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.

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.

Objective:To analyze the frequency and characteristics of polymyositis (PM) in idiopathic inflammatory myopathy (IIM), and to investigate whether PM is over-diagnosed.Methods:Patients diagnosed as IIM according to the Bohan & Peter criteria of IIM hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2008 to 2019 were involved in the study. Definite PM (dPM) was defined as typical clinical and pathological features including elevated creatine kinase (CK) level, muscle weakness and muscle biopsy findings with endomysial CD8 + T cell infiltration and expression of MHC-1 on sarcolemma. Meanwhile, dermatomyositis (DM), anti-synthase syndrome(ASS), immune-mediated necrotic myopathy(IMNM), sporadic inclusion body myositis(sIBM) and other myopathies were excluded according to the new classification criteria of IIM subtypes respectively. Statistical analysis was performed using SPSS software 24.0. The Kruskal-Wallis test and χ2 test were used to compare the clinical characteristics between the dPM group and other IIM subtypes. Results:A total of 1 259 patients with IIM including 1 015 (80.6%) DM and 244(19.4%) PM were enrolled in this study. According to the strict definition of PM criteria, only 0.5% of patients (6/1 259) in IIM could be diagnosed as dPM. Most PM patients were IMNM and ASS according to the new IIM subtypes criteria, of which 48.0% (117/244) were IMNM and 32.0% (78/244) were ASS. 66.7%(4/6) of dPM patients were women. One complicated with RA, and one was dPM overlaped with systemic sclerosis. All of them had muscle weakness, mild elevation of CK level [611(391,1 451) U/L], and were myositis-specific autoantibodies negative. Except one dPM patients who did not receive immunoregulatory therapy due to chronic obstructive pulmonary disease, the others were administrated with low or medium dose prednisone combined with or without immunosuppressive agents. After a median follow-up of (38±26) months, the muscle strength of dPM patients were improved.Conclusion:dPM is a very rare clinical subtype of IIM. PM is an over-diagnosed entity in clinical practice. Patients with dPM have mild symptoms and good outcome.

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

Objective:To explore the independent risk factors that predict 10-year mortality in patients with stable chronic obstructive pulmonary disease(COPD).Methods:The baseline data from a prospective cohort study were analyzed and long-term follow-up were performed. Patients with confirmed diagnosis of stable COPD were consecutively enrolled in the outpatient clinic from January 2010 to December 2010, and were followed up until December 31, 2020. Cox regression analysis was used to determine the independent risk factors for all-cause mortality and mortality from respiratory causes in stable COPD patients.Results:A total of 182 stable COPD patients were enrolled and followed up for a median of 89 months. The 10-year mortality was 51.1%(93/182), and 9 patients died within one year. The leading cause of death was respiratory disorder, followed by cardiovascular and cerebrovascular diseases. The risk factors independently associated with all-cause mortality included old age( HR=1.936,95% CI: 1.610~2.328, P<0.01), increased baseline COPD Assessment Test(CAT)( HR=1.331,95% CI: 1.049-1.689, P=0.02) and the increased CAT in one year( HR=1.314,95% CI: 1.197-1.420, P<0.01). The risk factors independently associated with respiratory cause mortality included increased baseline CAT( HR=1.719,95% CI: 1.026-2.880, P=0.04), emphysema index(LAA%)( HR=1.062,95% CI: 1.007-1.120, P=0.03), and one year inecreased CAT( HR=1.342,95% CI: 1.198-1.505, P<0.01)was a protective factor. Conclusions:Old age, baseline CAT, one year increased in CAT and LAA% were independent influencing factors for 10-year mortality of stable COPD patients.

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 clinical features and implication of restless legs syndrome (RLS) in ischemic stroke patients. METHODS: A total of 199 ischemic stroke patients were enrolled and assessed by polysomnography (PSG). RLS was identified according to criteria of International Restless Legs Syndrome Study Group. Epworth Sleepiness Scale (ESS), Mini-mental State Examination (MMSE) and Patient Health Questionnaire (PHQ-9) were used to evaluate the sleep quality, cognitive function and post-stroke depression, respectively. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the neurological function 3 months after stroke onset. Gender-and age-matched non-ischemic stroke patients with RLS (primary PLS) were selected as controls. RESULTS: Twenty-two cases of RLS were identified among 199 ischemic stroke patients (11.1%). Generalized linear model and logistic regression showed that low serum ferritin level (=-133.3 mg/L, 95%:-200.4--0.1, <0.01), subcortical infarction (=4.05, 95%:1.15-14.18, <0.05) and female (=2.54, 95%:1.04-6.23, <0.05) were identified as the risk factors of RLS in ischemic stroke patients. Compared with ischemic stroke patients without RLS, ESS increased by 4.37 (95%:2.33-6.41, <0.01), PHQ-9 increased by 2.17 (95%:0.39--3.94, <0.05), and reduced NIHSS from the baseline deceased by 0.97 (95%:-1.79--0.15, <0.05) in ischemic stroke patients with RLS. In addition, the incidence of moderate-severe depression increased (=4.27, 95%:1.40-13.10, <0.05) in ischemic stroke patients with RLS. The index of periodic leg movements of sleep (PLMS) with arousal in ischemic stroke patients with RLS was significantly higher than that in patients with primary RLS (=12.85, 95%:2.04-23.67, <0.05). CONCLUSIONS RLS is common in ischemic stroke patients and has adverse influences on patients.
Brain Ischemia ; complications ; pathology ; Depression ; complications ; Female ; Humans ; Male ; Polysomnography ; Restless Legs Syndrome ; complications ; pathology ; Stroke ; complications ; pathology

