ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsHuman gastric mucosal epithelial cells （GES-1） were initially induced by MNNG to establish a precancerous cell model （MC cells）. The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection （CCK-8） assay， and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group， a model group， and treatment groups with Renqing Mangjue at concentrations of 1， 3， 10， and 30 mg·L^-1. Furthermore， the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition （EMT） characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays， wound healing assays， and real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR）. Additionally， candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database， and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus （GEO） database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally， the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L^-1， MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells （P<0.01）， and at this concentration， the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast， Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells， but significantly inhibited the proliferation of MC cells （P<0.01） and markedly reduced their migratory capacity （P<0.01）. Moreover， it also increased the mRNA expression level of E-cadherin during the EMT process （P<0.05）， while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA （P<0.05， P<0.01）. Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore， Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB （B-type natriuretic peptide receptor） proteins in the cGMP/PKG pathway （P<0.01）， while downregulating the expression of the downstream proteins MEK and ERK （P<0.05， P<0.01）. ConclusionIn summary， Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells， thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.

This study aims to develop a fully automated method for tooth segmentation and root canal measurement based on cone beam computed tomography (CBCT) images, providing objective, efficient, and accurate measurement results to guide and assist clinicians in root canal diagnosis grading, instrument selection, and preoperative planning. The method utilized Attention U-Net to recognize tooth descriptors, cropped regions of interest (ROIs) based on the center of mass of these descriptors, and applied an integrated deep learning method for segmentation. The segmentation results were mapped back to the original coordinates and position-corrected, followed by automatic measurement and visualization of root canal lengths and angles. The results indicated that the Dice coefficient for segmentation was 96.42%, the Jaccard coefficient was 93.11%, the Hausdorff Distance was 2.07 mm, and the average surface distance was 0.23 mm, all of which surpassed existing methods. The relative error of the root canal working length measurement was 3.15% (< 5%), the curvature angle error was 2.85 °, and the correct classification rate of the treatment difficulty coefficient was 90.48%. The proposed methods all achieved favorable results, which can provide an important reference for clinical application.
Cone-Beam Computed Tomography/methods* ; Deep Learning ; Humans ; Dental Pulp Cavity/diagnostic imaging* ; Image Processing, Computer-Assisted/methods*

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective To investigate the knowledge,demand,and use of clinical practice guide-lines(CPGs)among anesthesia professionals in Gansu province,and to explore the strategies and barriers during the implementation process.Methods A questionnaire survey was conducted to investigated the knowledge,demand,and use of CPGs,as well as the strategies and barriers during the process of guideline implementation.Statistical analysis was applied to the collected data.Results A total of 339 valid question-naires were collected,96.8%of the respondents were aware of the guidelines,and the majority of the re-spondents(86.4%)consulted the guidelines when they encountered problems in clinical practice.The main barriers for guideline utilization were identified as lack of convenience(70.2%),limited availability chan-nels(64.3%)or restricted access rights(56.9%)to obtain the guidelines,inadequate training(31.3%),and language barriers(21.5%).Multiple forms of assisting guideline use and opening up guideline access were considered by most respondents as important ways to promote guideline implementation.Conclusion Anesthesia professionals in Gansu province demonstrated good levels of awareness and compliance with guidelines.However,the primary barriers to utilization were attributed to the guidelines themselves or diffi-culties in accessing them.It is recommended to establish a national guideline clearinghouse,provide imple-mentation tools,and enhance healthcare professional training to facilitate the promotion and application of guidelines in the future.

Objective To evaluate the efficacy of preoperative electroacupuncture intervention in promoting postoperative gastrointestinal functional recovery by meta-analysis.Methods The databases of PubMed,Cochrane Library,Web of Science,Embase,CBM,CNKI,VIP,and WanFang were searched systematically.The search period ranged from the inception of the databases to March 2024.Two researchers screened the literature independently,extracted the data,used Cochrane Risk of Bias tools to evaluate the quality of the inclusion study,and used RevMan 5.3 software for meta-analysis.Results Twelve RCTs were included,with 773 patients.There were 421 patients in the preoperative electroacupuncture group and 352 patients in the control group.The results of the meta-analysis showed that,time to first flatus(SMD=-0.56,95%CI-0.84 to-0.28,P＜0.001),time to first defecation(MD=-6.40 hours,95%CI-9.27 to-3.53,P＜0.001),time to bowel sound recovery(MD=-8.45 hours,95%CI-10.37 to-6.52,P＜0.001),time to first oral feeding(MD=-16.88 hours,95%CI-23.92 to-9.83,P＜0.001),the incidence of PONV(RR=0.75,95%CI 0.57 to 0.98,P=0.04)and length of hospital stay(MD=-0.78 d,95%CI-1.38 to-0.19,P=0.010)were significantly lower than the control group.Conclusion Electroacupuncture intervention before operation can effectively promote the recovery of post-operative exhaust,defecation,and bowel sound,shorten the time of fasting and drinking,reduce the inci-dence of PONV,shorten the length of hospital stay,and has good clinical value in promoting the recovery of postoperative gastrointestinal function.

