1.Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine (version 2024)
Xiao CHEN ; Hao ZHANG ; Man WANG ; Guangchao WANG ; Jin CUI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Guohui LIU ; Zhongmin SHI ; Lili YANG ; Zhiwei WANG ; Guixin SUN ; Biao CHENG ; Ming CAI ; Haodong LIN ; Hongxing SHEN ; Hao SHEN ; Yunfei ZHANG ; Fuxin WEI ; Feng NIU ; Chao FANG ; Huiwen CHEN ; Shaojun SONG ; Yong WANG ; Jun LIN ; Yuhai MA ; Wei CHEN ; Nan CHEN ; Zhiyong HOU ; Xin WANG ; Aiyuan WANG ; Zhen GENG ; Kainan LI ; Dongliang WANG ; Fanfu FANG ; Jiacan SU
Chinese Journal of Trauma 2024;40(3):193-205
		                        		
		                        			
		                        			Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.
		                        		
		                        		
		                        		
		                        	
2.Significance of high expression of C5orf46 in gastric cancer and potential intervention of tarditional Chinese medicine based on bioinformatics, molecular docking, and cell experiments.
Ying-Jia ZHOU ; Jia-Ming LIU ; Bin LIU ; Zi-Xia WANG ; Xin-Yu FAN ; Pei-Zhen HUANG ; Yu-Xin HUANG ; Jing-Ning SUN ; Qi-Qi CHEN ; Hong-Mei SHEN
China Journal of Chinese Materia Medica 2023;48(9):2368-2378
		                        		
		                        			
		                        			This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 μmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Stomach Neoplasms/metabolism*
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			Molecular Docking Simulation
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Computational Biology
		                        			
		                        		
		                        	
3.The Efficacy and Safety of Daratumumab-Based Regimen in Treatment of Multiple Myeloma Patients with Renal Impairment.
Ling-Ling YIN ; Yang-Ling SHEN ; Feng-Ling MIN ; Wei-Ying GU ; Ying WANG ; Kun-Ming QI ; Zhen-Yu LI ; Kai-Lin XU
Journal of Experimental Hematology 2023;31(1):141-147
		                        		
		                        			OBJECTIVE:
		                        			To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI).
		                        		
		                        			METHODS:
		                        			The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed.
		                        		
		                        			RESULTS:
		                        			The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M2). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections.
		                        		
		                        			CONCLUSION
		                        			Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Multiple Myeloma/drug therapy*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Dexamethasone/therapeutic use*
		                        			;
		                        		
		                        			Antibodies, Monoclonal/therapeutic use*
		                        			;
		                        		
		                        			Bortezomib/therapeutic use*
		                        			;
		                        		
		                        			Renal Insufficiency/drug therapy*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			
		                        		
		                        	
4. Screening of key targets for diabetic cardiomyopathy based on transcriptomics and proteomics
Zhen-Ming LIN ; Ming-Chao ZHANG ; Meng-Ying HE ; Wen-Bin LIU ; Juan SHEN ; Xiao-Bao JIN
Chinese Pharmacological Bulletin 2023;39(5):910-917
		                        		
		                        			
		                        			 Aim To explore a potential new target for the prevention and treatment of diabetic cardiomyopathy ( DCM) in mice. Methods The myocardial proteomics of normal and diabetic mice was studied. The GEO database GSE161931 dataset was analyzed using R language with P < 0.05 and I log 
		                        		
		                        		
		                        		
		                        	
5.Preliminary analysis of the promotion effect of laparoscopic standardized surgical treatment for gastric cancer in regional medical centers in Shanghai.
Xiao Dong SHEN ; Ming XU ; Chang SU ; Min YE ; Wei LI ; Zhen Xi YANG ; Jiang HAN ; Zhi Qi ZHANG ; Hong Gang XIANG ; Lin Hai YU ; Peng SUN ; Wen Hai HUANG ; Bo Wen XIE ; Ying Xin GUAN ; Zeng Hao CAI ; Wenpeng ZHANG ; Lu ZANG
Chinese Journal of Gastrointestinal Surgery 2022;25(8):708-715
		                        		
