1. Mechanism of action of formononetin in alleviating allergic asthma through DRP1-NLRP3 signaling pathway
Mu CHEN ; Qiao-Yun BAI ; Yi-Lan SONG ; Jiao CHEN ; Yong-De JIN ; Guang-Hai YAN ; Jiao CHEN ; Yong-De JIN ; Qiao-Yun BAI ; Yi-Lan SONG ; Guang-Hai YAN
Chinese Pharmacological Bulletin 2024;40(3):529-536
		                        		
		                        			
		                        			 Aim To investigate the mechanism by which formononetin (FN) inhibits mitochondrial dynamic-related protein 1 (DRP1) -NLRP3 axis via intervening the generation of ROS to reduce allergic airway inflammation. Methods In order to establish allergic asthma mouse model, 50 BALB/c mice aged 8 weeks were divided into the control group, model group, FN treatment group and dexamethasone group after ovalbumin (OVA) induction. Airway inflammation and collagen deposition were detected by HampE and Masson staining. Th2 cytokines and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA, ROS in BEAS-2B cells was assessed by DCFH-DA staining, DRP1 expression in lung tissue and BEAS-2B cells was detected by immunohistochemistry and immunofluorescence, and the DRP1-NLRP3 pathway was analyzed by immunoblotting. Results FN treatment could effectively ameliorate the symptoms of asthmatic mouse model, including reducing eosinophil accumulation, airway collagen deposition, decreasing Th2 cytokine and IgE levels, reducing ROS and MDA production, increasing SOD and CAT activities, and regulating DRP1-NLRP3 pathway-related protein expression, thereby relieving inflammation. Conclusion FN ameliorates airway inflammation in asthma by regulating DRP1-NLRP3 pathway. 
		                        		
		                        		
		                        		
		                        	
2.Clinical safety and validity analysis of retrograde new endo-scopic visual field in miniature pigs
Zhe KUANG ; Peng LI ; Da-Qing JIN ; Yong-Chao ZHANG ; Hui-Li GUO ; Yu-Fei ZHANG ; Guang-Lin HE ; Guo-Feng SUN ; Yuan HE
Chinese Journal of Current Advances in General Surgery 2024;27(1):14-18
		                        		
		                        			
		                        			Objective:To study the clinical safety and validity of retrograde new endoscopic field of vision in miniature pigs.Methods:6 live miniature pigs were selected as study subjects,En-doscopic Retrograde New View(ERNV)was selected.The performance,image quality and intraoper-ative and postoperative complications were evaluated.To evaluate whether all the experimental ani-mals could complete the relevant endoscopy.Verify ERNV's operating performance,including whether the duodenoscope can enter the biliary tract smoothly,and made sure whether the injection,suction,and instrument channels were unobstructed.Choledochoscope image clarity,color resolu-tion,image deformation and distortion,accurate evaluation of lumen conditions and clear observation of mucosal surface conditions were analyzed.Whether there were operant injuries such as bleeding and perforation,as well as adverse events such as respiratory depression and cardiac arrest.The sur-vival status and adverse reactions of all pigs were observed.Results:The choledochoscope was successfully inserted into the bile duct of 6 miniature pigs.The product had good operation perfor-mance and could enter the bile duct through the duodenoscope smoothly.The injection,suction and instrument channels were relatively smooth.In addition,the endoscopic images are clear,with better color resolution,and without image deformation and distortion,which can realize accurate evaluation of the conditions in the lumen and observe the mucosal surface conditions more clearly.No bile duct stenosis or dilatation occurred in all miniature pigs,and the bile duct mucosa was smooth,without hyperemia and edema,and no abnormal thickening or bending of mucous vessels.During the exami-nation,there were no operational injuries such as bleeding and perforation,and no adverse events such as respiratory depression and cardiac arrest occurred.The vital signs of all miniature pigs tended to be stable after operation,and the survival state was good,and there were no complications such as cholangitis,bleeding and perforation.Conclusion:ERNV has good clinical safety and efficacy,ex-cellent operation performance and excellent image quality,and is worthy of clinical application.
		                        		
		                        		
		                        		
		                        	
3.Loong oil-lyotropic liquid crystals for the treatment of combined radiation and burn injury
Wan-ting GUO ; Xue-li JIA ; Yan LIU ; Ya-dan HU ; Ke WANG ; Lei ZHANG ; Yong ZHANG ; Yi-guang JIN
Acta Pharmaceutica Sinica 2024;59(5):1449-1457
		                        		
		                        			
		                        			 Combined radiation and burn injury (CRBI) is a severe syndrome, which is induced by the simultaneous or successive radiation and burn; but no appropriate clinical therapies are available. Loong oil (LO) is a traditional Chinese medicine oil composed of the oil extracts of cuttlebone, safflower, walnut oil, and rapeseed oil, which has been demonstrated to own anti-radiation and tissue healing functions. In this study, glyceryl monostearate (GMO) was used for the preparation of lyotropic liquid crystals that loaded LO to obtain Loong oil-lyotropic liquid crystals (LOL) for the treatment of skin CRBI. The hexagonal phase structure of LOL was proved by small X-ray scattering (SAXS) analysis with an approximate 
		                        		
		                        	
4.Bioequivalence study of olmesartan medoxomil tablet in Chinese healthy subjects
Na SHAN ; Da-Hai JIANG ; Lin-Lin MIAO ; Zhen-Li REN ; Peng-Bo JIN ; Pei-Qi HAO ; Li AN ; Hong ZHU ; Yong XIN ; Guang-De YANG ; Feng LIU
The Chinese Journal of Clinical Pharmacology 2024;40(20):3033-3037
		                        		
		                        			
		                        			Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90%confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00%-125.00%.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.
		                        		
