1.Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy
Rui WANG ; Tiantian BAN ; Lihui XUE ; Xinyi FENG ; Jiyuan GUO ; Jiaqi LI ; Shenghe JIANG ; Xiaolei HAN ; Baofeng HU ; Wenli ZHANG ; Naijun WU ; Shuang LI ; Yajuan QI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):66-77
		                        		
		                        			
		                        			ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang (BWT) on non-alcoholic fatty liver disease (NAFLD) and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups: normal control, model, positive drug (pioglitazone hydrochloride 1.95×10-3 g·kg-1), and low-, medium-, and high-dose BWT (1.3,2.5 and 5.1 g·kg-1). Following a 12-week high-fat diet (HFD) inducement, the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week, glucose tolerance (GTT) and insulin tolerance (ITT) tests were conducted. Subsequently, the mice were euthanized for the collection of liver tissue and serum, and the subcutaneous adipose tissue (iWAT) and epididymal adipose tissue (eWAT) were weighed. Serum levels of total triglycerides (TG) and liver function indicators,such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were determined. Histological examinations, including oil red O staining, hematoxylin-eosin (HE) staining, Masson staining, and transmission electron microscopy, were performed to evaluate hepatic lipid deposition, pathological morphology, and ultrastructural changes, respectively. Meanwhile, Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were employed to analyze alterations, at both gene and protein levels, the insulin signaling pathway molecules, including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 (IRS1/2/Akt/FoxO1), glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase (Pepck) and glucose-6-phosphatase (G6Pase), lipid metabolism-related genes stearoyl-coA desaturase-1 (SCD-1) and carnitine palmitoyltransferase-1 (CPT-1), fibrosis-associated molecules α-smooth muscle actin (α-SMA), type Ⅰ collagen (CollagenⅠ), and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3(TGF-β1/p-Smad/Smad2/3), inflammatory factors such as interleukin(IL)-6, IL-8, IL-11, and IL-1β, autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1, and the expression of mammalian target of rapamycin (mTOR). ResultCompared with the model group, BWT reduced the body weight and liver weight of NAFLD mice(P<0.05, P<0.01), inhibited liver lipid accumulation, and reduced the weight of white fat: it reduced the weight of eWAT and iWAT(P<0.05, P<0.01) as well as the serum TG content(P<0.05, P<0.01). BWT improved the liver function as reflected by the reduced ALT and AST content(P<0.05, P<0.01). It improved liver insulin resistance by upregulating IRS2, p-Akt/Akt, p-FoxO1/FoxO1 expressions(P<0.05). Besides, it improved glucose and lipid metabolism disorders: it reduced fasting blood glucose and postprandial blood glucose(P<0.05, P<0.01), improved GTT and ITT(P<0.05, P<0.01), reduced the expression of Pepck, G6Pase, and SCD-1(P<0.01), and increased the expression of CPT-1(P<0.01). The expressions of α-SMA, Collagen1, and TGF-β1 proteins were down-regulated(P<0.05, P<0.01), while the expression of p-Smad/Smad2/3 was downregulated(P<0.05), suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6, IL-8, IL-11 and IL-1β(P<0.01) and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression(P<0.05)while downregulating the expression of p62/SQSTM1 and mTOR(P<0.05). ConclusionBWT ameliorates NAFLD by multifaceted improvements, including improving IR and glucose and lipid metabolism, anti-inflammation, anti-fibrosis, and enhancing autophagy. In particular, BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway. 
		                        		
