ObjectiveThis paper aims to explore the action and molecular mechanism of modified Tongluo Tangtai Formula（MTLTT） on myelin damage in diabetic peripheral neuropathy （DPN） based on network pharmacology and in vitro experiments. MethodsThe chemical components of the MTLTT were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database and literature， and the component targets were collected from the SwissTargetPrediction database. The targets of DPN were collected from the GeneCards， OMIM， Disgenet， and GEO databases. Gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses were performed using the Metascape database， and a network diagram was constructed using Cytoscape software. The binding actions of core components with glycogen synthase kinase 3 beta （GSK-3β） and β-catenin were analyzed by Autodock Vina. An in vitro DPN model was established by high glucose-induced Schwann cells and dorsal root ganglion cells （SCs/DRGs）. The ultrastructural morphological changes of SCs and DRGs were observed by scanning electron microscope（SEM）， and the expressions of myelin-associated glycoprotein （MAG） and myelin basic protein （MBP） were detected by immunofluorescence staining. The mRNA and protein expression levels of MAG， MBP， myelin protein 0 （P0）， peripheral myelin protein 22 （PMP22）， and Wnt/β-catenin signaling pathway-related protein β-catenin， GSK-3β， Wnt family member 3α （Wnt3α）， and Wnt inhibitory factor-1 （Wif-1） were detected by real-time polymerase chain reaction （Real-time PCR） and Western blot. ResultsNetwork pharmacology analysis revealed that MTLTT components may treat DPN via the Wnt signaling pathway， involving key proteins such as GSK-3β， β-catenin and Wif-1. The molecular docking results indicate that atropine， apigenin， baicalein， isoflavanone， and albiflorin have good binding activity with GSK-3β， and that all 13 core components have stable binding activity with β-catenin. Cell experiments showed that compared with the blank group， SCs and DRGs in the model group exhibited severe morphological and structural abnormalities such as disintegration， shrinkage and axonal rupture， while these abnormal changes were improved after MTLTT intervention. Immunofluorescence results indicated that the fluorescence intensity of MAG and MBP was markedly decreased in the model group relative to the blank group（P<0.01）， while MTLTT treatment obviously upregulated the expression of MAG and MBP compared with the model group （P<0.01）. Real-time PCR and Western blot assays revealed that the expression levels of myelin-related molecules MAG， MBP， P0 and PMP22 were significantly reduced in the model group （P<0.05，P<0.01）， and MTLTT remarkably increased their expression levels （P<0.05）. In the Wnt/β-catenin signaling pathway， the mRNA levels of GSK-3β， Wif-1 and Wnt3α were elevated and β-catenin mRNA expression was declined in the model group （P<0.01）. Meanwhile， the protein expressions of GSK-3β and Wif-1 were upregulated， whereas those of Wnt3α and β-catenin were downregulated （P<0.01）. Compared with the model group， MTLTT at different doses reduced the mRNA and protein levels of GSK-3β and Wif-1 to varying degrees （P<0.05）， and distinctly enhanced the protein expression of Wnt3α and β-catenin（P<0.01）. ConclusionMTLTT can alleviate high glucose-induced myelin damage. Its protective mechanism may promote myelin repair by upregulating the expression of MAG， MBP， P0 and PMP22， and the therapeutic effect is possibly associated with the activation of Wnt/β-catenin signaling pathway.

[摘 要] 目的：利用单细胞RNA测序（scRNA-seq）解析结直肠癌（CRC）肿瘤微环境（TME）中B细胞的异质性特征，为基于B细胞的预后评估与免疫治疗提供理论依据。方法：采集原发CRC患者的新鲜手术切除样本（n = 36），进行scRNA-seq。采用Seurat（v5.0）进行细胞分群，Monocle3（v1.3）和scVelo（v0.3.0）分析细胞分化轨迹，GSEA识别功能通路，pySCENIC（v0.11.2）构建基因调控网络。结果：识别B细胞（24 652个）和浆细胞（49 138个）共11个功能亚型。拟时序分析显示B细胞从初始态向组织驻留态分化。应激适应性B细胞在肿瘤中富集（10.39%），其NOD样受体信号和抗原提呈通路显著激活。组织驻留性B细胞在肿瘤中占9.09%，其C型凝集素信号和内吞作用增强。迁移性B细胞在TNM Ⅱ期组织中比例最低（16.42%），氧化磷酸化等代谢通路显著富集。浆细胞呈终末分化状态，肿瘤中以IgG型为主（20.68%）。结论：应激适应性和组织驻留性B细胞可能促进肿瘤免疫逃逸，迁移性B细胞或具抗肿瘤潜力；同时，IgG型浆细胞可能与免疫抑制有关。