		                        			
		                        			Objective: To explore the promotion effect of laparoscopic standardized surgery for gastric cancer observational in some regional medical centers in Shanghai. Methods: A retrospective cohort study was carried out. Eleven regional medical centers in Shanghai received the promotion program of laparoscopic standardized surgery for gastric cancer, which was led by Ruijin Hospital, Shanghai Jiaotong University School of Medicine (Shanghai Minimally Invasive Surgery Center) from January to December 2020. Clinicopathological data of gastric cancer patients treated at these 11 regional medical centers before and after the promotion program were collected. Inclusion criteria were as follows: patients undergoing laparoscopic distal gastrectomy or total gastrectomy; gastric cancer confirmed by pathology; without distant metastasis or peritoneal metastasis. Patients who did not undergo laparoscopic D2 radical resection, or received neoadjuvant chemotherapy before surgery, or without complete clinical data were excluded. Patients undergoing laparoscopic surgery from January to December 2019 were included in the pre-promotion group (46 cases). Patients undergoing laparoscopic surgery from January to December 2021 were included in the post-promotion group (102 cases). In addition, patients undergoing laparoscopic surgery at Ruijin Hospital from January 2021 to December were included in the control group (138 cases). The baseline data, perioperative measurements postoperative complications, and pathological results of the three groups were analyzed and compared. Results: There were no significant differences in baseline characteristics among the three groups (all P>0.05). Compared with the pre-promotion group, the operation time in post-promotion group was significantly shorter [(207.3±36.0) minutes vs. (254.2±47.1) minutes, t=7.038,P<0.001], and the number of harvested lymph node was significantly more (24.4±12.2 vs. 18.9±5.5, t=2.900, P=0.004). However, there were no significant differences in the extent of resection, time to fluid intake, and postoperative hospital stay between the two groups (all P>0.05). Compared with the control group, the operation time [(207.3±36.0) minutes vs (172.6±26.0) minutes, t=8.281, P<0.001], time to fluid intake [(6.3±3.2) days than (5.5±3.0) days, t=2.029, P=0.044], and the postoperative hospital stay [(14.3±5.6) days vs. (10.1±4.8) days, t=6.036, P<0.001] in the post- promotion group were still longer. Total gastrectomy was less common in the post-promotion group compared with the control group [18 cases (17.6%) vs. 41 cases (29.7%), χ2=7.380, P=0.007]. However, there was no significant difference in the number of harvested lymph node between the two groups (P>0.05). The morbidity of postoperative complication in the post-promotion group (9.8%, 10/102) was significantly lower than that in the pre-promotion group (23.9%, 11/46) (χ2=5.183, P=0.023), while above morbidity was not significantly different between the post-promotion group and the control group [9.8% vs. 6.5% (9/138), χ2=0.867, P=0.352]. Conclusion: After the promotion of laparoscopic standardized surgery for gastric cancer in regional medical centers, the standardization degree of surgery has been improved, and the morbidity of postoperative complication decreases. Laparoscopic standardized surgery for gastric cancer can be promoted to more regional medical centers.
		                        		
		                        		
		                        		
		                        			China
		                        			;
		                        		
		                        			Gastrectomy/methods*
		                        			;
		                        		
		                        			Hospitals
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Laparoscopy
		                        			;
		                        		
		                        			Lymph Node Excision/methods*
		                        			;
		                        		
		                        			Postoperative Complications/etiology*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Stomach Neoplasms/pathology*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
6.Risk factors for recurrence and survival analysis in locally advanced T4a papillary thyroid carcinoma after R0 resection.
Jia Ming CHEN ; Ju Guo FANG ; Qi ZHONG ; Yan Song LIN ; Li Zhen HOU ; Hong Zhi MA ; Ling FENG ; Shi Zhi HE ; Qian SHI ; Meng LIAN ; Meng WANG ; Xixi SHEN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(9):1044-1051
		                        		