OBJECTIVE： To study the improvement effect and related mechanism of pyragrel sodium on nerve function of cerebral ischemia-reperfusion injury model rats. METHODS： Totally 72 SD rats were randomly divided into sham operation group， model group， positive control group （dizocilpine 0.8 mg/kg）， pyragrel sodium low-dose， medium-dose and high-dose groups （20， 30， 45 mg/kg）， with 12 rats in each group. Except sham operation group received sham operation， rats in the other groups were treated with middle cerebral artery ligation to induce cerebral ischemia-reperfusion injury model. The rats in the sham operation group and the model group were injected with the constant volume of normal saline， for consecutive 6 d， and the interval of administration was 24 hours. After 24 h reperfusion and last medication， neurological deficit score and postural reflex score in rats were evaluated. The situation of cerebral injury （including whole brain， insular cortex， putamen， striatum， somatic cortex， amygdala， motor cortex） was evaluated by using micropositron emission tomography. The rats were sacrificed， and the situation of cerebral infarction was observed by TTC and cerebral infarction volume was calculated. Na+-K+-ATPase， Ca2+-ATPase activity and Glu content were detected by ELISA. RESULTS： Compared with sham operation group， neurological deficit score and postural reflex score increased significantly in model group 24 h after ischemia-reperfusion and after last medication （P＜0.05 or P＜0.01）. After 24 hours of cerebral ischemia-reperfusion and the last medication， SUV of brain tissue， SUV ratio of right left brain of different cerebral areas were decreased significantly （P＜0.01）. After last medication， the percentage of cerebral infarction volume was increased significantly （P＜0.01）； the activities of Na+-K+-ATPase and Ca2+-ATPase were decreased significantly （P＜0.01）， while Glu content was increased significantly （P＜0.01）. Compared with model group， above indexes of pyragrel sodium low-dose， medium-dose and high-dose group， positive control group were all improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Pyragrel sodium can improve cerebral ischemia-reperfusion injury and nerve function， which is related to the activity up-regulation of Na+-K+-ATPase and Ca2+-ATPase， the down-regulation of Glu content.

Objective: To study the effect of growth differentiation factor (GDF) 11-silenced bone marrow stromal cells (BMSCs) on bone regeneration in early steroid-induced osteonecrosis of the femoral head in rats. Methods: After GDF11 expression in BMSCs was inhibited by siRNA, the knockdown efficiency and transfection cytotoxicity were detected. The further experiments both in vitro (n=3) and in vivo (n=8) were divided into 4 groups respectively: blank control group (without any intervention), model group (glucocorticoid treatment), experimental group (siRNA transfection and glucocorticoid treatment) and negative control group (negative control transfection and glucocorticoid treatment). The BMSCs were induced into osteogenic differentiation. Alkaline phosphatase (ALP) staining and alizarin red staining were applied to evaluate the osteogenic differentiation ability of the cells while reverse transcription polymerase chain reaction (qRT-PCR) was employed to detect the relative expression levels of osteogenic markers. The osteogenesis in the necrotic femoral head was evaluated by microCT, H&E staining, immunohistochemistry staining and biomechanical test. Results: No transfection cytotoxicity was found (P>0.05). The ALP staining and alizarin red staining showed that the osteogenic differentiation of BMSCs in the experimental group was better than that in the model group. At the level of mRNA, the relative expression of ALP, runt-related transcription factor (Runx) 2, osteocalcin (OCN) and type Ⅰ collagen (α1) (COL1A1) in the blank control group (1.00±0.09, 1.02±0.23, 1.03±0.30 and 1.02±0.25, respectively) were significantly higher than those in the model group (0.46±0.11, 0.50±0.11, 0.35±0.01 and 0.57±0.02, respectively) but significantly lower than those in the experimental group (1.97±0.30, 0.94±0.19, 1.50±0.18 and 1.28±0.37) (all P<0.05). MicroCT images and quantitative analysis showed that the bone mass in the experimental group was significantly increased compared with the model group (P<0.05). Histological examination showed better bone regeneration and higher expression of Runx2 and COL1 in the necrotic femoral head in the experimental group than in the model group. Improved biomechanical properties were shown in the experimental group compared with the model group (P<0.05). Conclusions Silence of GDF11 expression may alleviate the inhibitory effect of glucocorticoid on osteogenic differentiation of BMSCs. Early transplantation of GDF11-silenced BMSCs may promote osteogenesis in the necrotic femoral head in rats.

Objective: To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) . Methods: Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events. Results: Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51.9% (14/27) and 66.7% (18/27) respectively, including 1 sCR (3.7%) , 3 CR (11.1%) , 3 VGPR (11.1%) , and 7 PR (25.6%) . In 13 patients with prior Rd, ORR and CBR were 38.5% (5/13) and 61.5% (8/13) respectively, of which 5 patients with ≥MR carried high-risk cytogenetic[ (e.g.17p- or t (4;14) ] together with at least one of other adverse-prognostic cytogenetic (e.g.13q- and/or 1q21+) . In 24 patients with prior bortezomib-based therapy, ORR and CBR were 45.8 and 62.5%, respectively. With a median follow-up time of 14.9 (range 1.0-33.8) months, the median PFS and OS were 12.0 (95%CI 11.6-12.4) and 27.6 (95%CI 15.1-40.1) months, respectively. The BiRd regimen was well tolerated. Conclusion The BiRd regimen is an effective and safety protocol for RRMM, including those carrying high-risk cytogenetic markers.