Metallothionein(MT)is a group of low molecular weight metal-binding proteins rich in cysteine,which plays an important role in heavy metal detoxification,antioxidant,immune defense,cell proliferation,differentiation,and angiogenesis.In re-cent years,studies have found that MT can interact with a variety of immune cells to regulate innate and adaptive immune responses,thus playing an important role in the development of tumors,inflammatory diseases and autoimmune diseases.Therefore,this article reviews the biological characteristics of MT and its immunomodulatory effects,in order to provide new ideas for targeted therapy targeting MT.

Objective:To assess the safety and efficacy of Blinatumomab in treating children with acute B-lymphoblastic leukemia（B-ALL）.Methods:The clinical data of 10 B-ALL children who were admitted to the Department of Pediatrics，the First Affiliated Hospital of Xi’an Jiaotong University from May 2022 to April 2024 and treated with Blinatumomab were analyzed retrospectively.Results:All the 10 cases had a complete remission of bone marrow and all minimal residual disease（MRD）were negative. Serious adverse events were reported after chemotherapy，including intracranial venous sinus thrombosis with acute cerebral infarction，acute pancreatitis，paralytic ileus，syndrome of abnormal secretion of antidiuretic hormone，severe pneumonia，liver injury，sepsis（β-lactamase resistant Escherichia coli，Pseudomonas aeruginosa），oral mucositis，persistent agranulocytosis with bloodstream infection. All patients interrupted chemotherapy and received Blinatumomab injections for 14 days. During treatment，there was hematological toxicity，which resulted in grade 3-4 neutropenia in 5 cases within the first 7 days. Transient low-grade fever was observed in 4 cases of non-hematological toxicity during days 1-3 of treatment. One patient experienced a headache on the 7th day of treatment，which worsened on the 14th day，but it improved with mannitol treatment. Mild liver injury was present in 3 cases. Interleukin-6 reached a peak of 71.86 pg/mL on the second day of treatment in one case，whereas it was normal in others. All patients were found to be free of cytokine release syndrome. T lymphocyte count increased in 5 patients after 14 days of Blinatumomab treatment，but B lymphocyte count and serum immunoglobulin levels declined in 10 patients. Hypogammaglobulinemia was observed in 3 of these patients. The median follow-up time was 7.8（3.0-24.0）months. All patients achieved MRD-negative complete remission and 6-month overall survival rate and progression-free survival were both 100%.Conclusion:Children with B-ALL can benefit from using Blinatumomab，which is safer than conventional chemotherapy，as a new treatment strategy for those who cannot tolerate traditional chemotherapy.

Objective To explore the value of 18F-flortaucipir tau PET combined with APOE ε4 genotype status for diagnosing mild cognitive impairment(MCI).Methods A total of 213 MCI patients(MCI group)and 402 healthy controls(HC group)were selected from Alzheimer's disease neuroimaging initiative(ADNI)database.The neuropsychological information,APOE ε4 gene carrier status,tau PET and high-resolution structural MRI data were recorded.The random forest algorithm was used to screen the most informative brain regions of tau PET for diagnosing MCI,and the efficacy of tau PET for distinguishing MCI with or without APOE ε4 gene and HC were compared.Results Amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus in turn were the important brain regions of tau PET for diagnosing MCI.The accuracy and the area under the curve(AUC)of tau PET standardized uptake value ratio(SUVR)model for identifying MCI with APOE ε4 gene and HC was 86.68％and 0.784,respectively,both higher than those for identifying MCI and HC,as well as MCI without APOE e4 gene and HC(with accuracy of 70.57％and 75.05％,and AUC of 0.711 and 0.609).Conclusion 18F-flortaucipir tau PET SUVR model established based on amygdala,parahippocampal gyrus,entorhinal cortex,posterior cingulate gyrus,inferior temporal gyrus,fusiform gyrus and middle temporal gyrus could be used to diagnosing MCI.Combining with APOE ε4 gene could further improve its efficacy.

