Objective To elucidate the effect of curcumol on hepatic stellate cell iron death and epithelial-mesenchymal transition(EMT),and to investigate the molecular mechanism of its anti-liver fibrosis effect.Methods A model of hepatic stellate cell activation was constructed using normal cultured hepatic stellate cells in vitro,and the cells were divided into blank group and experimental-L,-M,-H groups.The blank group was given DMEM complete culture solution for normal culture;the experimental-L,-M,-H groups were given DMEM complete culture solution containing 12.5,25.0 and 50.0 mg·L-1 curcumol for 48 h of intervention.The effects of curcumol on the proliferation of hepatic stellate cells was observed by CCK-8.The expression levels of glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.The expression levels of E-cadherin and N-cadherin were detected by immunofluorescence.Results The cell proliferation rates of the experimental-M,-H groups and blank group were(68.97±5.61)％,(61.91±4.40)％and(118.07±10.01)％;the relative expression levels of GPX4 were 0.37±0.04,0.28±0.03 and 0.58±0.05;the relative expression levels of SLC7A11 were 0.38±0.04,0.28±0.03 and 0.60±0.05;E-cadherin levels were 6.76±1.09,9.57±1.73 and 2.05±0.72;N-cadherin levels were 5.66±0.66,3.44±0.78 and 10.37±0.66.The differences of above indicators were statistically significant between the blank group and the experimental-M,-H groups(P＜0.05,P＜0.01).Conclusion Curcumol promotes iron death in hepatic stellate cells,thereby inhibiting hepatic stellate cell EMT,which may be its molecular mechanism to prevent and treat liver fibrosis.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To observe the inhibitory effect of Guiqi Yiyuan ointment on tumor growth in mice with Lewis lung cancer,and to explore the molecular mechanism of Guiqi Yiyuan ointment combined with cisplatin through phosphoinositide 3-kinase/protein kinase B/mammalian rapamycin target protein(PI3K/Akt/mTOR)signal pathway.Methods Sixty C57BL/6 mice were randomly divided into 6 groups with 10 mice in each group.Except for the blank group(0.9％NaCl),Lewis lung cancer-bearing mice were randomly divided into model group(0.9％NaCl),control group(0.9％NaCl,cisplatin 5 mg·kg-1)and low,medium,high dose experimental groups(Guiqi Yiyuan ointment 1.6,3.3,6.6 g·kg-1,cisplatin 5 mg·kg-1).Flow cytometry was used to detect bone marrow-derived suppressor cells(MDSCs);the expression of related proteins in tumor tissues was detected by Western blot.Results The tumor inhibition rates in control group and low,medium,high dose experimental groups were(39.87±4.45)％,(45.74±14.97)％,(57.78±4.70)％and(69.82±11.05)％.The proportion of MDSCs in bone marrow of in blank group,model group,control group and low,medium,high dose experimental groups were(36.13±1.08)％,(68.63±2.94)％,(58.93±2.02)％,(58.00±1.50)％,(50.93±5.06)％and(43.07±2.41)％.The protein expressions of p-PI3K/PI3K in model group,control group and low,medium and high experimental groups were 0.97±0.03,0.77±0.02,0.72±0.01,0.68±0.03 and 0.53±0.02;PTEN were 0.21±0.07,0.65±0.07,0.74±0.06,0.99±0.13,1.11±0.13;p-Akt/Akt were 1.01±0.02,0.82±0.02,0.77±0.00,0.72±0.03 and 0.52±0.04;p-mTOR/mTOR were 1.01±0.01,0.76±0.05,0.69±0.07,0.59±0.06 and 0.47±0.06.There were significant differences between low,medium,high experimental groups and control group(all P＜0.05).Conclusion Guiqi Yiyuan ointment combined with cisplatin can significantly improve the quality of life and inhibit tumor growth in mice.The mechanism may be the inhibition of PI3K/Akt/mTOR signal pathway and the enhancement of tumor cell apoptosis and autophagy.

