet-based DA.Conclusion Internet-based DA has shown positive results in the application of colorectal cancer screening,and has unique advantages over the traditional paper version of the manual,but it still has certain limitations.In the future,we can learn from the relevant theoretical achievements of foreign decision-making assistance,research and develop a more comprehensive DA for colorectal cancer screening combined with China's national conditions.

Objective:To observe the effect of Ba Duan Jin(Eight-brocade Exercise)plus Tuina(Chinese therapeutic massage)in treating primary dysmenorrhea due to cold-induced blood stasis in female college students and on the score of fatigue scale-14(FS-14). Methods:Seventy-two female college students with primary dysmenorrhea due to cold-induced blood stasis were randomized into a Tuina group and a joint group,with 36 cases in each group.The Tuina group only received Tuina manipulations.In the joint group,besides the same Tuina manipulations,patients practiced Ba Duan Jin.For both groups,the once-daily intervention was conducted from 6 d before the menstrual period until menstrual day 1 for 3 menstrual cycles.Changes in the scores of COX menstrual symptom scale(CMSS),visual analog scale(VAS),and FS-14 after the intervention were observed.Clinical efficacy was also estimated. Results:During the process,1 case dropped out in the Tuina group,and 35 cases completed the intervention;2 cases dropped out in the joint group,and 34 cases completed the intervention.The total effective rate was 94.1%in the joint group,higher than 88.6%in the Tuina group(P<0.05).After treatment,the symptom duration and intensity scores in the scores of CMSS,VAS,and FS-14 declined in both groups(P<0.05 or P<0.01);the CMSS symptom duration score and FS-14 score were lower in the joint group than in the Tuina group(P<0.05). Conclusion:Tuina manipulations alone or combined with Ba Duan Jin practice can effectively treat primary dysmenorrhea due to cold-induced blood stasis in female college students;when combined with Ba Duan Jin practice,Tuina manipulations can more significantly improve pain duration and fatigue,suggesting the advantages of combining Tuina Gongfa and manipulations.

Circular RNAs (circRNAs) are a new class of non-coding RNAs, which have been confirmed to regulate insect gene expression and immune response through multiple manners such as competing endogenous RNA (ceRNA) regulatory network. Currently, function of circRNA in honey bee immune response remains unclear. In this study, PCR and Sanger sequencing were performed to validate the back splicing (BS) site of ame_circ_000115 (in short ac115). RT-qPCR was used to detect the expression profile of ac115 in larval guts of Apis mellifera ligustica stressed by Ascosphaera apis. Dual-luciferase reporter gene assay was conducted to verify the binding relationship between ac115 and ame-miR-13b. Interference of ac115 in larval guts was carried out by feeding specific siRNA, followed by determination of the effect of ac115 interference on expression of six genes relevant to host immune response. The results confirmed the existence of BS site within ac115. Compared with the un-inoculated group, the expression of ac115 in 4-day-old larval gut of the A. apis-inoculated group was up-regulated with extreme significance (P < 0.000 1), while that in 5- and 6-day-old larval guts were significantly up-regulated (P < 0.05). The brightness of specific band for ac115 in 4-, 5- and 6-day-old larval guts of the siRNA-circ_000115-fed group gradually became weak, whereas that of the siRNA-scrambl-fed group was pretty high without obvious variation. Compared with that of the siRNA-scramble-fed group, the expression of ac115 in 4-day-old larval gut of the siRNA-circ_000115-fed group was significantly down-regulated (P < 0.05), whereas that of the 5- and 6-day-old larval guts were down-regulated with extreme significance (P < 0.001). Ame-miR-13b was truly existed and expressed in A. m. ligustica larval guts, and there was true binding relationship between ac115 and ame-miR-13b. Compared with that of the siRNA-scramble-fed group, the expression of antimicrobial peptide genes hymenoptaecin and abaecin in 6-day-old larval gut of the siRNA-circ_000115-fed group was significantly up-regulated (P < 0.05), while that of ecdysone receptor (Ecr) was down-regulated with extreme significance (P < 0.01). These results indicate that ac115 is truly expressed in A. m. ligustica larval guts, BS site truly exists within ac115, and effective interference of ac115 in A. m. ligustica larval guts can be achieved via feeding siRNA. Moreover, ac115 potentially regulates Ecr expression through adsorption of ame-miR-13b and expression of hymenoptaecin and abaecin using a non-ceRNA manner, further participating in host stress-response.
Bees/genetics* ; Animals ; Larva/metabolism* ; RNA, Circular/genetics* ; RNA, Small Interfering/genetics* ; MicroRNAs/genetics*

In 2022, the European Association for the Study of the Liver issued Clinical practice guidelines on sclerosing cholangitis. With reference to the 2017 edition of Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline (2017) and in comparison to the corresponding contents in Guidelines on the diagnosis and management of primary sclerosing cholangitis (2021) issued by Chinese Society of Hepatology, Chinese Medical Association, in 2021, this article summarizes the updates in diagnosis, treatment, monitoring, and management of special populations and analyzes the basis for updated recommendations and their guiding significance in optimizing the clinical management of primary sclerosing cholangitis (PSC). The comparative analysis shows that the new version of the guidelines is similar to the Chinese guidelines in terms of diagnosis, treatment, and follow-up, and it is worth learning from the technical details such as the recommended dose of ursodeoxycholic acid and long-term follow-up plan. Since PSC is a chronic refractory disease, the drugs recommended by current guidelines cannot delay or reverse disease progression, and there is still a lack of consensus statements on immunotherapy and screening protocols for end-stage complications, which might be the directions for further research.