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.Awareness and influencing factors of chronic obstructive pulmonary diseases among residents in Yangpu District, Shanghai
Jingjing HU ; Yunlong ZHANG ; Xue HAN ; Ruihua FENG ; Xin GE ; Hongwei ZHANG
Shanghai Journal of Preventive Medicine 2024;36(1):53-58
		                        		
		                        			
		                        			ObjectiveTo understand the awareness of knowledge about chronic obstructive pulmonary disease (COPD) and influencing factors among residents in Yangpu District, Shanghai. MethodsWe used cluster random sampling method to conduct face-to-face questionnaire surveys on selected household residents in 12 streets of Yangpu District. The survey questions included their understanding of COPD name, lung function test, and COPD related knowledge. Multivariate logistic regression analysis was used to analyze the influencing factors of awareness rate. ResultsA total of 1 440 people were ultimately included in the analysis, and the awareness rates of COPD name, lung function test, and COPD awareness were 19.93%, 18.61%, and 14.95%, respectively. Among the people who knew the name of COPD, awareness rate of shortness of breath or dyspnea was the highest (84.12%) in the three main symptoms of COPD. Among the main risk factors of COPD, second-hand smoke(86.78%)and smoking (85.82%) were the highest. The main ways to obtain knowledge of COPD names were through television (12.60%) and the internet (11.97%). The results of multivariate logistic regression analysis showed that men were significantly higher than women in the awareness of COPD name, lung function test, and COPD knowledge, with the OR values of (OR=1.39, 95%CI:1.08‒1.79), (OR=1.47,95%CI:1.12‒1.92) and (OR=1.37,95%CI:1.02‒1.84), respectively. The awareness rate of COPD names and lung function tests was the highest among people aged ≥ 65 years old, while the awareness rate of COPD knowledge was the highest among people aged 35‒50 years old. The awareness rate of COPD names was the highest among people with college education or above, civil servants, teachers, and medical staff, people with an annual household income of 100 000‒200 000 yuan. ConclusionThe overall awareness rate of COPD names, lung function tests, and COPD related knowledge among residents in Yangpu District is still at a low level. We should intensify the promotion and education of COPD among key groups such as women, young people, and those with low income, in order to improve the overall awareness rate of COPD among the population. 
		                        		
		                        		
		                        		
		                        	
3.Effect and mechanism of Astragalus polysaccharide on peritoneal fibrosis and angiogenesis in peritoneal dialysis rats
Xue FENG ; Bin PENG ; Li FENG ; Shuangyi ZHU ; Xi HU ; Wei XIONG ; Zhi GAO
China Pharmacy 2024;35(6):712-717
		                        		
		                        			
		                        			OBJECTIVE To investigate the effect and mechanism of Astragalus polysaccharide (APS) on peritoneal fibrosis and angiogenesis in rats with peritoneal dialysis (PD). METHODS Rats were randomly divided into normal control group (Control group), model group (PD group), 70 mg/kg APS group (APS-L group), 140 mg/kg APS group (APS-H group), and 140 mg/kg APS+40 mg/kg hypoxia-inducible factor-1α (HIF-1α) agonist DMOG group (APS-H+DMOG group), with 12 rats in each group. PD rat models were constructed in the last four groups of rats. Administration groups were given APS intragastrically and DMOG intraperitoneally. Control group and PD group were given constant volume of normal saline intragastrically, once a day, for 4 consecutive weeks. After the last medication, the peritoneal ultrafiltration (UF), mass transfer of glucose (MTG), the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected in rats; peritoneal histomorphology and peritoneal fibrosis (peritoneal thickness and proportion of collagen fiber deposition) were observed; the microvascular density and the expression levels of α-smooth muscle actin (α-SMA), laminin (LN), HIF-1α and vascular endothelial growth factor (VEGF) proteins were detected in peritoneal tissue of rats. RESULTS Compared with Control group, the mesothelium of rats in the PD group was loosely arranged and shed, inflammatory cells infiltrated, the peritoneal thickness and proportion of collagen fiber deposition were increased significantly (P<0.05). The levels of MTG, Scr and BUN in serum, microvascular density and the expressions of α-SMA, LN, HIF-1α and VEGF proteins were significantly increased, while the level of UF was significantly decreased (P< 0.05); compared with PD group, the levels of above indexes were significantly reversed in APS-L and APS-H groups (P<0.05), and the improvement of APS-H group was better than APS-L group (P<0.05). Compared with APS-H group, the levels of above indexes in APS-H+DMOG group were all reversed (P<0.05). CONCLUSIONS APS inhibits peritoneal fibrosis and angioge-nesis in PD rats by inhibiting HIF-1α/VEGF signaling pathway.
		                        		