Objective To systematically review the efficacy of acupuncture in the treatment of post-operative gastroparesis syndrome.Methods Computer searches were conducted on PubMed,Embase,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,and Chinese biomedical literature database.The ran-domized controlled trial(RCT)on postoperative gastroparesis syndrome after acupuncture treatment was in-cluded.The retrieval time was from the establishment of the database to May 2023.Meta-analysis was per-formed using RevMan 5.3 software.Results Fifteen RCTs involving 1 072 patients were included,545 pa-tients in the acupuncture group and 527 patients in the control group.Compared with the control group,the effective rate of treatment in the acupuncture group was significantly increased(RR=1.08,95％CI 1.09 to 1.27,P＜0.01),the levels of gastrin(SMD=1.86,95％CI 1.40 to 2.32,P＜0.01)and motilin(SMD=1.53,95％CI 0.99 to 2.06,P＜0.01)after operation were significantly increased,the recovery time of postoperative gastrointestinal function was significantly shortened(MD=-4.53 d,95％CI-6.51 to-2.55 d,P＜0.01).Conclusion Acupuncture can improve the effective rate of PGS treatment,in-crease the levels of Gastrin and motilin after operation,and promote the recovery of gastric motility after op-eration.

Objective:To investigate the drug resistance status and genomic characterization of Proteus mirabilis (PM) isolated from outpatient cases with diarrhea in Tai′an City and Laizhou City, Shandong Province. Methods:A total of 510 fecal samples were collected from 510 patients with acute diarrhea admitted to 43 sentinel hospitals in Tai′an City and Laizhou City, Shandong Province, between January 2021 and December 2022. The samples were cultured and isolated to identify Proteus spp. by direct inoculation, the drug susceptibility testing was performed by microbroth dilution method, and resistance genes and virulence genes were obtained by whole genome sequencing and bioinformatic analysis, thereby revealing the genetic environment surrounding the blaOXA-1 and blaCTX-M-65 genes. Single nucleotide polymorphism (SNP) analysis and core genome multilocus sequence typing (cgMLST) were conducted on the current strains and 100 PM isolates downloaded from the National Center for Biotechnology Information (NCBI) database via customizable methods utilizing RidomSeqSphere+ software, with the objective of exploring the phylogenetic relationships among the strains. Results:A total of 35 strains of Proteus were isolated from 510 fecal samples, including 31 strains of PM with a detection rate of 6.08% (31/510) and four strains of Proteus vulgaris.The multidrug resistance rate of PM was 100.00% (31/31).The 35 isolates carried a total of 43 resistance genotypes.Thirteen strains of PM carried blaOXA-1, six strains carried both blaOXA-1 and blaCTX-M-65, and 15 PM strains carried at least 15 antibiotic resistance genes (ARGs). The virulence genes included ureA, mrpA, ZapA, hpmA and so on. blaOXA-1 and blaCTX-M-65 genes were surrounded by mobile elements such as Tn3, ISL3 and IS6. cgMLST showed consistency with the SNP clustering results. Isolate 2022LZ41 from Laizhou City clustered with isolates 2022TA018, 2022TA017 and 2022TA019 from Tai′an City, with the number of allelic differences ranging from zero to two, and the Laizhou City isolate 2022LZ40 was highly genetically related to strain CRK0056 (human, USA, 2015). Conclusions:PM isolated from patients with diarrhea is multidrug-resistant, carrying many resistance and virulence genes.The presence of mobile genetic elements can lead to horizontal transfer of resistance genes.

Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.

Evoked Potentials ; Social Isolation ; Attention ; Humans