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.

OBJECTIVES: To investigate the effect of curcumin on lipid metabolism in non-small cell lung cancer (NSCLC) and its molecular mechanism. METHODS: The inhibitory effect of curcumin (0-70 μmol/L) on proliferation of A549 and H1299 cells was assessed using MTT assay, and 20 and 40 μmol/L curcumin was used in the subsequent experiments. The effect of curcumin on lipid metabolism was evaluated using cellular uptake assay, wound healing assay, triglyceride (TG)/free fatty acid (NEFA) measurements, and Oil Red O staining. Western blotting was performed to detect the expressions of PGC-1α, PPAR-α, and HIF-1α in curcumin-treated cells. Network pharmacology was used to predict the metabolic pathways, and the results were validated by Western blotting. In a nude mouse model bearing A549 cell xenograft, the effects of curcumin (20 mg/kg) on tumor growth and lipid metabolism were assessed by measuring tumor weight and observing the changes in intracellular lipid droplets. RESULTS: Curcumin concentration-dependently inhibited the proliferation of A549 and H1299 cells and significantly reduced TG and NEFA levels and intracellular lipid droplets. Western blotting revealed that curcumin significantly upregulated PGC-1α and PPAR‑α expressions in the cells. KEGG pathway enrichment analysis predicted significant involvement of the HIF-1 signaling pathway in curcumin-treated NSCLC, suggesting a potential interaction between HIF-1α and PPAR‑α. Western blotting confirmed that curcumin downregulated the expression of HIF-1α. In the tumor-bearing mice, curcumin treatment caused significant reduction of the tumor weight and the number of lipid droplets in the tumor cells. CONCLUSIONS Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.
Curcumin/pharmacology* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Animals ; Lipid Metabolism/drug effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Mice, Nude ; Down-Regulation ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PPAR alpha/metabolism* ; Signal Transduction/drug effects* ; A549 Cells

Objective To compare the effects of upper limb remote ischemic preconditioning(RIPC)with different pressure modes on enhancing high-altitude acclimatization in healthy adult males rapidly exposed to high-altitude environments.Methods In May 2024,86 male adult residents living plain areas planning a high-altitude travel were recruited through advertisements in Chongqing by Department of Anesthesiology at the Second Affiliated Hospital of Army Medical University.The participants were randomly divided into a variable pressure training group(n=29),a constant pressure training group(n=29),and a control group(n=28).The variable pressure training group underwent RIPC training in a variable pressure mode[occlusion pressure was set at systolic blood pressure(SBP)+40 mmHg],while the constant pressure training group received RIPC training in a constant pressure mode(fixed occlusion pressure of 200 mmHg).Both groups completed a bilateral upper limb RIPC training(twice daily,5 cycles per time of 10-min occlusion followed by 5-min reperfusion)for 14 d.The control group received no such training.On the 3rd day post-training,all participants entered a simulated 4 500 m altitude chamber for 7 h.The incidence and severity of acute mountain sickness(AMS)were observed and evaluated,and the vital signs and cerebral tissue oxygenation index(CTOI)were recorded.Results The incidence of AMS was 23.1%in the variable pressure training group(RR=0.4,95%CI:0.2～0.8,Chi-square=9.433,P=0.002)and 16.0%in the constant pressure training group(RR=0.2,95%CI:0.1～0.6,Chi-square=12.833,P<0.001),and both incidences were significantly lower than that in the control group(65.4%).The AMS symptom score in the variable pressure training group[1.5(0.8,3.0)vs(3.1±1.9),P=0.018]and the score in the constant pressure training group[1.0(1.0,2.0)vs(3.1±1.9),P=0.001]were significantly lower than that in the control group.The dizziness score was obviously lower in the variable pressure training group[0(0,1.0)vs 1.0(1.0,1.0),P=0.001]and the constant pressure training group[1.0(0,1.0)vs 1.0(1.0,1.0),P=0.003]than the control group,so was the fatigue/weakness score in the variable pressure training group[0(0,0.3)vs 1.0(0,1.0),P=0.006],the constant pressure training group[0 vs 1.0(0,1.0),P<0.001],and the control group.The change of CTOI(ΔCTOI)in the variable pressure training group(P=0.010)and the constant pressure training group(P=0.042)was significantly lower than that in the control group.There were no statistical differences in the 3 groups in terms of SpO2,HR,SBP or DBP(P>0.05).What's more,no significant differences were observed in the incidence of AMS,AMS score,dizziness score,fatigue/weakness score,or ΔCTOI between the variable pressure training group and the constant pressure training group(P>0.05).Conclusion Both upper limb RIPC protocols,variable-pressure(SBP+40 mmHg)and fixed-pressure(200 mmHg),can effectively enhance high-altitude acclimatization by reducing AMS incidence,symptom severity,and cerebral oxygen desaturation.

