BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Neck dissection(ND)is one of the main treatment methods for oral and maxillofacial malignancies.Although ND type is in con-stant improvement,but intraoperative peal-pull-push injury of the accessory nerve,muscle,muscle membrane,fascia and ligament induced shoulder syndrome(SS)is still a common postoperative complication,combined with the influence of radiochemotherapy,not only can cause pain,stiffness,numbness,limited dysfunction of shoulder neck and arm,but also may have serious impact on patient's life quality and phys-ical and mental health.At present,there is still a lack of a systematic evaluation and rehabilitation management program for postoperative SS of oral and maxillofacial malignant tumors.Based on the previous clinical practice and the current available evidence,refer to the relevant lit-erature at home and abroad,the experts in the field of maxillofacial tumor surgery and rehabilitation were invited to discuss,modify and reach a consenusus on the etiology,assessment diagnosis,differential diagnosis,rehabilitation strategy and prevention of SS,in order to provide clinical reference.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Objective To investigate the effectiveness of a new health education pathway for echinococcosis control among primary school students in regions highly prevalent for echinococcosis in China. Methods Six primary schools were randomly selected from echinococcosis hyper-endemic regions, with 13 classes assigned to the intervention group and 9 to the control group, and all students in these 21 classes were recruited as the study subjects. Echinococcosis health education was performed through the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices in the intervention group, while routine health education was given in the control group. A questionnaire survey was performed to assess the score of echinococcosis control knowledge (including theoretical knowledge score and mean daily practical capability score) before and after the health education interventions to evaluate the effectiveness of this new health education pathway for echinococcosis control. Results The mean score of echinococcosis control knowledge was 68.86 ± 18.70 points at baseline, with the mean theoretical knowledge score of 40.97 ± 10.75 points, and the mean daily practical capability score of 27.89 ± 12.50 points. Clustering analysis showed three types of populations, including “unsatisfactory”, “learn and apply creatively”, and “rote learning”, which accounted for 24.62% (240/975), 45.74% (446/975) and 29.64% (289/975), respectively. The mean score of echinococcosis control knowledge was 81.08 ± 18.15 points in the intervention group during the final assessment, with the mean theoretical knowledge score of 43.65 ± 9.40 points, and the mean daily practical capability score of 37.43 ± 12.22 points, and both were significantly higher relative to baseline (t = −4.201 and −15.202, both P values < 0.01). The mean score of echinococcosis control knowledge was comparable between at baseline (70.55 ± 19.46 points) and final assessment (71.74 ± 19.37 points) in the control group (t = −0.87, P > 0.05). Conclusions The awareness of echinococcosis control knowledge is fair among primary school students in echinococcosis hyper-endemic regions; however, the capability of combining theoretical learning and practices requires to be improved. The health education mode based on the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices seems to remarkably improve the understanding of echinococcosis control knowledge among primary school students in echinococcosis hyper-endemic regions.

As the famous Chinese patent medicine, Yinhua Miyanling Tablets, which was derived from ancient prescription denominated Bazhengsan, has not only the effects in clearing away heat and purging pathogenic fire, removing dampness and relieving stranguria, but also have the functions of detoxifying and tonifying. A great number of scientific studies have demonstrated that Yinhua Mi-yanling Tablets played significant roles in destroying harmful microbes and resisting inflammatory and diuresis. Compared with antibiotics, traditional antibacterial Chinese patent medicine Yinhua Miyanling Tablets has the advantage in bacterial resistance in long-term use. Fundamental studies about the content of pharmaceutical ingredients and the modern pharmacology of Yinhua Miyanling Tablets were collected and summarized, which conduces to indicating the active ingredients of Yinhua Miyanling Tablets with the medicinal efficacy from the molecular level and the internal mechanism of Yinhua Miyanling Tablets in the treatment of urinary tract infection(UTI) from the scientific perspective. In the field of clinical research, literatures associated with Yinhua Miyanling Tablets for the treatment of UTI were summarized and analyzed in terms of treatment type, administration mode, dosage, frequency of medication, course, efficiency, side effects and whether combined with healthy lifestyle. These literatures confirmed the medicinal values and the application prospect of Yinhua Miyanling Tablets in treating UTI, especially acute UTI, which provides a scientific theoretical foundation and a correct direction for the clinical application of Yinhua Miyanling Tablets. In conclusion, this article contributes to the standardization of Yinhua Miyanling Tablets in the treatment of UTI, in the expectation of giving the scientific guidance for clinical practice.
Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Research ; Tablets ; Urinary Tract Infections ; drug therapy