Objective To observe the functional connectivity and glucose metabolism of insular subregions in behavior variant of frontotemporal dementia(bvFTD)patients,also their correlations with cognitive function.Methods Thirty-eight bvFTD patients(bvFTD group)and 44 healthy individuals(control group)were retrospectively enrolled.The average time series signals of insular subregions were extracted as seed points based on functional MRI(fMRI)and 18F-FDG PET,then whole brain functional connectivity map was obtained.Meanwhile,the pons was selected as the reference brain region,and the standard uptake value ratio(SUVR)of insular subregions were calculated.The above parameters were compared between groups,and the correlations of SUVR of insular subregions with clinical cognitive function scale scores in bvFTD group were analyzed.Results Compared with control group,the functional connections between all insular subregions and bilateral frontal lobe,temporal lobe,anterior cingulate gyrus,anterior cingulate gyrus and middle cingulate gyrus,as well as between some subregions and bilateral parietal and occipital lobes were weakened in bvFTD group(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05).SUVR of all insular subregions significantly decreased(GRF correction,voxel level all P＜0.001,cluster level all P＜0.05),which in right ventral agranular insula(vIa),dorsal agranular insula(dIa),dorsal dysgranular insula(dId)and left dorsal agranular insula(dIa)were negatively correlated with frontal behavioral inventory(FBI)score in bvFTD group(r=-0.452--0.330,all P＜0.05).Conclusion In bvFTD patients,the functional connectivity and glucose metabolism of insular subregions changed,and SUVR of right vIa,dIa,dId and left dIa were negatively correlated with FBI score.

Objective To analyse the clinical efficiency of endolymphatic sac surgery (ESS) in the management of Meniere’s disease (MD). Methods A retrospective analysis was conducted on 274 patients with MD who were hospitalized for treatment in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University from January 2009 to August 2023. All patients received lifestyle management and drug treatment such as diuretics. For those whose conditions were not well controlled 3 to 6 months after the initial treatment, intratympanic glucocorticoid (ITG) or ESS treatment was carried out. Six months after the treatment, the classes of vertigo relief and hearing changes in the patients were evaluated. After adjusting the confounding factors through propensity score matching (PSM), the impact of ESS on the prognosis of MD patients was evaluated. Results Among 274 patients, 194 and 80 patients underwent ITG and ESS, respectively. Eighty patients were enrolled into each group after PSM. Before and after PSM, the rate of patients reaching vertigo relief class A in ESS group was higher than that in the ITG group (P＝0.004); there was no significant difference in hearing preservation between the two groups. Kaplan-Meier curve analysis showed that vertigo relief in the ESS group was better than that in the ITG group (P=0.029); there was no statistically significant difference in hearing preservation between the two groups. Conclusion When the initial treatment for patients with MD is ineffective, choosing ESS is more beneficial than ITG for controlling vertigo.

Objective:To investigate the long-term efficacy and influencing factors of transcatheter adrenal ablation in patients with primary aldosteronism (PA).Methods:This cohort study retrospectively enrolled PA patients who underwent transcatheter adrenal ablation at Daping Hospital, Army Medical University between January 2021 and December 2024. According to PASO criteria, patients were categorized into groups based on clinical outcomes (complete, partial, or no remission), biochemical outcomes (complete, partial, or no remission), and composite outcomes (complete or incomplete remission). All participants underwent 1-year follow-up, with intergroup comparisons of clinical characteristics and surgical approaches. Multivariate logistic regression models were used to identify factors influencing long-term efficacy post-transcatheter adrenal ablation in PA patients.Results:A total of 122 PA patients were enrolled, aged (47.7±11.1) years, including 55 males (45.1%). Baseline aldosterone-to-renin ratio was 0.43(0.19,0.86)(pmol·L -1)/(μU·L -1). Bilateral adrenal lesions were present in 33 cases (27.1%), while 70 (57.4%) had nodules or adenomas. Adrenal venous sampling confirmed lateralized hypersecretion in 107 patients (87.7%, left or right dominance). According to PASO criteria, 93.4% (114/122) and 95.1% (116/122) of patients achieved complete or partial remission in biochemical and clinical parameters at 1-year post-ablation, respectively. For biochemical outcomes: 40 complete, 74 partial, and 8 no remission. Patients in the partial-remission group were older than those in the no-remission group ((49.4±11.2) vs. (39.6±9.8) years), while complete-remission group had higher bilateral non-lateralized secretion rates than partial remission group (27.5% vs. 4.1%, both P<0.05). For clinical outcomes: 26 complete, 90 partial, 6 no remission. Compared to complete-remission group, partial-remission group had higher male proportion (51.1% vs. 26.9%), longer hypertension duration (4.0 (0.7, 10.0) years vs. 1.5 (0.1, 5.0) years), but lower office diastolic blood pressure ((88±11) mmHg vs. (94±12 mmHg), 1 mmHg=0.133 kPa, all P<0.05). For composite outcomes: 56 complete and 66 incomplete remission. Compared with incomplete remission group, complete remission group had lower prevalence of diabetes (8.9% vs. 22.7%) and higher proportion of bilateral non-lateralized secretion (21.4% vs. 4.6%, both P<0.05). Multivariate logistic regression identified diabetes ( OR=3.635, 95% CI 1.029-12.834, P=0.045) and lateralized secretion ( OR=9.056, 95% CI 2.039-40.212, P=0.004) as independent risk factors for poor composite outcomes after transcatheter adrenal ablation in PA patients, whereas higher office diastolic blood pressure acts as a protective factor ( OR=0.957, 95% CI 0.925-0.992, P=0.015). Conclusion:One year after transcatheter adrenal ablation, the majority of patients achieved complete or partial remission in biochemical and clinical parameters.Patients with non-lateralized adrenal hypersecretion demonstrated a higher likelihood of sustained biochemical remission and superior composite outcomes compared to those with lateralized hypersecretion.

