BACKGROUND:The authors found that when the bilateral percutaneous vertebral augmentation is used to treat osteoporotic vertebral compression fractures with a total bone cement injection of 4 mL or more,different distribution patterns were usually presented on the X-rays;however,there were few reports addressing the effects of these patterns of bone cement distribution on the biomechanical properties of fractural vertebrae. OBJECTIVE:To further explore the biomechanical effects of different bone cement filling doses and distribution patterns on biomechanics of the fractural vertebrae using the finite element method. METHODS:The L1-L3 finite element models of osteoporosis were established,and the vertebral compression fractures were simulated in L2.Four distribution patterns bilateral partial fusion(FH type),full fusion(FO type),symmetrical separation(SA type),and asymmetric segregation(SN type)were simulated in 4 and 6 mL injections in the osteoporotic vertebral compression fracture models,respectively,and a total of nine sets of models were obtained.These models were solved under the same boundary conditions and compared with the stress and displacement of the L2 fractural vertebra. RESULTS AND CONCLUSION:(1)The maximum stresses of the nine groups of models were concentrated in the L2 fractural area,and the maximum stress and maximum displacement of each filling model were lower than in the osteoporotic vertebral compression fracture model,indicating the effectiveness of bone cement filling in the treatment of osteoporotic vertebral compression fracture.(2)Compared with 4 mL bone cement filling,6 mL bone cement filling could significantly reduce the stress of fractured vertebrae and enhance the strength of fractured vertebrae while improving the stability of fractured vertebrae.(3)In the same state of movement,the FH type stress was the least,followed by the SA type,both of which were close.FO type stress was the largest,especially in the lateral bend,which might be associated with its cluster shape resulting in the concentration of lateral stress.In the aspect of displacement,FH type was the least and FO type was the largest.(4)The results show that increased dose of bone cement injection reduces fractural vertebral stress and improves stability,but increases the risk of leakage.Bilateral symmetrical dispersed bone cement(FH type,SA type)is superior in restoring vertebral strength and stability than full fusion(FO type),asymmetric separated(SN type)bone cement.Therefore,when clinically performing bilateral percutaneous vertebral augmentation treatment of osteoporotic vertebral compression fractures,the bilateral symmetric dispersions of the distribution are first guaranteed;priority is recommended for FH type distribution,for appropriate stress stimulation and best stability.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

Objective To study the effect of leucine rich repeat kinase 2(LRRK2)on pain sensitivity in neuro-pathic pain(NP)rats and explore its possible mechanism.Methods 48 SD rats were randomly divided into four groups:sham surgery(Sham),model,LRRK2 inhibitor(MLi-2),and LRRK2 inhibitor+p3 8 mitogen activated pro-tein kinase(MAPK)agonist(MLi-2+Anisomycin),with 12 rats in each group.The NP rat model was induced by chronic constriction injury(CCI)of the sciatic nerve.Intrathecal injection of MLi-2(1 mg/kg,10 μl)or Anisomy-cin(20 μmol/L,10 μl)was started from the 8th day after surgery,once a day for 7 consecutive days.Pain sensi-tivity tests were conducted before surgery(day 0)and on postoperative days 7 and 14,respectively.The changes in mechanical withdrawal threshold(MWT)and paw withdraw thermal latency(PWTL)were analyzed in each group of rats.ELISA was used to detect the levels of interleukin-1 β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)in the dorsal horn of the rat spinal cord.Nissl staining was used to observe the pathological changes of neurons in rat spinal cord tissue.Immunofluorescence staining was used to observe the expression levels of ionized calcium-binding adapter molecule-1(Iba-1),a marker of microglia in the spinal cord of rats.Western blot was used to detect the protein expression levels of LRRK2,p-p38 mitogen activated protein kinase(MAPK),p38 MAPK,and Iba-1 in the dorsal horn of the rat spinal cord.Results Compared with the sham group,the model group showed a significant decrease in MWT and PWTL in the right hind limb of rats(P＜0.01).The levels of IL-1,IL-6,and TNF in the spi-nal dorsal horn tissue,as well as the expression levels of LRRK2,Iba-1 proteins and p-p38 MAPK/p38 MAPK pro-tein ratio significantly increased(P＜0.01).The proportion of Iba-1 positive cells in the spinal cord tissue signifi-cantly increased(P＜0.01),while Nissl bodies were significantly reduced(P＜0.01).Compared with the model group,the MLi-2 group showed a significant increase in MWT and PWTL in the right hind limb of rats(P＜0.01),a significant increase in Nissl bodies(P＜0.01),a significant decrease in the proportion of Iba-1 positive cells in the spinal cord tissue(P＜0.01),and a significant decrease in the levels of IL-1,IL-6,and TNF and the expression levels of LRRK2,Iba-1 proteins and p-p38 MAPK/p38 MAPK protein ratio(P＜0.01).However,Anisomychin in-tervention could activate the p38 MAPK signaling pathway and partially reverse the beneficial effects of MLi-2 on pain sensitivity and neuroinflammation in rats with neuropathic pain.Conclusion Inhibiting the expression of LRRK2 can alleviate pain sensitivity in NP rats induced by microglia activation mediated neuroinflammation,and its mechanism of action may be related to regulating the p38 MAPK signaling pathway.