		                        			
		                        			Objective: To investigate the treatment outcomes and risk factors of postoperative recurrence in T4a papillary thyroid carcinoma (PTC). Methods: A total of 185 patients with locally advanced T4a PTC treated in Beijing Tongren Hospital, Capital Medical University from January 2006 to December 2019 were retrospectively analyzed, including 127 females and 58 males, aged between 18 and 80 years, with 74 patients aged over 55 years. According to AJCC thyroid tumor staging, 111 cases were stage I (T4aN0M0 26 cases, T4aN1aM0 35 cases, and T4aN1bM0 50 cases) and 74 cases were stage Ⅲ (T4aN0M0 29 cases, T4aN1aM0 19 cases, and T4aN1bM0 26 cases). Kaplan-Meier method was used to calculate the overall survival and the recurrence-free rate, and univariate and multivariate logistic regression analyses on the clinical data were performed. Results: Recurrent laryngeal nerve invasion was observed in 150 cases, trachea invasion in 61 cases, esophagus invasion in 30 cases, and laryngeal structure invasion in 10 cases. Postoperative follow-up periods were 24-144 months, with an average of 68.29 months. Of the 185 patients, 18 (9.73%) had recurrences or metastases, including 9 cases (4.86%) died of recurrences or metastases. The 5-year and 10-year overall survival rates were respectively 95.21% and 93.10%. The 5-year and 10-year disease-free survival rates were respectively 89.65% and 86.85%. Univariate analysis showed that age of onset, tumor diameter, preoperative recurrent laryngeal nerve palsy, esophageal invasion and cervical lymph node metastasis were the risk factors for postoperative recurrence of T4a PTC(all P<0.05). Multivariate analysis showed that preoperative recurrent laryngeal nerve palsy (OR=3.27, 95%CI: 1.11-9.61, P=0.032) and lateral cervical lymph node metastasis (OR=4.71, 95%CI: 1.19-18.71, P=0.027) were independent risk factors for T4a PTC recurrence. Survival rate of patients with T4a PTC involving only the recurrent laryngeal nerve or the outer tracheal membrane was significantly better than that of patients with tracheal invasion (P<0.05). Conclusions: T4a PTC patients with R0 resection can still achieve good efficacy. Preoperative recurrent laryngeal nerve palsy and lateral cervical lymph node metastasis are independent risk factor for postoperative recurrence in the patients.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Carcinoma/pathology*
		                        			;
		                        		
		                        			Carcinoma, Papillary/surgery*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lymphatic Metastasis
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Neoplasm Recurrence, Local/surgery*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Risk Factors
		                        			;
		                        		
		                        			Survival Analysis
		                        			;
		                        		
		                        			Thyroid Cancer, Papillary/surgery*
		                        			;
		                        		
		                        			Thyroid Neoplasms/pathology*
		                        			;
		                        		
		                        			Thyroidectomy/adverse effects*
		                        			;
		                        		
		                        			Vocal Cord Paralysis/etiology*
		                        			;
		                        		
		                        			Young Adult
		                        			
		                        		
		                        	
7.MiR-125b-5 suppresses ovarian cancer cell migration and invasion by targeted downregulation of CD147.
Zhen HUANG ; Hao Ming SHEN ; Hong Yu DENG ; Li Sha SUN ; Bin QÜ
Journal of Southern Medical University 2022;42(9):1389-1396
		                        		
		                        			OBJECTIVE:
		                        			To investigate whether miR-125b-5p regulates biological behaviors of ovarian cancer cells by targeted regulation of CD147 expression.
		                        		
		                        			METHODS:
		                        			RT-qPCR was used to detect the expression of miR-125b-5p and CD147 mRNA in ovarian cancer tissues and cancer cell lines. SKOV3 cells transfected with miR-125b-5p mimic and HO8910 cells transfected with miR-125b-5p inhibitor were examined for changes in proliferation, migration and invasion using CCK-8 assay, colonyforming assay and Transwell assay. Starbase was used to predict the potential binding sites between miR-125b-5p and CD147, and double luciferase reporter gene assay was used to verify the targeting relationship. In SKOV3 cells, the effects of cotransfection with miR-125b-5p mimic and pcDNA3.1-CD147 (or pcDNA3.1) plasmid on cell proliferation, migration and invasion were assessed with CCK-8 assay and Transwell assay.
		                        		
