Objective To compare the effects of three nickel-titanium file systems,ProTaper Next,TruNatomy,and VDW.RO-TATE,on the morphology of the Danger Zone of the mesial buccal root of mandibular first molar after root canal preparation using Mi-cro-CT and 3D printing technology.Methods 3D-printed mandibular first molars were selected and designed for purpose.They were randomly divided into three groups according to the used NiTi files(n=20).Micro-CT was used to scan the cross-sectional images of the Danger Zone 2 mm below the furcation of the mesial buccal root before and after root canal preparation.The changes in the root ca-nal wall thickness,root canal volume,surface area,cross-sectional area,and root canal transportation in the Danger Zone were ob-served.Statistical analysis was performed using one-way ANOVA(P＜0.05).Results Statistically significant differences were observed before and after root canal preparation in the Danger Zone among the three groups(P＜0.05).Among the three groups,the PTN files caused the largest change before and after preparation,followed by VDW files,and the TRU files had the smallest change.Conclusion The study highlights TruNatomy's conservative shaping capacity,advocating its use in minimally invasive endodontics,whereas Pro-Taper Next may be reserved for cases requiring aggressive canal preparation.

Objective To compare the effects of three nickel-titanium file systems,ProTaper Next,TruNatomy,and VDW.RO-TATE,on the morphology of the Danger Zone of the mesial buccal root of mandibular first molar after root canal preparation using Mi-cro-CT and 3D printing technology.Methods 3D-printed mandibular first molars were selected and designed for purpose.They were randomly divided into three groups according to the used NiTi files(n=20).Micro-CT was used to scan the cross-sectional images of the Danger Zone 2 mm below the furcation of the mesial buccal root before and after root canal preparation.The changes in the root ca-nal wall thickness,root canal volume,surface area,cross-sectional area,and root canal transportation in the Danger Zone were ob-served.Statistical analysis was performed using one-way ANOVA(P＜0.05).Results Statistically significant differences were observed before and after root canal preparation in the Danger Zone among the three groups(P＜0.05).Among the three groups,the PTN files caused the largest change before and after preparation,followed by VDW files,and the TRU files had the smallest change.Conclusion The study highlights TruNatomy's conservative shaping capacity,advocating its use in minimally invasive endodontics,whereas Pro-Taper Next may be reserved for cases requiring aggressive canal preparation.

Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.

OBJECTIVE To investigate the inhibitory effect and mechanism of lead(Pb2+)on γ-amino-butyric acid(GABA)A receptor-mediated currents(IGABA)and GABAergic synaptic transmission in rat cortical neurons.METHODS ①The cortical neurons from 0 d Sprague Dawley(SD)rats were cultured for experiments.The cultured cells(7-14 d)were recorded using the patch-clamp technique to analyze the effects of Pb2+ at different concentrations(1,5,10,50 and 100 μmol·L-1)on IGABA induced by GABA 100 μmol·L-1.② The effects of Pb2+ 50 μmol·L-1 on IGABA induced by GABA at different concentrations(1,10,50,100,500 and 100 μmol·L-1)were detected.③Brain slices(350 μm)were prepared from SD rats(15-19 d).The spontaneous inhibitory post-synaptic currents(sIPSCs),miniature inhibitory post-synaptic currents(mIPSCs)and current injection-induced action potential(AP)were recorded to detect the effects of Pb2+ 10 μmol·L-1 on the amplitude and frequency of sIPSCs and mIPSCs,and the frequency of AP.RESULTS ①Pb2+ inhibited IGABA in a concentration-dependent manner,and IC50 was(68±20)μmol·L-1.②Pb2+ also suppressed the maximum current induced by GABA(P<0.01),with a significant increase of the GABA′s EC50 from(20±6)μmol·L-1 to(87±39)μmol·L-1,indicating that Pb2+ might inhibit IGABA in a non-competitive mechanism.③Pb2+ 10 μmol·L-1 inhibited the frequency(P<0.01)rather than the ampli-tude of sIPSCs reversibly,but had no effect on eigher the frequency or amplitude of mIPSCs.In addi-tion,Pb2+ decreased the frequency of evoked AP by current injection(P<0.01)and reduced the overall excitability of rat cortical neurons.CONCLUSION Pb2+ can significantly inhibit IGABA in primary cultured neurons.In the brain slice experiment,Pb2+ may affect sIPSCs frequency by inhibiting the AP of cortical neurons,suggesting that there are different intrinsic mechanisms through which Pb2+ inhibits both IGABA in primary cultured neurons and the frequency of sIPSCs in brain slice neurons,which points to the complexity of the mechanism of Pb2+ poisoning.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Ligand-gated ion channels transduce chemical signals into ionic currents while being bonded with specific ligands,thereby facilitating signal transduction and intercellular communication.These channels have become critical therapeutic targets for a variety of diseases.Ginsenosides,triter-penoid saponins primarily derived from herbs of the Panax genus,are known for their broad range of biological activities.Ginsenosides and their metabolites can regulate the functions of various ligand-gated ion channels,including nicotinic acetylcholine receptors,5-hydroxytryptamine type-3 receptors,γ-aminobu-tyric acid type-A receptors,glycine receptors,ionotropic glutamate receptors,ATP-gated P2X chan-nels,and transient receptor potential channels.They play important roles in anti-inflammation,analge-sics,immune regulation,anti-epilepsy,cognitive enhancement and neuroprotection.Further investiga-tion into the mechanisms by which ginsenosides regulate these channels will provide important evidence for their clinical applications and the development of new drugs.