Objective:To compare the clinical efficacy of navigation system and orthopedic robot-assisted nail placement in the treatment of lower cervical fracture and dislocation.Methods:A retrospective cohort study was conducted to analyze the clinical data of 49 patients with fracture and dislocation of the lower cervical spine who were admitted to Honghui Hospital, Xi′an Jiaotong University School of Medicine from May 2021 to October 2022, including 38 males and 11 females, aged 29-61 years [(39.3±7.3)years]. Injury segments involved C 3 in 12 patients, C 4 in 11, C 5 in 8, C 6 in 9 and C 7 in 9. Twenty-one patients were treated with S8 navigation system (navigation group, 84 screws), and 28 with TINAVI orthopedic robot (robot group, 112 screws). The two groups were compared in terms of the total surgical duration, single screw placement time, total screw placement time, distance between the screw and the anterior cortex, incision length, intraoperative radiation dose, intraoperative blood loss and length of hospital stay. The height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and American Spinal Injury Association (ASIA) grade were assessed before surgery and at 3 days after surgery. Visual analogue scale (VAS), Japanese Orthopedic Association (JOA) score and neck dysfunction index (NDI) before surgery, at 3 days, 3 months after surgery and at the last follow-up were compared. The accuracy of screw placement, intraoperative invasion rate of adjacent facet joints and rate of postoperative complications (infection, screw loosening, etc.) were evaluated. Results:All the patients were followed up for 12-16 months [(13.6±1.9)months]. In the navigation group, the total surgical duration, distance from the screw to the anterior cortex and the intraoperative radiation dose were (236.2±30.6)minutes, (2.0±0.2)mm and (374.3±90.3)mGy respectively, which were significantly shorter or less than those in the robot group [(278.4±20.7)minutes, (10.6±2.9)mm and (448.4±77.9)mGy] ( P<0.01). The single screw placement time, total screw placement time, incision length and intraoperative blood loss were (3.5±0.4)minutes, (23.9±0.5)minutes, (9.1±2.4)cm and (422.2±30.4)ml respectively, which were significantly longer or more than those in the robot group [(2.6±0.2)minutes, (17.9±0.7)minutes, (6.6±2.6)cm and (360.3±56.3)ml] ( P<0.01). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). No significant differences were observed in the height of the intervertebral space, Cobb angle, sliding distance between the vertebral bodies and ASIA grade between the two groups ( P>0.05). At 3 days after surgery, the height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and ASIA grade in both groups were significantly improved when compared with those before surgery ( P<0.05 or 0.01). There were no significant differences in VAS, JOA scores or NDI between the two groups before surgery, at 3 days, 3 months after surgery and at the last follow-up ( P>0.05). The VAS, JOA scores and NDI in both groups were gradually improved at 3 days, 3 months and at the last follow-up after surgery when compared with those before surgery ( P<0.05). There was no significant difference in the accuracy of screw placement of levels 0 and 0+1 between the two groups ( P>0.05). No significant difference in the intraoperative invasion rate of adjacent facet joints between the two groups was found ( P>0.05). There were no serious complications such as infection or screw loosening after surgery in both groups. Conclusions:For lower cervical fracture and dislocation, although there are more advantages in total surgical duration, screw holding force and radiation control regarding the navigation system, and more outstanding performance in screw placement efficiency, incision length and intraoperative blood loss regarding the orthopedic robot, both of them can effectively rebuild the cervical structure, improve neurological function, relieve postoperative pain, improve screw placement accuracy and reduce facet joint injury and serious complications. Selection of the best auxiliary screw placement system should comprehensively consider patients′ conditions and the experience of the surgical team.