Objective:To elucidate the primary elements pertaining to the perception of relapse risk and to in-vestigate the characteristics and alterations of perception of the risk of recurrence in patients with schizophrenia.Methods:By using the method of phenomenological study,semi-structured in-depth interviews were conducted among schizophrenic patients with first onset,first recurrence and multiple recurrences.Twenty-three 23 outpatient and inpatient cases that met the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were included,and all patients had PANSS scores below 60.The interview data were collated and analyzed according to Colaizzi analysis.Results:The perception of recurrence risk in patients with schizophrenia en-compassed 4 major themes and 11 sub-themes,namely susceptibility(limited overall understanding,transition from optimism to objectivity),detection of early warning symptoms(dynamic escalation,assistance from family mem-bers in identification),understanding risk factors(lack of understanding,the relationship between psychosocial fac-tors and relapse,dynamic understanding of medication-relapse relationship),and apprehension of the consequences of recurrence(care burden and financial constraints,impaired social functioning and maladjustment,impact on pub-lic safety,personal health risks).Conclusion:The content of risk perception of recurrence in patients with schizo-phrenia is relatively substantial.The overall level of risk perception of recurrence in patients with schizophrenia is low.

Objective:To assess the understanding level of Family Resilience Scale for Schizophrenic Patients among respondents using cognitive interviews and revise the items accordingly.Methods:Using the purposive sampling method, two cognitive interviews were conducted on schizophrenia patients admitted to Chifeng An Ding Hospital from April to June 2023. A Question Appraisal System (QAS-99) was used to encode the interview data to find the problems existing in the scale structure, and at the same time, the scale items were revised based on expert opinions.Results:The first round of cognitive interviews showed ten questions, mainly focusing on "clarification"questions. The results of the second round of cognitive interviews showed that all respondents could correctly understand the scale items revised by the first round of lognitive interviews, and no further revision was required. The final Family Resilience Scale for Schizophrenic Patients included 24 items.Conclusions:Cognitive interviews can help to find and solve the differences in the understanding of items between researchers and interviewees in the compilation of the Family Resilience Scale for Schizophrenic Patients so as to improve the accuracy and reliability of the scale.

A case of adult spindle cell sarcoma with NTRK3-C22orf34 gene fusion is reported. The patient, a 35-year-old-male, developed lateral swelling of the right thigh without obvious inducement 7 months before admission and was not accompa-nied by limited movement. The patient was diagnosed with adult spindle cell sarcoma with NTRK3-C22orf34 gene fusion based on the medical history, imaging findings, histomorphology, immunohistochemistry and molecular phenotype. The patients underwent tumor resection without drug-targeted therapy and followed up for 8 months after tumor resection and survived without tumor. In recent years, the number of adult spindle cell sarcomas with neurotrophic tyrosine kinase receptor 3 (NTRK3) gene fusions have been increasing year by year, and most of them are difficult to diagnose based on HE sections due to the varied morphology and small number of these tumors. With the wide application of high-throughput sequencing in soft tissue tumors, the difficulty of diagnosis of spindle cell tumors with the NTRK fusion gene has decreased. High-throughput sequencing of the patient showed that NTRK3-C22orf34 (mutation abundance 5%) gene fusion combined with BRCA1 (mutation abundance 15%) rearrangement and deletion of CDKN2A and TP53 genes were found to be of definite or potential clinical significance. The morphologic spectrum of NTRK fusion spindle cell tumors, especially sarcomas, is still evolving. Treatment of NTRK fusion gene spindle cell tumors is based on surgical resection in combination with tropomyosin receptor kinase (TRK) inhibitors. The emergence of secondary or acquired resistance is primarily associated with point mutations associated with the structural domain of the kinase, and mutations may reduce the efficacy of TRK inhibitors.

Objective:To investigate the effect of the ratio of the maximum diameter of aneurysm sac to age (R) on the long-term efficacy of endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in patients with infrarenal abdominal aortic aneurysm (IAAA).Methods:This is a retrospective cohort study.The clinical data of 317 patients with IAAA who underwent surgical repair in the Department of Vascular Surgery,the Third Affiliated Hospital of Sun Yat-Sen University from January 2016 to October 2022 were retrospectively collected.There were 266 males and 51 females,aged (69.7±8.3) years (range:37 to 87 years).The R value of the patient was calculated and the receiver operating characteristic(ROC) curve was used to establish a model to calculate the optimal cut-off value.The propensity score matching method was used to match the baseline data of patients in the EVAR and OSR group by 3∶1 (the caliper value was 0.05),and the patients were stratified according to the cutoff value of R, and the postoperative efficacy and survival of the patients were analyzed.The primary endpoint was the total mortality rate,and the secondary endpoints included the occurrence of postoperative complications and reintervention.Pearson χ2 or Fisher ′s exact test was used for categorical variables, and independent sample t test or Wilcoxon rank sum test was used for continuous variables to compare differences between groups.The survival curves of the two groups were described by Kaplan-Meier method. Results:After propensity score matching,198 cases were in the EVAR group and 66 cases were in the OSR group.The ROC model showed that the best cut-off value of R value was 0.90,and the two groups were divided into two layers:R<0.90 and R≥0.90.Among them,112 patients with R<0.90 (84 cases of EVAR,28 cases of OSR);there were 152 patients with R≥0.90 (114 cases of EVAR and 38 cases of OSR).The follow-up time was (23.6±1.6) months (range:1 to 70 months).In the R≥0.90 stratification,the total mortality (26.3% vs.5.3%, χ2=7.600， P=0.006),complication rate (44.7% vs.26.3%, χ2=4.025， P=0.045), and secondary intervention rate (31.6% vs.13.2%, χ2=4.910， P=0.027) in the EVAR group were higher than those in the OSR group.In the R<0.90 stratification,there was no significant difference in the total mortality rate (13.1% vs.10.7%, χ2=0.109， P=0.741), complication rate (28.6% vs.35.7%, χ2=0.507， P=0.477) and secondary intervention rate (14.3% vs.21.4%, χ2=0.353， P=0.552) between the two groups. Conclusions:When R≥0.90 in IAAA patients,OSR maybe more beneficial to patients in terms of survival rate,postoperative complication rate and secondary intervention rate than EVAR.When R<0.90,there are no significant differences in survival rate,complication rate and secondary intervention rate between the two surgical methods.

