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 observe the effect of high-frequency repetitive transcranial magnetic stimulation on hemiplegic shoulder pain during convalescence of stroke.Methods A total of 40 patients with hemiplegic shoulder pain during convalescing stroke who were hospitalized in Rehabilitation Medicine Department of Jiaxing Second Hospital from January 2021 to June 2022 were selected and randomly divided into treatment group(rTMS group)and control group(sham rTMS group),with 20 cases in each group.Both groups were given anti-inflammatory and analgesic drugs and conventional rehabilitation treatment.On this basis,the treatment group was combined with rTMS treatment(stimulation frequency was 10.0Hz,stimulation intensity was 80%resting motor threshold,stimulation time was 10s,interval was 50s,total treatment time was 20 minutes,once a day from Monday to Friday,continued treatment 2 days apart,20 times as a course of treatment,a total of 4 weeks),while the control group received sham rTMS.Before treatment,2 and 4 weeks after treatment,numerical pain rating scale(NPRS)was used to assess the degree of shoulder pain,passive shoulder range of motion was measured by protractor,upper limb motor function of hemiplegic side was assessed by Fugl Meyer assessment upper extremity(FMA-UE),and the ability of daily living activities was assessed by modified Barthel index(MBI).Results After treatment,NPRS score of shoulder pain in 2 groups was significantly decreased compared with before treatment(P<0.001),passive shoulder motion and Fugl-Meyer upper limb motor function were significantly improved compared with before treatment(P<0.001),and the treatment group was significantly better than the control group,the difference between groups was statistically significant(P<0.05).The modified Barthel index in 2 groups was significantly improved compared with before treatment(P<0.001),but there was no statistical significance between 2 groups(P>0.05).Conclusion 10.0Hz high-frequency repetitive transcranial magnetic stimulation can significantly relieve hemiplegic shoulder pain during the convalession of stroke,improve the passive range of motion of the affected shoulder,and improve the upper limb motor function of the affected side,but the effect is not significant in improving the ability of daily living activities.

Cell Cycle Proteins ; Microtubule-Associated Proteins

SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

Objective To study the different ischemic characteristics of cerebral gray matter and deep white matter in patients with chronic cerebral artery severe stenosis or occlusion. Methods A retrospective study was conducted on 30 patients with chronic unilateral cerebral artery severe stenosis or occlusion from April 2014 to April 2018 in our hospital. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time of peak time (TTP) and time to delay(TTD) of cerebral cortex gray matter and deep white matter in the blood supply area of the responsible artery (the affected side) and the contralateral hemisphere (the healthy side) were measured. Statistical analysis of the perfusion parameters of cerebral cortex gray matter and deep white matter in the affected side and contralateral side were performed using SPSS13.0 software package. T test was used for variance homogeneity, and t′test was used for variance discrepancy, and P<0.05 was statistically significant. Results The average values of CBF and CBV of the ipsilateral and contralateral cerebral cortex were increased than those of ipsilateral and contralateral cerebral deep white matter respectively(P<0.01). MTT, TTP and TTD of the ipsilateral and contralateral cerebral cortex were decreased than that of ipsilateral and contralateral cerebral deep white matter (P<0.01); CBF of ipsilateral cerebral cortex and CBV of ipsilateral cerebral deep white matter were not different from those of the contralateral cerebral cortex and deep white matter respectively, but CBF of ipsilateral cerebral deep white matter is decreased than that of the contralateral deep white matter (P<0.01). CBV of ipsilateral cerebral cortex is increased than that of the contralateral cerebral cortex (P<0.01). MTT, TTP and TTD of ipsilateral cerebral cortex and deep white matter were increased than those of contralateral cerebral cortex and deep white matter respectively(P<0.01). Conclusion Deep cerebral white matter perfusion decreased more significantly than cortical gray matter in the supply region of chronic cerebral artery severe stenosis or occlusion. CT perfusion imaging can quantify the degree of chronic cerebral ischemia and can provide quantitative diagnostic information for clinical treatment and efficacy evaluation.

