BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

BACKGROUND:Type 2 diabetes mellitus is a secondary causative factor for osteoporosis.As highly heterogeneous innate immune cells,macrophages may be polarized in a hyperglycemic environment,which affects osteogenesis-angiogenesis coupling.This may be a research target for improving bone quality in patients with type 2 diabetic osteoporosis.OBJECTIVE:To explore the role of modulating macrophage M1/M2 polarization to influence osteogenesis-angiogenesis coupling in type 2 diabetic osteoporosis and to summarize the effects of commonly used anti-glucose and anti-osteoporosis drugs and bone biorepair materials on bone osteogenesis-angiogenesis coupling by regulating macrophage M1/M2 polarization.METHODS:The keywords of"macrophage polarization,type 2 diabetes,osteoporosis,osteogenesis-angiogenesis coupling"in Chinese and"macrophages,macrophage polarization,osteogenesis-angiogenesis coupling"in English were used to search for relevant literature in CNKI and PubMed,respectively.Seventy-nine pieces of literature were screened and analyzed.RESULTS AND CONCLUSION:(1)Type 2 diabetes mellitus causes the body to be in a hyperglycemic environment and increases the secretion of inflammatory-related factors in the body,which promotes macrophage polarization towards M1 and decreases the number of M2 macrophages.(2)In type 2 diabetes,promoting M2 macrophage polarization is beneficial for osteogenesis-angiogenesis coupling.(3)Some anti-glycemic drugs,active ingredients in traditional Chinese medicine and bone biorepair materials can improve type 2 diabetic osteoporosis by regulating macrophage M1/M2 polarization,reducing M1/M2 ratio,and promoting osteogenesis-angiogenesis coupling.

OBJECTIVE: To compare the effectiveness of a zero-profile three-dimensiaonal (3D)-printed microporous titanium alloy Cage and a conventional titanium plate combined with a polyether-ether-ketone (PEEK)-Cage in the treatment of single-segment cervical spondylotic myelopathy (CSM) by anterior cervical discectomy and fusion (ACDF). METHODS: The clinical data of 83 patients with single-segment CSM treated with ACDF between January 2022 and January 2023 were retrospectively analyzed, and they were divided into 3D-ZP group (35 cases, using zero-profile 3D-printed microporous titanium alloy Cage) and CP group (48 cases, using titanium plate in combination with PEEK-Cage). There was no significant difference in gender, age, disease duration, surgical intervertebral space, and preoperative Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) score, neck disability index (NDI), vertebral height at the fusion segment, Cobb angle, and other baseline data between the two groups (P>0.05). The operation time, intraoperative blood loss, hospital stay, complications, interbody fusion, and prosthesis subsidence were recorded and compared between the two groups. VAS score, NDI, and JOA score were used to evaluate the improvement of pain and function before operation, at 3 months after operation, and at last follow-up, and the vertebral height at the fusion segment and Cobb angle were measured by imaging. The degree of dysphagia was assessed by the Bazaz dysphagia scale at 1 week and at last follow-up. RESULTS: The operation was successfully completed in all the 83 patients. There was no significant difference in intraoperative blood loss and hospital stay between the two groups (P>0.05), but the operation time in the 3D-ZP group was significantly shorter than that in the CP group (P<0.05). Patients in both groups were followed up 24-35 months, with an average of 25.3 months, and there was no significant difference in the follow-up time between the two groups (P>0.05). The incidence and grade of dysphagia in CP group were significantly higher than those in 3D-ZP group at 1 week after operation and at last follow-up (P<0.05). There was no dysphagia in 3D-ZP group at last follow-up. There was no complication such as implant breakage or displacement in both groups. The intervertebral fusion rates of 3D-ZP group and CP group were 65.71% (23/35) and 60.42% (29/48) respectively at 3 months after operation, and there was no significant difference between the two groups [OR (95%CI)=1.256 (0.507, 3.109), P=0.622]. The JOA score, VAS score, and NDI significantly improved in the 3D-ZP group at 3 months and at last follow-up when compared with preoperative ones (P<0.05), but there was no significant difference between the two groups (P>0.05). There was no significant difference in the improvement rate of JOA between the two groups at last follow-up (P>0.05). At 3 months after operation and at last follow-up, the vertebral height at the fusion segment and Cobb angle significantly improved in both groups, and the two indexes in 3D-ZP group were significantly better than those in CP group (P<0.05). At last follow-up, the incidence of prosthesis subsidence in 3D-ZP group (8.57%) was significantly lower than that in CP group (29.16%) (P<0.05). CONCLUSION The application of zero-profile 3D-printed Cage and titanium plate combined with PEEK-Cage in single-segment ACDF can both reconstruct the stability of cervical spine and achieve good effectiveness. Compared with the latter, the application of the former in ACDF can shorten the operation time, reduce the incidence of prosthesis subsidence, and reduce the incidence of dysphagia.
Humans ; Spinal Fusion/instrumentation* ; Titanium ; Cervical Vertebrae/surgery* ; Diskectomy/instrumentation* ; Bone Plates ; Male ; Printing, Three-Dimensional ; Female ; Retrospective Studies ; Middle Aged ; Treatment Outcome ; Benzophenones ; Adult ; Spondylosis/surgery* ; Aged ; Polymers ; Ketones ; Polyethylene Glycols

