Objective To study the effect and mechanisms of TW-37 on cell proliferation,apoptosis,invasion and angiogenesis in pancreatic cancer cells in vitro and further explore the potential mechanism.Methods BxPC3 and HPAC cells were pretreated with TW-37 using untransfected or transfected with NF-κB p65 cDNA(p65 cDNA)or NF-κB p65 siRNA(siRNA-p65)cells as controls.Cell viability was determined by MrTT assay.Cell apoptosis was assessed by enzyme-linked immunosorbent assay (ELISA).Cell invasion and angiogenesis was detected by Transwell and endothelial tube formation assay of HUVECs.ELISA assay was used to measure the activity of NF-κB,and its target proteins of MMP-9 and VEGF were detected by western blot.Results TW-37 suppressed cell growth and induced apoptosis (A405:1.29 ± 0.21 vs 0.09 ± 0.01,1.07 s0.18 vs 0.08 ± 0.01),inhibited NF-κB activity and protein expression of NF-κB p65,VEGF and MMP-9(all P ＜0.05)in a dose-and time-dependent manner.The number of cells that invaded across the matrigel in the transwell chamber was (46.7 ±5.24) and (10.3 ± 1.26)/×200 in BxPC3 control and 0.75 μmol/L TW-37 group (P=0.001).The number of tube formation was (39.4 ±4.36) and (7.84 ± 1.25)/×200,(P =0.001).NF-κB activity was increased by p65 cDNA transfection,and decreased by TW-37 treatment in both of the two cell lines (P ＜0.05).However,NF-κB activity was decreased by p65 siRNA transfection,and greatly decreased by TW-37 treatment in both two cell lines (P ＜0.05 or P ＜0.01).Transfection of p65 cDNA did not significantly affect cell apoptosis.Transfection of p65 siRNA increased cell apoptosis,and greatly increased by TW-37 treatment in both two cell lines (all P ＜ 0.01).Conclusions TW-37 could inhibit the proliferation,invasion and angiogenesis in pancreatic cancer cells by regulating NF-κB signal pathway.

Objective To preliminarily explore the effects and brain protective mechanism of intermittent hypoxia preconditioning ( IHP) on rats with seizures induced by lithium-pilocarpine ( Li-pilo) .Methods A total of 96 8-week old male Sprague Dawley rats ( clean grade ) were randomly divided into control group , seizure group and four IHP-seizure groups.The animal model of epilepsy was established by intraperitoneal injection of Li-pilo in the seizure group and four IHP-seizure groups (Li-pilo was injected at 1, 3, 7, or 14 days after a 5-day regimen of IHP).Subsequent seizure behavior , the latency period and percentage of generalized seizures were quantitatively evaluated for 240 min and the cognitive function was tested by Morris water maze task , and followed by the detection of hippocampus neuron apoptosis and related protein (BCL-2, Bax, and cleaved-caspase-3) by TUNEL labeling and Western blot, respectively.Results The induced seizure peaked on an average between 50-150 min after Li-pilo administration , scored using a modified Racine scale.The average scores of modified Racine scale in the IHP-3d seizure group was significantly lower than that in the other groups.The latency period and percentage of generalized seizures in the IHP-3d seizure group rats were significantly different from the parameters in the seizure group rats (P<0.05).IHP-3d seizure rats showed lower escape latency, neuronal apoptosis counts and higher percentage of time in the probe quadrant compare with the seizure group and the other three IHP-seizure groups ( P <0.05 ) .Compared with the control group , the parameters of water maze and apoptosis detection in the IHP-3d seizure group showed no significant changes (P>0.05).Conclusions The results indicate that IHP treatment may help to decrease the susceptibility to epilepsy by reducing abnormal apoptosis , and has a brain protective effect on the seizure rats .

Objective To discuss the treatment method and opportunity for patients with gallbladder stones and extrahepatic bile duct stones who failed endoscopic removal of common bile duct stones by endoscopic retrograde cholangiopancreaticography (ERCP). Methods 12 patients, with gallbladder stones and extrahepatic bile duct stones, failed endoscopic stone extraction (ESE), underwent emergency one-stage laparoscopic cholecystectomy (LC) and Laparoscopic common bile duct exploration (LCBDE). Results All of the patients were successfully completed LC +LCBDE and stones were completely removed. Hyperamylasemia occurred in 3 cases and there was no bile leakage, intestinal leakage, cholangitis, pancreatitis, biliary bleeding and other complications. Conclusions Emergency LCBDE has been shown to be a safe and effective salvage procedure for failed ESE.

