OBJECTIVE: Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved. METHODS: Transgenic mice were used to trace Nestin⁺/nerve growth factor receptor (Ngfr)⁺ ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms. RESULTS: EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein⁺ glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice. CONCLUSION EA facilitates ENS repair by promoting Nestin⁺/Ngfr⁺ ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin⁺/Ngfr⁺ ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.
Animals ; Electroacupuncture ; Enteric Nervous System/physiology* ; Gastrointestinal Motility/physiology* ; Glial Cell Line-Derived Neurotrophic Factor/metabolism* ; Diabetes Mellitus, Experimental/therapy* ; Signal Transduction ; Mice ; Gastrointestinal Diseases/physiopathology* ; Proto-Oncogene Proteins c-ret/metabolism* ; Mice, Transgenic ; Male ; Nerve Regeneration ; Neural Stem Cells ; Mice, Inbred C57BL ; Acupuncture Points

This study was analyzed the spatial-temporal distribution and aggregation characteristics of Yersinia pestispositive host animals and vector pathogens in marmot natural foci in the Qilian-Altun mountains,Gansu Province,to provide a scientific basis for precise plague prevention and control.Y.pestissurveillance data for marmot natural foci in Qilian-Altun Mountains of Gansu Province from 2014 to 2023 were obtained from the Disease Control and Prevention Center of Gansu Province.Origin 2024 software was used for data visualization and presentation.Global and local spatial autocorrelation analyses and trend analyses were conducted in ArcGIS 10.8 software,with townships as the spatial scale.Cumulatively,440 strains of Y.pestis were isolated from the natural marmot foci in the Qilian-Altun mountainsof Gansu Province from 2014 to 2023.Most strains was isolated from marmots(345 strains,78.41%),and the remainder were isolated from vectors.Temporal distribution analysis indicated that the highest number of detected bacteria was reported in July and August(both 121 strains,27.50%).Regional distribution analysis revealed that Aksai County reported the highest number of detected bacteria(255 strains,57.95%).Global spatial autocorrelation analysis showed a spatially clustered distribution of the number of bacteria detected annually in the townships containing natural foci,except in2014,2016,and 2021-2023.The strongest spatial clustering was observed in 2020(Moran's I=0.521 2,Z=14.397 0,P<0.001).Local spatial autocorrelation analysis indicated a"high-high"aggregation area in the natural foci every year from 2014 to 2023,primarily in Hongliuwan Town of Aksai County and Dangchengwan Town of Subei County.The distribution of the"low-low"aggregation area was essentially consistent with the low activity area of the Yersinia pestisepidemic.The trend in annual total bacterial count gradually increased from east to west,and peaked in the western part of the epidemic focus.Clear spatial aggregation characteristics of the number of Y.pestis were detected in the marmot natural foci in the Qilian-Altun mountains at the townshiplevel as a whole in Gansu Province from 2014 to 2023.The aggregation area was mainly in the western section of Qilian Mountain to the Altun mountain section of the epidemic source area.Monitoring and prevention and control efforts should be focused in this key area,with prevention and control measures tailored to the local conditions,and classified guidance to decrease the risk of plague occurrence and spread.