BACKGROUND:Transcranial magnetic stimulation has been used in the treatment of Alzheimer's disease,but its mechanism has not been fully clarified. OBJECTIVE:To explore the mechanism of repetitive transcranial magnetic stimulation to increase neural excitability in mice with Alzheimer's disease. METHODS:Sixteen C57BL/6 mice were randomized into control group (n=8) and control+magnetic stimulation group (n=8). Another 16 APP/PS1 mice were randomized into dementia group (n=8) and dementia+magnetic stimulation group (n=8). Mice in the two magnetic stimulation groups were given repetitive transcranial magnetic stimulation,2 hours daily,for 14 continuous days. The water maze was then used to detect the cognitive function of mice. Whole-cell membrane-clamp technique was used to collect action potentials and analyze the effect of Alzheimer's disease on action potentials;and the potassium channe currents were collected and analyzed for the role of their kinetic properties on neural excitability. RESULTS AND CONCLUSION:The results of Morris water maze showed that normal mice could find and determine the original platform more accurately after receiving repetitive transcranial magnetic stimulation,while Alzheimer's disease led to a decrease in the learning and memory ability of mice,a decrease in the number of times they found the platform,and a degeneration of neurons in the hippocampal dentate gyrus. Repetitive transcranial magnetic stimulation could improve the learning and memory ability of mice with Alzheimer's disease. Whole-cell membrane clamp technique assay showed that repetitive transcranial magnetic stimulation could trigger neuronal depolarization and enhance neuronal excitability in Alzheimer's disease mice. Analysis of potassium channel currents showed that Alzheimer's disease caused an increase in the transient outward potassium channel half-activation voltage. The inactivation curve was shifted in the direction of depolarization and the resuscitation time constant was prolonged,causing the delayed rectifier potassium channel activation curve to be shifted in the direction of depolarization. Whereas repetitive transcranial magnetic stimulation delayed the opening and closing of the potassium channel and inhibit the efflux of intracellular potassium ions,which resulted in the retention of a higher intracellular potassium concentration and increased neuronal excitability. To conclude,repetitive transcranial magnetic stimulation may alleviate cognitive decline by increasing neuronal excitability in the hippocampal dentate gyrus.