Objective:To evaluate the effect of sevoflurane postconditioning on early inflammatory responses during intestinal ischemia-reperfusion (I/R) in rats.Methods:Sixty clean-grade Sprague-Dawley rats, aged 8-10 weeks, weighing 200-230 g, were divided into 3 groups ( n=20 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), and sevoflurane postconditioning group (Sevo group). Intestinal I/R was produced by occlusion of the superior mesenteric artery for 60 min followed by reperfusion for 2 h in anesthetized rats in I/R group and Sevo group.Laparotomy was performed, and the superior mesenteric artery was only isolated in Sham group.The rats inhaled 1.15% sevoflurane for 30 min for postconditioning in Sevo group.Blood samples were collected by cardiac puncture at 2 h of reperfusion, and then the rats were sacrificed.Samples of intestine were obtained for examination of the pathological changes of intestinal tissues (with a light microscope) which were scored according to Chiu and for determination of the neutrophil L-selectin levels in blood (by flow cytometry), tumor necrosis factor-alpha (TNF-a) expression (by Western blot), myeloperoxidase (MPO) activity (by spectrophotometry). Results:Compared with group Sham, the neutropil L-selectin level in blood was significantly increased in group I/R and decreased in group Sevo, and Chiu′s score, TNF-a expression and MPO activity were significantly increased in I/R and Sevo groups ( P<0.05). Compared with group I/R, the neutropil L-selectin level in blood, Chiu′s score, TNF-a expression, TNF-a expression and MPO activity were significantly decreased ( P<0.05), and the pathological changes were significantly attenuated in group Sevo. Conclusion:The mechanism by which sevoflurane postconditioning reduces intestinal I/R injury may be related to inhibiting early inflammatory responses in rats.

Objective:To investigate the correlations of dynamic iodine nutrition status and thyroid function in pregnant women and newborns in Lingang of Shanghai, so as to provide an evidence for whether urine iodine testing and iodine supplementation should be carried out.Methods:A prospective study was conducted by randomly selecting pregnant women from October 2017 to October 2018 in Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine & Health Sciences. The pregnant women were divided into early (5-12 weeks), middle (22-24 weeks), late pregnancy (36-37 weeks). Samples of serum and 24 hours urine were collected to test on thyrotropin (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), anti-thyroid peroxidase (TPOAb), anti-thyroglobulin (TgAb) and urinary iodine. TSH in neonatal heel blood was analyzed 72 h after birth (newborns from pregnant women in the late pregnancy). The differences of thyroid function of pregnant women with different pregnant periods and different urinary iodine levels were analyzed, as well as the neonatal TSH levels of pregnant women with different urinary iodine levels. Results:A total of 109, 90 and 54 cases of pregnant women in early, middle and late pregnancy were investigated and the medians of urinary iodine were 120.95, 136.30 and 116.80 μg/L, respectively. There was no significant difference in urinary iodine content among different pregnant periods( P > 0.05). The proportions of urinary iodine level less than 150 μg/L in early, middle and late pregnancy were 75.2% (82/109), 61.1% (55/90) and 59.3% (32/54), respectively. The median values of serum TSH in early, middle and late pregnancy were 1.81, 1.95 and 2.29 mU/L, mean values of FT 3 were (5.21 ± 0.84), (4.79 ± 0.72) and (4.13 ± 0.56)pmol/L, and means of FT 4 were (16.48 ± 2.58), (15.02 ± 2.78) and (13.31 ± 1.87) pmol/L, respectively. The FT 3 and FT 4 levels in the late pregnancy were lower than those in the early and middle pregnancy, while the TSH levels in the late pregnancy were higher than those in the early and middle pregnancy. There were no significant difference in serum FT 3, FT 4 and TSH levels among early, middle and late pregnancy under different urinary iodine levels. The median TSH of newborn heel blood was 1.48 mU/L. There was no statistically significant difference between the neonatal heel blood TSH level of pregnant women with urinary iodine < 150 μg/L [1.45(1.09, 2.23)mU/L] in late pregnancy and those with urinary iodine ≥150 μg/L [1.42 (1.14, 2.61) mU/L, Z=- 0.354, P > 0.05]. Conclusions:There is mild iodine deficiency in pregnant women in Lingang of Shanghai. However, due to the compensatory regulation, it has no significant effect on the thyroid function of mother and newborn. Monitoring of iodine nutrition of pregnant women should be carried out and iodine supplementation should be done scientifically and reasonably.

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chro-matography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine mono-phosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mecha-nism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of puri-nergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic re-ceptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-KB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

Digital guided therapy (DGT) has been advocated as a contemporary computer-aided technique for treating endodontic diseases in recent decades. The concept of DGT for endodontic diseases is categorized into static guided endodontics (SGE), necessitating a meticulously designed template, and dynamic guided endodontics (DGE), which utilizes an optical triangulation tracking system. Based on cone-beam computed tomography (CBCT) images superimposed with or without oral scan (OS) data, a virtual template is crafted through software and subsequently translated into a 3-dimensional (3D) printing for SGE, while the system guides the drilling path with a real-time navigation in DGE. DGT was reported to resolve a series of challenging endodontic cases, including teeth with pulp obliteration, teeth with anatomical abnormalities, teeth requiring retreatment, posterior teeth needing endodontic microsurgery, and tooth autotransplantation. Case reports and basic researches all demonstrate that DGT stand as a precise, time-saving, and minimally invasive approach in contrast to conventional freehand method. This expert consensus mainly introduces the case selection, general workflow, evaluation, and impact factor of DGT, which could provide an alternative working strategy in endodontic treatment.
Humans ; Consensus ; Endodontics/methods* ; Tooth ; Printing, Three-Dimensional ; Dental Care ; Cone-Beam Computed Tomography ; Root Canal Therapy