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.

Host cell residue DNA is one of the most common impurity which can affect the safety of biological products,therefore,domestic and international regulatory agencies have required the limit for host cell residue DNA in different biological products,either at the final product qualification or the appropriate intermediate control stage.The removal effect is verified by monitoring the residue DNA of products in different production stages,which is beneficial for assuring the scientificity and stability of the production process.In order to strengthen the understanding of control strategy about host cell residual DNA,the paper reviews progress in host cell residual DNA in biological products by authors'work experience and other's research,which provides reference for future work.

Background/Aims: This study aimed to investigate the biological function and regulatory mechanism of TCN1 in colorectal cancer (CRC). Methods: We studied the biological function of TCN1 by performing gain-of-function and loss-offunction analyses in HCT116 cell lines; examined the effects of TCN1 on the proliferation, apoptosis, and invasion of CRC cells; and determined potential molecular mechanisms using HCT116 and SW480 CRC lines and mouse xenotransplantation models. Tumor xenograft and colonization assays were performed to detect the tumorigenicity and metastatic foci of cells in vivo. Results: TCN1 knockdown attenuated CRC cell proliferation and invasion and promoted cell apoptosis. Overexpression of TCN1 yielded the opposite effects. In addition, TCN1-knockdown HCT116 cells failed to form metastatic foci in the peritoneum after intravenous injection. Molecular mechanism analyses showed that TCN1 interacted with integrin subunit β4 (ITGB4) to positively regulate the expression of ITGB4. TCN1 knockdown promoted the degradation of ITGB4 and increased the instability of ITGB4 and filamin A. Downregulation of ITGB4 at the protein level resulted in the disassociation of the ITGB4/plectin complex, leading to cytoskeletal damage. Conclusions TCN1 might play an oncogenic role in CRC by regulating the ITGB4 signaling pathway.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

Objective:To investigate the expression level of Ki-67 in the bone marrow biopsy of newly diagnosed MM patients, and its relationship with clinical efficacy and prognosis.Methods:Bone marrow pathological samples of 124 newly diagnosed MM patients in Jiangsu Province Hospital from January 2012 to June 2017 were collected. The expression level of Ki-67 in myeloma cells was detected by using immunohistochemistry. X-tile software was applied to find a cutoff of Ki-67. The patients were divided into the high Ki-67 expression group and the low Ki-67 expression group, and the clinical characteristics, therapeutic efficacy and survival of both groups were compared. Chi-square test or Fisher's exact test was used to analyze the counting data. Kaplan-Meier method was applied to make survival anlaysis. Cox regression model was used for univariate prognostic analysis and multivariate prognostic analysis.Results:A total of 124 newly diagnosed MM patients were enrolled with median follow-up of 36 months. The proportion of the positive myeloma cells in abnormal plasmocytes was used to quantize the expression level of Ki-67. Using a cutoff of 20%, these cases could be divided into two groups; the proportion of positive cells was lower than 20% (the low Ki-67 expression group) and the proportion of positive cells was 20% or above (the high Ki-67 expression group). There were 27 cases (21.7%) in the high expression group and 97 cases (78.2%) in the low expression group. There were no statistically significant differences in the clinical characteristics and treatment regimens (all P > 0.05). The overall remission rate (ORR) of patients in the high Ki-67 expression group was lower than that of patients in the low Ki-67 expression group [59.3% (16/27) vs. 83.5% (81/97)], and the difference was statistically significant (χ 2 = 7.290, P = 0.007). The percentage of patients who achieved very good partial remission (VGPR) and complete remission in the high Ki-67 expression group was lower than that of those in the low Ki-67 expression group [33.3% (9/27) vs. 66.0% (64/97)], and the difference was statistically significant (χ 2 = 9.297, P = 0.002). There were statistically significant differences in the median progression free survival (PFS) time (12.0 months vs. 31.0 months, P < 0.01) and 3-year PFS rate (10% vs. 37%, P = 0.002). The median overall survival (OS) time was 39.0 months and 56.5 months in the high and low Ki-67 expression groups, respectively ( P = 0.003). The multivariate analysis showed that high Ki-67 expression was an independent affecting factor for PFS ( HR = 3.592, 95% CI 1.921-6.719, P < 0.01) and OS ( HR = 3.511, 95% CI 1.537-8.022, P = 0.003). Conclusions:High expression of Ki-67 is an independent poor prognostic factor affecting therapeutic effect and survival for newly diagnosed MM patients.

OBJECTIVE: To detect chromosomal aberrations by using cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH), and to explore the correlation of del(17p13) with clinical characteristics, drug response and prognosis among patients with newly diagnosed multiple myeloma (NDMM). METHODS: Clinical data of 198 cases of NDMM was collected. cIg-FISH and a specific probe (TP53) were used to detect karyotypic abnormalities in bone marrow samples derived from the patients. Correlation between karyotypic abnormalities and clinical data was analyzed. RESULTS: Nineteen of the 198 patients (9.6%) were found to have a karyotype involving del(17p13). The overall survival (OS) and progression-free survival (PFS) for patients with or without del(17p13) was significantly different (P<0.01). No significant difference was found in OS and PFS between patients carrying a del(17p13) on bortezomib and non-bortezomib regimen (OS: P = 0.873; PFS: P = 0.610). CONCLUSION cIg-FISH is a simple and convenient method for the detection of karyotypic anomalies in multiple myeloma. Del(17p13) is an indicator for poor prognosis for multiple myeloma patients. Bortezomib cannot improve the survival disadvantage of del(17p13).

