1.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
2.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
3.Risk factors for postoperative infectious endophthalmitis,pathogens,peripheral blood IL-17,MMP-2 and IGF-1 in patients with cataract
Yutao MA ; Yanjiang FU ; Cuicui FU ; Hengtao QI ; Bohua ZHANG ; Lijia WANG ; Dan WANG
Chinese Journal of Nosocomiology 2025;35(5):682-686
OBJECTIVE To explore the risk factors for postoperative infectious endophthalmitis,distribution of pathogens and peripheral blood interleukin-17(IL-17),matrix metalloproteinase-2(MMP-2)and insulin-like growth factor-1(IGF-1)in the patients with cataract and analyze the significance.METHODS A total of 60,000 patients with cataract who received surgical procedures in Daqing Eye Hospital from Jan.2018 to Jun.2024 were recruited as the research subjects.The aqueous humor and vitreous humor were collected from the patients with postoperative infectious endophthalmitis,and the isolated pathogens were identified.The baseline data were com-pared,the risk factors for the infectious endophthalmitis were analyzed.The levels of serum IL-17,MMP-2 and IGF-1 were compared,and the efficiencies of the indexes in prediction of infectious endophthalmitis were analyzed.RESULTS Totally 65,600 eyes involving 60,000 patients were enrolled in the study,21 of which(21 patients)were diagnosed with infectious endophthalmitis,with the incidence rate 0.032%.All of the 21 eyes were cultured positive for pathogens,among which gram-positive bacteria(73.08%)were dominant.Univariate analysis and multivariate analysis showed that complication with diabetes mellitus and vitreous overflow were the risk factors for the postoperative infectious endophthalmitis in the cataract patients.There were significant differences in the levels of serum IL-7,MMP-2 and IGF-1 between the infection group and the non-infection group after the surgery for 3 days(P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the levels of serum IL-17,MMP-2 and IGF-1 after the surgery for 3 days could predict the occurrence of postoperative infectious endoph-thalmitis in the cataract patients,and the joint detection of the three indexes has highest predictive efficiency(P<0.05),the area under the curve was 0.950,with the sensitivity 95.24%,the specificity 81.91%.CONCLUSIONS The incidence rate of postoperative endophthalmitis is 0.032%among the cataract patients.The complication with diabetes mellitus and vitreous outflow are the risk factors.The gram-positive bacteria are dominant among the pathogens.The changes of serum IL-17,MMP-2 and IGF-1 levels are closely associated with the occurrence of en-dophthalmitis,which has predictive value.
4.Relationship between spleen volume and non-alcoholic fatty liver disease by three-dimensional computed tomography reconstruction
Xiao LIANG ; Caixia DONG ; Guodong LI ; Qi SHANG ; Bowen QIN ; Dan WAN ; Qian WANG ; Lu LI ; Xin CHEN ; Zongfang LI
Journal of Clinical Hepatology 2025;41(8):1548-1555
Objective To investigate the association of spleen volume with the risk of non-alcoholic fatty liver disease(NAFLD)as well as their causal relationship.Methods We included 90 NAFLD cases and 47 healthy controls who had received contrast-enhanced computed tomography(CT)scan of the abdomen at the Second Affiliated Hospital of Xi'an Jiaotong University from November 2022 to November 2023.We conducted three-dimensional reconstruction of the spleen through a deep learning network model using a two-stage coarse-to-fine segmentation approach.We compared the two groups using the two-sample t test or Mann-Whitney U test for continuous data and using the chi-square test for categorical data;evaluated the correlation between spleen volume and liver function indicators through Pearson correlation or Spearman rank correlation analyses;determined the factors influencing the development of NAFLD through multivariable Logistic regression analysis;and further assessed the casual relationship between spleen volume and NAFLD using the inverse variance-weighted two-sample Mendelian randomization(IVW-MR)method.Results Spleen volume was significantly larger in NAFLD cases than in controls(272.93±104.16 vs 204.37±81.20 cm3,P<0.001).The Spearman rank correlation analysis showed that spleen volume was positively correlated with the hepatic steatosis index(rs=0.422,P<0.001)and gamma-glutamyl transferase levels(rs=0.211,P=0.047)in patients with NAFLD.The multivariable Logistic regression analysis indicated that spleen volume was an independent risk factor for the development of NAFLD(odds ratio[OR]=1.01,95%confidence interval[CI]:1.00-1.02,P=0.049).The IVW-MR analysis detected a causal relationship between spleen volume and NAFLD(OR=1.16,95%CI:1.05-1.28,P=0.005).Conclusion Increased spleen volume may be a risk factor for the development and progression of NAFLD.Further studies are still needed to investigate the specific mechanism.
