Spinal tuberculosis (STB), a prevalent form of extrapulmonary tuberculosis, remains incompletely understood at the mechanistic level. This study investigates the role of miR-29a-3p in modulating STB-associated inflammation and extracellular matrix degradation via targeted regulation of the PI3K/Akt signaling pathway, thereby identifying novel molecular targets for improved diagnosis and therapeutic intervention. Twenty patients with histopathologically confirmed STB and twenty age- and sex-matched controls with Intervertebral disc degeneration were prospectively enrolled. Genome-wide miRNA profiling was performed on spinal tissue specimens and BCG-infected THP-1–derived macrophages using small RNA sequencing, followed by qRT-PCR validation. Macrophage polarization and mycobacterial infection were modeled by PMA-induced differentiation of THP-1 cells and subsequent challenge with Bacillus Calmette–Guérin (BCG). Functional gain- and loss-of-function assays were conducted via transfection of miR-29a-3p mimics or inhibitors. Cytokine secretion (IL-6, IL-1β, TNF-α) and MMP-9 protein expression were quantified by ELISA, Western blotting, immunofluorescence microscopy, and qRT-PCR. Target prediction and dual-luciferase reporter assays validated direct binding of miR-29a-3p to the 3′-UTR of PI3K. Rescue experiments employed co-treatment with the selective PI3K inhibitor LY294002 to determine pathway-specific dependency. miR-29a-3p was significantly downregulated in both STB patient-derived spinal tissue specimens and BCG-infected THP-1–derived macrophages, concomitant with marked upregulation of MMP-9. Overexpression of miR-29a-3p markedly suppressed the secretion of pro-inflammatory cytokines—including IL-6, IL-1β,and TNF-α—as well as MMP-9 protein expression in BCG-infected macrophages; conversely, miR-29a-3p knockdown enhanced the production of these mediators. Mechanistically, miR-29a-3p directly bound to the 3′-UTR of PI3K—thereby inhibiting phosphorylation-dependent activation of the PI3K/Akt signaling axis. Crucially, pharmacological inhibition of PI3K with LY294002 reversed the pro-inflammatory response and matrix degradation effects induced by miR-29a-3p inhibition, confirming the functional dependence of this pathway. miR-29a-3p negatively regulates STB-associated inflammatory responses and MMP-9-mediated matrix degradation by targeting the PI3K/Akt signaling pathway, establishing a novel miR-29a-3p-PI3K/Akt-inflammatory cytokines/MMP-9 regulatory axis. This molecule represents a promising candidate biomarker and therapeutic target for the clinical diagnosis and targeted intervention of STB.

BackgroundVγ9Vδ2 T cells constitute the predominant human circulating γδ T cell subset and serve as key mediators of anti-mycobacterial immunity through major histocompatibility complex (MHC)-unrestricted phosphoantigen recognition and rapid effector activation.SummaryThis review evaluates Vγ9Vδ2 T cell biology in the context of tuberculosis (TB). We delineate the three-stage developmental pathway of Vγ9Vδ2 T cells in the postnatal thymus and the butyrophilin 3A1/2A1 (BTN3A1/BTN2A1)-mediated “inside-out” antigen sensing mechanism, noting the limitations of extrapolating in vitro findings to in vivo TB infection. The multifaceted activation networks—involving TCR-dependent signaling, cytokine amplification, and accessory co-receptor pathways—are examined in relation to distinct phases of Mtb infection. Vγ9Vδ2 T cells exert anti-TB protection through direct cytotoxicity (perforin/granzyme B, granulysin, FasL/TRAIL), cytokine-mediated immunoregulation, and orchestration of αβ T cell and dendritic cell responses; however, the functional significance of granulysin-dependent killing and the paradoxical Vδ2→Vδ1 subset shift during chronic infection warrant further investigation. Mtb immune evasion through metabolic antigen camouflage and chronic infection-induced exhaustion is also analyzed. Emerging evidence for Vγ9Vδ2 T cell immunological memory—including BCG-induced trained immunity and phosphoantigen-driven memory-like expansion in non-human primates —provides a rationale for novel vaccine strategies, although the translatability of these findings to human TB remains to be established. Translational approaches, including synthetic phosphoantigen prodrugs, BTN-targeted monoclonal antibodies, and adoptive cell therapy, are assessed for their clinical potential against drug-resistant TB, with discussion of current limitations.ConclusionVγ9Vδ2 T cells offer distinct advantages for TB immunotherapy and vaccine design, but significant translational barriers remain. Future studies must address subset heterogeneity across infection stages, the epigenetic and metabolic reprogramming governing functional fate decisions, standardized correlates of protection, and BTN-targeted strategies validated in TB-specific preclinical models. The integration of single-cell multi-omics and CRISPR-based functional screening with γδ T cell biology offers a promising path toward clinical translation.