Objective:To investigate the effect of astragaloside IV (AS-IV) regulating the signal axis of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) on the mobilization of bone marrow endothelial progenitor cells (EPCs) to peripheral blood in diabetes skin ulcer (DSU) rats.Methods:Twenty four SPF grade male Sprague Dawley (SD) rats were selected to make the model of type 2 diabetes rats by intraperitoneal injection of 30 mg/kg 1% (plastid ratio) streptozotocin, and then round full-thickness skin with a diameter of 2 cm was cut on both sides of the waist and back to make the skin ulcer model of diabetes rats. After that, they were randomly divided into AS-IV group (50 mg/kg AS-IV), blocker group (50 mg/kg AS-IV+ 5 mg/kg AMD3100) and model group. At the same time, a blank group ( n=8) was set up, The drug was administered via intraperitoneal injection, and the model group and blank group were treated with 0.9% NaCl of equal volume. On the 10th day, peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats were collected. The number of EPCs in peripheral blood of each group of rats was measured by flow cytometry, and the protein expression of SDF-1α and CXCR4 in peripheral blood, femoral bone marrow, and wound neovascularization tissues of rats was detected by enzyme-linked immunosorbent assay (ELISA); At the same time, the wound healing rates of each group were tested. Results:On the 10th and 21st day after modeling, the wound healing rate of each group of rats was compared. The blank group healed the fastest, while the model group healed the slowest. The AS-IV group had better healing than the model group and the blocker group, and the difference was statistically significant (all P<0.05). On the 10th day after modeling, the positive rates of peripheral blood EPCs in the white group, AS-IV group, and blocker group were significantly higher than those in the model group (all P<0.05), while the positive rates of peripheral blood EPCs in the blocker group were significantly lower than those in the AS-IV group (all P<0.05). On the 10th day after modeling, the protein expression of SDF-1α and CXCR4 in the wound, serum, and bone marrow of the model group was the lowest, while the protein expression in the blank group was the highest (all P<0.05). The protein expression of SDF-1α and CXCR4 in the wound, serum, bone marrow of the AS-IV group was significantly higher than that of the blocker group and model group, and the difference was statistically significant (all P<0.05). Conclusions:Astragaloside IV can promote the mobilization and migration of endothelial progenitor cells from bone marrow to peripheral blood in diabetes ulcer rats by regulating SDF-1α/CXCR4 signal axis, and can participate in angiogenesis of diabetes ulcer wounds as seed cells to promote the healing of diabetes skin ulcers.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