Objective:To compare the efficacy of robot system-assisted versus freehand screw revision for ankylosing spondylitis (AS) with lower cervical fractures.Methods:A multicenter retrospective cohort study was conducted to analyze the clinical data of 57 patients with AS combined with lower cervical fractures admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, and Qilu Hospital of Shandong University, including 46 males and 11 females, aged 38-77 years [(65.4±9.5)years]. Injury segments involved C 3 in 7 patients, C 4 in 13, C 5 in 25, C 6 in 10, and C 7 in 2. All the patients underwent revision surgery, among whom, 22 patients were treated with robot system-assisted cervical pedicle screw placement (robot nailing group, with 190 screws), and 35 with freehand cervical pedicle screw placement (freehand nailing group, with 300 screws). The operative duration, intraoperative bleeding volume, frequency of intraoperative fluoroscopy, incision length, and length of hospital stay of the two groups were compared; the time of single nscrew insertion, the number of single nail revisions, the distance between screws and the anterior cortex, the accuracy of screw placement of grade 0 and grade 0+1 were recorded in the two groups. The visual analogue scale (VAS), Japanese Orthopedic Society (JOA) score, neck dysfunction index (NDI), American Spine Injury Association (ASIA) classification before operation, at 3 days, 3 months after operation and at the last follow-up were compared between the two groups. The complication rate was also noted. Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operative duration, intraoperative bleeding volume, and frequency of intraoperative fluoroscopy were (186.4±12.9)minutes, (486.1±68.6)ml, and (3.4±1.3)times in the robot nailing group, which were shorter or less than (206.7±14.4)minutes, (660.3±45.2)ml, and (13.5±3.6)times in the freehand nailing group ( P<0.01). The incision length was (9.4±2.4)cm in the robot nailing group, longer than (5.6±1.2)cm in the freehand nailing group ( P<0.01), and the length of hospital stay was (3.7±0.4)days, shorter than (4.4±1.4)days in the freehand nailing group ( P<0.01). The length of single nail insertion, the number of single nail revision, and the distance between the screws and the front cortex were (6.5±0.4)minutes, (1.1±0.1)times, and (3.5±1.3)mm in the robot nailing group, which were shorter or less than (11.6±0.2)minutes, (1.5±0.2)times, and (12.4±4.7)mm in the freehand nailing group ( P<0.01). The accuracy of the screw placement in the robot nailing group was 90.0% (171/190) and 95.8% (182/190) with level 0 and 0+1 screws, better than 80.0% (240/300) and 89.0% (267/300) in the freehand nailing group ( P<0.05). There was no significant difference in VAS, JOA score, NDI, or ASIA grading between the two groups before operation ( P>0.05). The VAS, JOA, and NDI scores at 3 days after operation were (3.1±0.6)points, (12.1±1.2)points, and (15.6±2.9)points, respectively in the robot nailing group, which were better than (5.0±1.4)points, (11.3±1.1)points and (22.5±3.7)points, respectively in the freehand nailing group ( P<0.05). No statistically significant difference was observed in the ASIA grade between the two groups at 3 days after operation ( P>0.05). There were no significant differences in VAS, JOA, NDI scores, or ASIA grading between the two groups at 3 months after operation and at the last follow-up ( P>0.05). Compared with those before operation, the VAS, JOA, NDI scores, and ASIA grading were significantly improved at 3 days, 3 months after operation and at the last follow-up in the two groups, which were further improved with the passage of time. Two patients in the robot nailing group had pneumonia, with a complication rate of 9% (2/22), while 2 patients in the freehand nailing group had dural sac rupture and cerebrospinal fluid leakage and 3 had lung infection after operation, with a complication rate of 14% (5/35) ( P<0.05). Conclusion:Compared with freehand nailing, the robot system-assisted nailing revision for AS with lower cervical fracture has more advantages in terms of the operative duration, length of hospital stay, intraoperative bleeding volume, frequency of intraoperative fluoroscopy nailing speed and accuracy, screw holding force, early pain relief, function restoration, and complication rate, despite longer surgical incision.