Tuberculosis of the lower cervical spine often results in vertebral destruction, kyphotic deformity, and neural compression, substantially impairing patients’ quality of life. Anterior surgical approaches allow direct access to the lesion, enabling thorough debridement and neural decompression. Autologous iliac crest bone grafting is regarded as the preferred material for spinal reconstruction. However, comprehensive evaluations of the systemic efficacy of this surgical modality in managing cervical tuberculosis complicated by kyphosis remain limited. A retrospective review was conducted on 49 patients diagnosed with lower cervical spinal tuberculosis presenting with kyphotic deformity, who were treated at the Affiliated Hospital of Ningxia Medical University from January 2007 to December 2023. All patients underwent a single-stage anterior debrided lesion resection combined with autologous iliac crest structural grafting and short-segment internal fixation, following at least two weeks of standardized anti-tuberculosis therapy preoperatively. Perioperative data—including operative duration and intraoperative blood loss—were recorded. Clinical and radiographic follow-up was maintained for no less than 12 months postoperatively, with assessments including visual analog scale (VAS) for pain, Frankel neurological grading, local Cobb angle, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and graft union status. The mean operative time was 120.8 ± 12.5 min, with intraoperative blood loss averaging 90.6 ± 12.2 mL. The mean follow-up duration was 18.23 ± 4.12 months. At final follow-up, the local Cobb angle improved from −3.87 ± 1.15° preoperatively to 4.63 ± 0.98° (mean correction of 8.50°, P < 0.05). Pain scores decreased significantly from 6.51 ± 1.00 to 1.41 ± 0.91 (P < 0.05). ESR and CRP levels demonstrated significant reductions (P < 0.05). Neurological function, as indicated by Frankel grading, markedly improved postoperatively. The graft fusion rate was 100

BackgroundThe association between peripheral blood immune-inflammatory markers and neurological involvement in patients with spinal tuberculosis, and to develop a predictive model for early risk assessment. Spinal tuberculosis with neurological impairment is a major cause of disability, yet simple, cost-effective early warning indicators remain lacking. Peripheral blood immune-inflammatory markers are valuable in infectious disease prognostication, but their predictive role in spinal tuberculosis neurological involvement remains unclear.MethodsA retrospective study was conducted on 294 patients with spinal tuberculosis who underwent surgical treatment in the Department of Orthopedics, General Hospital of Ningxia Medical University, between December 2019 and December 2024. Patients were stratified into two groups: the uncomplicated spinal tuberculosis group (n=194, ASIA grade E) and the neurological involvement group (n=100, ASIA grades A–D). Fasting venous blood test results collected at the initial presentation were analyzed. Immune-inflammatory markers, including lymphocyte percentage (LYM), mixed cell percentage (MXD), and platelet-to-lymphocyte ratio (PLR), were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to identify influencing factors, followed by the establishment of a predictive model. Receiver operating characteristic (ROC) curves and a nomogram were constructed to evaluate the diagnostic efficacy of the model.ResultsThe neurological involvement group exhibited a significantly lower LYM [23.150% (16.900, 29.525) vs. 26.150% (19.750, 32.900)], and significantly higher MXD [9.000% (7.375, 10.200) vs. 8.100% (6.725, 9.900)] and PLR compared with the uncomplicated group (P < 0.05). Multivariate analysis revealed that LYM (odds ratio [OR]=0.961, 95% confidence interval [CI]: 0.935–0.989) and MXD (OR = 1.107, 95% CI: 1.013–1.209) were independent predictors of neurological involvement in spinal tuberculosis. Specifically, each 1% increase in LYM was associated with a 3.9% reduction in the risk of neurological impairment, whereas each 1% increase in MXD correlated with a 10.7% increase in risk. The combined predictive model achieved an AUC of 0.803 (95% CI: 0.749–0.857), with a sensitivity of 70.0% and specificity of 80.9%. The calibration curve confirmed good model fit (χ²=4.215, P = 0.837). In addition, the Brier score was 0.185, indicating favorable overall accuracy of the probabilistic predictions.ConclusionDecreased peripheral blood LYM and increased MXD are independent risk factors for neurological involvement in spinal tuberculosis. The combined predictive model shows favorable diagnostic efficacy and calibration. The nomogram is a simple, economical clinical tool for early high-risk patient identification, guiding individualized treatment decisions.