Objective To observe the effects of traditional Chinese medicine compound Platycodon grandiflorum Bai powder on the growth of subcutaneously implanted tumor and the expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cysteinyl aspartate specific proteinase(caspase)-3 and caspase-9 in subcutaneously implanted tumor of Lewis lung cancer mice.Methods The model of transplanted tumor of Lewis lung cancer in mice was established.Seventy SPF male C57BL/6 mice were randomly divided into blank group,model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combined group.Blank group and model group were given 0.9％NaCl 0.2 mL by gavage;control group was given 0.9％NaCl by gavage and 25 mg·kg-1cisplatin intraperitoneally;high,medium,low dose experimental groups were given 193,96,48 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,respectively;combined group was given 96 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,and 25 mg·kg-1 cisplatin intraperitoneally,once every other day.The myelogenous suppressor cells(MDSCs)of mouse bone marrow were detected by flow cytometry,and the expressions of Bel-2,Bax,caspase-3 and caspase-9 in tumor cells were detected by immunofluorescence.Results The percentage of MDSCs in bone marrow of mice in blank group,model group,low dose experimental,medium,high dose experimental group,control group and combination group were(32.50±2.76)％,(63.13±3.14)％,(48.43±2.23)％,(42.53±1.28)％,(32.93±3.56)％,(51.30±4.25)％and(19.90±6.21)％,respectively.The fluorescence intensities of Bax in model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combination group were 10.42±0.68,12.40±1.23,15.14±0.65,22.95±1.76,27.18±1.62 and 31.61±1.28;Bel-2 were 36.85±0.80,33.92±4.20,28.88±1.01,20.04±2.21,15.69±2.36 and 6.05±0.73;caspase-3 were 5.28±0.44,7.63±0.55,9.66±0.85,14.73±1.18,17.95±1.29 and 22.92±1.95;caspase-9 were 9.48±0.90,11.57±0.72,13.45±0.93,15.73±1.44,19.20±0.96 and 23.21±1.51.There were significant differences between medium,high dose experimental groups and model group(all P＜0.05),and there were significant differences between combined group and control group(all P＜0.05).Conclusion Platycodon grandiflorum Bai powder can up-regulating the expression of Bax,caspase-3 and caspase-9,down-regulating the expression of Bel-2,inhibiting MDSCs,promoting tumor cell apoptosis and inhibiting tumor growth.

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.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective To investigate the changes in distribution of Oncomelania hupensis snails in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023, so as to provide insights into formulation of O. hupensis snail surveillance programs. Methods The reports on O. hupensis snail surveillance in Songjiang District, Shanghai Municipality from 2009 to 2023 were collected, and the snail surveillance data in forestlands were extracted. The trends in the proportion of areas with snails in forestlands in total areas with snails, occurrence of frames with living snails and density of living snails were evaluated using a Joinpoint regression model in Songjiang District from 2009 to 2023, and the annual percent change (APC) and average annual percent change (AAPC). Results A total of 40 sites with snails were found in forestlands in 14 administrative villages of 4 townships, Songjiang District, Shanghai Municipality from 2009 to 2023. A total of 39 065 frames were surveyed for snails in settings covering an area of 609 600 m², and there were 6 084 frames with snails, covering 151 250 m² snail habitats. A total of 22 210 snails were captured, with the highest density of 260.00 snails/0.1 m², and 6 262 snails were dissected, with no Schistosoma japonicum infection identified in snails. The proportion of areas with snails in forestlands in total areas with snails appeared a tendency towards a rise in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023 (APC = AAPC = 24.9%, P > 0.05); however, there were no turning points in the trend curve, with the highest proportion seen in 2009 (53.81%), the lowest in 2011 and 2023 (both 0) and a mean proportion of 24.81%. The occurrence of frames with living snails appeared a tendency towards a rise from 2009 to 2023 (APC = AAPC = 41.5%, P > 0.05); however, there were no turning points in the trend curve, with the highest occurrence in 2009 (53.81%), the lowest in 2011 and 2013 (both 0), and the mean occurrence of 15.57%. In addition, the density of living snails appeared a tendency towards a rise from 2009 to 2023 (APC = AAPC = 55.0%, P > 0.05); however, there were no turning points in the trend curve, with the highest density in 2023 (0.96 snails/0.1 m²), the lowest in 2011 and 2013 (both 0), and a mean density of 0.57 snails/0.1 m². Conclusions The difficulty in O. hupensis snail control and risk of imported snails appeared a tendency towards a rise in forestlands in Songjiang District, Shanghai Municipality over years from 2009 to 2023. Supervision and assessment prior to seedling transplantation and intensified surveillance post-transplantation are recommended to reduce the risk of O. hupensis snail importation and spread.