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

This study was analyzed the spatial-temporal distribution and aggregation characteristics of Yersinia pestispositive host animals and vector pathogens in marmot natural foci in the Qilian-Altun mountains,Gansu Province,to provide a scientific basis for precise plague prevention and control.Y.pestissurveillance data for marmot natural foci in Qilian-Altun Mountains of Gansu Province from 2014 to 2023 were obtained from the Disease Control and Prevention Center of Gansu Province.Origin 2024 software was used for data visualization and presentation.Global and local spatial autocorrelation analyses and trend analyses were conducted in ArcGIS 10.8 software,with townships as the spatial scale.Cumulatively,440 strains of Y.pestis were isolated from the natural marmot foci in the Qilian-Altun mountainsof Gansu Province from 2014 to 2023.Most strains was isolated from marmots(345 strains,78.41%),and the remainder were isolated from vectors.Temporal distribution analysis indicated that the highest number of detected bacteria was reported in July and August(both 121 strains,27.50%).Regional distribution analysis revealed that Aksai County reported the highest number of detected bacteria(255 strains,57.95%).Global spatial autocorrelation analysis showed a spatially clustered distribution of the number of bacteria detected annually in the townships containing natural foci,except in2014,2016,and 2021-2023.The strongest spatial clustering was observed in 2020(Moran's I=0.521 2,Z=14.397 0,P<0.001).Local spatial autocorrelation analysis indicated a"high-high"aggregation area in the natural foci every year from 2014 to 2023,primarily in Hongliuwan Town of Aksai County and Dangchengwan Town of Subei County.The distribution of the"low-low"aggregation area was essentially consistent with the low activity area of the Yersinia pestisepidemic.The trend in annual total bacterial count gradually increased from east to west,and peaked in the western part of the epidemic focus.Clear spatial aggregation characteristics of the number of Y.pestis were detected in the marmot natural foci in the Qilian-Altun mountains at the townshiplevel as a whole in Gansu Province from 2014 to 2023.The aggregation area was mainly in the western section of Qilian Mountain to the Altun mountain section of the epidemic source area.Monitoring and prevention and control efforts should be focused in this key area,with prevention and control measures tailored to the local conditions,and classified guidance to decrease the risk of plague occurrence and spread.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Objective:To explore the value of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) of MRI in evaluating the response of osteosarcoma to neoadjuvant chemotherapy (NAC) in different cycles, and to analyze the diagnostic efficacy of each ADC and its difference.Methods:A total of 31 patients with pathologically confirmed osteosarcoma in the Nanjing Drum Tower Hospital, Nanjing University Medical School from January 2019 to December 2022 were retrospectively analyzed. All patients received NAC before surgery, and routine MRI and DWI were performed before and during chemotherapy. The ADC values were measured before, during and after chemotherapy (ADCpre, ADCmid, ADCpost), and the difference were calculated. According to whether the tumor necrosis rate was more than 90%, the patients were divided into good response group and poor response group. The differences of ADC values in each stage within the two groups were compared, and the differences of related parameters between the two groups were compared, and the diagnostic efficacy of each parameter in predicting tumor necrosis rate was analyzed by receiver operating characteristic(ROC) curve.Results:The ADC values of the two groups at different stages of NAC were compared. Except for the intermediate ADCmid and ADCpost in the poor response group ( P = 0.226), all the ADC values were statistical differences ( P<0.05). There were significant differences in ADCmid and ADCpost between the good response group and the poor response group (1.52 ± 0.39 vs. 1.39 ± 0.25, 1.65 ± 0.16 vs. 1.46 ± 0.44, P<0.05), but there was no significant difference in ADCpre between the two groups ( P>0.05). ROC curve showed that the area under the curve of ADCmid, ADCpost and △ADC3 (ADCpost -ADCpre) were 0.897, 0.810 and 0.714, respectively, and ADCmid had the best diagnostic efficiency. Conclusions:ADCmid, ADCpost and △ADC3 can be used to evaluate the efficacy of NAC in osteosarcoma. The ADCmid can provide some reference for the adjustment and improvement of clinical treatment.

Objective The aim of this study was to compare the effect of injection of indocyanine green(ICG)through peripheral vein and gallbladder in laparoscopic cholecystectomy(LC)of difficult gallbladder.Methods Patients with difficult gallbladder who underwent LC by the same surgical team from May to October 2023 in the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Anhui University of Science and Technology were divided into three groups according to A random number table.Group A was injected ICG through peripheral vein before operation,group B was injected ICG through gallbladder during operation,and group C was the control group.The differences of operation time,intraoperative blood loss,hospitalization time,hospitalization cost and postoperative complications among the three groups were compared,and the effects of fluorescence mode cholangio-gram in group A and group B were compared.One-way analysis of variance was used to compare the normal distri-bution of the measurement data among groups,and LSD-t test was used to compare the two groups.The counting data was compared by chi-square test.The Boferroni test was appied to compare the two groups.Results There were no differences in length of stay,hospitalization cost and postoperative complications among the three groups(P＞0.05).The operative time and intraoperative blood loss of group A and group B were lower than those of group C(P＜0.05),but there was no difference between group A and group B(P＞0.05).The total imaging rate of the first three tubes of free gallbladder triangle(early stage)in group A was 41.67%,which was significantly lower than that in group B(63.89%)(P＜0.05).Conclusion ICG is beneficial for the identification of extrahepatic bile duct structures during LC of difficult gallbladder,and ICG injection through the gallbladder is helpful for the early identification of extrahepatic bile duct.