ObjectiveTo validate the safety and multicenter technical feasibility of an innovatively designed percutaneous paramedian small-angle lateral intervertebral foramen Kambin’s triangle approach for lumbar puncture biopsy in early spinal infection (SI), and to evaluate the diagnostic yield and etiological identification rate of the tNGS-based multimodal etiological detection protocol using specimens obtained via this approach.MethodsThis was a multicenter retrospective cohort study that enrolled 94 consecutive patients with SI who underwent the aforementioned puncture biopsy at 3 medical centers between January 2024 and January 2026. We systematically evaluated the procedure-related indicators and perioperative complications of this puncture approach. All puncture specimens were synchronously subjected to histopathological examination, routine bacterial culture, Xpert MTB/RIF assay, and tNGS detection. With the final comprehensive clinical diagnosis as the reference standard, we compared and analyzed the diagnostic performance of each detection method.ResultsAll 94 patients successfully completed biopsy via this modified puncture approach, with an overall puncture-related complication rate of only 7.45%. All adverse events were mild, and no severe complications occurred, and the approach was feasible and appeared safe in this retrospective cohort, though prospective validation across multiple operators is warranted before widespread clinical adoption. For etiological detection, the overall positive rate of tNGS reached 87.23%, which was significantly higher than that of routine bacterial culture (25.53%), specific histopathological diagnosis (17.02%), and Xpert MTB/RIF assay (17.02%) (all P < 0.0001). Meanwhile, tNGS maintained a stable and high detection rate across all major SI subtypes. The tNGS-centered multimodal combined detection achieved an overall positive rate of 91.49%. Notably, in early-stage cases where histopathology only indicated non-specific inflammatory cell infiltration, the combined detection achieved an etiology confirmation rate of 95.65%, effectively compensating for the deficiency of detection methods in early diagnosis.ConclusionsThe puncture approach designed in this study addresses the core bottleneck of specimen acquisition in early SI. The tNGS-based multimodal detection system using this approach has excellent diagnostic performance in early-stage infection, and can provide critical evidence-based support for the early accurate diagnosis and treatment as well as targeted antimicrobial therapy of SI.

BackgroundThe safety and efficacy of placing pedicle screws within infected vertebral bodies during surgery for acute pyogenic spondylitis remains controversial. The conventional “skip-level” fixation strategy avoids instrumentation at the infected site but may compromise spinal biomechanical stability and alignment. Conversely, fixation that includes the infected vertebrae can provide immediate stability, facilitate deformity correction, and promote bone fusion, although it carries potential risks of infection recurrence and implant failure.ObjectiveTo describe the short-term outcomes of direct pedicle screw fixation in infected vertebrae for acute pyogenic spondylitis, combined with radical debridement and targeted antimicrobial therapy.MethodsA retrospective analysis was conducted on 32 patients with pyogenic spondylitis who underwent surgical treatment between January 2021 and January 2025. All patients had a confirmed etiological diagnosis obtained via microbiological culture or next-generation sequencing (NGS) of surgical specimens and received individualized perioperative anti-infective therapy guided by clinical pharmacists. The surgical protocol included debridement of the infectious focus and posterior pedicle screw fixation incorporating the infected vertebrae, performed via single-stage posterior, single-stage combined anterior-posterior, or staged combined anterior-posterior approaches. Primary outcomes focused on perioperative adverse events, including implant-related complications, infection recurrence, and wound healing. Secondary outcomes assessed clinical efficacy and involved comparisons of Visual Analog Scale (VAS) pain scores, Oswestry Disability Index (ODI), inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and white blood cell count [WBC]), spinal Cobb angle, Frankel neurological grade, and bone fusion rates. Inflammatory markers and Cobb angle were assessed preoperatively and at 1, 3, and 6 months postoperatively; VAS and ODI were assessed preoperatively and at 1, 3, 6, and 12 months postoperatively; and bone fusion was assessed at 6 and 12 months postoperatively. Bone fusion was independently evaluated by two blinded assessors using Bridwell or modified Lenke criteria.ResultsAll 32 patients completed the 12-month follow-up. One osteoporotic patient developed asymptomatic minor screw loosening, and one diabetic patient experienced delayed wound healing that resolved after treatment. No implant failure, infection recurrence, or severe neurological complications occurred. Friedman tests demonstrated significant overall time effects for all dynamic indicators (all P < 0.0001): ESR (χ²(3) = 62.87, W = 0.65), CRP (χ²(3) = 67.22, W = 0.70), WBC (χ²(3) = 37.93, W = 0.40), Cobb angle (χ²(3) = 34.71, W = 0.36), VAS (χ²(4) = 95.90, W = 0.75), and ODI (χ²(4) = 127.02, W = 0.99). By 6 months, inflammatory markers had decreased markedly: ESR from 55.19 ± 31.05 to 6.00 (3.50, 12.25) mm/h; CRP from 34.10 (13.97, 85.15) to 2.12 (0.96, 3.90) mg/L; and WBC from 9.08 (5.75, 11.27) to 5.46 ± 1.01 ×109/L. The Cobb angle improved from 7.94 (6.84, 14.22)° to 8.34 ± 2.43°. At 12 months, VAS improved from 4.00 (4.00, 5.00) to 1.00 (0.75, 1.00), and ODI decreased from 28.72 ± 8.82% to 5.00 (2.25, 8.00)%. Neurological function recovered to Frankel grade E in 93.8% (30/32) of patients. The overall descriptive fusion rate (successful fusion in at least one graft site) was 78.13% at 6 months and 93.75% at 12 months postoperatively.ConclusionsIn this single-arm retrospective study of 32 patients with acute pyogenic spondylitis, direct pedicle screw fixation involving infected vertebrae was performed in conjunction with radical debridement and targeted antimicrobial therapy. At 12 months, patients demonstrated favorable short-term outcomes, including a low incidence of implant-related complications, significant improvements in pain and disability, a high radiographic fusion rate, and no observed infection recurrence. These findings provide preliminary evidence that this comprehensive protocol is a viable strategy for achieving favorable short-term outcomes in selected patients, and may serve as a practical reference for surgeons considering direct instrumentation in infected vertebrae.

