1.Interactions between gut microbiota-producing enzymes and natural drugs affect disease progression
Zhi-yu WANG ; Hao-ran SHEN ; Yan-xing HAN ; Jian-dong JIANG ; Wei JIANG ; Hui-hui GUO
Acta Pharmaceutica Sinica 2024;59(8):2183-2191
		                        		
		                        			
		                        			 Naturally derived metabolites are valuable resources for drug research and development, and play an important role in the treatment of diseases. As the "second genome" of the body, gut microbiota is rich in metabolic enzymes, which interacts with external substances such as drugs, thus affecting the progression of diseases. This article summarizes the interaction between gut microbiota-producing enzymes and natural medicines, and focuses on the impact of this interaction on disease progression, hoping to provide new ideas for the development and pharmacological mechanism of natural medicines. 
		                        		
		                        		
		                        		
		                        	
2.Sertraline hydrochloride combined with compound chamomile lidocaine gel for the treatment of premature ejaculation
Shu-Gen LI ; Shang GAO ; Zhen-Wei GU ; Dao-Hua ZHAO ; Jie JIANG ; Xiao-Ting LU ; Lan-Xiang LIU ; Hao-Ran LIU ; Ze CHEN
National Journal of Andrology 2024;30(9):809-812
		                        		
		                        			
		                        			Objective:To investigate the effect of sertraline hydrochloride combined with compound chamomile lidocaine gel in the treatment of premature ejaculation(PE).Methods:We selected 80 cases of PE treated in our hospital from June 2021 to May 2023 and equally randomized them into a control and an observation group,the former medicated with compound chamomile lidocaine gel while the latter with sertraline hydrochloride in addition,both for 6 weeks.We recorded and compared the intravaginal ejaculation latency time(IELT),the number of successful sexual intercourses per week,the Premature Ejaculation Diagnostic Tool(PEDT)scores,and the incidence of adverse reactions between the two groups of patients.Results:After the treatment,the IELT was signif-icantly longer([5.39±1.17]vs[2.49±0.73]min,P<0.05),the weekly number of successful sexual intercourses remarkably higher(1.82±0.45 vs 0.93±0.19,P<0.05)and the PEDT scores markedly lower(7.42±2.04 vs 9.85±2.36,P<0.05)in the observation than in the control group,but no statistically significant differences were observed in the baseline PEDT scores or the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Sertraline hydrochloride combined with com-pound chamomile lidocaine gel is definitely effective in the treatment of PE,which can significantly improve the patients'quality of sexual life,with a high safety and low incidence of adverse reactions.
		                        		
		                        		
		                        		
		                        	
3.Short chain fatty acid: a messenger of gut-organ axis for disease regulation
Hui-hui GUO ; Hao-ran SHEN ; Yan-xing HAN ; Jian-dong JIANG
Acta Pharmaceutica Sinica 2023;58(3):593-604
		                        		
		                        			
		                        			 Gut microbiota is a complex and dynamic system, and is essential for the health of the body. As the "second genome" of the body, it can establish communication with the important organs by regulating intestinal nerves, gastrointestinal hormones, intestinal barrier, immunity and metabolism, thus affecting host′s physiological functions. Short chain fatty acid (SCFA), known as one important metabolite of intestinal microbiota, is regarded as a significant messenger of the gut-organ communication, due to its extensive regulation in the body′s immunity, metabolism, endocrine and signal transduction. In this review, we summarize the interaction between gut-liver/brain/kidney/lung axis and diseases, and focus on the role and mechanism of SCFA in the gut-organ communication, hoping to provide new ideas for the treatment of the related diseases. 
		                        		
		                        		
		                        		
		                        	
4.Molecular mechanism of ligustilide attenuating OGD/R injury in PC12 cells by inhibiting ferroptosis.
Lei SHI ; Chen-Chen JIANG ; Jia-Jun LU ; Zi-Xu LI ; Wang-Jie LI ; Xiu-Yun YIN ; Zhuo CHEN ; Xin-Ya ZHAO ; Hui ZHANG ; Hao-Ran HU ; Lu-Tan ZHOU ; Jun HAN
China Journal of Chinese Materia Medica 2023;48(11):3046-3054
		                        		
		                        			
		                        			The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			PC12 Cells
		                        			;
		                        		
		                        			Ferroptosis/genetics*
		                        			;
		                        		
		                        			Reactive Oxygen Species
		                        			;
		                        		
		                        			Transcription Factors
		                        			;
		                        		
		                        			Glutathione
		                        			
		                        		
		                        	