Objective: To study the different ischemic characteristics of cerebral gray matter and deep white matter in patients with chronic cerebral artery severe stenosis or occlusion. Methods: A retrospective study was conducted on 30 patients with chronic unilateral cerebral artery severe stenosis or occlusion from April 2014 to April 2018 in our hospital. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time of peak time (TTP) and time to delay(TTD) of cerebral cortex gray matter and deep white matter in the blood supply area of the responsible artery (the affected side) and the contralateral hemisphere (the healthy side) were measured. Statistical analysis of the perfusion parameters of cerebral cortex gray matter and deep white matter in the affected side and contralateral side were performed using SPSS13.0 software package. T test was used for variance homogeneity, and t′ test was used for variance discrepancy, and P<0.05 was statistically significant. Results: The average values of CBF and CBV of the ipsilateral and contralateral cerebral cortex were increased than those of ipsilateral and contralateral cerebral deep white matter respectively(P<0.01). MTT, TTP and TTD of the ipsilateral and contralateral cerebral cortex were decreased than that of ipsilateral and contralateral cerebral deep white matter (P<0.01); CBF of ipsilateral cerebral cortex and CBV of ipsilateral cerebral deep white matter were not different from those of the contralateral cerebral cortex and deep white matter respectively, but CBF of ipsilateral cerebral deep white matter is decreased than that of the contralateral deep white matter (P<0.01). CBV of ipsilateral cerebral cortex is increased than that of the contralateral cerebral cortex (P<0.01). MTT, TTP and TTD of ipsilateral cerebral cortex and deep white matter were increased than those of contralateral cerebral cortex and deep white matter respectively(P<0.01). Conclusion Deep cerebral white matter perfusion decreased more significantly than cortical gray matter in the supply region of chronic cerebral artery severe stenosis or occlusion. CT perfusion imaging can quantify the degree of chronic cerebral ischemia and can provide quantitative diagnostic information for clinical treatment and efficacy evaluation.

Objective The aim of this study was to discuss the effect and clinical value of plasma Tissue Plasminogen Activator-Plasminogen Activator Inhibitor-1 Complex ( t-PAIC) in the coronary heart disease (CAD).Methods This is a retrospective study.From January 2017 to March 2018, 203 patients with CAD were recruited from Renmin Hospital of Wuhan University .130 cases were selected for control group at the same period.Plasma concentrations of t-PAIC, blood RBC, Hb, WBC and other routine biochemical markers were quantified .Results The plasma t-PAIC level in CAD group 12.75(9.0-17.93) ng/ml was significantly higher than that in healthy control group 7.70(6.10-9.41) ng/ml (Z＝9.208, P＜0.001).Logistic regression analysis showed that the TG ,LPa,t-PAIC were independent risk factors for CAD [OR(95%CI)],[1.762(1.076-2.884); 1.002(1.000-1.003); 1.338 (1.171-1.529)].The t-PAIC level was positively correlated with the severity of CAD .Compared with control group, the level of t-PAIC was higher in mild group (11.64 ±0.59) ng/ml and severe group (15.84 ±0.72) ng/ml, and the plasma t-PAIC level was positively correlated with Gensini score (r＝0.471, P＜0.001).Multiple linear regression analysis showed that there was a positive correlation among the plasma t-PAIC and LDL-C,Glu,WBC ( β coefficien t＝0.673,0.305,0.263, P＝0.037,0.002,0.006).In addition, there was abnormal increase of plasma t-PAIC in CAD patients with poor prognosis (H＝82.210, P＜0.001).Conclusion Plasma t-PAIC is an independent risk factor of CAD .The significantly increase of plasma t-PAIC might be an important predictor of incidence of CAD and unfavourable prognosis.

OBJECTIVETo explore the factors affecting the operative difficulty of triple-port laparoscopic surgery (TLS) in anterior resection.

METHODSA retrospective case-control study was carried out. Clinical and MRI imaging data of 106 colorectal cancer cases undergoing TLS anterior resection at Department of Colorectal Surgery of Ruijin Hospital between 2013 and 2016 were retrospectively analyzed.

INCLUSION CRITERIA(1) patients receiving TLS anterior resection (Dixon operation); (2) preoperative stageI( to III( malignant tumor;(3) distance of 5-15 cm from inferior margin of tumor to anal verge; and (4) available preoperative rectal MRI.

EXCLUSION CRITERIA(1) patients receiving preoperative adjuvant therapy; (2) patients with low rectal cancer or with local advanced disease; (3) T4b tumor. Rectal MRI was introduced to measure the structure of pelvis. In sagittal view, superior margin of the first sacral vertebrae, superior margin of the third sacral vertebrae, apex of coccyx, and the line of superior margin of pubic symphysis were used to form a pentagon. The 5 lines were marked as N, O, P, Q, R, and the 5 included angles were marked as angle 1, 2, 3, 4, 5. Organs (uterus and prostate) and tumor (transverse diameter, longitudinal diameter, section area, lesion length, distance to circumference cutting edge) were also measured on MRI. The operative time was applied to be the indicator of operative difficulty and patients were divided into 2 groups according to median operative time. Baseline information (age, gender, BMI, distance from inferior margin of tumor to anal verge, operative history, length of tumor), preoperative tumor staging, and MRI measurements (pelvis, tumor, uterus, prostate), etc were compared between two groups. Factors affecting operative difficulty of TLS were analyzed with logistic regression model.

