Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome

Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

The relationship between hyperuricemia (HUA) and erectile dysfunction (ED) remains inadequately understood. Given that HUA is often associated with various metabolic disorders, this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA. A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine (Nanjing, China), aged 18 to 60 years. General demographic information, medical history, and laboratory results were collected to assess metabolic disturbances. Sexual function was evaluated using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Based on univariate analysis, variables associated with IIEF-5 scores were identified, and the correlations between them were evaluated. The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models. Fasting plasma glucose ( β = -0.628, P < 0.001), uric acid ( β = -0.552, P < 0.001), triglycerides ( β = -0.088, P = 0.047), low-density lipoprotein cholesterol ( β = -0.164, P = 0.027), glycated hemoglobin (HbA1c; β = -0.562, P = 0.012), and smoking history ( β = -0.074, P = 0.037) exhibited significant negative impacts on erectile function. The coefficient of determination ( R ²) for the model was 0.239, and the adjusted R ² was 0.230, indicating overall statistical significance ( F -statistic = 26.52, P < 0.001). Metabolic parameters play a crucial role in the development of ED. Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.
Humans ; Male ; Erectile Dysfunction/metabolism* ; Hyperuricemia/metabolism* ; Adult ; Middle Aged ; Cross-Sectional Studies ; Glycated Hemoglobin/metabolism* ; Blood Glucose/metabolism* ; Uric Acid/blood* ; Young Adult ; Triglycerides/blood* ; Adolescent ; Cholesterol, LDL/blood* ; Penile Erection/physiology* ; Surveys and Questionnaires

BACKGROUND: Our understanding of the correlation between postdischarge cancer and mortality in patients with coronary artery disease (CAD) remains incomplete. The aim of this study was to investigate the relationships between postdischarge cancers and all-cause mortality and cardiovascular mortality in CAD patients. METHODS: In this retrospective cohort study, 25% of CAD patients without prior cancer history who underwent coronary artery angiography between January 1, 2011 and December 31, 2015, were randomly enrolled using SPSS 26.0. Patients were monitored for the incidence of postdischarge cancer, which was defined as cancer diagnosed after the index hospitalization, survival status and cause of death. Cox regression analysis was used to explore the association between postdischarge cancer and all-cause mortality and cardiovascular mortality in CAD patients. RESULTS: A total of 4085 patients were included in the final analysis. During a median follow-up period of 8 years, 174 patients (4.3%) developed postdischarge cancer, and 343 patients (8.4%) died. A total of 173 patients died from cardiovascular diseases. Postdischarge cancer was associated with increased all-cause mortality risk (HR = 2.653, 95% CI: 1.727-4.076, P < 0.001) and cardiovascular mortality risk (HR = 2.756, 95% CI: 1.470-5.167, P = 0.002). Postdischarge lung cancer (HR = 5.497, 95% CI: 2.922-10.343, P < 0.001) and gastrointestinal cancer (HR = 1.984, 95% CI: 1.049-3.750, P = 0.035) were associated with all-cause mortality in CAD patients. Postdischarge lung cancer was significantly associated with cardiovascular death in CAD patients (HR = 4.979, 95% CI: 2.114-11.728, P < 0.001), and cardiovascular death was not significantly correlated with gastrointestinal cancer or other types of cancer. CONCLUSIONS Postdischarge cancer was associated with all-cause mortality and cardiovascular mortality in CAD patients. Compared with other cancers, postdischarge lung cancer had a more significant effect on all-cause mortality and cardiovascular mortality in CAD patients.