		                        		
		                        		
		                        	
2.Historical Evolution and Modern Research Overview of Traditional Chinese Medicine Simmering Method
Zhenhui LI ; Benye WANG ; Yuhang SHU ; Qipan JIAN ; Jiyuan TU ; Yanju LIU ; Guangzhong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):293-298
		                        		
		                        			
		                        			Simmering method is one of the traditional processing methods of Chinese materia medica, which has been documented in the herbal literature and medical books of the past dynasties and has a great variety, but at present, there are not many specific varieties of Chinese materia medica involved, and there are few related researches. By reviewing the ancient and modern related information, the authors have organized and analyzed the historical evolution, processing purpose, modern representative Chinese materia medica(processing technology, quality evaluation, pharmacological research) of simmering method. After sorting out, it was found that the simmering method was widely used in ancient times, which was first seen in Huashi Zhongzangjing of the Eastern Han dynasty, and was enriched and developed through the Tang, Song, Jin, Yuan, Ming and Qing dynasties, and entered its heyday in Ming and Qing dynasties along with the economic prosperity and development of the Ming dynasty, involving as many as 159 varieties of Chinese materia medica, and gradually perfecting the processing theory of the simmering method. However, the number of varieties that still use the simmering method in modern times significantly decreased. The main purposes of using simmering method in modern Chinese materia medica are to reduce adverse reactions, moderate medicinal properties, enhance therapeutic effects, remove non-medicinal parts, and facilitate further processing, etc. This paper combed the key information of simmering methods for Chinese materia medica from ancient to modern times, which can provide a literature basis for the clinical application and modern research of simmered products of Chinese materia medica. 
		                        		
		                        		
		                        		
		                        	
3.Effects of different fractions of inspired oxygen during general anesthesia on postoperative recovery in patients undergoing laparoscopic hernia repair and hysterectomy in a sub-plateau region
Jiyuan HAN ; Lichun HUAI ; Minghui WANG ; Yuzhen LI ; Bo FANG
Journal of China Medical University 2024;53(8):719-724
		                        		
		                        			
		                        			Objective To investigate the effects of different fractions of inspired oxygen administered during general anesthesia on post-operative recovery in patients undergoing laparoscopic hernia repair and hysterectomy in a sub-plateau region.Methods Clinical data of 111 patients undergoing laparoscopic hernia repair and hysterectomy under general anesthesia were collected from the People's Hospital of Datong Hui and Tu Autonomous County between April 2022 and November 2023.Based on the concentration of inhaled oxygen during general anesthesia,patients were randomly divided into three groups:100%oxygen(n=36),80%oxygen(n=38),and 60%oxygen(n=37).Respiratory-related parameters,including arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),and oxygenation index(OI),were compared among the three groups before anesthesia induction,30 min after pneumoperito-neum,and 1 d after surgery.Postoperative pulmonary complications,incision infections,first gastrointestinal exhaust time,and length of hospitalization were recorded.Postoperative delirium and cognitive function were also assessed.Results At 30 min after pneumoperi-toneum induction,the OI in the 60%oxygen group was higher than that in the 100%oxygen group(P=0.009),whereas there was no sta-tistical difference in OI between the 80%oxygen and 100%oxygen groups(P>0.05).PaO2 and OI were lower(P<0.05)and PaCO2 was higher(P<0.05)in all groups on the 1st day after surgery than before the induction of anesthesia.PaO2 and OI were higher in the 80%oxygen group than in the 100%oxygen group(all P<0.05).PaO2 and OI were higher in the 60%oxygen group than in the 100%oxygen and 80%oxygen groups(all P<0.05).PaCO2 was lower in the 60%oxygen group than in the 100%oxygen group(P<0.001).The first gastrointestinal exhaust time was shorter in the 60%oxygen group than in the 100%oxygen group(P=0.019).No postoperative incision infections were observed in any of the three groups,and there were no statistically significant differences in the incidence of postoperative pulmonary complications,length of hospitalization,incidence of postoperative delirium,and cognitive dysfunction among the three groups(all P>0.05).Conclusion During general anesthesia for patients undergoing laparoscopic hernia repair and hysterectomy in a sub-pla-teau region,appropriately reducing the concentration of inspired oxygen(60%)is beneficial for postoperative respiratory and gastrointes-tinal function recovery without increasing the incidence of incision infections,postoperative delirium,and cognitive dysfunction.
		                        		