5.Relationship between spleen volume and non-alcoholic fatty liver disease by three-dimensional computed tomography reconstruction
Xiao LIANG ; Caixia DONG ; Guodong LI ; Qi SHANG ; Bowen QIN ; Dan WAN ; Qian WANG ; Lu LI ; Xin CHEN ; Zongfang LI
Journal of Clinical Hepatology 2025;41(8):1548-1555
Objective To investigate the association of spleen volume with the risk of non-alcoholic fatty liver disease(NAFLD)as well as their causal relationship.Methods We included 90 NAFLD cases and 47 healthy controls who had received contrast-enhanced computed tomography(CT)scan of the abdomen at the Second Affiliated Hospital of Xi'an Jiaotong University from November 2022 to November 2023.We conducted three-dimensional reconstruction of the spleen through a deep learning network model using a two-stage coarse-to-fine segmentation approach.We compared the two groups using the two-sample t test or Mann-Whitney U test for continuous data and using the chi-square test for categorical data;evaluated the correlation between spleen volume and liver function indicators through Pearson correlation or Spearman rank correlation analyses;determined the factors influencing the development of NAFLD through multivariable Logistic regression analysis;and further assessed the casual relationship between spleen volume and NAFLD using the inverse variance-weighted two-sample Mendelian randomization(IVW-MR)method.Results Spleen volume was significantly larger in NAFLD cases than in controls(272.93±104.16 vs 204.37±81.20 cm3,P<0.001).The Spearman rank correlation analysis showed that spleen volume was positively correlated with the hepatic steatosis index(rs=0.422,P<0.001)and gamma-glutamyl transferase levels(rs=0.211,P=0.047)in patients with NAFLD.The multivariable Logistic regression analysis indicated that spleen volume was an independent risk factor for the development of NAFLD(odds ratio[OR]=1.01,95%confidence interval[CI]:1.00-1.02,P=0.049).The IVW-MR analysis detected a causal relationship between spleen volume and NAFLD(OR=1.16,95%CI:1.05-1.28,P=0.005).Conclusion Increased spleen volume may be a risk factor for the development and progression of NAFLD.Further studies are still needed to investigate the specific mechanism.
6.Effects of GGH genetic polymorphisms on serum concentrations and chemotherapy toxicities of methotrexate in children with intracranial tumors
Dan-qi ZHAO ; Zheng-yuan SHI ; Xi-qiao XU ; Shu-mei WANG
The Chinese Journal of Clinical Pharmacology 2025;41(2):183-187
Objective To investigate the effects of γ-glutamyl hydrolase(GGH)rs11545078 C>T polymorphisms on serum concentrations,chemotherapy toxicities of methotrexate(MTX),and prognosis in children with intracranial tumors.Methods Peripheral blood samples were obtained from children with intracranial tumors to extract genome DNA.Matrix-assisted laser desorption/ionization-time of flight mass spectrometry was used to detect the genotypes of GGH rs11545078 C>T polymorphisms.Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX.The incidences of toxicities,relapse,and metastasis were recorded after chemotherapy with MTX.The associations of GGH rs11545078 C>T polymorphisms with concentration-to-dose ratios(C/D ratios),chemotherapy toxicities of MTX,relapse,and metastasis of tumors were analyzed.Results A total of 75 children were included in the present study.The frequencies of rs11545078 CC and CT genotypes were 82.67%and 17.33%,respectively.The frequencies of C and T alleles were 91.33%and 8.67%,respectively.There were no statistically significant differences for these frequencies among the children with intracranial tumors,the children with acute lymphoblastic leukemia,and the health population in Beijing.Children with the CC genotype had higher median C/D ratios of MTX in 24 and 42 h(25.19 and 0.14 μmol·L-1 per g·m-2,respectively),higher metastasis rates(46.77%),and lower relapse rates(17.74%)than those in CT genotype carriers(22.01 and 0.11 μmol·L-1 per g·m-2,38.46%,and 30.77%,respectively),and the differences were no statistically significant(all P>0.05).The incidences of gastrointestinal disorders(76.92%)in children with the CT genotype were significantly higher than those in CC genotype carriers(45.16%,P<0.05).There were no statistically significant differences in the incidences of other adverse events between patients with the CC genotype and patients with the CT genotype(all P>0.05).Conclusion GGH rs11545078 CT might be a risk factor for gastrointestinal disorders in children with intracranial tumors treated with MTX.
