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 efficacy of sintilimab combined with paclitaxel and docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:Prospective cohort study was performed. A total of 90 patients with advanced NSCLC receiving second-line treatment in Baotou Cancer Hospital from October 2019 to October 2022 were prospectively selected. All patients were divided into the study group (sintilimab combined with paclitaxel and docetaxel as second-line treatment, 45 cases) and the control group (paclitaxel or docetaxel alone, 45 cases) according to random number table method. The short-term efficacy, serum cytokine levels, quality of life and T-cell subsets of the two groups were compared. The survival of patients within 6 months was followed up. Kaplan-Meier method was used to analyze the overall survival (OS) of both groups, and log-rank test was used to make comparison among groups.Results:There were 25 males (55.56%) in the study group with the age of (63±5) years and 28 males (62.22%) in the control group with the age of (65±6) years. There were no statistically significant differences in the gender, age, Eastern Cooperative Oncology Group scores, the body mass (all P>0.05). The total effective rate was 88.89% (40/45) in the study group and 71.11% (32/45) in the control group, and the difference was statistically significant ( χ2 = 4.44, P = 0.035). The levels of serum vascular endothelial growth factor (VEGF) and carbohydrate antigen 125 (CA125) of both groups after treatment were lower than those before treatment (all P<0.001); the levels of VEGF and CA125 in the study group after treatment were lower than those in the control group [VEGF: (223±15) pg/ml vs. (289±15) pg/ml, t=20.82, P<0.001;CA125: (23±6) ng/ml vs. (75±4) ng/ml, t=51.28, P<0.001].Quality of life scale score, Karnofsky score of both groups after treatment were higher than those before treatment (all P<0.05); quality of life scale score and Karnofsky score in the study group after treatment were higher than those in the control group [quality of life scale score: (63±6) scores vs. (51±5) scores, t=10.29, P<0.001; Karnofsky score: (80.5±5.7) scores vs.(78.8±3.7) scores, t=1.70, P=0.041]. T-cell subsets indicators of both groups after treatment were higher than those before treatment (all P<0.001). T-cell subsets indicators in the study group after treatment were higher than those in the control group [CD3 + cell proportion: (68±5)% vs. (65±5)%, t=2.52, P = 0.014; CD4 + cell proportion:(42.5±1.7)% vs. (36.5±3.7)%, t=9.91, P<0.001;CD4 +/CD8 +: 1.78±0.54 vs. 1.46±0.27, t=3.56, P<0.001]. There was no significant difference in the incidence of adverse reactions between the two groups [11.11% (5/45) vs. 15.55% (7/45), χ2=0.39, P=0.534]. The follow-up time was 6 months. The OS in the study group was better than that in the control group ( χ2=3.86, P = 0.044). Conclusions:Sintilimab combined with taxoid chemotherapy drugs is effective in the second-line treatment of advanced NSCLC, and it improves immune function and shows a favorable safety.

OBJECTIVE To study the protective effect of saikosaponin b2(SSb2)on corticosterone(CORT)induced PC12 cell injury and its mechanism.METHODS ① PC12 cells were divided into the cell control group(24 h of culture with RPMI-1640 medium),CORT group(24 h of culture with CORT 100-800 μmol·L-1)and SSb2 group(24 h of culture with SSb2 1.5625,3.125,6.25,12.5,25,50 and 100 μmol·L-1).MTT assay was used to detect the cell survival rate.②PC12 cells were divided into the cell control group(24 h of culture with RPMI 1640 medium),model group(24 h of culture with CORT 400 μmol·L-1),and model+SSb2 group(3 h pretreatment with SSb2 1.5625,3.125,6.25,12.5 and 25 μmol·L-1,removal of the supernatant before cells were co-incubated with CORT 400 μmol·L-1 and corresponding concentrations of SSb2 for 24 h).MTT assay was used to detect the cell survival rate while micro-plate assay was used to detect the lactate dehydrogenase(LDH)leakage rate of PC12 cells.③PC12 cells were divided into the cell control group,model group and model+SSb2 12.5 μmol·L-1 group.AnnexinV-FITC/PI flow cytometry assay was used to detect PC12 cell apoptosis,ultra-perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)cell metabonomics was used to detect metabolic profile changes and colorimetric assay was employed to detect the glutamic acid content and glutaminase activity in PC12 cells.RESULTS Compared with the cell control group,the cell viability decreased to(55±6)%(P<0.01)when the concentration of CORT was 400 μmol·L-1.When the concentration of SSb2 was higher than 50 μmol·L-1,there was significant toxicity to PC12 cells(P<0.01).②Compared with the cell control group,the cell survival rate was signif-icantly decreased(P<0.01),while the release rate of LDH was significantly increased(P<0.01)in the model group.Compared with the model group,the cell survival rate significantly increased(P<0.05,P<0.01),while the LDH release rate significantly decreased(P<0.01)in the model+SSb2 group.③ Com-pared with the cell control group,cell apoptosis was significantly increased in the model group(P<0.05).Compared with the model group,cell apoptosis was significantly decreased(P<0.05)in the model+ SSb2 group.Metabolomics results show that SSb2 significantly back-regulated nine differential metabo-lites of glutamate,creatine,N-acetylaspartate,L-tyrosine,citric acid,L-isoleucine,lactic acid,glutamine and choline.Further network analysis of the key metabolites regulated by SSb2 yielded five major metabolic pathways:D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,alanine,aspartate and glutamate metabolism,tyrosine metabolism and arginine biosynthesis.Compared with the cell control group,the content of glutamate and activity of glutaminase were significantly decreased in the model group(P<0.01).Compared with the model group,the content of glutamate(P<0.01)and activity of glutaminase(P<0.05)were significantly increased in the model+SSb2 group.CONCLUSION SSb2 has a neuroprotective effect on CORT-injured PC12 cells,and the mechanism of which is related to inhibition of apoptosis and regulation of metabolic disorders.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