Objective Genetic testing and prenatal diagnosis were conducted in 18 congenital insensitivity to pain with anhidrosis(CIPA)families,laying the foundation for reducing the incidence of CIPA.Methods Genetic testing was performed using whole-genome sequencing and/or PCR-Sanger sequencing to identify candidate patho-genic vari-ants in the probands.For deep intronic variants,the pathogenicity was validated through minigene assays,RT-PCR,Sanger sequencing,and co-segregation analysis.DNA extracted from chorionic villus or amniotic fluid cells was analyzed by PCR and Sanger sequencing to determine the genotype of the fetuses.Maternal DNA contamination was excluded by microsatellite allele genotyping.Additionally,multiplex ligation-dependent probe amplification(MLPA)was employed to detect common chromosomal aneuploidies.Results A total of 21 NTRK1 variants were identified across 18 CIPA pedigrees,including 9 missense variants,2 nonsense variants,5 frameshift variants,and 5 deep intronic variants.Among them,3 were novel pathogenic variants.Prenatal genetic diagnosis was performed in 20 high-risk fetuses,revealing 2 normal fetuses,12 carriers,and 6 affected with CIPA.Microsatellite genotyping confirmed the absence of maternal DNA contamination in fetal samples.Moreover,MLPA analysis excluded common chromosomal aneuploidies associated with syndromic conditions in all tested fetuses.Conclusions This study achieved a 100%molecular diagnosis rate in CIPA families,identified three novel pathogenic variants,and enabled the simultaneous prevention of CIPA and common chromosomal syndromes through integrated prenatal ge-netic testing,thereby providing critical insights for genetic counseling.

BACKGROUND:Transcranial magnetic stimulation has been used in the treatment of Alzheimer's disease,but its mechanism has not been fully clarified. OBJECTIVE:To explore the mechanism of repetitive transcranial magnetic stimulation to increase neural excitability in mice with Alzheimer's disease. METHODS:Sixteen C57BL/6 mice were randomized into control group (n=8) and control+magnetic stimulation group (n=8). Another 16 APP/PS1 mice were randomized into dementia group (n=8) and dementia+magnetic stimulation group (n=8). Mice in the two magnetic stimulation groups were given repetitive transcranial magnetic stimulation,2 hours daily,for 14 continuous days. The water maze was then used to detect the cognitive function of mice. Whole-cell membrane-clamp technique was used to collect action potentials and analyze the effect of Alzheimer's disease on action potentials;and the potassium channe currents were collected and analyzed for the role of their kinetic properties on neural excitability. RESULTS AND CONCLUSION:The results of Morris water maze showed that normal mice could find and determine the original platform more accurately after receiving repetitive transcranial magnetic stimulation,while Alzheimer's disease led to a decrease in the learning and memory ability of mice,a decrease in the number of times they found the platform,and a degeneration of neurons in the hippocampal dentate gyrus. Repetitive transcranial magnetic stimulation could improve the learning and memory ability of mice with Alzheimer's disease. Whole-cell membrane clamp technique assay showed that repetitive transcranial magnetic stimulation could trigger neuronal depolarization and enhance neuronal excitability in Alzheimer's disease mice. Analysis of potassium channel currents showed that Alzheimer's disease caused an increase in the transient outward potassium channel half-activation voltage. The inactivation curve was shifted in the direction of depolarization and the resuscitation time constant was prolonged,causing the delayed rectifier potassium channel activation curve to be shifted in the direction of depolarization. Whereas repetitive transcranial magnetic stimulation delayed the opening and closing of the potassium channel and inhibit the efflux of intracellular potassium ions,which resulted in the retention of a higher intracellular potassium concentration and increased neuronal excitability. To conclude,repetitive transcranial magnetic stimulation may alleviate cognitive decline by increasing neuronal excitability in the hippocampal dentate gyrus.