Objective: To evaluate the prognostic significance of comprehensive geriatric assessment (CGA) in Chinese elderly acute myeloid leukemia (AML) patients. Methods: 73 AML patients over the age of 60 were enrolled. CGA stratification included the following 3 instrument assessment: activity of daily living (ADL) ; instrumental activity of daily living (IADL) ; comorbidity score according to the Modified cumulative illness rating score for geriatrics (MCIRS-G) . According to CGA and age, the enrolled patients were grouped into 'fit', 'unfit' and 'frail' categories. Results: The median age of 73 elderly AML patients were 75 years old. According to CGA, 37 (50.1%) patients were classified as 'fit', 14 (19.2%) as 'unfit', and 22 (30.7%) as 'frail'. 33 (89.2%) patients in fit group received induction chemotherapy, or demethylation treatment, as 8 (57.9%) in unfit, 10 (45.5%) in frail. The overall response rate was 68.7%、62.5%, 75.0% in fit, unfit, and frail group, respectively (χ(2)=0.615, P=0.769) .The early mortality (8 weeks) in three groups were different: 5.4%, 7.1%, 27.3%, respectively (P<0.05) . The 1-year overall survival in the 'fit', 'unfit' and 'frail' groups was 64.9%, 28.6% and 22.7%, respectively (P<0.05) . The CGA score, age, ECOG score, WHO classification (2016) were the prognostic factors of AML patients. Conclusion: CGA can be used to determine the prognosis of elderly AML patients.
Aged ; Comorbidity ; Geriatric Assessment ; Humans ; Leukemia, Myeloid, Acute ; Prognosis

Objective In emergency situations where simultaneous immunization by multiple vaccines are required,how to rapidly evaluate the effect of combined immunization is an urgent issue that needs to be solved.This study aimed to investigate the po-tential role and application value of the phenotypic changes of macrophages in rapid evaluation of the effect of combined Yersinia pestis and Brucella bovis vaccine immunization at early stage.Methods Y.pestis and B.bovis vaccines were injected into mice alone or in combination to establish animal models.The changes of the macrophage phenotypes(M1 or M2 polarization)and the CD8+T cell pheno-types and functions were detected in the early(4 d)and the late(14 d)stage of the immunization,respectively.The effect of the immuno-phenotype of macrophages at early stage on the function of CD8+T cells at late stage was analyzed.Results The co-immunization by Y.pestis and B.bovis vaccines led to the attenuation of the M1-polarization of macrophages at early stage,which were marked by de-creased expression of CD16/32 and increased expression of Detectin-1 on cell surface as well as decreased expression of IL-12 and in-creased expression of IL-4 inside the macrophage,in comparison with single vaccine groups,suggesting an interference between the two vaccines.Meanwhile,the activity of CD8+T cells(including the ratio of CD8+CD69+T,CD8+IFN-γ+T and CD8+GranzymeB+T cells) in combined immunization group showed similar tendency to the attenuated phenotypic M1-polarization of macrophages. Conclusion The phenotype of macrophages at the early stage of the co-immunization by Y.pestis and B.bovis vaccines showed consistency with the phenotype and function of CD8+T cells at late stage.It might give us some hint about the possibility of utilizing the phenotypic changes of macrophages to rapidly evaluate the effect of the co-immunization at early stage.

A questionnaire survey of 1 000 clinicians having experience in treating uncomplicated lower urinary tract infections from different levels of hospitals was conducted to mainly evaluate the applicability and effectiveness of clinical application of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for uncomplicated lower urinary tract infection(hereinafter referred to as Guideline). The research was conducted with the three-level quality control strictly throughout the process, and the data was real and reliable. The survey's results showed that: most clinicians considered that the Guideline had good clinical applicability. The availability and price of the recommended medicine were moderate. Traditional Chinese medicine had obvious features and advantages in treating lower urinary tract infection for it could reduce the usage of antibiotics and shorten the course of antibiotic application. In the recommendation section, clinicians proposed increasing medication guidance, updating the Guideline timely, as well as increasing treating methods and techniques, strengthen propaganda and promotion, and improve the use of evidence-based methods. In the evaluation of effectiveness, the majority of clinicians agreed that the definition in both traditional Chinese medicine (TCM) and Western medicine and differential diagnosis in the Guideline were accurately described and the basic principle of treatment as well as the treating method of TCM were recommended appropriately. The TCM formulas and Chinese patent medicine had good effect. Some clinicians suggested refining the syndrome differentiation of stranguria. Some clinicians considered that the formulas and herbs recommended in Guideline didn't have obvious effect and some had doubts about the manipulation of fumigation and washing in the part of other methods recommended in Guideline. Moreover, specification and procedure of manipulation of fumigation and washing using herbs and the acupuncture included in characteristic TCM therapy treating uncomplicated lower urinary tract infection remained to be developed.
Acupuncture Therapy ; Anti-Bacterial Agents ; Diagnosis, Differential ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Urinary Tract Infections