		                        		
		                        		
		                        	
4.Real-time Analysis of Organic Composition of Oral and Nasal Breath Air by High Resolution Mass Spectrometry
Kang-Yi WANG ; Chen TAO ; Xin LUO ; Zhi-Feng TANG ; Te BAI ; Hang LI ; Li-Gang HU ; Wei ZHANG ; Xue LI
Chinese Journal of Analytical Chemistry 2024;52(1):72-79,中插14-中插37
		                        		
		                        			
		                        			Human exhaled breath has great application prospects,e.g.,monitoring pharmacokinetics,disease diagnosis,due to its advantages such as non-invasive and high-frequency sampling.Breath samples can be collected from the oral and nasal cavity.However,the oral and nasal environment affect the chemical composition of breath sample.Therefore,the investigation on the chemical composition of mouth-exhaled breath and nose-exhaled breath is crucial for selection of appropriate sampling strategy for individual studies.In this work,secondary electrospray ionization-high resolution mass spectrometry(SESI-HRMS)was applied to analysis of respiratory metabolomics in real time.A quantitative analysis approach was established for 9 kinds of volatile organic compounds(VOCs)e.g.2-butanone,2-pentanone,ethyl acetate,methyl methacrylate,toluene,styrene,mesitylene,isoprene and limonene.The limit of detection was 2.3?240.8 ng/m3.The intra-day(n=6)and inter-day(n=18)relative standard deviations were 0.6%?4.6%and 4.3%?12.2%,respectively.Nine healthy subjects were recruited to investigate the chemical composition of mouth-exhaled and nose-exhaled breath.The results showed the good performance in quantitative analysis of 9 VOCs in breath air.It was found that the number of unique component(m/z)detected in mouth-exhaled breath(167)was 2.2 times greater than that detected in nose-exhaled breath(76),which might result from the complex environment in oral cavity.The signal intensity of commun component(163)was significantly different between mouth-exhaled breath and nose-exhaled breath.Additionally,the elemental composition analysis showed that the proportion of polar compounds detected in nose-exhaled breath was higher than that in mouth-exhaled breath.This study demonstrated that there was significant differences in the chemical composition between mouth-exhaled and nose-exhaled breath,which provided a theoretical basis for selection of exhalation mode.
		                        		
		                        		
		                        		
		                        	
5.Magnetic Resonance Imaging-Based Vertebral Bone Quality Score for Prediction of Cage Subsidence and Screw Loosening in Patients Undergoing Degenerative Lumbar Surgery: A Meta-analysis
Fangke HU ; Lu XUE ; Dong ZHAO ; Chao CHEN ; Feng JING ; Qiang YANG
Neurospine 2024;21(3):913-924
		                        		
		                        			 Objective:
		                        			Poor bone quality is a risk factor for postoperative complications after degenerative lumbar fusion surgery. The magnetic resonance imaging-based vertebral bone quality (VBQ) score is a good tool for assessing bone quality, and this is the first meta-analysis performed to summarize the predictive value of the VBQ score for cage subsidence and screw loosening in patients undergoing degenerative lumbar surgery. 
		                        		
		                        			Methods:
		                        			Studies were comprehensively searched in electronic databases. The quality of the studies was assessed. The pooled sensitivity, specificity and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. 
		                        		