Combined with teaching practice, this study summarizes the teaching contents, methods and effect evaluation of pathological technology for professional postgraduates majoring in pathology. According to the basic conditions of postgraduates, the pathological technology training program has been formulated, student-centered heuristic teaching is carried out by using diversified teaching methods such as flipped classroom, interactive theoretical teaching is carried out by using the intelligent teaching platform, and practical teaching is carried out by using the problem-based learning mode, aiming to improve the theoretical literacy and practical level of pathological technology of professional postgraduates majoring in pathology, improve their clinical research thinking, and lay a foundation for clinical pathological diagnosis and scientific research in the future.

Objective:To investigate the application value of modified Overlap esophago-gastric tube (MO-EG) reconstruction in totally laparoscopic radical proximal gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 7 patients with upper gastric cancer or adenocarcinoma of esophagogastric junction (AEG) who underwent totally laparoscopic radical proximal gastrectomy with MO-EG reconstruction in the Second Hospital of Jilin University from January 2019 to December 2020 were collected. There were 4 males and 3 females, aged 62(range, 55-72)years. The body mass index of the 7 patients was 21.5(range, 18.5-26.0)kg/m 2. Of the 7 patients, 2 cases had early upper third gastric cancer and 5 cases had Siewert Ⅱ AEG. All patients underwent totally laparoscopic radical proximal gastrectomy with MO-EG recons-truction using barbed sutures. Observation indicators: (1) surgical situations; (2) postoperative recovery situations; (3) postoperative histopathological examinations; (4) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect postoperative esophageal reflux, endoscopic classification of esophageal reflux, anastomotic complications, tumor recurrence and metastasis and survival of patients up to December 2021. Measurement data with normal distribution were represented as Mean±SD and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All the 7 patients underwent totally laparoscopic radical proximal gastrectomy and D 1+ lymph node dissection with MO-EG reconstruction through abdominal transhiatal approach. None of the 7 patients underwent conversion to open surgery or additional thoracotomy. The operation time, time of digestive reconstruction, volume of intraoperative blood loss and length of esophagus dissected of 7 patients were (271±36)minutes, (44±10)minutes, (53±26)mL and (6.4±0.3)cm, respec-tively. (2) Postoperative recovery situations. The time to postoperative initial out-of-bed activities, time to postoperative first flatus, time to postoperative initial liquid food intake and duration of hospital stay of 7 patients were (21±5)hours, (2.9±0.9)days, (5.0±0.7)days and (10.1±1.9)days, respectively. None of the 7 patients had postoperative severe complications such as bleeding, anasto-motic leakage or mortality. One patient had postoperative pulmonary infection and recovered after anti-infection treatment. Two patients had pleural effusion and were improved after conserva-tive treatment. (3) Postoperative histopathological examinations. The tumor diameter of 7 patients was (2.5±0.7)cm. Histopathological examination of upper margins of 7 patients was negative. The distance between the esophagus margin and the superior margin of the tumor of patients with AEG was (1.8±0.6)cm. The number of lymph node dissected and the number of inferior mediastinum lymph node dissected of 7 patients were 26.0±3.6 and 3.7±1.1, respectively. Pathological TNM stages of 7 patients were 2 cases of stage ⅠB, 4 cases of ⅡA, 1 case of ⅡB. (4) Follow-up. All the 7 patients were followed up for 18(range, 12?36)months. Of the 7 patients, 4 cases reported asymptomatic, 2 cases had symptoms of reflux and 1 case had chocked feeling after eating. All the 7 patients underwent barium meal examination of gastrointestinal tract without anastomotic dysfunction or anastomotic stenosis. Six of the 7 patients underwent gastroscopy at postoperative 1 year and only 1 of them reported grade B reflux esophagitis according to Los Angeles classification, while the rest of 5 patients had no evidence of obvious reflux. None of the 7 patients had postoperative gastric cancer tumor recurrence, metastasis or death. Conclusion:Application of MO-EG reconstruction in totally laparoscopic radical proximal gastrectomy is safe and feasible, with satisfactory short-term effects.