BackgroundSpinal tuberculosis (STB) is characterized by an insidious onset, nonspecific clinical manifestations, and diagnostic challenges in early stages. Circular RNAs (circRNAs), a class of stable single-stranded endogenous RNAs with covalently closed-loop structures, play crucial regulatory roles in various biological processes. However, their involvement in STB pathogenesis remains largely unexplored.MethodsWe collected intervertebral disc tissue specimens and peripheral blood samples from STB patients. CircRNAs sequencing was performed on three representative lesion tissues, followed by comprehensive screening and validation in both tissue and blood samples to elucidate the functional mechanisms of circRNAs in STB.ResultsChip sequencing indicated that a total of 1,396 circRNAs were differentially expressed (fold change >2, P < 0.05). Among them, 757 circRNAs were upregulated, while 639 were downregulated. GO analysis of the parental genes of these differentially expressed circRNAs demonstrated that they were predominantly involved in cellular protein catabolic processes, GTPase binding, covalent chromatin modification, histone modification, and other processes. KEGG pathway analysis revealed that these genes were mainly enriched in signal pathways such as protein processing in the endoplasmic reticulum, apoptosis, and proteolysis. Validation in peripheral blood samples showed that the expressions of hsa_circ_0001021, hsa_circ_0043898, and hsa_circ_0093669 were significantly higher in the preoperative group than in the control group (P < 0.05). Moreover, the expression levels of these circRNAs decreased at 6 months and 1 year postoperatively compared to the preoperative levels. ROC curve analysis suggested that these circRNAs could serve as promising diagnostic biomarkers for STB in academic research scenarios.ConclusionThe differentially expressed circRNAs identified in intervertebral disc lesions of STB patients demonstrate significant involvement in disease pathogenesis, positioning them as promising candidates for both diagnostic and therapeutic targeting. Specifically, hsa_circ_0001021, hsa_circ_0043898, and hsa_circ_0093669 exhibit robust potential as peripheral blood-based diagnostic biomarkers for STB. When combined with conventional inflammatory markers ESR and CRP, these circRNAs significantly enhance diagnostic accuracy. Furthermore, longitudinal monitoring revealed their unique value in postoperative therapeutic evaluation, with expression levels showing strong correlation with treatment response.

N6-methyladenosine (m6A) is the most common and abundant internal modification in RNA. However, the role of m6A in spinal tuberculosis (STB) remains incompletely elucidated. In our previous study, miRNA-seq was performed on peripheral blood and tissues from STB patients, and miR-29a-3p was identified as differentially expressed in STB patients through screening. In this study, we mainly explored the regulation of miR-29a-3p by ALKB homolog 5 (ALKBH5) in STB. Tissue specimens were obtained from 20 patients with lumbar degenerative disease and 20 patients with STB. The expression levels of ALKBH5 and miR-29a-3p in STB were assessed using qRT-PCR, immunohistochemistry, and immunofluorescence assays. MeRIP analyses were performed to investigate the role of ALKBH5 in regulating the m6A modification of miR-29a-3p. Additionally, Western blot, ELISA, and qRT-PCR techniques were employed to validate the regulatory mechanism of ALKBH5-mediated miR-29a-3p in the inflammatory response associated with STB. ALKBH5 was upregulated in both spinal tuberculosis tissues and cellular models, whereas miR-29a-3p exhibited marked downregulation. Inhibition of miR-29a-3p expression led to increased levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-17 A (IL-17 A). Conversely, overexpression of miR-29a-3p effectively suppressed the production of inflammatory factors. Furthermore, ALKBH5 was found to directly target miR-29a-3p and regulate its methylation modification, thereby inhibiting the maturation of miR-29a-3p. Additionally, ALKBH5 suppressed the expression of miR-29a-3p, which in turn promoted the release of inflammatory factors associated with spinal tuberculosis.