		                        			Results:
		                        			We ultimately included 9 studies with a total of 1,404 patients with a mean age of 60.4 years and a percentage of females of 57.0%. According to the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to assess methodological quality, the quality of the included studies was relatively low and risks of bias might exist. Results showed that a high VBQ was significantly associated with cage subsidence and screw loosening, and risk factor analysis revealed that the merged odds ratio was 5.37 for cage subsidence and 3.87 for screw loosening. With a VBQ cutoff value of 3.34±0.45, the pooled sensitivity and specificity for the diagnosis of postoperative complications were 0.75 and 0.75, respectively, and the area under the curve was 0.82 (95% confidence interval, 0.78–0.85). 
		                        		
		                        			Conclusion
		                        			A high VBQ was associated with a high risk of cage subsidence and screw loosening in patients who underwent degenerative lumbar surgery. The VBQ score could be considered for identifying high-risk patients for further evaluation. 
		                        		
		                        		
		                        		
		                        	
6.Magnetic Resonance Imaging-Based Vertebral Bone Quality Score for Prediction of Cage Subsidence and Screw Loosening in Patients Undergoing Degenerative Lumbar Surgery: A Meta-analysis
Fangke HU ; Lu XUE ; Dong ZHAO ; Chao CHEN ; Feng JING ; Qiang YANG
Neurospine 2024;21(3):913-924
		                        		
		                        			 Objective:
		                        			Poor bone quality is a risk factor for postoperative complications after degenerative lumbar fusion surgery. The magnetic resonance imaging-based vertebral bone quality (VBQ) score is a good tool for assessing bone quality, and this is the first meta-analysis performed to summarize the predictive value of the VBQ score for cage subsidence and screw loosening in patients undergoing degenerative lumbar surgery. 
		                        		
		                        			Methods:
		                        			Studies were comprehensively searched in electronic databases. The quality of the studies was assessed. The pooled sensitivity, specificity and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. 
		                        		
		                        			Results:
		                        			We ultimately included 9 studies with a total of 1,404 patients with a mean age of 60.4 years and a percentage of females of 57.0%. According to the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool to assess methodological quality, the quality of the included studies was relatively low and risks of bias might exist. Results showed that a high VBQ was significantly associated with cage subsidence and screw loosening, and risk factor analysis revealed that the merged odds ratio was 5.37 for cage subsidence and 3.87 for screw loosening. With a VBQ cutoff value of 3.34±0.45, the pooled sensitivity and specificity for the diagnosis of postoperative complications were 0.75 and 0.75, respectively, and the area under the curve was 0.82 (95% confidence interval, 0.78–0.85). 
		                        		
		                        			Conclusion
		                        			A high VBQ was associated with a high risk of cage subsidence and screw loosening in patients who underwent degenerative lumbar surgery. The VBQ score could be considered for identifying high-risk patients for further evaluation. 
		                        		
		                        		
		                        		
		                        	
7.Research progress on clinical application of ruxolitinib
Shiquan FENG ; Zhenmiao QIN ; Xue HU ; Deqiao DONG ; Haoyang PENG ; Changran GAN ; Chengcheng DUAN ; Yanan GAO
China Pharmacy 2024;35(13):1668-1672
		                        		
		                        			
		                        			Ruxolitinib, a small molecule inhibitor, selectively targets Janus kinase (JAK) by competitively binding to adenosine triphosphate on the catalytic site of the JAK1 and JAK2 domain, thereby inhibiting JAK activation and signal transducer and activator of transcription (STAT) phosphorylation and prevents the expressions of the JAK-STAT signaling pathway. Oral ruxolitinib has demonstrated promising efficacy for myelofibrosis and polycythemia vera. The topical Ruxolitinib cream, approved by the US FDA as the first non-segmental vitiligo home treatment drug, is set to be launched in domestic medical pioneer areas in August 2023 and is expected to bring about a breakthrough in the treatment of vitiligo. Clinical cases have also shown that Ruxolitinib cream has significant curative effects on atopic dermatitis, alopecia areata, and other conditions, indicating great application prospects.
		                        		