		                        		
		                        		
		                        	
5.Genotyping Characteristics of Human Fecal Escherichia coli and Their Association with Multidrug Resistance in Miyun District, Beijing.
Wei Wei ZHANG ; Xiao Lin ZHU ; Le Le DENG ; Ya Jun HAN ; Zhuo Wei LI ; Jin Long WANG ; Yong Liang CHEN ; Ao Lin WANG ; Er Li TIAN ; Bin CHENG ; Lin Hua XU ; Yi Cong CHEN ; Li Li TIAN ; Guang Xue HE
Biomedical and Environmental Sciences 2023;36(5):406-417
		                        		
		                        			OBJECTIVE:
		                        			To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.
		                        		
		                        			METHODS:
		                        			Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS).
		                        		
		                        			RESULTS:
		                        			This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24).
		                        		
		                        			CONCLUSION
		                        			We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Escherichia coli/genetics*
		                        			;
		                        		
		                        			Escherichia coli Infections/epidemiology*
		                        			;
		                        		
		                        			Multilocus Sequence Typing
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			Beijing
		                        			;
		                        		
		                        			Drug Resistance, Multiple, Bacterial/genetics*
		                        			;
		                        		
		                        			Anti-Bacterial Agents/pharmacology*
		                        			;
		                        		
		                        			Diarrhea
		                        			;
		                        		
		                        			Microbial Sensitivity Tests
		                        			
		                        		
		                        	
6.Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study.
Fang JIN ; Yu CHEN ; Yi-Xun LIU ; Su-Ying WU ; Chao-Ce FANG ; Yong-Fang ZHANG ; Lu ZHENG ; Li-Fang ZHANG ; Xiao-Dong SONG ; Hong XIA ; Er-Ming CHEN ; Xiao-Qin RAO ; Guang-Quan CHEN ; Qiong YI ; Yan HU ; Lang JIANG ; Jing LI ; Qing-Wei PANG ; Chong YOU ; Bi-Xia CHENG ; Zhang-Hua TAN ; Ya-Juan TAN ; Ding ZHANG ; Tie-Sheng YU ; Jian RAO ; Yi-Dan LIANG ; Shi-Wen XIA
Chinese Journal of Contemporary Pediatrics 2023;25(7):697-704
		                        		
		                        			OBJECTIVES:
		                        			To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.
		                        		
		                        			METHODS:
		                        			A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.
		                        		
		                        			RESULTS:
		                        			Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.
		                        		
		                        			CONCLUSIONS
		                        			The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
		                        		
		                        		
		                        		
		                        			Infant, Newborn
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Nomograms
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Cesarean Section
		                        			;
		                        		
		                        			Risk Factors
		                        			;
		                        		
		                        			Asphyxia Neonatorum/etiology*
		                        			
		                        		
		                        	
7.Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.
Yi-Lun QU ; Zhe-Yi DONG ; Hai-Mei CHENG ; Qian LIU ; Qian WANG ; Hong-Tao YANG ; Yong-Hui MAO ; Ji-Jun LI ; Hong-Fang LIU ; Yan-Qiu GENG ; Wen HUANG ; Wen-Hu LIU ; Hui-di XIE ; Fei PENG ; Shuang LI ; Shuang-Shuang JIANG ; Wei-Zhen LI ; Shu-Wei DUAN ; Zhe FENG ; Wei-Guang ZHANG ; Yu-Ning LIU ; Jin-Zhou TIAN ; Xiang-Mei CHEN
Chinese journal of integrative medicine 2023;29(4):308-315
		                        		
		                        			OBJECTIVE:
		                        			To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine.
		                        		
		                        			METHODS:
		                        			Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.
		                        		
		                        			RESULTS:
		                        			Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD.
		                        		