		                        		
		                        		
		                        	
4.Long-term donor safety analysis after related renal transplantation in a single center
Jiyuan WANG ; Yu CHEN ; Jinghui YANG ; Xueyang ZHENG ; Yue DING ; Shu HAN
Academic Journal of Naval Medical University 2024;45(11):1390-1394
		                        		
		                        			
		                        			Objective To evaluate the long-term safety of related kidney donors after unilateral nephrectomy.Methods A total of 91 related donors who received nephrectomy in our hospital from 2006 to 2011 were followed up for at least 10 years by outpatient,telephone,or WeChat.During the follow-up period,the serum creatinine,serum uric acid,blood urea nitrogen,estimated glomerular filtration rate(eGFR),hematuria,urinary protein,blood pressure,blood glucose and blood lipids of the donors were detected,and the changes before and after nephrectomy were analyzed.Results At 1 month after operation,the levels of serum creatinine,blood urea nitrogen and serum uric acid of the donor were significantly higher than those before operation(all P<0.05),but still within the normal range.The patients were followed up for 1,3,5 and 10 years after operation.Compared with 1 month after operation,the serum creatinine,blood urea nitrogen and serum uric acid were relatively stable(all P>0.05).The eGFR of donors of different ages remained relatively stable for a long time after operation.There were 3 cases of endoscopic hematuria and 4 cases of proteinuria after surgery,and these symptoms were relieved after rest and symptomatic treatment.Ten(11.0%)donors developed hypertension 5(5.5%)developed hyperlipidemia,and 5(5.5%)developed diabetes mellitus.No patient died.Conclusion Nephrectomy is safe and feasible for healthy related donors.To ensure the safety of the donors,comprehensive evaluation before nephrectomy and regular follow-up after nephrectomy are essential.
		                        		
		                        		
		                        		
		                        	
5.Clinical research progress of lusutrombopag for the treatment of thrombocytopenia in chronic liver disease
Zheng XU ; Jiyuan ZHANG ; Fusheng WANG
Chinese Journal of Hepatology 2024;32(10):943-947
		                        		
		                        			
		                        			Thrombocytopenia is one of the common complications with the hematologic system in patients with chronic liver disease, which often causes poor quality of life and high risk of bleeding, thereby affecting their diagnosis, treatment, and prognosis. Platelet transfusion can improve the patient's declining platelet count to a certain extent, but it has problems such as high price and being easy to cause immune rejection. Thrombopoietin (TPO), as an important cytokine that affects platelet production, can bind to TPO receptors and activate megakaryocytes to produce platelets. Lusutrombopag is a newly developed small-molecule TPO receptor agonist that can induce bone marrow progenitor cells to differentiate into megakaryocytes and increase platelet production, posing characteristics of oral convenience, safety and effectiveness; thus, it has been used in many countries and regions for the treatment of patients with chronic liver diseases concurrent with thrombocytopenia. Herein, the pharmacological features and clinical research are reviewed.
		                        		
		                        		
		                        		
		                        	
6.Clinical characteristics and risk factors of complications after kidney transplantation in children at a single-center
Fanyuan ZHU ; Xueyang ZHENG ; Jinghui YANG ; Jiyuan WANG ; Yue DING ; Yu CHEN ; Shu HAN
Chinese Journal of Organ Transplantation 2024;45(6):391-398
		                        		