		                        		
		                        		
		                        	
8.Effect and mechanism of pachymic acid on renal function and fibrosis in rats with chronic renal failure
Bin PENG ; Xue FENG ; Li FENG ; Wei XIONG ; Xi HU ; Shuangyi ZHU ; Yang XIAO ; Fang CHEN ; Zhi GAO
China Pharmacy 2024;35(12):1489-1494
		                        		
		                        			
		                        			OBJECTIVE To investigate the effect of pachymic acid (PA) on renal function and fibrosis in chronic renal failure (CRF) rats and its potential mechanism based on the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. METHODS Using male SD rats as subjects, the CRF model was established by 5/6 nephrectomy; the successfully modeled rats were divided into model group, PA low-dose, medium-dose and high-dose groups (5, 10, 20 mg/kg PA), high-dose PA+ROCK pathway activator lysophosphatidic acid (LPA) group (20 mg/kg PA+1 mg/kg LPA), with 15 rats in each group. Another 15 rats were selected as the sham operation group with only the kidney exposed but not excised. The rats in each drug group were gavaged and/or injected with the corresponding liquid via the caudal vein, once a day, for 12 consecutive weeks. During the experiment, the general condition of rats was observed in each group. After the last administration, the serum renal function indexes (blood urea nitrogen, serum creatinine, uric acid) of rats in each group were detected, the renal histopathological changes were observed; the renal tubule injury score and the area of renal fibrosis were quantified. The levels of oxidative stress indexes [malondialdehyde (MDA), superoxide dismutase (SOD)] and inflammatory factors (tumor necrosis factor-α, interleukin-1β, interleukin-6), the positive expression rates of connective tissue growth factor (CTGF) and collagen Ⅰ were detected as well as the expression levels of pathway-related proteins (RhoA, ROCK1) and fibrosis- related proteins (transforming growth factor-β1, bare corneum homologs 2, α-smooth muscle actin) were determined. RESULTS Compared with the sham operation group, the rats in model group had reduced diet, smaller body size, listless spirit and sluggish response, reduced and atrophied glomeruli, dilated renal tubules with chaotic structure, and a large number of inflammatory cells infiltrated interstitium; the serum levels of renal function indexes, renal tubule injury score, renal fibrosis area proportion, the levels of MDA and inflammatory factors, the positive expression rates of CTGF and collagen Ⅰ, and the expression levels of pathway-related proteins and fibrosis-related proteins in renal tissues were significantly increased, while SOD level was significantly decreased (P<0.05). Compared with the model group, the general condition and pathological injuries of kidney tissue of rats in PA groups were improved to varying degrees,and the above quantitative indexes were significantly improved in a dose-dependent manner (P<0.05). LPA could significantly reverse the improvement effect of PA on the above indicators (P<0.05). CONCLUSIONS PA can improve renal function and alleviate renal fibrosis in CRF rats, which may be related to inhibiting the activation of RhoA/ROCK signaling pathway.
		                        		
		                        		
		                        		
		                        	
9.A novel chalcone derivative C13 inhibits the growth of human gastric cancer cells through suppressing ErbB4/PI3K/AKT signaling pathway
Peng TAN ; Yun-feng ZHANG ; Long-yan WANG ; Hui-ming HUANG ; Fei WANG ; Xue-jiao WEI ; Zhu-guo WANG ; Jun LI ; Zhong-dong HU
Acta Pharmaceutica Sinica 2024;59(4):957-964
		                        		
		                        			
		                        			 3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of 
		                        		
		                        	
		                				10.Study on the characteristic branch sites of oligosaccharides of Astragalus  polysaccharide APS-Ⅱ enzymolysis based on high resolution mass spectrometry
		                			
		                			Yu-chong LIU ; Hu-feng LI ; Ke LI ; Xue-mei QIN ; Yu-guang DU ; Zhen-yu LI
Acta Pharmaceutica Sinica 2024;59(7):2108-2116
		                        		
		                        			
		                        			 italic>Astragalus polysaccharides are the most immunoregulatory active and abundant substances in 
		                        		
		                        	
            
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