Objective:To compare the clinical characteristics and outcomes of patients newly diagnosed with multiple myeloma(NDMM)with bone-related extramedullary(EM-B)disease and those with extraosseous extramedullary(EM-E)disease and to address their prognostic factors.Methods:The clinical features, outcomes, and prognostic factors were retrospectively analyzed in 80 patients with NDMM with extramedullary disease.Results:Among 80 patients with extramedullary disease, 51 had EM-B and 29 EM-E. The level of β 2-microglobulin(5.82 mg/L vs 3.99 mg/L, P=0.030), lactate dehydrogenase(256 U/L vs 184 U/L, P=0.003), 1q21 amplification rate(78.6% vs 53.1%, P=0.035), and Ki-67 proliferation index(50% vs 25%, P=0.002)in the EME group were significantly higher than those in the EM-B group. The posieive rate of CD56(14.3% vs 66.7%)and overall response rate(60% vs 82.3%)in EM-E group were significantly lower than those in EM-B group. The median overall survival (OS)of patients with EM-E and EM-B was 14.5 and 49.5 months, and the median progression-free survival(PFS)of the two groups was 9.0 and 18.0 months. Patients with EM-E had a significantly shorter OS( P=0.035)and PFS( P < 0.001)than those of patients with EM-B, whereas the PFS did not significantly differ( P=0.263)when patients accepted proteasome inhibitor(PI)-based regimens for induction therapy. Multivariate analysis with Cox model showed the best response that did not achieve partial response(PR)was an independent poor prognostic factor for both OS and PFS in NDMM patients with EM-E( P=0.031, P=0.005), ISS-III, and the best response that did not achieve PR were independent prognostic factors for the shorter OS in patients with NDMM with EM-B( P=0.009, P=0.044). Conclusions:The clinical characteristics and outcomes of patients with NDMM with EM-E are different from patients with EM-B. Outcomes of patients with EM-E is significantly poor. PI induction therapy improved the PFS of patients with EM-E.

Objective To evaluate the effect of surgery-radiotherapy interval (SRI) on clinical prognosis of locally advanced stage c Ⅱ-Ⅲ breast cancer patients treated with neoadjuvant chemtherapy and modified radical mastectomy.Methods Clinical data of 1 087 breast cancer patients treated with neoadjuvant chemotherapy and modified radical mastectomy from 11 hospitals in China were retrospectively analyzed.The optimal threshold value of SRI upon clinical prognosis was determined by maxstat method.The effect of SRI on clinical prognosis was evaluated by using multivariate Cox regression analysis and propensity score matching (PSM).Results The median follow-up time was 72.9 months.The 5-year disease-free survival (DFS) and overall survival (OS) rates were 68.1％ and 81.8％.All patients were divided into SRI ≤18 weeks (n=917) and SRI＞ 18 weeks groups (n=170).Multivariate Cox regression analysis demonstrated that hormone receptor status (P＜0.001),pathological T stage (P＜0.001),pathological N stage (P＜0.001) and SRI (P=0.023) were independent influencing factors of DFS.Hormone receptor status (P=0.013),pathological T stage (P=0.006),pathological N stage (P＜0.001),endocrine therapy (P=0.013) and SRI (P=0.001) were significantly associated with OS.After balancing the clinical and pathological factors with PSM,patients with SRI＜ 18 weeks had superior DFS and OS to those with SRI＞ 18 weeks.Conclusions SRI affects the clinical prognosis of locally advanced breast cancer patients treated with neoadjuvant chemotherapy and modified radical mastectomy.Radiotherapy should be performed within 18 weeks after mastectomy.

Objective: To investigate the clinical value of combined detection of serum angiopoietin 2 (Ang-2) and Clara cell protein 16 (CC16) in the early diagnosis of acute respiratory distress syndrome (ARDS). Methods: Two hundred critical patients, treated at the Department of Critical Care Medicine, Bao'an District People's Hospital, Shenzhen during March 2015 and September 2016,were included in the study. According to the Berlin standard, patients were divided into two groups (n=100 each group): the ARDS group and non-ARDS group.The serum levels of Ang-2 and CC16 were measured by enzyme-linked immunosorbent assay (ELISA) on the first and second day of admission for each patient, in addition to completing APACHEⅡ score, medical history, vital signs collection and other biochemical indicators detection. Finally, paired-samples t test was used to analyze the data. The multiple ROC curve was used to calculate the area under the curve of the reference index of the serum levels of Ang-2 and CC16 on the first and second day. Results: On the first and second day, the serum levels of Ang-2 and CC16 were significantly higher in ARDS patients than those in non-ARDS patients, and there was a correlation between the serum levels of Ang-2 and CC16 in ARDS patients. The ROC curve showed that the combined detection of Ang-2 and CC16 on the first day achieved a highest sensitivity of 75.9% and detection of CC16 on the first day achieved a highest specificity of 70.2%. Conclusion Single-detection of serum levels of Ang-2 and CC16 could be used for early diagnosis of ARDS, and the combined detection of both has a higher sensitivity than single detection.