5.Mechanism of total flavonoids of Rhododendra simsii in alleviating ischemic brain injury.
Chen-Chen JIANG ; Lei SHI ; Xin-Ya ZHAO ; Hui ZHANG ; Zi-Xu LI ; Jia-Jun LU ; Yu-Xiang HE ; Di CAO ; Hao-Ran HU ; Jun HAN
China Journal of Chinese Materia Medica 2023;48(2):455-464
		                        		
		                        			
		                        			This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Apoptosis
		                        			;
		                        		
		                        			Brain Ischemia/metabolism*
		                        			;
		                        		
		                        			Caspase 3
		                        			;
		                        		
		                        			Interleukin-1
		                        			;
		                        		
		                        			Interleukin-6
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Reperfusion Injury/metabolism*
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha/genetics*
		                        			;
		                        		
		                        			Flavonoids/pharmacology*
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		                        			Rhododendron/chemistry*
		                        			
		                        		
		                        	
6.Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm.
Guo-Zhen ZHAO ; Hai-Tian LU ; Shi-Yan YAN ; Yu-Hong GUO ; Hao-Ran YE ; Li JIANG ; Yao-Fu ZHANG ; Jing HU ; Shi-Qi GUO ; Yuan DU ; Fang-Yu LIU ; Bo LI ; Qing-Quan LIU
China Journal of Chinese Materia Medica 2023;48(4):1132-1136
		                        		
		                        			
		                        			In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			COVID-19
		                        			;
		                        		
		                        			Algorithms
		                        			;
		                        		
		                        			Databases, Factual
		                        			;
		                        		
		                        			Prescriptions
		                        			;
		                        		
		                        			Plant Extracts
		                        			
		                        		
		                        	
7.Not Available.
Ze-Hao CHEN ; Jia-Kai HE ; Ran LI ; Yu-Hang JIANG ; Bao-Hui JIA
Chinese Acupuncture & Moxibustion 2023;43(12):1454-1456
8.A prospective study on implication value of lesion microenvironment's immune cell infiltration range on liver sampling in hepatic alveolar echinococcosis
Aini ABUDUSALAMU ; Abulizi ABUDUAINI ; Tiemin JIANG ; Bo RAN ; Renyong LIN ; Chuanshan ZHANG ; Aji TUERGANAILI ; Hao WEN ; Yingmei SHAO
Chinese Journal of Endemiology 2023;42(10):781-785
		                        		
		                        			
		                        			Objective:To investigate the immune cell infiltration width on lesion microenvironment (LME) based on different hepatic alveolar echinococcosis lesion features to underlie referential sampling range for experimental and control tissues aiming at avoiding false negativity in basic researches.Methods:Using prospective research methods, from January 2017 to December 2019, patients with hepatic alveolar echinococcosis who were diagnosed and treated surgically at the First Affiliated Hospital of Xinjiang Medical University and met the multi-site sampling method (MSS method) were investigated. A total of 26 cases were included, aged 34 (15, 65) years old, with a gender ratio of 12/14. Lesions were classified into six groups based on heterogenic scales of calcification and liquefaction: A. non-calcified and non-liquefied; B. obvious calcified and non-liquefied; C. partial calcified and partial liquefied; D. obvious calcified and partial liquefied; E. partial calcified and subtotal liquefied; F. obvious calcified and subtotal liquefied. Liver specimens were acquired with 5 mm interval off the lesion shore in LME area using MSS method. Performed immunohistochemical staining of CD3, CD19, CD68, and Masson staining of fibrous tissue, and after pathological evaluation, the layer with a sharp decrease in immune cell infiltration abundance was determined as the maximum infiltration range (width, W value). The experimental group conservatively estimated the maximum sampling range for the integer value of Q1 of W value. The control group conservatively estimated the minimum sampling range for the integer value after Q3 rounding plus 5 mm of W value. Results were analyzed using Kruskal-Wallis H and Mann-Whitney U tests, referential ranges were concluded. Results:Median W values (interquartile) for each group were 20.0 (12.5, 22.5), 15.0 (10.0, 15.0), 10.0 (10.0, 15.0), 5.0 (5.0, 10.0), 12.5 (6.3, 15.0), and 5.0 (5.0, 10.0) mm, among which A > D, A > F, C > D, and C > F ( P≤0.05); from the perspective of calcification, A > C + E, A > B + D + F ( P < 0.05), while A + B > C + D, A + B > E + F ( P < 0.05) from the perspective of liquefaction. In these groups, the experimental group conservatively estimated the maximum distance for sampling to be 12.0, 10.0, 10.0, 5.0, 6.0, and 5.0 mm, while the control group conservatively estimated the minimum distance for sampling to be 28.0, 20.0, 20.0, 15.0, 20.0, and 15.0 mm. Conclusions:Less calcification and liquefaction implicates wider immune cell infiltration range in those lesions. Tissue sampling should be individualized based on different lesion features in basic research to avoid false negativity.
		                        		