Ligand-gated ion channels transduce chemical signals into ionic currents while being bonded with specific ligands,thereby facilitating signal transduction and intercellular communication.These channels have become critical therapeutic targets for a variety of diseases.Ginsenosides,triter-penoid saponins primarily derived from herbs of the Panax genus,are known for their broad range of biological activities.Ginsenosides and their metabolites can regulate the functions of various ligand-gated ion channels,including nicotinic acetylcholine receptors,5-hydroxytryptamine type-3 receptors,γ-aminobu-tyric acid type-A receptors,glycine receptors,ionotropic glutamate receptors,ATP-gated P2X chan-nels,and transient receptor potential channels.They play important roles in anti-inflammation,analge-sics,immune regulation,anti-epilepsy,cognitive enhancement and neuroprotection.Further investiga-tion into the mechanisms by which ginsenosides regulate these channels will provide important evidence for their clinical applications and the development of new drugs.

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.

Objective:To study the real-world outcome of China FDA-approved Sofosbuvir (SOF)/Velpatasvir (VEL) in Northwest China.Methods:In this multicenter, prospective, real-world cohort study, we recruited patients from 10 sites from Northwest China, who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019. Patients received SOF (400mg)/VEL (100mg) for 12 weeks, and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis. The primary endpoint was sustained virological response at 12-weeks post-treatment (SVR12) and safety. The secondary endpoint was the change of liver function after the achievement of SVR12.Results:Totally, 143 patients were enrolled in the study, four patients were lost to follow-up and one died during the follow-up, 138 patients were included in per-protocol analysis. Of the 138 patients, the mean age 53 years, 53.6% male, 94.2% Han nationality, 53.6% liver cirrhosis, 10.1% HBsAg +, 6.5% renal dysfunction, 5.1% treatment-experienced, and 16.7% patients received ribavirin treatment. The genotype distribution was as follows: 35.5% GT1, 42.8% GT2, 15.9% GT3, and 5.8% un-typed. The SVR12 rate was 96.5% (138/143, 95% CI: 93.5%-99.6%) for intention-to-treat analysis, and in per-protocol analysis, all 138 patients obtained SVR12 (100%). Compared with baseline, the serum total bilirubin, ALT and AFP levels decreased (all P < 0.05), as well as increased ALB and platelet count (all P < 0.001) at post-treatment 12-weeks. Overall adverse events (AEs) rate is 29.0%, and the most common AEs were anemia (14.5%) and fatigue (8.0%). Severe side effects (edema and fatigue) occurred in 2 patients, one of whom needed a short-term interruption of treatment due to fatigue. Conclusion:In this real-world cohort study, 12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates (96.5%-100% overall) with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis, and led to improvement of liver function.

Objective:To explore the predictive value of regional leptomeningeal collateral circulation scale (rLMC) based on multimodal CT in recanalization of blood vessels in patients with acute ischemic stroke after thrombectomy.Methods:A retrospective analysis was conducted on clinical data of patients with acute ischemic stroke within 6 h of first onset, admitted to our hospital from October 2017 to December 2019. Before operation, the conditions of their vessels were evaluated by rLMC based on multimodal CT. Two areas, anterior cerebral artery (ACA)-middle cerebral artery (MCA) area and posterior cerebral artery (PCA)-MCA area, were divided. The total rLMC scores of two areas (0-10) were calculated: scores of 0-3, scores of 4-7, scores of 8-10. After admission, the recanalization of the blood vessels after thrombectomy was evaluated immediately according to grading of thrombolysis in cerebral infarction (TICI) after completion of thrombectomy within the time window; TICI grading≥II was defined as succeed recanalization. The correlation between rLMC scores and vascular recanalization in patients with acute ischemic stroke was evaluated.Results:Among the 80 patients, 17 were in the rLMC scores of 0-3 group, 25 in the group of rLMC scores of 4-7, and 38 in the group of rLMC scores of 8-10; 68 patients (85.00%) had vascular recanalization, and the success rate of vascular recanalization in patients from the group of rLMC scores of 8-10 was significantly higher than that in the group of rLMC scores of 0-3 (97.36% vs. 58.82%, P<0.05). Correlation analysis results showed that the rLMC score was positively correlated with success rate of vascular recanalization ( r s=0.625, P=0.000); whose sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 89.5%, 90.9%, 94.45%, 83.3% and 90.0%, respectively. Conclusion:The rLMC is closely related to the recanalization rate in patients with acute ischemic stroke after thrombectomy; the success rate of recanalization after intravascular treatment is relatively high in patients with rLMC scores of 8-10.