OBJECTIVE: To explore the immunophenotypic characteristics of bone marrow granulocytes (G) and their clinical significance in patients with multiple myeloma (MM). METHODS: The granulocyte immunophenotypes of bone marrow in 70 MM patients (MM group) and 40 anemia patients (control group) were detected by flow cytometry, and its correlation with clinical characteristics was further analyzed. Univariate and multivariate regression analysis were used to screen factors that affected prognosis. RESULTS: The CD56⁺G%, CD13⁺G%, CD22⁺G% and CD117⁺G% in MM group were higher than those in the control group (all P <0.05). CD56⁺G% and CD117⁺G% in CR⁺VGPR group were significantly lower than those in PR+MR+PD group (both P <0.05). The CD10⁺G% in RISS Ⅲ stage and Ca²⁺ ≥2.65 mmol/L groups were increased (both P <0.05). The CD56⁺G% in elevated lactate dehydrogenase, β₂-microglobulin≥5.5 mg/L and hemoglobin <85 g/L groups were increased (all P <0.05), while the CD117⁺G% in high-risk cytogenetic positive group was decreased (P <0.05). The expression rate of CD molecules on granulocytes was divided into low (L) and high (H) groups according to the median value. The overall survival (OS) of the LCD56⁺G%, LCD13⁺G% and LCD22⁺G% groups was significantly prolonged (all P <0.05). CD13⁺G% and CD22⁺G% were independent risk factors for OS in MM patients (HR=0.443, 0.410, both P <0.05). CONCLUSION The CD56⁺G%, CD10⁺G% and CD117⁺G% are closely correlated with clinical features in MM patients, while CD13⁺G% and CD22⁺G% are closely correlated with prognosis. Detection of CD molecules expression on granulocytes may be used to evaluate prognosis and guide treatment.
Humans ; Multiple Myeloma/immunology* ; Granulocytes/immunology* ; Prognosis ; Immunophenotyping ; Male ; Bone Marrow ; Female ; Flow Cytometry ; Middle Aged ; Aged ; Clinical Relevance

The oxytocin receptor (OXTR) has garnered increasing attention for its role in regulating both mature behaviors and brain development. It has been established that OXTR mediates a range of effects that are region-specific or period-specific. However, the current studies of OXTR expression patterns in mice only provide limited help due to limitations in resolution. Therefore, our objective was to generate a comprehensive, high-resolution spatiotemporal expression map of Oxtr mRNA across the entire developing mouse brain. We applied RNAscope in situ hybridization to investigate the spatiotemporal expression pattern of Oxtr in the brains of male mice at six distinct postnatal developmental stages (P7, P14, P21, P28, P42, P56). We provide detailed descriptions of Oxtr expression patterns in key brain regions, including the cortex, basal forebrain, hippocampus, and amygdaloid complex, with a focus on the precise localization of Oxtr⁺ cells and the variance of expression between different neurons. Furthermore, we identified some neuronal populations with high Oxtr expression levels that have been little studied, including glutamatergic neurons in the ventral dentate gyrus, Vgat⁺Oxtr⁺ cells in the basal forebrain, and GABAergic neurons in layers 4/5 of the cortex. Our study provides a novel perspective for understanding the distribution of Oxtr and encourages further investigations into its functions.
Animals ; Receptors, Oxytocin/metabolism* ; Male ; Brain/growth & development* ; Mice ; Mice, Inbred C57BL ; Neurons/metabolism* ; Single-Cell Analysis ; Gene Expression Regulation, Developmental ; RNA, Messenger/metabolism* ; Animals, Newborn