Spinal Tuberculosis (STB) constitutes a common form of tuberculosis and is more widespread in developing countries. Not only is it one of the principal causes of spinal deformity but also it may trigger severe neurological impairments, thereby significantly influencing the quality of life of patients. Additionally, microRNAs (miRNAs) participate in the signal transduction among macrophages through multiple means. In the earlier work of our research group, spinal tuberculosis tissues were subjected to miRNA differential analysis and sequencing. The results indicated that miR-29a-3p was under-expressed in patients with spinal tuberculosis relative to the normal population. Nevertheless, it remains unknown at present how methyltransferase 14(METTL14)-mediated miR-29a-3p regulates the inflammatory response of spinal tuberculosis via the Mitogen-Activated Protein Kinase Kinase 6(MAP2K6) signaling pathway. This study aimed to validate the expression levels of METTL14 and miR-29a-3p in spinal tuberculosis and explore the regulatory role of METTL14 in mediating miR-29a-3p via the MAP2K6 signaling pathway during spinal tuberculosis-associated inflammation. Twenty cases of peripheral blood samples from patients with spinal tuberculosis and normal individuals were collected respectively. Through the construction of a BCG-infected THP-1 macrophage model, the expression of METTL14 and miR-29a-3p in spinal tuberculosis was verified by means of clinical sample analysis and cell experiments such as RT-qPCR, immunohistochemistry, and Western blot. The regulation of METTL14-mediated miR-29a-3p through the MAP2K6 signaling pathway in the inflammatory response of spinal tuberculosis was explored via immunofluorescence, RT-qPCR, and ELISA. The expressions of METTL14 and miR-29a-3p were significantly downregulated in patients with spinal tuberculosis, while the expression of MAP2K6 was upregulated. METTL14 regulated the expression of miR-29a-3p through m6A modification, thereby targeting and inhibiting the expression of MAP2K6. Overexpression of METTL14 and miR-29a-3p could suppress the MAP2K6 signaling pathway, alleviated inflammatory responses and spinal tissue damage; conversely, inhibition of METTL14 and miR-29a-3p activated the MAP2K6 signaling pathway, intensifying inflammatory responses and spinal tissue damage. This research uncovers the crucial role of the METTL14/ miR-29a-3p/ MAP2K6 axis in spinal tuberculosis, providing experimental evidence for the utilization of non-coding RNA as molecular targets in spinal tuberculosis, providing references for the study of the pathogenesis of spinal tuberculosis, and offering novel ideas and perspectives for the diagnosis and treatment of spinal tuberculosis. This indicates that the treatment targeting METTL14 may provide a new strategy for the treatment of STB and facilitate its early clinical detection.

This study is designed to investigate the roles of MMP-2, MMP-9, and MMP-13 in intervertebral disc destruction resulting from different types of spinal infections and their correlations with clinical quantitative data. Disc tissue samples were collected from 60 patients with spinal infections (20 cases each of STB, BS, and PS in the infection group) and 20 patients with intervertebral disc herniation (control group). The expressions of MMP-2, MMP-9, and MMP-13 were detected by RT-qPCR. Correlation analysis was carried out with clinical quantitative data such as preoperative erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and related blood routine indicators in the infection group. In the analysis between the infection group and the control group, MMP-13 was expressed in the diseased intervertebral disc tissue of STB patients, but the result was not statistically significant (P = 0.2172). There was a significant difference in the expression of MMP-13 in the diseased intervertebral discs of BS and PS patients. The expressions of MMP-9 and MMP-2 were markedly increased in the diseased intervertebral disc tissue of STB, BS, and PS patients (all P < 0.05). In the inter-group analysis of the infection group, the expression of MMP-13 in the diseased intervertebral disc tissue of PS patients was significantly different from that of STB and BS (P < 0.0001), while there was no significant difference between the STB and BS groups (P = 0.2393). The expression of MMP-9 in the diseased intervertebral disc tissue of STB patients was significantly different from that of BS and PS (P < 0.0001), but there was no statistically significant difference between the BS and PS groups (P = 0.9643). There was no statistically significant difference in the expression of MMP-2 among the STB, BS, and PS groups. In the correlation analysis with clinical quantitative data, MMP-13 was positively correlated with CRP, ESR, IL-6, WBC, and NEUT levels (r values were 0.7346, 0.3465, 0.3326, 0.6347, and 0.5152 respectively), and negatively correlated with LYM level (r = -0.5152, P < 0.05), and had no correlation with PCT and MXD levels. MMP-9 was positively correlated with ESR level (r = 0.3412, P < 0.05) and had no correlation with CRP, IL-6, PCT, WBC, NEUT, and LYM levels. MMP-2 was positively correlated with NEUT and LYM levels (r values were 0.3021 and 0.3306 respectively, P < 0.05) and had no correlation with ESR, CRP, IL-6, PCT, and WBC levels. MMP-2, MMP-9, and MMP-13 play crucial roles in intervertebral disc destruction due to spinal infections. The differential expression of MMPs may be one of the reasons for the varying degrees of intervertebral disc destruction in different types of spinal infections. Moreover, when clinical indicators such as CRP, ESR, IL-6, WBC, and NEUT increase, it suggests that the expression of MMP-13 in the intervertebral disc at the lesion site significantly rises, and it may become a new target for the treatment of spinal infections in the future.

