Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

Objective To assess the comparative efficacy of different methods for difficult biliary cannulation in endoscopic retrograde cholangio-pancreatography(ERCP)through a network meta-analysis.Methods Randomized controlled trials(RCTs)that compared the efficacy of different adjunctive methods(early or late needle-knife technique,pancreatic guidewire-assisted technique,pancreatic stent-assisted technique,transpancreatic sphincterotomy,persistent standard cannulation technique)for difficult biliary cannulation with each other were identified.The success rate of biliary cannulation and the incidence of post-ERCP pancreatitis(PEP)were the outcomes of interest.Pairwise and network meta-analysis and ranking according to surface under the cumulative ranking curve(SUCRA)for all methods were performed.Results Eighteen RCTs were identified according to selection criteria,and 2 033 patients were enrolled.The use of transpancreatic sphincterotomy over persistent standard cannulation technique(RR=1.34,95%CI:1.02-1.77)and over pancreatic guidewire-assisted technique(RR=1.26,95%CI:1.00-1.60)significantly increased the success rate of biliary cannulation.Based on SUCRA ranking,transpancreatic sphincterotomy followed by early needle-knife techniques were ranked highest in terms of increasing the success rate of biliary cannulation.Only early needle-knife technique significantly decreased PEP rate when compared with persistent standard cannulation technique(RR=0.53,95%CI:0.30-0.94),whereas both early needle-knife techniques and transpancreatic sphincterotomy led to lower PEP rates as compared with pancreatic guidewire-assisted technique(RR=0.41,95%CI:0.17-0.99;RR=0.49,95%CI:0.25-0.96;respectively).Based on SUCRA ranking,early needle-knife technique followed by transpancreatic sphincterotomy were ranked highest for decreasing the PEP rate of biliary cannulation.Conclusions Transpancreatic sphincterotomy increases the success rate of difficult biliary cannulation in ERCP;early needle-knife technique and transpancreatic sphincterotomy are superior to other interventions in decreasing PEP rates and should be considered as a choice of difficult biliary cannulation.

Objective To establish sepsis-associated encephalopathy (SAE) animal models by using neurobiology score,electroencephalography (EEG),somatosensory evoked potentials in order to provide evidence for early clinical diagnosis of SAE.Methods A total of 30 rats were weighted,numbered,and monitored with EEG electrodes 10 days before modeling.Ten days later,rats were weighted,numbered,and divided randomly (random number) into groups.Rat models of sepsis were made by cecal ligation and puncture (CLP).The changes of their neurological behaviors were observed and EEG was used to monitor at 4,6,8,12 and 24 hours after CLP.The changes of EEG waveform and somatosensory evoked potentials were analyzed and recorded.Rat models of sepsis were divided into sepsis + non-SAE group and SAE group based on the presence or absence of EEG or somatosensory evoked potentials changes ~thin 24 hours.Rats were sacrificed 24 hours later,and histopathological changes of brain tissue were observed under electronic microscopy.Thus,the feasibility of establishing early SAE animal model by monitoring the changes of neurological behaviors,EEG and somatosensory evoked potentials was evaluated.Results SAE could be early diagnosed by using neurobiology score,reduced α wave and markedly increased δ wave on EEG,reduced amplitudes of evoked potentials P1,and significantly prolonged latency of S-P1 and NI-P1.In survived septic rats,6 had changes on neurological behaviors,EEG and somatosensory evoked potentials,and thus were diagnosed as SAE.The incidence of SAE was 46％.Conclusions SAE can be diagnosed in early stage by using neurobiology score,EEG and somatosensory evoked potentials,confirming the SAE rat models to be successfully established.