Objective To investigate the relationship between the levels of peripheral blood iri-sin,myostatin(MSTN),and 25-hydroxyvitamin D[25(OH)D]and the risk and predictive value of sarcopenia in elderly patients with type 2 diabetes mellitus(T2DM)complicated by heart failure.Methods Elderly patients with T2DM complicated by heart failure who visited Xingtai Central Hospi-tal from March 2023 to March 2024 were selected as the study subjects.The sample size was calculated based on the effect size.Patients were divided into modeling set(n=140)and validation set(n=60)at a ratio of 7 to 3 using a simple randomization method.Additionally,according to the occur-rence of sarcopenia,patients in the modeling set were divided into sarcopenia group and non-sar-copenia group.Clinical data and the levels of peripheral blood irisin,MSTN,and 25(OH)D were compared between the modeling and validation sets.The receiver operating characteristic(ROC)curve was used to analyze the predictive efficacy of peripheral blood irisin,MSTN,and 25(OH)D for sarcopenia.Multivariate logistic regression analysis was employed to identify the influencing fac-tors of sarcopenia in elderly patients with T2DM complicated by heart failure,and a relevant predic-tive model was constructed using R software.Results Among 200 elderly patients with T2DM com-plicated by heart failure,71 cases developed sarcopenia,with an incidence rate of 35.50％.The proportion of regular exercise,bone mineral content,and the levels of irisin and 25(OH)D in the sarcopenia group were lower than those in the non-sarcopenia group,while the MSTN level was high-er in the sarcopenia group,and the differences were statistically significant(P＜0.05).The areas under the curve(AUCs)for predicting sarcopenia by irisin,MSTN,and 25(OH)D were 0.878(95％CI,0.812 to 0.927),0.848(95％CI,0.778 to 0.903),and 0.826(95％CI,0.753 to 0.885),respectively.The sensitivities were 74.16％,79.78％,and 88.76％,and the specifici-ties were 74.16％,79.79％,and 88.76％,respectively.The results of multivariate logistic regres-sion analysis showed that lack of exercise habits(OR=2.489,95％CI,1.665 to 3.735),de-creased bone mineral content(OR=2.340,95％CI,1.596 to 3.595),irisin ≤105.44 ng/mL(OR=3.111,95％CI,2.004 to5.147),MSTN＞19.06 μg/L(OR=2.667,95％CI,2.015 to 4.693),and25(OH)D ≤12.23 ng/mL(OR=2.547,95％CI,1.285 to 4.492)were all inde-pendent risk factors for sarcopenia in these patients(P＜0.05).The results of ROC curve analysis showed that the AUCs of the nomogram model for predicting postoperative recurrence in the modeling and validation sets were 0.875 and 0.853,respectively.The Hosmer-Lemeshow test for the model-ing and validation sets showed the following results:x2=0.715,P=0.510;x2=0.651,P=0.568.The calibration curves were basically consistent with the standard curves.The threshold probability range of decision curve analysis(DCA)was 0.1 to 0.9.Within this range,both the modeling and validation sets showed good clinical net benefits.Conclusion Peripheral blood iri-sin,MSTN,and 25(OH)D all have certain predictive values for the occurrence of sarcopenia in elderly patients with T2DM complicated by heart failure.The nomogram model constructed based on irisin,MSTN,and 25(OH)D can provide a quantitative basis for the early screening of sarcopenia in these patients.

BACKGROUND:Reconstruction of the medial patellofemoral ligament is the primary and basic treatment for patellofemoral dislocation.Generally,autologous or allogeneic tendons are used to fix the patellofemoral podogram area and the femoral insertion,respectively.There are various fixation methods.Patellar lateral insertion fixation methods are relatively diverse,mainly traditional transosseous fixation and recent anchoring methods,including single tunnel,double-tunnel transosseous fixation,and two-wire anchor fixation.However,which fixation method is more effective in reducing patellofemoral joint stress and is more biomechanical has not been determined. OBJECTIVE:To observe the mechanical effects of patellofemoral joint and medial patellofemoral ligament reconstruction with transosseous and wire anchor fixation. METHODS:A three-dimensional finite element model of the knee joint was constructed.The medial patellofemoral ligament was reconstructed by a single tunnel through the bony canal or two wire anchors at the medial edge of the patella.The femoral side was fixed by extrusion nails to the medial epicondyle of the femur and the midpoint of the adductor tubercle.We observed the effects of the two fixation methods on patellofemoral joint and medial patellofemoral ligament loading during knee flexion at 0°,30°,60°,90°,and 120°. RESULTS AND CONCLUSION:(1)The stress on the patellofemoral joint was large when the knee was at flexion of 0-60°,peaked at 30°,and gradually decreased at 90° and 120°.The two fixation methods had little difference in the stress on the patellofemoral joint.(2)The stress on the medial patellofemoral ligament peaked at 30° and decreased significantly at 60°,and the load on the medial patellofemoral ligament was significantly greater at all angles with anchor fixation than with bony canal fixation.(3)The results showed that there was no significant difference in patellofemoral joint loading between the two fixation methods,but the stress on the medial patellofemoral ligament in anchoring was significantly greater than that in transosseous fixation.