Objective:To investigate the effect of the ratio of the maximum diameter of aneurysm sac to age (R) on the long-term efficacy of endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in patients with infrarenal abdominal aortic aneurysm (IAAA).Methods:This is a retrospective cohort study.The clinical data of 317 patients with IAAA who underwent surgical repair in the Department of Vascular Surgery,the Third Affiliated Hospital of Sun Yat-Sen University from January 2016 to October 2022 were retrospectively collected.There were 266 males and 51 females,aged (69.7±8.3) years (range:37 to 87 years).The R value of the patient was calculated and the receiver operating characteristic(ROC) curve was used to establish a model to calculate the optimal cut-off value.The propensity score matching method was used to match the baseline data of patients in the EVAR and OSR group by 3∶1 (the caliper value was 0.05),and the patients were stratified according to the cutoff value of R, and the postoperative efficacy and survival of the patients were analyzed.The primary endpoint was the total mortality rate,and the secondary endpoints included the occurrence of postoperative complications and reintervention.Pearson χ2 or Fisher ′s exact test was used for categorical variables, and independent sample t test or Wilcoxon rank sum test was used for continuous variables to compare differences between groups.The survival curves of the two groups were described by Kaplan-Meier method. Results:After propensity score matching,198 cases were in the EVAR group and 66 cases were in the OSR group.The ROC model showed that the best cut-off value of R value was 0.90,and the two groups were divided into two layers:R<0.90 and R≥0.90.Among them,112 patients with R<0.90 (84 cases of EVAR,28 cases of OSR);there were 152 patients with R≥0.90 (114 cases of EVAR and 38 cases of OSR).The follow-up time was (23.6±1.6) months (range:1 to 70 months).In the R≥0.90 stratification,the total mortality (26.3% vs.5.3%, χ2=7.600， P=0.006),complication rate (44.7% vs.26.3%, χ2=4.025， P=0.045), and secondary intervention rate (31.6% vs.13.2%, χ2=4.910， P=0.027) in the EVAR group were higher than those in the OSR group.In the R<0.90 stratification,there was no significant difference in the total mortality rate (13.1% vs.10.7%, χ2=0.109， P=0.741), complication rate (28.6% vs.35.7%, χ2=0.507， P=0.477) and secondary intervention rate (14.3% vs.21.4%, χ2=0.353， P=0.552) between the two groups. Conclusions:When R≥0.90 in IAAA patients,OSR maybe more beneficial to patients in terms of survival rate,postoperative complication rate and secondary intervention rate than EVAR.When R<0.90,there are no significant differences in survival rate,complication rate and secondary intervention rate between the two surgical methods.

Objective To analyze the influence of different processing methods,including frying,ginger frying,and salt frying,on the volatile components of A.fructus.Methods The volatile components in different processed products of A.fructus were detected and analyzed by gas chromatography-mass spectrometry(GC-MS)based on multivariate statistical analysis.After OPLS-DA analysis,the different components were screened under the conditions of VIP＞1.5 and P＜0.05 and were qualitatively searched using the NIST 11 spectral library.Results A total of 49 different components were identified,with 14 components only changing in the seed mass and 22 components changing in the peel.The content of camphor could be significantly reduced in the seed mass after A.fructus was processed and the content of bornyl acetate significantly increased in the peel of frying A.fructus.Salt frying had a great influence on the alkanes in A.fructus,and ginger processing did not only increase the volatile components in ginger,which reflected the complexity of the processing mechanism.Conclusion At present,the specific processing mechanism is not clear,but the experimental results provide theoretical data for the "detoxification and efficiency enhancement" effect of A.fructus processing,reflecting the scientific nature of the processing,enriching the processing theory of A.fructus,and providing a reference for further in-depth research on the activity of different processed products of A.fructus.

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*