		                        		
		                        		
		                        	
9.Study on the characteristics of 18F-flurodeoxyglucose uptake in the microenvironment of hepatic alveolar echinococcosis
Abulizi ABUDUAINI ; Aini ABUDUSALAMU ; Bo RAN ; Tiemin JIANG ; Ruiqing ZHANG ; Qiang GUO ; Xiaohong LI ; Jian WANG ; Chuanshan ZHANG ; Renyong LIN ; Hao WEN ; Yingmei SHAO ; Aji TUERGANAILI
Chinese Journal of Hepatobiliary Surgery 2023;29(3):176-180
		                        		
		                        			
		                        			Objective:To investigate characteristics of the 18F-flurodeoxyglucose ( 18F-FDG) uptake intensity and ranges in distinct hepatic alveolar echinococcosis lesions. Methods:The clinical data of 39 patients with position emission tomography during Jan 2017 to Dec 2019 in the First Affiliated Hospital of Xinjiang Medical University were enrolled. Among them, there were 17 males and 22 females, aging from 15 to 65 years (median 34 years). Lesions were classified into six groups based on heterogenic scales of calcification and liquefaction: A. non-calcified and non-liquefied ( n=7); B. obvious calcified and non-liquefied ( n=7); C. partial calcified and partial liquefied( n=10); D. obvious calcified and partial liquefied ( n=5); E. partial calcified and subtotal liquefied ( n=5); F. obvious calcified and subtotal liquefied ( n=5). Tumor to background ratio (TBR) and width (W) of lesion infiltrative boundary were measured and calculated. Statistical comparison using Mann-Whitney U test as well as correlation analysis was performed. Results:TBR values [ M( Q1, Q3)] for each group were 4.40(3.66, 7.03), 2.55(1.69, 3.60), 3.73(3.37, 5.21), 2.90(2.75, 3.60), 3.80(3.49, 6.36), 2.49(2.21, 3.97), among which A>B, A>D, A>F, C>B, E>B ( U=3.0, 4.0, 4.5, 11.0, 5.0, all P<0.05); From the perspective of the calcification in each group, it was found that the lighter the calcification was, the greater the TBR value was. W values [ M( Q1, Q3)] for each group were [12.5(10.0, 19.5), 11.2(10.5, 12.5), 12.2(10.9, 13.2), 7.8(7.3, 9.3), 10.0(7.3, 13.4), 7.3(6.8, 7.6)] mm, among which A>D, A>F, B>D, B>F, C>D, C>F (all U=0, all P<0.05); According to the degree of calcification and liquefaction of lesions in each group, the lighter the calcification was, the greater the W value was; The heavier the liquefaction was, the smaller the W value was. A mild strength linear correlation has been observed between the TBR value and W value ( r=0.4136, P<0.05). Conclusions:Less calcification and liquefaction implicated higher 18F-FDG uptake intensity and wider range. Radical resection margins and tissue sampling should be individualized based on different lesion features in surgical treatment.
		                        		
		                        		
		                        		
		                        	
		                				10.Dengzhan Shengmai inhibits nonalcoholic fatty liver disease via  regulating intestinal microenvironment
		                			
		                			Hui-hui GUO ; Hao-ran SHEN ; Hong-juan ZHANG ; Lu-lu WANG ; Yan-xing HAN ; Jian-dong JIANG
Acta Pharmaceutica Sinica 2022;57(12):3524-3534
		                        		
		                        			
		                        			 The aim of this study was to investigate the efficacy and mechanism of Dengzhan Shengmai (DZSM) against nonalcoholic fatty liver diseases (NAFLD). The animal experiment program was reviewed and approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The NAFLD model of Syrian golden hamsters was established by high fat diets. After 6 weeks of DZSM treatment, the serum lipid, hepatic lipid accumulation, liver function and inflammatory response were determined. The regulations of gut microbiota and short-chain fatty acids were detected by 16S rRNA gene sequencing and gas chromatography-mass spectrometry method, respectively. The gut barrier function was evaluated by enzyme linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot and histopathological methods and further verified in HepG2 cells. The results showed that the efficacy of DZSM against NAFLD was remarkably reduced after removal of the gut microbiota. The study of mechanism showed that DZSM significantly regulated the composition of gut microbiota, promoted the production and absorption of intestinal short-chain fatty acids, then leading to the reduction of hepatic lipid accumulation. Moreover, after DZSM treatment, the decreased lipopolysaccharide (LPS) level by improving the intestinal barrier function significantly inhibited the hepatic inflammation through down-regulating Toll like receptor 4 (TLR4)-nuclear factor kappa B (NFKB) signaling pathway. These results indicate that DZSM inhibits NAFLD 
		                        		
		                        	
            
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