		                        			
		                        			Objective:To explore the clinical characteristics and risk factors of pediatric kidney transplantation (KT).Methods:From January 1, 2010 to September 30, 2022, retrospective analysis was performed for the relevant clinical data of 81 pediatric recipients of primary KT at Organ Transplant Center of Shanghai Changzheng Hospital. The occurrences of acute rejection (AR) ,delayed graft function (DGF), infection, myelosuppression, tumor and other complications were observed within 1 year post-KT. They were grouped according to whether or not AR/DGF occurred. Univariate analysis speculated the effect of AR and DGF on renal function at 1 year after transplantation. Binary Logistic regression was employed for examining the risk factors related to AR/DGF.Results:During follow-ups, transplanted kidney was removed due to an embolization of renal vessels and dialysis resumed (n= 5). One child had failed graft due to the recurrence of original disease and dialysis resumed. The remaining 75 children had an excellent recovery of graft function. At the end of follow-ups, survival for transplant recipients and transplanted kidneys was 100% (81/81 ) and 92.6% (75/81) respectively. 23 patients (28.4%) developed DGF, including 20 child recipients of C-I donors. Among DGF recipients, 21 (91.3%) were immune induced with anti-CD25 humanized monoclonal antibody and 2 (8.7 %) with porcine antihuman lymphocyte immunoglobulin (pALG). Within the first year post-KT, 13 patients (16.1%) developed AR, including 11 child recipients of C-I donors. Induction was made with anti-CD25 humanized monoclonal antibody (n=8), pALG (n=4) and anti-human T lymphocyte rabbit immunoglobulin (n=1). And 12 cases were reversed with MP (methylprednisolone) shock therapy while another ineffective case was rescued by an intravenous infusion of rATG (rabbit anti-human thymocyte immunoglobulin). During postoperative follow-ups, 14 (17.3 %) KT recipients had an onset of pulmonary infection (n=7), upper respiratory tract infection (n=3), urinary tract infection (n=5), gastrointestinal infection (n=2) and abdominal cavity infection (n=1). The causative pathogens were bacteria (n=14) and viruses (n=4). Among 7 cases (8.6%) of myelosuppression, there were leukopenia (n=6) and thrombocytopenia (n=1 ). During 1-year follow-ups, no malignancy occurred. At the last follow-up, blood creatinine was (72.79±21.07) μmol/L in non-AR/DGF recipients. For AR/DGF recipients, blood creatinine levels were (68.83±10.78) and (74.20±18.70) μmol/L. There was no significant inter-group difference ( F=0.14, P=0.87). In groups with and without DGF, the incidence of bone marrow suppression in the children with DGF was significantly higher (21. 74 %) than that in the untreated group (3.45%), with a statistically significant difference ( P=0.02). However, there was no statistically significant difference in the age, sex, donor source, infection, and types of immune-induced drugs in AR, DGF occurrence and no occurrence group. logistic Regression analysis showed that immunoinduction therapy with lymphocyte inhibitor ( OR=0.074, 95 %CI: 0.009-0.0643, P=0.018) and bone marrow suppression ( OR=0.045, 95%CI: 0.004-0.515, P=0.013) were risk factors for DGF. Conclusion:KT in children may obtain decent outcomes. Immunoinduction therapy with lymphocyte inhibitors and occurrence of myelosuppression are risk factors for postoperative DGF. The occurrence of AR/DGF in early postoperative period does not affect the level of kidney function in children at 1 year post-KT. It is recommended to closely follow up and accumulate experiences for optimizing long-term outcomes.
		                        		
		                        		
		                        		
		                        	
7.Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors.
Feifei FANG ; Yang DAI ; Hao WANG ; Yinchun JI ; Xuewu LIANG ; Xia PENG ; Jiyuan LI ; Yangrong ZHAO ; Chunpu LI ; Danyi WANG ; Yazhou LI ; Dong ZHANG ; Dan ZHANG ; Meiyu GENG ; Hong LIU ; Jing AI ; Yu ZHOU
Acta Pharmaceutica Sinica B 2023;13(12):4918-4933
		                        		
		                        			
		                        			As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.
		                        		