		                        			RESULTS:
		                        			The expression of miR-125b-5p was significantly lowered and that of CD147 was increased in both ovarian cancer tissues and ovarian cancer cell lines (P < 0.05). Overexpression of miR-125b-5p in SKOV3 cells resulted in significantly suppressed cell proliferation, migration and invasion, while downregulation of miR-125b-5p in HO8910 cells promoted cell proliferation, migration and invasion. Bioinformatic analysis predicted that miR-125b-5p binds to CD147, which was confirmed by luciferase reporter gene assay. RT-qPCR and Western blotting showed that miR-125b-5p negatively regulated CD147 expression (P < 0.05). In SKOV3 cells, the inhibitory effects of miR-125b-5p mimic on cell proliferation, invasion and migration were significantly attenuated by co-transfection of the cells with pcDNA3.1-CD147 plasmid.
		                        		
		                        			CONCLUSION
		                        			miR-125b-5p inhibits the migration and invasion of ovarian cancer cells by negatively regulating the expression of CD147.
		                        		
		                        		
		                        		
		                        			Basigin
		                        			;
		                        		
		                        			Carcinoma, Ovarian Epithelial
		                        			;
		                        		
		                        			Cell Line, Tumor
		                        			;
		                        		
		                        			Cell Movement/genetics*
		                        			;
		                        		
		                        			Cell Proliferation/genetics*
		                        			;
		                        		
		                        			Down-Regulation
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Gene Expression Regulation, Neoplastic
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			MicroRNAs/metabolism*
		                        			;
		                        		
		                        			Neoplasm Invasiveness/genetics*
		                        			;
		                        		
		                        			Ovarian Neoplasms/genetics*
		                        			;
		                        		
		                        			RNA, Messenger/genetics*
		                        			;
		                        		
		                        			Sincalide/metabolism*
		                        			
		                        		
		                        	
8.Effects of propofol on malignant biological behaviors of prostate cancer DU145 cells and its mechanism
Ming JIN ; Shuqing ZHEN ; Yanqiao WANG ; Hongxia SHEN ; Aimin ZHANG ; Limei HUI
Journal of International Oncology 2022;49(8):453-458
		                        		
		                        			
		                        			Objective:To investigate the effects of propofol on malignant biological behaviors of prostate cancer DU145 cells and its possible mechanism.Methods:Control group, 5-fluorouracil group (200 ng/ml) , low-dose propofol group (100 ng/ml) and high-dose propofol group (400 ng/ml) were set up. CCK-8 kit was used to measure the level of cell proliferation, Transwell method was used to measure the abilities of cell invasion and migration, flow cytometry was used to measure the level of apoptosis, and qRT-PCR and Western blotting were used to measure hepatocyte growth factor (HGF) and c-Met mRNA and protein levels.Results:The survival rates of the control group, 5-fluorouracil group, low-dose propofol group and high-dose propofol group were (83.32±3.02) %, (36.29±3.54) %, (62.01±4.69) % and (40.20±5.48) % ( F=8.65, P=0.006) ; the apoptosis rates were (2.36±0.41) %, (12.47±0.40) %, (6.28±0.39) % and (10.24±0.37) % ( F=26.73, P=0.001) . Further pairwise comparison showed that there were statistically significant differences (all P<0.05) . The numbers of penetrating membranes of the four groups were 617.45±29.86, 125.27±24.38, 407.02±32.27 and 230.74±31.59 ( F=18.33, P=0.002) ; the migration distances were (603.85±27.74) μm, (121.69±25.85) μm, (395.59±28.37) μm and (233.52±30.42) μm ( F=27.02, P=0.001) . Further pairwise comparison showed that there were statistically significant differences (all P<0.05) . HGF mRNA expression levels of the four groups were 6.26±0.39, 1.94±0.35, 4.15±0.37 and 2.90±0.33 ( F=25.31, P=0.001) ; c-Met mRNA expression levels were 5.85±0.30, 2.04±0.32, 3.89±0.31 and 2.94±0.32 ( F=12.12, P=0.003) ; HGF protein expression levels were 1.43±0.04, 0.34±0.08, 0.86±0.06 and 0.63±0.09 ( F=17.02, P=0.001) ; c-Met protein expression levels were 1.63±0.14, 0.39±0.15, 0.93±0.11 and 0.64±0.17 ( F=19.89, P=0.001) . Further pairwise comparison showed that there were statistically significant differences (all P<0.05) . Conclusion:Propofol has obvious inhibitory effects on the malignant biological behaviors of prostate cancer DU145 cells, and the inhibitory effect of high-dose propofol is more obvious. The mechanism may be related to the inhibition of HGF and c-Met mRNA and protein expressions of DU145 cells by propofol, which inhibits the activation of HGF/c-Met pathway.
		                        		