The aim of this study was to explore the effects of in-hospital exercise rehabilitation on glucose and lipid metabolism and healthy physical fitness in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM) combined with sarcopenia, and to provide a reference for the effective implementation of exercise rehabilitation for middle-aged and elderly patients with T2DM combined with sarcopenia in healthcare institutions. This study retrospectively included 122 patients with T2DM combined with sarcopenia treated at the General Hospital of Ningxia Medical University from August 2017 to August 2020 and randomly divided into a control group and an experimental group. The control group was given conventional treatment and the experimental group was given exercise rehabilitation in the hospital for 12 weeks to compare the indexes related to glucose and lipid metabolism and healthy fitness in the two groups. After the intervention, the experimental group showed significant decreases in fasting blood glucose (FPG), glycated haemoglobin (HbA1c), insulin resistance index (HOMA-IR), triglycerides (TG), total cholesterol (TC), low-density cholesterol (LDL-C) and body fat percentage (P < 0.05), while high-density cholesterol (HDL-C), grip strength, lower limb extension, lower limb flexion, peak oxygen uptake were significantly higher (P < 0.05) and were more significant at 12 weeks compared to the 6-week intervention (P < 0.05). However, there were no significant changes in any of the glucose metabolism indicators in the control group before and after the intervention. A two-way repeated measures ANOVA showed that at control baseline levels, HbA1c decreased significantly in the experimental group after both 6 and 12 weeks of intervention compared to the control group (p < 0.05). After 6 weeks of intervention, the experimental group showed a significant decrease in body fat percentage and a significant increase in grip strength. After 12 weeks of intervention, the experimental group showed an increase in glycaemic control from 33.3–73.3%, a significant decrease in body fat percentage and a significant increase in grip strength, lower limb extension and lower limb flexion strength and peak oxygen uptake. In-hospital exercise rehabilitation can effectively improve the glycaemic and lipid profiles of patients with T2DM combined with sarcopenia and enhance their health fitness, with good clinical rehabilitation effects.

Rationale: Highly virulent multidrug-resistant Klebsiella pneumoniae (KP) is becoming more and more common in clinical practice, especially the rise of carbapenem-resistant KP in clinical practice, resulting in the emergence of KP liver abscess in Ningxia, China. For the prognosis of liver abscess patients, it is particularly important to identify the types of pathogens and identify antibiotics that are sensitive to the pathogens.Patient concerns: A 73-year-old man from China presents to our hospital with abdominal pain, jaundice and fever. Patients have no obvious cause of abdominal pain, abdominal distension, and abdominal pain is persistent. Abdominal examination showed hepatomegaly, no tenderness 2 cm from the right costal margin, abdominal distension and other general examinations did not have obvious abnormalities. He had no history of hypertension and diabetes, ERCP was performed for cholangiocarcinoma 1 year before the current visit, and no significant complications occurred.Diagnoses: His initial diagnosis was obstructive cholangitis, and computed tomographic images and liver drainage fluid bacterial culture and genetic polymerase chain reaction tests later determined that the patient had KP liver abscess.Interventions: Drainage by liver catheter and antibiotic treatment for 7 weeks.Outcomes: The patient liver abscess is basically gone.Lession: It is particularly important to optimize the diagnosis of liver abscess pathogens for timely and effective treatment of patients.

目的 采用酶放大免疫法对万古霉素(VAN)试剂进行系统评价,探讨万古霉素血药浓度、疗效及肝肾功能的关系,为临床合理用药提供依据.方法 参考美国临床和实验室标准协会(CLSI)EP15-A方案,从精密度、正确度、线性范围、可报告范围、携带污染率 5 个方面进行性能验证,对 69 例患者万古霉素血药浓度、病原学结果、疗效及肝肾功能等进行检测分析.结果 酶放大免疫法检测万古霉素的重复性精密度变异系数(CV)≤6.25%、总精密度CV≤8.30%;线性范围为 0～62.33 μg·mL-1,回归方程为y=0.951x+1.158,r2=0.997;可报告范围为 0～62.33 μg·mL-1;携带污染率≤2%,均符合要求.69 例患者中病原菌分离率为 82.6%(57/69),临床治疗有效率为 89.9%(62/69);万古霉素血浓度检测 147 例次,万古霉素平均值为(17.89±12.59)μg·mL-1;万古霉素治疗后天冬氨酸氨基转移酶(AST)升高(P＜0.05),尿素氮(BUN)、肌酐(CREA)、丙氨酸转氨酶(ALT)治疗前后差异均无统计学意义(P均＞0.05);有 5 例患者出现肾功能损害.结论 酶放大免疫法检测万古霉素试剂重复性好、线性范围宽、抗干扰能力强,血药浓度监测能为临床提供可靠的数据信息,指导临床个体化给药.