ObjectiveTo analyze the monitoring results and trends of Oncomelania in Songjiang District of Shanghai from 2007 to 2023， and to provide reference for future monitoring work. MethodsThe data of snail monitoring in Songjiang District from 2007 to 2023 were collected， including the location of snail spots， the number of survey frames， the area with snails， the number of frames with snails， the total number of snails， etc. The density of living snails and the occurrence rate of living snail frames were calculated. ResultsFrom 2007 to 2023， a total of 158 snail spots were found in 22 administrative villages in 4 towns in Songjiang District， including 131 emerging snail habitats （82.91%） and 27 reemerging snail habitats （17.09%）. The total snail area was 175 980 m²， the number of snail frames was 10 061， and 33 302 snails were captured. The highest density was 260/0.11 m²， and 15 662 snails were dissected. No positive snails were found. The average density of living snails was 0.60/0.11 m² and the average occurrence rate of living snail frames was 17.99%. The snail areas in different areas were Yexie Town 126 000 m² （71.60%）， Maogang Town 26 470 m² （15.04%）， Xinbang Town 17 040 m² （9.68%）， and Shihudang Town 6 470 m² （3.68%）. The average density of living snails in different areas was 0.89/0.11 m² in Yexie Town， 0.65/0.11 m² in Maogang Town， 0.26/0.11 m² in Shihudang Town and 0.24/0.11 m² in Xinbang Town. The snail areas of different snail habitats were as follows： woodland 151 250 m²（85.95%）， river 13 810 m²（7.85%）， ditch 6 910 m²（3.93%）， farmland 4 010 m²（2.28%）. The average density of living snails in different snail habitats： ditch 1.01/0.11 m²， beach 0.86/0.11 m²， woodland 0.57/0.11 m²， river 0.40/0.11 m². The occurrence rate of living snail frames in different regions and different snail environment types showed a downward trend and the difference was statistically significant. ConclusionAlthough the snail monitoring indicators such as snail area， average living snail density and average living snail frame occurrence rate in Songjiang District are still at its historically low level， the average living snail density and average living snail frame occurrence rate are still high compared with other regions or the national average. We should focus on the upper reaches and tributaries of the Huangpu River， especially the key areas of seedling transplantation， and strengthen monitoring and supervision to reduce the risk of snail input.

BACKGROUND:Type 2 diabetes is often accompanied by renal dysfunction.Increasing studies have shown that exercise can alleviate metabolic disorders and renal dysfunction in diabetic patients.However,the specific mechanism underlying the renal protective effect of exercise in patients with type 2 diabetes is rarely reported. OBJECTIVE:To investigate whether aerobic exercise can improve renal function in type 2 diabetic rats by inhibiting transforming growth factor β1/Notch1 pathway. METHODS:Male Sprague-Dawley rats were randomly divided into normal control group and diabetes model group.After successful modeling,they were randomly divided into diabetes control group and diabetes exercise group.Rats in the diabetes exercise group were subjected to an 8-week aerobic exercise.Samples were collected after exercise,and the relevant indexes of glucose and lipid metabolism and renal function were detected by automatic biochemical analyzer and ELISA.The microscopic structure of renal cortex was observed by electron microscope.ELISA and RT-PCR were used to detect the expression of related proteins and genes in rat kidney tissue. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,total cholesterol,and triglyceride levels and insulin resistance index were significantly increased in the diabetic control group(P＜0.05).Aerobic exercise could significantly reduce fasting blood glucose and triglyceride levels(P＜0.05).Compared with the normal control group,the diabetic control group had significantly increased contents of urinary microalbumin,serum urea nitrogen and serum creatinine(P＜0.01),thickened renal basement membrane,mesangial matrix hyperplasia,accompanied by a certain degree of foot process fusion,and obvious lesion of the kidney.Aerobic exercise could significantly down-regulate the overexpressions of urinary microalbumin,serum urea nitrogen and serum creatinine in type 2 diabetic rats(P＜0.01),and significantly improve the pathological changes of the kidney in diabetic rats.Compared with the normal control group,the protein and gene expression levels of transforming growth factor β1,Notch1,Jagged1 and Hes1 in rat kidney tissue were significantly increased in the diabetic control group(P＜0.01).Aerobic exercise had a highly significant inhibitory effect on the overexpression of transforming growth factor β1,Notch1 and Jagged1 proteins and genes(P＜0.01)and also significantly inhibited the overexpression of Hes1 protein(P＜0.05).In conclusion,aerobic exercise can protect renal function and delay the pathological progression of the kidney in diabetic rats,which may be achieved by inhibiting the overexpression of transforming growth factor β1/Notch1 signaling pathway.