ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

Central sensitization(CS) is an important factor in inducing neuropathic pain(NPP), and the association between signal transduction protein 1(Epac1) and piezoelectric type mechanosensitive ion channel component 2(Piezo2) is a new and significant pathway for initiating CS. This study whether the central analgesic effect of Maxiong Powder is achieved through the synchronized regulation of the Epac1-Piezo2 signaling pathway in the medial habenular nucleus(MHb) and interpeduncular nucleus(IPN) of the brain. Dynamic in vivo microdialysis, combined with high-performance liquid chromatography-fluorescence detection(HPLC-RFC), behavioral assessments, immunohistochemistry, Western blot, and quantitative reverse transcription PCR, were employed in rats with partial sciatic nerve injury(SNI) to investigate the distribution and expression of Epac1 and Piezo2 proteins and genes in the MHb and IPN regions, and the changes in the extracellular levels of glutamate(Glu), aspartic acid(Asp), and glycine(Gly). Compared with the sham group, rats in the SNI group showed significantly reduced analgesic activity, a significant increase in cold pain sensitivity scores, and elevated Glu levels in the MHb and IPN regions. Additionally, the number of Piezo2-positive cells in these regions, as well as the expression levels of Epac1 and Piezo2 proteins and genes, were significantly increased. Compared with the SNI group, after Maxiong Powder administration, the analgesic activity in rats significantly increased, and cold pain sensitivity scores were significantly reduced. Maxiong Powder also significantly decreased the Glu content in the MHb and IPN regions and the Gly content in the MHb region, while significantly increasing the Asp content in both regions. Furthermore, Maxiong Powder significantly reduced the number of Piezo2-positive cells and lowered the protein and gene expression levels of Epac1 and Piezo2 in both brain regions. The central analgesic effect of Maxiong Powder may be related to its inhibition of Glu and Gly release in the extracellular fluid of the MHb and IPN regions, the increase of Asp levels in these regions, and the regulation of the Epac1-Piezo2 pathway through the reduction of Epac1 and Piezo2 protein and gene expression. These results provide partial scientific evidence for the clinical analgesic efficacy of Maxiong Powder and offer new ideas and approaches for the clinical treatment of NPP.
Animals ; Neuralgia/genetics* ; Rats ; Signal Transduction/drug effects* ; Male ; Rats, Sprague-Dawley ; Guanine Nucleotide Exchange Factors/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Habenula/drug effects* ; Ion Channels/genetics* ; Humans

OBJECTIVE: To compare the efficacy of percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar fractures. METHODS: A retrospective case-control study was used to analyze the clinical data of 78 patients with osteoporotic thoracic and lumbar fractures admitted from October 2017 to May 2019. According to the surgical method, it was divided into percutaneous pedicle screw combined with unilateral nail placement combined with unilateral bone cement strengthening group(bone cement group) and percutaneous pedicle screw combined with bilateral nail placement(screw group). In the bone cement group, 40 patients included 16 males and 24 females, with a mean age of (62.1±8.1) years old. In the screw group, 38 patients included 18 males and 20 females with a mean age of (65.1±9.3) years old. The operation time, intraoperative blood loss, length of hospital stay and postoperative complications were compared between two groups. The kyphosis Cobb angle, anterior edge height ratio, central height ratio and pain visual analogue score(VAS) were compared. RESULTS: All patients were followed up for 25 to 36 months. The operation time (70.1±17.3) min of the cement group was shorter than that of the screw group (78.6±18.2) min(P<0.05). There were no significant differences in intraoperative blood loss and length of hospital stay(P>0.05). The VAS in the cement group 1 year 1.5±0.5 and the latest follow-up 0.5±0.3 after operation were lower than 1 year 1.8±0.3 and the latest follow-up 0.8±0.4 in the screw group(P<0.05). The kyphosis Cobb angle, anterior edge height ratio, central height ratio in bone cement group, 1 year (6.2±1.2)°, (86.6±3.5)%, (91.1±2.5)%, the last follow-up (6.4±0.7)°, (85.5±3.3)%, (90.5±6.3)% were better than that of the screw group 1 year (6.8±1.4)°, (83.1±2.4)%, (89.9±3.4)% and the latest follow-up (7.1±1.1)°, (82.6±4.1)%, (87.6±5.9)%(P<0.05). There were 3 cases of bone cement leakage in the cement group, all of which had no clinical symptoms;and 2 cases of pedicle screws were extracted in the screw group, and the screws were removed at the last follow-up. CONCLUSION Percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar compression fractures in the elderly can achieve satisfactory efficacy and effectively relieve the pain of patients, but the former internal fixation system is more stable, and the long-term follow-up can effectively maintain the height of the anterior middle column and the correction of kyphosis deformity, and the incidence of chronic low back pain is lower.
Humans ; Male ; Female ; Aged ; Bone Cements ; Middle Aged ; Thoracic Vertebrae/surgery* ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Case-Control Studies ; Bone Nails ; Pedicle Screws

Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism. The clinical data of 854 children with cryptorchidism who underwent orchiopexy between January 2013 and December 2016 in Shenzhen Children's Hospital (Shenzhen, China) were retrospectively analyzed. The mean (standard deviation) age of the patients was 2.8 (2.5) years, and the duration of follow-up ranged from 1 year to 5 years. Ultrasonography was conducted preoperatively and postoperatively. The variables analyzed included age at the time of surgery, type of surgical procedure, laterality, preoperative testicular position, preoperative and postoperative testicular volumes, and the testicular volume ratio of them. The average testicular volumes preoperatively and at 1 year, 2 years, 3 years, and 5 years postoperatively were 0.27 ml, 0.38 ml, 0.53 ml, 0.87 ml, and 1.00 ml, respectively ( P < 0.001). The corresponding testicular volume ratios were 0.67, 0.76, 0.80, 0.83, and 0.84 ( P < 0.001). The mean volume of the undescended testes was significantly smaller than the mean normative value ( P < 0.001, lower than the 10 th percentile). The postoperative testicular volumes in children with cryptorchidism were generally lower than those in healthy boys but were still greater than the 10 th percentile and exhibited an increasing trend. The older the child is at the time of surgery, the larger the gap in volume between the affected and normal testes. Although testicular volume tends to gradually increase after orchiopexy for cryptorchidism, it could not normalizes. Earlier surgery results in affected testicular volumes closer to those of healthy boys.
Humans ; Male ; Cryptorchidism/diagnostic imaging* ; Orchiopexy ; Child, Preschool ; Testis/surgery* ; Retrospective Studies ; Organ Size ; Ultrasonography ; Infant ; Child ; Postoperative Period ; Follow-Up Studies

OBJECTIVES: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL). METHODS: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05). CONCLUSIONS Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans ; Hodgkin Disease/pathology* ; Male ; Child ; Female ; Adolescent ; Retrospective Studies ; Child, Preschool ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Infant

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.