目的 探讨脓毒症患者淋巴细胞亚群联合Th1/Th2细胞因子等相关指标的特征,为早期识别脓毒症生物标志物变化及判断预后提供思路.方法 收集脓毒症患者84例,根据疾病转归分为预后良好组和预后不良组,同期选取120名健康人作为对照组.流式细胞仪检测外周血淋巴细胞亚群(CD3+、CD4+T、CD8+T细胞、CD19+B细胞、NK细胞)及血清Th1/Th2细胞因子谱白介素2(IL-2)、白介素4(IL-4)、白介素6(IL-6)、白介素10(IL-10)、γ-干扰素(IFN-γ)和α-肿瘤坏死因子(TNF-α)水平;全自动血液分析仪检测白细胞、中性粒细胞、血小板、中性粒细胞和淋巴细胞的比值(NLR)等;全自动血浆蛋白分析仪检测C反应蛋白(CRP);免疫层析法检测降钙素原(PCT);全自动血凝分析仪检测PT、APTT;血气分析(氧分压、乳酸、二氧化碳分压等).Pearson方法分析细胞因子和淋巴细胞亚群的相关性,二元logistic回归分析评价各指标与脓毒症严重程度的关联,绘制受试者工作特征曲线(ROC)评价各指标对脓毒症的诊断价值.结果 与对照组相比,脓毒症组CD3+、CD3+CD4+、CD3+CD8+、CD3-CD16+56+、CD3-CD19+数量及CD4+/CD8+比值显著性下降,TNF-α、IL-6水平显著性升高(P＜0.05).脓毒症患者预后良好组和预后不良组相比,CD4/CD8比值及IL-6水平差异有统计学意义(P＜0.05).Pearson相关性分析显示,患者血清CD8+T细胞和IL-2水平间呈正相关(P＜0.05);二元logistic回归分析CD4/CD8比值为影响脓毒症的独立危险因素;ROC曲线结果显示,IL-6、TNF-α、CD4/CD8比值对于脓毒症病情的评估具有较好的临床价值.结论 脓毒症患者TNF-α、IL-6、CD4/CD8比值对脓毒症监测及预后判断具有较好的临床参考价值.

OBJECTIVE To understand the clinical distribution of Klebsiella pneumoniae and carbapenem-resistant K. pneumoniae（CRKP） strains and analyze the changes of drug resistance in 7 years so as to provide data for reasonable clinical use of antibiotics. METHODS The clinical isolates of K. pneumoniae and CRKP were collected from a hospital between 2015 and 2021. The specimens sources, department sources, result for drug susceptibility testing and changes of drug resistance to commonly used antibiotics were retrospectively analyzed by WHONET 5.6 software and SPSS 26.0 software. RESULTS Totally 8181 strains of non-repetitive K. pneumoniae were isolated from 2015 to 2021, the isolation rate was the highest（15.69%） in emergency department, and 51.83% of the strains were isolated from sputum specimens. The drug resistance rates of the K. pneumoniae strains to cefazolin, imipenem and amikacin were 64.36%, 3.97% and 3.31%, respectively. The drug resistance rates of the K. pneumoniae strains to the commonly used antibiotics were remarkably increased in 2015-2018, and the drug resistance rates to the commonly used antibiotics and carbapenems such as imipenem and meropenem began to decline from 2018. Totally 327 strains of CRKP were isolated between 2015 and 2021, the isolation rate showed upward trend and declined in recent two years. The CRKP strains showed highly drug resistance to the commonly used antibiotics like cephalosporins, the drug resistance rates to gentamycin and levofloxacin were decreased, and the strains were sensitive to polymyxin B and tigecycline. CONCLUSION The drug resistance rates of the clinical isolates of K. pneumoniae and CRKP to most of the antibiotics generally rise at the beginning and then go down. The overall status of drug resistance rate shows upward trend. Regular surveillance of the bacterial drug resistance may facilitate the understanding of change of the drug resistance and control of the occurrence and spread of CRKP strains.

目的:基于PI3K-AKT-mTOR信号通路探讨参附注射液对心力衰竭大鼠的作用及其机制.方法:60只SD大鼠随机分为正常对照组(n=20)、心力衰竭模型组(n=20)、参附注射液治疗组(n=20),正常对照组不做任何处理,其余两组采取腹主动脉缩窄法构建心力衰竭模型,给予心力衰竭模型组氯化钠溶液,参附注射液治疗组给予参附注射液.比较各组大鼠心脏功能、氧化应激、炎症因子、P13K-Akt-mTOR表达.结果:与正常对照组相比,参附注射液治疗组、心力衰竭模型组左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)水平依次升高,而左心室射血分数(LVEF)水平依次下降(P＜0.05).与正常对照组相比,参附注射液治疗组、心力衰竭模型组血清丙二醛(MDA)水平依次升高,血清超氧化物歧化酶(SOD)水平依次下降(P＜0.05).与正常对照组相比,参附注射液治疗组、心力衰竭模型组血清白介素6(IL-6)、白介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平依次升高(P＜0.05).与正常对照组相比,参附注射液治疗组、心力衰竭模型组P13K-Akt-mTOR表达依次下降(P＜0.05).结论:参附注射液能够保护心力衰竭大鼠心脏功能,并可减轻氧化应激反应、抑制炎症因子表达,其作用机制可能与激活P13K-Akt-mTOR信号通路有关.