		                        			CONCLUSIONS
		                        			Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Diabetes Mellitus, Type 2
		                        			;
		                        		
		                        			Diabetic Nephropathies
		                        			;
		                        		
		                        			Hyperuricemia
		                        			;
		                        		
		                        			Kidney
		                        			;
		                        		
		                        			Proteinuria
		                        			;
		                        		
		                        			Renal Insufficiency, Chronic/complications*
		                        			
		                        		
		                        	
8.Clinical analysis of laparoscopic treatment of chronic traumatic diaphragmatic hernia in 29 cases.
Yu Gang CHENG ; Qiao Nan LIU ; Li LUAN ; Chang Jin CUI ; Zhi Bo YAN ; Bo LI ; Guang Yong ZHANG
Chinese Journal of Surgery 2023;61(6):474-480
		                        		
		                        			
		                        			Objective: To examine the safety and effectiveness of laparoscopic individualized surgical treatment for chronic traumatic diaphragmatic hernia (CTDH). Methods: The clinical data and follow-up data of 29 CTDH cases admitted to the Qilu Hospital of Shandong University or the First Affiliated Hospital of Shandong First Medical University from June 2015 to January 2023 were retrospectively analyzed. There were 21 males and 8 females, aged (49.4±17.8) years (range: 19 to 79 years). The main clinical manifestations were symptoms of the digestive system and respiratory system, and only 4 cases were asymptomatic. All patients received laparoscopic treatment (conversion to open surgery was not excluded). Intraoperative exploration (location of the hernia, contents of the hernia, diameter of the hernia ring), surgical conditions (surgical repair plan, operation time, blood loss, postoperative complications) and postoperative follow-up were analyzed and discussed. Results: Laparoscopic repair was successfully completed in 27 cases, including simple suture in 6 cases, suture and patch repair in 17 cases, the anterior abdominal wall muscle flap reversal suture and patch repair of in 3 cases, and patch bridge repair in 1 case. The operation time was (112.8±44.7) minutes (range: 60 to 200 minutes). The amount of bleeding (M(IQR)) was 35 (58) ml (range: 10 to 300 ml). The other 2 patients were converted to laparotomy. Except for one patient with transverse colon strangulation necrosis who died of aggravated pulmonary infection after surgery, the remaining 28 patients were discharged successfully. The follow-up time was 36 (24) months (range: 1 to 60 months). During the follow-up period, only two patients had occasional left upper abdominal discomfort. Twenty-seven patients with left diaphragmatic hernia had no recurrence, and the symptoms of 1 patient with right diaphragmatic hernia were relieved. Conclusion: Customized laparoscopic surgical repair for CTDH according to the location and size of the diaphragmatic defect can achieve good surgical results.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hernia, Diaphragmatic, Traumatic/surgery*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Laparoscopy/methods*
		                        			;
		                        		
		                        			Postoperative Complications
		                        			;
		                        		
		                        			Laparotomy
		                        			;
		                        		
		                        			Surgical Mesh
		                        			
		                        		
		                        	
10. JTE-013 mediates RhoA/ROCKl/Drpl signaling axis regulating mitochondrial damage and apoptosis to alleviate allergic rhinitis
Jiao CHEN ; Long-Zhu DAI ; Mu CHEN ; Yi-Lan SONG ; Guang-Hai YAN ; Chong-Yang WANG ; Yong-De JIN ; Jiao CHEN ; Mu CHEN ; Yong-De JIN ; Long-Zhu DAI ; Yi-Lan SONG ; Guang-Hai YAN ; Chong-Yang WANG
Chinese Pharmacological Bulletin 2023;39(9):1638-1647
		                        		
		                        			
		                        			 Aim To investigate the protective effect and mechanism of JTE-013 on allergic rhinitis (AR) by regulating mitochondrial injury and apoptosis through RhoA/ROCKl/Drpl pathway. Methods AR model was established by ovalbumin (OVA) in mice. Nasal tissue sections were then stained with HE, TUNEL and DHE. Western blot assay. In vitro, human nasal epithelial cells (HNEpCs) were stimulated with human recombinant interleukin-13 (IL-13), and the effects of JTE-013 and Y27632-related protein expression were detected by Western blot. Immunofluorescence was used to observe the effects of JTE-013 and Y 27632 on total ROS, mitochondrial membrane potential and mitochondrial ROS generation, Drpl translocation and Cyt-c expression in cells. Results JTE-013 reduced the frequency of nose rubbing and sneezing, reduced nasal mucosal thickening and decreased eosinophil infiltration in AR mice. TUNEL and DHE staining results suggested that JTE-013 could inhibit apoptosis and reduce ROS expression in mouse nasal epithelial cells. Western blot showed that both JTE-013 and Y 27632 could significantly reduce RhoA, ROCK1, Drpl and p-Drpl(616), inhibit the expression of apoptotic proteins Bax, cleaved-caspase-3, Cyt-c, cleavedcaspase-9 and up-regulate the expression of p-Drpl (637) and Bcl-2. Immunofluorescence showed that inhibitors of JTE-013 or ROCK1 almost blocked IL-13mediated increase in ROS and mtROS production, inhibited decrease in mitochondrial membrane potential, and blocked Cyt-c expression and Drpl translocation in nasal mucosal epithelial cells. Conclusion JTE-013 can regulate the morphology and function of mitochondria by inhibiting RhoA/ROCKl/Drpl signaling axis, thereby alleviating nasal epithelial cell inflammation in mice with allergic rhinitis. 
		                        		
		                        		
		                        		
		                        	
            
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