7.Design and implementation of an outpatient guidance system utilizing internet hospital framework
Junqing LIU ; Shiyun LI ; Henglei DONG ; Yanjie XU ; Ruozhen WANG ; Jingkai ZHAO ; Dan KONG ; Chenkang QI ; Weixi LIU ; Jianfeng LIU
Modern Hospital 2025;25(2):274-277,281
Objective To enhance the patient's medical experience by facilitating real-time reading monitoring of their offline outpatient medical progress,providing a centralized display of the status of various medical processes,and proactively de-livering the essential message notifications to patients at designated intervals.Methods The system was developed by adopting a message reminder functionality and integrating with the display of critical diagnostic and treatment processes(including registra-tion,payment,examination,testing,medication collection,and evaluation)so as to ensure that patients receive timely informa-tion that guides their subsequent actions.Results Following the developement and implementation of the system,empirical evi-dence demonstrated that patients were able to clearly comprehend their diagnostic and treatment progress.The system reduced waiting time and confusion.In addition,it enhanced the coherence and convenience of medical services.Conclusion The out-patient medical guidance system,grounded on the Internet hospital model,has effectively minimized patient confusion and stre-amlined operational procedures through an active service approach.Future enhancements are anticipated to further elevate the in-telligence of medical services by broadening business coverage and integrating advanced technologies such as big data and artificial intelligence and other technologies in the future.
8.The efficacy of different surgical approaches in full-endoscopic treatment for degenerative lumbar lateral recess stenosis:A propensity score-matched cohort study
Ran LIU ; Dan CHEN ; Yingzhao QI ; Jiayu WANG ; Zhixin LIU
The Journal of Practical Medicine 2025;41(22):3544-3551
Objective To compare the clinical efficacy of the transforaminal endoscopic lumbar discectomy(TELD)approach with that of the interlaminar endoscopic lumbar discectomy(IELD)approach,both performed using a single-channel spinal endoscope,in the treatment of L4-L5 degenerative lumbar lateral recess stenosis(DLLRS).Methods A retrospective analysis was conducted on 78 patients with L4-L5 DLLRS who underwent single-channel endoscopic spinal surgery at our institution between March 2020 and March 2024.Patients were classified into the TELD group(lateral transforaminal approach,n=34)and the IELD group(interlaminar approach,n=44).Propensity score matching(PSM)was performed in a 1∶1 ratio using age,sex,body mass index(BMI),and duration of symptoms as covariates,yielding 25 matched pairs for final comparative analysis.Perioperative outcomes were systematically compared between groups.Visual analog scale(VAS)scores for low back pain and leg pain,as well as the Oswestry Disability Index(ODI),were evaluated preoperatively and at 3 days,3 months,6 months,and 1 year postoperatively.Lumbar computed tomography(CT)scans obtained 3 days after surgery were used to measure the lateral recess angle(LRA)and assess the extent of decompression.Spinal stability was evaluated using dynamic lumbar radiographs at 3 months postoperatively.Clinical outcomes were assessed 1 year after surgery based on the modified MacNab criteria.Results Both groups showed significant reductions in VAS scores for low back and leg pain,as well as in ODI scores,at all postoperative time points compared to baseline values(P<0.05).However,no statistically significant differences were observed between the two groups(P>0.05).Lumbar CT scans performed on postoperative day 3 demonstrated a significant increase in LRA in both groups relative to preoperative measurements(P<0.05).Although the magnitude of increase was greater in the IELD group,the intergroup difference did not reach statistical significance(P>0.05).At 3 months postoperatively,dynamic lumbar radiographs revealed no deterioration in spinal stability in either group compared to preoperative conditions,with no significant difference between groups(P>0.05).According to the modified MacNab criteria at 1 year postoperatively,the excellent and good outcome rate was 88.0%in the TELD group and 92.0%in the IELD group,with no statistically significant difference between the groups(P>0.05).Conclusions Both the TELD and IELD techniques are safe and effective for managing L4-L5 DLLRS,yielding comparable clini-cal outcomes.The selection of surgical approach should be guided by the anatomical location of ventral disc protru-sions,as well as the degree of facet joint hypertrophy and neural compression.