Objective To investigate the values of systemic inflammatory response index(SIRI),systemic immunoinflammatory index(SII),neutrophil count/lymphocyte count(NLR),platelet count/lymphocyte count(PLR)and lymphocyte count/monocyte count(LMR)in prediction of the severity of acute pancreatitis(AP)at early stage.Methods The clinical data on 666 AP patients admitted to the department of hepatobiliary surgery,the First Affiliated Hospital of Anhui University of Science and Technology,from January 2020 to November 2023 were retrospectively analyzed.The patients were divided into a mild group(MAP group,mild acute pancreatitis)and a non-mild group(non-MAP group,including moderate to severe acute pancreatitis).Blood routine and biochemical indicators were collected at admission and 24 hours after admission.The differences in SIRI,SII,NLR,PLR and LMR between the two groups were compared,so were the values of these five indexes in prediction of non-MAP.Results Of the 666 AP patients,507 were in the MAP group and 159 in the non-MAP group.In the non-MAP group,C-reactive protein(CRP),SIRI,SII,and NLR were higher than those in the MAP group 24 hours after admission,while LMR was lower than that in the MAP group,and the differences were statistically significant(P<0.05).CRP(HR=1.008,95%CI:1.004～1.012,P<0.05)and SIRI(HR=1.216,95%CI:1.029～1.436,P<0.05)were identified as the risk factors for the severity of AP.The ROC curve showed that the AUC and sensitivity of SIRI for predicting non-MAP 24 hours after admission were 0.718 and 75.00%,respectively,higher than those of SII,CRP,NLR,and LMR.Both SIRI and CRP had AUC values greater than 0.7,and the combined AUC was 0.788(0.738～0.837),the sensitivity was 86.00%and the specificity was 81.44%.Conclusions SIRI can be used as a predictor of disease severity in early AP patients,and combined with CRP can improve the predictive value.

Objective:To investigate the correlation between the level of treponema pallidum specific antibodies(TPAb)and immunoglobulin A/E/M/G(IgA/E/M/G)and IgG subtypes in active syphilis patients,so as to provide a basis for the comprehensive di-agnosis and treatment and prognosis evaluation of clinical syphilis.Methods:Active syphilis patients admitted to the First Affiliated Hospital of Soochow University in 2023 were divided into 1∶4+and 1∶16+groups according to the syphilis toluidine red unheated se-rum test(TRUST),and healthy control group were selected for the detection of TPAb by chemiluminescence microparticle immunoas-say(CMIA).The contents of IgA/E/M/G and IgG1/2/3/4 were determined by immunoturbidimetry.Results:A total of 206 patients with active syphilis(125 males and 81 females)aged(46.05±19.58)years were included in this study.Compared with the healthy control group,IgG2 was decreased and TPAb,IgA/E/M/G and IgG1/3/4 levels were increased in the active syphilis group,with statistically significant differences in TPAb,IgE and IgG1/2/3 levels(P<0.05).Compared with the healthy control group,TRUST 1∶4+group had statistical differences in TPAb,IgE and IgG2,and TPAb was significantly correlated with IgE and IgG2/4.The levels of TPAb,IgA/E/M/G and IgG1/2/3 in TRUST 1∶16+group were statistically significant,and TPAb was significantly correlated with IgE and IgG4(P<0.05).In addition,there were significant differences in TPAb,IgG and IgG1/3 between the two positive groups(P<0.05).Conclu-sion:The levels of TPAb and Ig in active syphilis patients with different TRUST titers are significantly different.TPAb combined with Ig can be used to monitor the strength of syphilis activity,IgA/M/G and IgG1/3 may be candidate biomarkers.

Hepatohilar cholangiocarcinoma is a common malignant tumor of the biliary system,and radical surgery is one of the important treatment methods.Due to the narrow space at the hi-lum and the high rate of anatomical variation,radical surgery is challenging.By using medical imag-ing technology and 3D reconstruction,surgeons can accurately determine the stage and classifica-tion of hilar cholangiocarcinoma preoperatively.They can assess the tumor's resectability by Ac-cording to the bile duct separation limit points(U point,P point)and anticipate the impact of portal vein,bile duct,and arterial variations on the surgical plan,thereby improving the rate of radical re-section and reducing complication rates.