Objective:To investigate the etiologies and clinical characteristics of bilateral adrenal lesions.Methods:The clinical data of 143 patients with bilateral adrenal lesions hospitalized in the First Affiliated Hospital of Chongqing Medical University from Jan. 2013 to Mar. 2018 were collected and analyzed.Results:140 patients were retained for final analysis. 79 were men, and 61 were women. The age was (51.53±13.93) years. Regarding the etiologies, there were primary aldosteronism ( n=44, 31.43%) , Cushing’s syndrome ( n=27, 19.29%) , non-functional lesions ( n=23, 16.43%) , adrenal tuberculosis ( n=17, 12.14%) , pheochromocytoma ( n=11, 7.86%) , congenital adrenal hyperplasia ( n=5, 3.57%) , adrenal metastases ( n=5, 3.57%) , and adrenal lymphoma ( n=4, 2.86) . These patients were classified into the following groups according to the mass size: ≤2 cm, 2-4 cm and ≥4 cm. The highest proportion of primary aldosteronism (62.79%) , Cushing’s syndrome (46.15%) and pheochromocytoma (31.25%) was observed in the ≤2 cm, 2-4 cm and ≥4 cm groups, respectively. The mass sizes of primary aldosteronism, Cushing’s syndrome and pheochromocytoma were compared, with pheochromocytoma the largest, followed by Cushing’s syndrome, non-functional lesion, and primary aldosteronism. Conclusions:For patients with bilateral adrenal lesions in our hospital, primary aldosteronism and Cushing’s syndrome are more common than non-functional lesion. Mass size is of great value in the diagnosis of endocrinological etiology, as well as distinguishing malignant tumors from the benign ones. The imaging phenotype is helpful to determine tumor types.

Objective:To evaluate the clinical value of suspensory incision and suture technique in endoscopic full-thickness resection (EFTR) for muscularis propria tumor of gastric fundus.Methods:A retrospective analysis was performed on the data of 20 patients with muscularis propria tumor in gastric fundus and undergoing EFTR in the First Medical Center of PLA General Hospital from June 2017 to June 2019. Patients were divided into the observation group (9 cases) treated with suspensory incision and suture technique in EFTR and the control group (11 cases) treated with traditional EFTR method. The baseline data and perioperative data of the two groups were analyzed.Results:EFTR was successfully performed on all 20 patients. The tumor size of the observation group and the control group was 10.0 (7.5, 21.0) mm and 14.0 (10.0, 20.0) mm, respectively. The resection time of the two groups was 26.4±6.3 min and 35.5±11.4 min, respectively. The postoperative hospital stay was 6.4±1.0 d and 7.7±1.5 d, respectively. No postoperative delayed bleeding, perforation, or other complications occurred in the two groups.Conclusion:Using suspensory incision and suture technique is safe and effective during EFTR for muscularis propria tumor in gastric fundus, and can reduce operation time. This technique is worth applying in clinic.

Objective:To explore the current situation of understanding of medical and nursing interns on organization culture so as to provide a reference for the comprehensive training and management of trainees.Methods:From July 2019 to November 2019, this study selected full-time nursing or clinical medical interns in the First Affiliated Hospital of Soochow University as subjects by purposive sampling. Semi-structured in-depth interview was used to totals of 19 medical and nursing interns with the method of phenomenological research in qualitative research. Giorgi phenomenological analysis method was applied to analysis induction and theme refinement of interview data.Results:A total of two themes of understanding of medical and nursing interns on organization culture were induced. The awareness theme of organization culture involved lack of cognition and understanding, blurry self-orientation and varying degrees of culture perception. The theme of coping with the cultural conflicts consisted of compromise and being in a pickle.Conclusions:Teaching hospitals should pay attention to the management of cognition, psychology and cultural construction, strengthen the information transmission of hospital organization culture, increase the sense of belonging and team of trainees while improving skill levels of trainees so as to help them be competent for the future work and with self-realization.

As the proceeding of the Belt and Road, TCM industry in Russia develops steadily. Acupuncture and Tuina therapies have been accepted by the local people, while Chinese medicine is still around the acceptance. Right now, Russian economy is on a recovering stage, so it's good time for TCM to carry service trading during this time. TCM development in Russia need to focus on the input of medical resources, managements and regulations, proceeding TCM teaching work and bringing along TCM service trade by acupuncture therapy.