9.Analysis of the safety and efficacy of PD-1 inhibitor combined with cord blood-derived NK cells in the treatment of advanced malignant solid tumors
Yunxia FAN ; Jun GAO ; Zhihai HAN ; Bingqiao HUANG ; Bing QI ; Yinjiashu CHEN ; Feng XI ; Dan WANG ; Peipei NIAN ; Weijun FAN
Chinese Journal of Cancer Biotherapy 2025;32(6):628-635
Objective:To preliminarily investigate the safety and efficacy of programmed death-1(PD-1)inhibitor combined with cord blood-derived natural killer cells(NK cells)in the treatment of advanced malignant solid tumors in an exploratory clinical trial.Methods:Three patients with advanced solid tumors treated at the Second Affiliated Hospital of Xi'an Medical University from December 2019 to December 2021 were enrolled.According to tumor type and CSCO guidelines,patients received multiple treatment cycles(21 days per cycle)consisting of standard chemotherapy,targeted therapy,or bevacizumab combined with PD-1 inhibitor.Umbilical cord blood-derived NK cells(8×107 cells per infusion)were infused at appropriate intervals during the treatment course.Target lesion size,tumor markers,levels of 12 peripheral blood cytokines,and lymphocyte subsets were assessed in each treatment cycle.Adverse events were also monitored throughout the treatment.Results:Following the treatment with PD-1 inhibitor combined with cord blood NK cells,2 patients achieved stable disease(SD,per RECIST 1.1 criteria),with durations of 118 days and 92 days,respectively.After NK cell infusion,patient#1 exhibited a marked decrease in the tumor marker CA199 to normal range and sustained for three follow-up periods;patient#2 showed significant reductions in tumor markers CA199,CA242,and CA724.Conclusion:The combination of NK cells with chemotherapy and PD-1 inhibitor demonstrates potential therapeutic efficacy for solid tumors.No severe immune-related adverse reactions were observed in the three patients enrolled in this study.
10.Tiaojing Zhuyun formula combined with Dai meridian moxibustion method improves endometrial fibrosis in rats with uterine adhesion by regulating M2 type macrophage polarization
Dan CHOU ; Dan FENG ; Wenwen LIU ; Qian CHEN ; Ruyi XU ; Yuan QI ; Shuxiang HU ; Xinni WANG
Chinese Journal of Immunology 2025;41(10):2334-2340
Objective:To explore the improvement effect of Tiaojing Zhuyun formula combined with Dai meridian moxibustion on endometrial fibrosis in rats with intrauterine adhesions(IUA)by regulating M2 type macrophage polarization.Methods:SD rats were selected to establish an IUA model using a dual injury method of mechanical curettage and lipopolysaccharide infection,which were randomly separated into model group,Tiaojing Zhuyun formula group,Dai meridian moxibustion group,Tiaojing Zhuyun formula+Dai meridian moxibustion group and Bujiale group,with 10 rats in each group,another 10 rats were regarded as a sham operation(control)group,after grouping and treatment,the number of embryo implantation of rats in each group after cage closure was detected;HE staining was applied to detect pathological morphology of uterine tissue in rats in different groups,and their endometrial thickness and glandular number were compared;Masson staining was applied to detect endometrial fibrosis in rats of each group,and the collagen volume fraction(CVF)was compared;ELISA was applied to detect serum levels of profibrotic factor TGF-β1,pro-inflammatory factors IL-1β and IL-6,and levels of procollagen type Ⅰ carboxy-terminal peptide(PⅠNP)and procollagen Ⅲ N-terminal peptide(PⅢNP)of rats in each group;immunofluorescence staining was applied to detect expressions of M2 type macrophage markers CD163 and CD68 in endometrium of rats in each group.Results:Compared with control group,model group showed obvious pathological damage to uterine tissue,thickness of endometrium was thinner,the number of glands and embryo implantation were obviously reduced(P<0.05),endometrial CVF,levels of serum PⅠNP,P Ⅲ NP,TGF-β1,IL-1β and IL-6,and the number of CD163 and CD68 positive cells in endometrium were increased(P<0.05);compared with model group,pathological damage to uterine tissue of rats in Tiaojing Zhuyun formula group,Dai meridian moxibustion group,Tiaojing Zhuyun formula+Dai meridian moxibustion group and Bujiale group was reduced,thickness of endometrium,the number of glands and embryo implantation,and the numbers of CD163 and CD68 positive cells in endometrium were increased(P<0.05),endometrial CVF and levels of serum PⅠNP,P Ⅲ NP,TGF-β1,IL-1β and IL-6 were reduced(P<0.05);compared with Tiaojing Zhuyun formula group and Dai meridian moxibustion group,pathological damage to uterine tissue of rats in Tiaojing Zhuyun formula+Dai meridian moxibustion group and Bujiale group was alleviated,thickness of endometrium,the number of glands and embryo implantation,and the number of CD163 and CD68 positive cells in endometrium were increased(P<0.05),endometrial CVF and levels of serum PⅠNP,P Ⅲ NP,TGF-β1,IL-1β and IL-6 were reduced(P<0.05);there was no obvious change in all indicators between Tiaojing Zhuyun formula+Dai meridian moxibustion group and Bujiale group(P>0.05).Conclusion:Combination of Tiaojing Zhuyun formula and Dai meridian moxibustion can promote the polarization of M2 type macrophages,thereby inhibiting inflammation and endometrial fibrosis in IUA rats,and improving their symptoms of uterine adhesions.

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