		                        		
		                        		
		                        	
9.Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter.
Bing JIANG ; Ruo-Ming WU ; Hai-Dong LI ; Kun LI ; Hui LI ; Wen-Zhen DANG ; Gui-Ze FENG ; Wei-Lian BAO ; Guan YE ; Xiao-Yan SHEN
Chinese journal of integrative medicine 2022;28(7):586-593
		                        		
		                        			OBJECTIVE:
		                        			To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism.
		                        		
		                        			METHODS:
		                        			The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights, including control, model, fluoxetine (FLXT, 10 mg/kg), low-dose YXNS (LYXNS, 100 mg/kg), and high-dose YXNS (HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase (IDO1), kynurenine 3-monooxygenase (KMO), and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction.
		                        		
		                        			RESULTS:
		                        			Compared with the model group, the cardiac function of rats treated with YXNS improved significantly (P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (P<0.01 or P<0.05), promoted AMPK phosphorylation, and increased PGC-1α protein expression (P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH, and CORT (all P<0.05). Moreover, HYXNS decreased the mRNA expressions of IDO1, KMO and KYNU (P<0.05).
		                        		
		                        			CONCLUSIONS
		                        			YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.
		                        		
		                        		
		                        		
		                        			AMP-Activated Protein Kinases/metabolism*
		                        			;
		                        		
		                        			Adrenocorticotropic Hormone
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Comorbidity
		                        			;
		                        		
		                        			Depression/drug therapy*
		                        			;
		                        		
		                        			Energy Metabolism
		                        			;
		                        		
		                        			Interleukin-6/metabolism*
		                        			;
		                        		
		                        			Myocardial Infarction/pathology*
		                        			;
		                        		
		                        			Neurotransmitter Agents
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Serotonin/metabolism*
		                        			;
		                        		
		                        			Tablets
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha/metabolism*
		                        			
		                        		
		                        	
10.LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells.
Zhen SUN ; Hua YU ; Jing ZHAO ; Tianyu TAN ; Hongru PAN ; Yuqing ZHU ; Lang CHEN ; Cheng ZHANG ; Li ZHANG ; Anhua LEI ; Yuyan XU ; Xianju BI ; Xin HUANG ; Bo GAO ; Longfei WANG ; Cristina CORREIA ; Ming CHEN ; Qiming SUN ; Yu FENG ; Li SHEN ; Hao WU ; Jianlong WANG ; Xiaohua SHEN ; George Q DALEY ; Hu LI ; Jin ZHANG
Protein & Cell 2022;13(7):490-512
		                        		
		                        			
		                        			LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Cell Differentiation
		                        			;
		                        		
		                        			Embryo, Mammalian/metabolism*
		                        			;
		                        		
		                        			Embryonic Development
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Pluripotent Stem Cells/metabolism*
		                        			;
		                        		
		                        			RNA, Messenger/genetics*
		                        			;
		                        		
		                        			RNA, Ribosomal
		                        			;
		                        		
		                        			RNA-Binding Proteins/metabolism*
		                        			;
		                        		
		                        			Transcription Factors/metabolism*
		                        			;
		                        		
		                        			Zygote/metabolism*
		                        			
		                        		
		                        	
            
Result Analysis
Print
Save
E-mail