目的 探讨地高辛血药浓度对心力衰竭患者的影响因素及其疗效和安全性,为临床安全、合理、有效使用药物提供参考.方法 选取103例口服地高辛住院患者,分别检测治疗前后血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、尿素氮(BUN)、肌酐(CREA)、N末端B型利钠肽原(NT-proBNP)、钾离子(K+)指标、左心室射血分数(LVEF)及地高辛血药浓度,观察其影响因素、临床疗效及安全性.结果 103例患者中地高辛血药浓度平均值为(1.71±1.84)ng/mL,29.13％的人群出现中毒浓度水平(＞2.0 ng/mL).随着BUN、CREA水平的升高,地高辛血药浓度水平呈上升趋势,女性地高辛血药浓度略高于男性,低血K+的地高辛血药浓度略高于高血K+的血药浓度.地高辛治疗后血清NT-proBNP明显下降、LVEF％明显升高,总有效率为87.38％.18例患者(17.48％)出现不良反应,其中女性11例(61.11％),毒性地高辛血药浓度患者14例(77.78％)有中毒表现,30例毒性血药浓度16例(53.33％)未出现中毒表现.结论 地高辛在治疗心力衰竭的同时,应综合考虑性别、电解质、肾功能状况及联合用药等影响因素,及时监测血清地高辛血药浓度以确保其疗效与安全性.

目的 分析生物膜形成相关的酪氨酸磷酸酶A(TpbA)经调节3,5-环鸟苷二磷酸(c-di-GMP)影响鲍曼不动杆菌ATCC17978生物膜的形成.方法 通过上海生工合成TpbA基因序列,构建pET-28a-TpbA载体,原核重组表达目的蛋白TpbA经亲和层析纯化后并用western blot验证,将该载体转入鲍曼不动杆菌ATCC17978,采用western blot和磷酸酶活性实验鉴定TpbA表达及活性,分析c-di-GMP表达水平及生物膜形成情况.结果 在成功构建pET-28a-TpbA载体并证实表达TpbA的基础上,将该载体转入鲍曼不动杆菌ATCC17978,western blot表明TpbA过表达(P＜0.05),磷酸酶活性实验证实过表达的TpbA具有酶活性(P＜0.05).进一步分析发现,ATCC17978中TpbA过表达能够降低c-di-GMP的水平(P＜0.05),表明TpbA能够有效调节鲍曼不动杆菌的c-di-GMP.ATCC17978中c-di-GMP相关的生物膜形成在TpbA过表达作用下能够被显著抑制(P＜0.05).结论 本研究初步证实了 TpbA通过调节c-di-GMP,可以抑制ATCC17978生物膜形成,为抑制鲍曼不动杆菌生物膜的形成提供了新的潜在靶点和实验数据.

BACKGROUND:The Notch signaling pathway regulates various cellular processes, including cell growth, inflammation response, and autophagy, thereby participating in the occurrence and development of various diseases. The present study aimed to investigate the molecular mechanism of Notch signaling in regulating alveolar type II epithelial cell viability and autophagy after Klebsiella pneumonia (KPN) infection.METHODS:KPN-infected human alveolar type II epithelial cells A549 (ACEII) were constructed. The autophagy inhibitor 3-methyladenine (3-MA) and Notch1 signaling inhibitor (DAPT) were used to pretreat A549 cells for 24 hours, 48 hours, and 72 hours before KPN infection. Real-time fluorescent quantitative PCR (qRT-PCR) and western blot assays were applied to detect the mRNA and protein expressions of LC3 and Notch1, respectively. ELISA was used to detect the levels of INF-γ, TNF-α, and IL-1β in the cell supernatants.RESULTS:The results showed that KPN-infected A549 cells presented significantly upregulated Notch1 and autophagy-related protein LC3 levels, along with increased IL-1β, TNF-α, INF-γ levels in a time-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) counteracted the promotive effects of LC3 and inflammatory cytokine levels in KPN-infected A549 cells; however, 3-MA did not influence Notch1 level. Notch1 inhibitor DAPT could suppress Notch1 and LC3 levels, thereby inhibiting inflammation response in KPN-treated A549 cells in a time-dependent way.CONCLUSIONS:KPN infection can activate the Notch signaling pathway and induce autophagy in type Ⅱ alveolar epithelial cells. Inhibiting the Notch signaling pathway may restrain KPN-induced A549 cell autophagy and inflammation response, shedding new insights for the treatment of pneumonia.

目的 研究口腔扁平苔藓(OLP)患者外周血淋巴细胞亚群、免疫球蛋白及补体水平变化情况,探讨免疫因素与OLP的关系及其临床意义.方法 选取2019年10月至2020年9月宁夏医科大学总医院的100例OLP患者作为OLP组,同期体检的100例健康人群作为对照组.采用流式细胞术检测细胞免疫(淋巴细胞亚群CD3+T细胞、CD4+T细胞、CD3+CD8+T细胞、CD16+CD56+自然杀伤细胞、CD3-CD19+B细胞、CD4+/CD8+)水平,采用免疫散射比浊法检测体液免疫(免疫球蛋白IgG、IgA、IgM及补体C3、C4)水平.结果 OLP组CD3+CD8+T细胞水平低于对照组,CD4+/CD8+水平高于对照组,差异均有统计学意义(P<0.05);OLP组免疫球蛋白IgM水平低于对照组,差异有统计学意义(P<0.05).结论 OLP患者细胞免疫与体液免疫均存在一定的失衡.