		                        		
		                        		
		                        	
8.Research progress and prospect of artificial intelligence in nursing management
Na LIU ; Qing WANG ; Xiaotong DING ; Lin WANG ; Shuaifang WEI ; Mingyue ZHU ; Jiyuan SHI
Chinese Journal of Modern Nursing 2023;29(19):2521-2525
		                        		
		                        			
		                        			Artificial intelligence has shown broad application prospects in the field of nursing management, and is expected to become an important breakthrough point in improving the efficiency and level of nursing management. This study reviewed the current research status of artificial intelligence in the field of nursing management, summarized the progress of artificial intelligence in nursing personnel scheduling, disease risk management and optimizing nursing management processes, analyzed the opportunities and challenges of artificial intelligence application in nursing management, and provides reference for the development and application of artificial intelligence in nursing management in the future.
		                        		
		                        		
		                        		
		                        	
9.Efficacy and Safety of Apatinib Monotherapy as Subsequent-line Therapy on Patients with Advanced Esophageal Squamous Cell Carcinoma
Jiyuan HOU ; Peihong QI ; Haixia WANG ; Zhe GONG ; Guoyong SHAN
Cancer Research on Prevention and Treatment 2022;49(3):219-224
		                        		
		                        			
		                        			Objective To investigate the efficacy and safety of apatinib monotherapy as subsequent-line therapy on patients with advanced ESCC. Methods We included 56 patients with advanced ESCC who were administered with apatinib monotherapy. The initial dosage of apatinib was 500mg or 250mg daily. Clinicopathological characteristics, adverse reaction and prognosis of the patients were analyzed. The primary endpoint of this study was PFS, the secondary endpoints were ORR, DCR, OS and safety of apatinib administration. Results All the 56 patients with ESCC corresponded with the eligibility criteria and were available for the evaluation of efficacy and adverse reaction. The ORR of the 56 patients who received apatinib monotherapy was 8.9% (95%
		                        		
		                        	
10.Comparison Between Integrated and Traditional Decoction Pieces of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine Based on Quality and Pharmacological Effect
Caixia TAO ; Yukun ZHENG ; Qipan JIAN ; Yuhang SHU ; Jiyuan TU ; Yanju LIU ; Guangzhong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(23):174-181
		                        		
		                        			
		                        			ObjectiveTo compare the consistency and difference between the integrated decoction pieces (IDP) and traditional decoction pieces (TDP) of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA) in the component content and pharmacological effect, so as to explain the rationality of the integrated production of PRPZA. MethodThin layer chromatography (TLC), extract determination, ultraviolet spectrophotometry and high performance liquid chromatography (HPLC) were used to analyze and determine the TLC identification, the contents of water-soluble extract, alum residue, needle-like calcium oxalate crystal, protein, total alkaloids, polysaccharides and three nucleosides (inosine, guanosine and adenosine) of IDP and TDP of PRPZA, and the statistical comparison was made. The anti-inflammatory effect and irritation of IDP and TDP of PRPZA were compared by xylene-induced mouse auricle swelling test and rabbit conjunctival irritation test. ResultCompared with the TDP of PRPZA, the contents of alum residue, needle-like calcium oxalate crystal, protein, polysaccharides, inosine, guanosine and the total amount of three nucleosides in the IDP of PRPZA decreased by 16.95%, 21.27%, 23.78%, 4.74%, 52.12%, 0.24% and 26.04%, the contents of water-soluble extract, total alkaloids and adenosine increased by 7.62%, 114.83% and 125.42%, respectively. IDP and TDP of PRPZA had obvious inhibitory effects on ear edema in mice, but there was no significant difference between them, indicating that the anti-inflammatory effect was consistent. The two decoction pieces of PRPZA had no irritation to the conjunctiva of rabbits, and the difference was not statistically significant between them, suggesting that the safety was similar. ConclusionThere is a certain difference in the component content between the IDP and the TDP of PRPZA, but their anti-inflammatory and irritant effects are similar, and the quality of IDP is slightly better than TDP, which provides a reference for the industrial production and clinical application of the IDP of PRPZA. 
		                        		
		                        		
		                        		
		                        	
            
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