RESULTSOf 106 enrolled patients, 73 were male and 33 female with mean age of (59.8±12.2) years and mean BMI of (22.8±3.3) kg/m; 25 patients had previous abdominal surgery; distance from inferior margin of tumor to anal verge was (7.4±2.0) cm and the tumor diameter was (3.7±1.4) cm; 24, 36 and 46 patients were in stage I(, II( and III( respectively. All operations were completed successfully. The median number of harvested lymph node was 13(11-16); the median length of distal resection margin was 2.5(2.0-3.1) cm; the median operative time was 2.0(1.5-2.6) hours; the median intraoperative blood loss was 50(0-100) ml; the median time to liquid diet was 4(3-5) days; the median hospital stay was 7(6-10) days. Ten cases (9.4%) developed complications within 30 days after surgery. Patients were divided into ≤2 h group and > 2 h group according to median operative time, and both groups had 53 patients. As compared to ≤2 h group, >2 h group had shorter distance from inferior margin of tumor to anal verge [(6.8 ± 1.5) cm vs. (8.0 ± 2.4) cm, t = 3.174, P = 0.004], lower ratio of (R+N)/(O+P)(1.61±0.27 vs. 1.73±0.19, t = 2.494, P = 0.014), larger transverse distance of tumor [(3.45±0.72) cm vs. (3.05±0.89) cm, t = 0.224, P = 0.027]. Multivariate logistic regression analysis showed the distance from inferior margin of tumor to anal verge was the independent factor affecting operative difficulty(OR=0.584, 95%CI:0.429-0.796, P = 0.001).

CONCLUSIONSSurgeons may have less difficulty in performing TLS anterior resection for patients with longer distance from inferior margin of tumor to anal verge. In preoperative assessment of operative difficulty of TLS, comprehensive evaluation should be performed. Distance from inferior margin of tumor to anal verge should be regarded as the main factor, and MRI (R+N)/(O+P) and transverse diameter of tumor should be used as important reference, leading to reasonable choice of cases for TLS and smooth pass of study curve.

Aged ; Anal Canal ; Case-Control Studies ; Female ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Rectal Neoplasms ; diagnostic imaging ; surgery ; Retrospective Studies ; Treatment Outcome

Objective To study the effect from personalized insoles with different structural heel pads on plantar stress concentration of patients with heel pain. Methods Base on statistics and finite element analysis method, the finite element model of foot and personalized insoles for patient with heel pain were established. The effects from different insoles on stress of soft tissues and plantar fascia were simulated. Results The internal stress of plantar soft tissues was higher than that of plantar epidermis, and the stress of the third plantar fascia was the highest. During barefoot standing, the internal peak stress of plantar soft tissues was 1.34 times of plantar epidermis, and the stress of the third plantar fascia was 1.50 MPa. The result of orthogonal experiment showed that the optimized insole model could reduce the internal peak stress of plantar soft tissues by 51%, meanwhile relieve the stress of the third plantar fascia by 11.3%. Conclusions The optimum scheme of personalized buffer insole is the design of vertical ellipse and honeycomb groove. Such structure can assist the absorption or buffering of concussion from calcaneal fat pad, and relieve the plantar stress concentration and tension of the plantar fascia. This study is helpful to understand plantar stress distributions of patients with heel pain, which is of great significance to the study of pathology and prevention of heel pain.

BACKGROUND: The clinical features of patients with common single-mutation of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) has been well characterized. There is a high adenocarcinoma incidence rate among female patients with none or shorter smoking history. Those patients have higher objective response rate (ORR) and progression free survival (PFS) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, it is still unclear that the clinical features of patients with EGFR double mutation and the sensitivity towards EGFR-TKIs treatment. METHODS: We performed a retrospective cohort study of 1,238 primary NSCLC patients who had EGFR gene testing in Affiliated Hospital of Qingdao University from January 1, 2015 to December 31, 2016 and identified 603 patients with single mutation and 59 patients with double mutation. All genes were uniformly detected by using ARMS-PCR technology. We analyze the gene of 32 double-mutant patients with specific genotyping, and randomly selected 60 patients with single mutation and compared the clinical features with 59 patients with double mutation. Furthermore, we examined the efficacy of EGFR-TKIs treatment in lung cancer patients with double mutation and single mutation in EGFR. RESULTS: The rare single mutation gene is the most common in patients with double mutation of EGFR. There is no significant statistical difference in gender, smoking history, age, pathological type or tumor-node-metastasis (TNM) staging among patients with single and double EGFR mutantion. In the double mutation patients treated with EGFR-TKIs, the objective response rate was 36.80%, the disease control rate was 68.40%. The objective response rate was 60.00% and the disease control rate was 90.00% in the patients with single mutation. However, overall PFS was significantly higher in EGFR single mutation patients (P=0.003), with median PFS of 12.0 months compared with 6.0 months in EGFR double mutation patients. CONCLUSIONS There was no significant difference between the clinical features of patients with EGFR double mutation and single mutation. Patients with EGFR double mutation is associated with poor survival underwent the first generation of EGFR-TKIs treatment compared with patients with a single mutation.
Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Exons ; genetics ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Retrospective Studies ; Treatment Outcome