Objective To investigate the risk factors of diabetic retinopathy(DR)in elderly patients with type 2 diabetes mellitus(T2DM)and establish the related prediction model.Methods A total of 426 elderly T2DM patients admitted to the Endocrinology Department of our hospital from January 2021 to March 2023 were enrolled in this study and divided into DR group(n=104)and T2DM group(n=322)according to the occurrence of DR.Results The DM duration≥10 years,hypertension,DPN,smoking,HbA1c,SUA,and high myopia were higher in the DR group than in the T2DM group(P<0.05).Pearson correlation analysis showed that DR was positively correlated with DM duration≥10 years,HbA1c,hypertension,DPN,smoking,SUA and high myopia in elderly T2DM patients(P<0.05).Logistic regression analysis showed that DM duration≥10 years,HbA1c,hypertension,DPN,smoking history,SUA,and high myopia were risk factors for DR in elderly T2DM patients.The analysis of the working characteristic curve of the subjects showed that the area under the curve for the occurrence of DR in elderly T2DM patients was 0.863,with a sensitivity of 78.8%and a specificity of 81.1%.Conclusions The duration of diabetes≥10 years,hypertension,DPN,smoking,HbA1c,SUA and high myopia are risk factors for the occurrence of DR in elderly patients with T2DM.The prediction model of DR has good accuracy in elderly patients with T2DM.

Objective To identify the clinical features and pathogenic variants in two unrelated families with gna-thodiaphyseal dysplasia(GDD),a rare genetic bone disorder.Methods Facial and limb deformities and skeletal morphology were observed in the probands and their family members.Peripheral blood samples(3-4 mL)were col-lected from the probands and their parents.Genomic DNA was extracted by standard phenol-chloroform method.Whole exome sequencing(WES)was performed to screen for candidate pathogenic gene variants of the probands.PCR-Sanger sequencing was used to validate the candidate pathogenic variants in the probands and their family members.The pathogenic variants responsible for GDD in the target families were determined through co-segregation of the pathogenic variants in the affected families,evolutionary conservation at the mutation sites,population allele frequency analysis and bioinformatics analysis.Results Heterozygous missense variants in the ANO5 gene were identified in both GDD probands.In family 1,the pathogenic variant was c.1 066T＞G located in the exon 11 of the ANO5 gene,while in family 2,the pathogenic variant was c.1 553G＞A located in the exon 15 of the ANO5.These two variants resulted in the substitutions of amino acid cysteine with glycine at position 356(p.Cys356Gly)and amino acid glycine with glutamic acid at position 518(p.Gly518Glu)in the ANO5 protein,respectively.Conclusions This study first identified the pathogenic variant c.1 066T＞G(p.Cys356Gly)in Chinese population,provided important evidence for prediction of disease prognosis and development of potential prenatal genetic diagnosis.

Abstract: Objective　To evaluate the application of variable number tandem repeats (VNTR) and whole genome sequencing (WGS) in tracing the transmission of Mycobacterium tuberculosis in a tuberculosis outbreak in school, and explore the roles of these genetic methodologies in addressing tuberculosis transmission in school environments. Methods Identification of mycobacterial strains, spacer oligonucleotide typing (Spoligotyping), VNTR, and WGS were performed on six Mycobacterium tuberculosis strains obtained from TB cases in the first multidrug-resistant tuberculosis outbreak happened in a school in Beijing. Genotyping characteristics were analyzed to identify the transmission chain. Results The 6 culture-positive strains involved 6 students from 4 classes across 2 grades. One of them was the first case, three were close contacts of the first case, and the other two were general contacts. All 6 strains were identified as Mycobacterium tuberculosis. Spoligotyping results indicated that 5 of the strains were of the Beijing genotype; the other one had no result. VNTR genotyping divided the 6 strains into 3 clusters with a clustering rate of 66.7%. The largest one of the 3 clusters contained 4 strains with the same genotype, indicating a significant level of recent transmission. The remaining two strains, differing by 1.0-1.6 copies at 1-2 loci from the other four strains, were identified as individual strains. The results of WGS showed that the genomic SNP differences among the 6 strains were greater than 12 SNPs. According to the molecular biology identification criteria of this study, the strains exhibited significant heterogeneity with no homology. Conclusions WGS offers higher accuracy and advantages over VNTR genotyping in evaluating the recent transmission of tuberculosis. WGS can more accurately characterize recent TB transmission in the case of TB outbreaks in schools, especially when there are drug-resistant TB cases, and should be used as a supplement to traditional epidemiology.

Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.