Aim To investigate the impact of Cinobu-facini on the proliferation,invasion,and apoptosis of HepG2 cells and the underlying mechanism.Methods The proliferation of HepG2 cells was assessed using the CCK-8 method following treatment with Cinobufaci-ni.The invasion capability of HepG2 cells was evalua-ted through Transwell assay after exposure to Cinobufa-cini.The apoptosis rates of HepG2 cells post Cinobufa-cini intervention were measured using flow cytometry,and the expression levels of VEGF in the culture medi-um of HepG2 cells were determined using enzyme-linked immunoassay.Furthermore,qRT-PCR and Western blot analyses were conducted to assess the im-pact of Cinobufacini on mRNA and protein expression levels related to the CXCL5/FOXD1/VEGF pathway.The interaction between CXCL5 and FOXD1 was inves-tigated via co-immunoprecipitation.Results Cinobufa-cini treatment led to a gradual decrease in HepG2 cell viability in a dose-dependent manner compared to the control group(P＜0.05).Moreover,Cinobufacini sig-nificantly suppressed HepG2 cell invasion(P＜0.05)while enhancing cell apoptosis(P＜0.05).Notably,Cinobufacini exhibited inhibitory effects on the CX-CL5/FOXD1/VEGF pathway,as evidenced by re-duced expression of related mRNA and proteins(P＜0.05).FOXD1 was identified as the binding site of CXCL5.Overexpression of CXCL5 resulted in in-creased proliferation and VEGF secretion by HepG2 cells(P＜0.05),and increased expression of FOXD1 and VEGF(P＜0.05).However,Cinobufacini inter-vention effectively inhibited liver cancer cell prolifera-tion and invasion(P＜0.05),promoted apoptosis(P＜0.05),reduced VEGF secretion by HepG2 cells(P＜0.05),and downregulated the expression of CXCL5 and FOXD1 in HepG2 cells(P＜0.05);but com-pared with the unexpressed group of Cinobufacini,its ability to inhibit cell activity was weakened(P＜0.05),and its ability to inhibit the expression of CX-CL5,FOXD1,and VEGF was weakened(P＜0.05).Conclusion Cinobufacini may inhibit HepG2 cell pro-liferation and invasion and promote HepG2 cell apopto-sis by regulating the CXCL5/FOXD1/VEGF pathway.

Aging has become an increasingly important topic in the field of geriatrics, with the exploration of aging-related biomarkers providing a foundation for interventions aimed at delaying and reversing aging.Over the years, numerous biomarkers have been developed at both the cellular level(aging mechanisms, histology)and individual level(composite biomarkers, functional biomarkers).This article systematically discusses the characteristics and application scenarios of significant biomarkers at these two levels, and also outlines comparative studies conducted on aging biomarkers.Future research should consider synthesizing multidimensional aging biomarkers at all levels to achieve a more accurate and reliable assessment of aging.Furthermore, there is great potential for further exploration of aging biomarkers through the analysis of histologic data.

Objective:To evaluate the safety and efficiency of China-made Toumai Robot-assisted laparoscopic radical prosta-tectomy(LRP).Methods:This study included 40 cases of PCa treated from January 2023 to May 2023 by robot-assisted LRP with preservation of the bladder neck and maximal functional urethral length,15 cases with the assistance of Toumai Robot(the TMR group)and the other 25 with the assistance of da Vinci Robot as controls(the DVR group).We recorded the docking time,laparo-scopic surgery time,vesico-urethral anastomosis time,intraoperative blood loss and postoperative urinary continence,and compared them between the two groups.Results:Operations were successfully completed in all the cases.No statistically significant differ-ences were observed between the TMR and DVR groups in the docking time(6 min vs 5 min,P＞0.05)or intraoperative blood loss(200 ml vs 150 ml,P＞0.05).The TMR group,compared with the DVR group,showed a significantly longer median laparoscopic surgery time(146 min vs 130 min,P＜0.05)and median vesico-urethral anastomosis time(19 min vs 16 min,P＜0.05).There were no statistically significant differences between the TMR and DVR groups in the rates of urinary continence recovery immediately af-ter surgery(60.0％[9/15]vs 64.0％[16/25],P＞0.05)or at 1 month(80.0％[12/15])vs(76.0％[19/25],P＞0.05),3 months(93.3％[14/15])vs(92.0％[23/25],P＞0.05)and 6 months postoperatively(100％[15/15])vs(96％[24/25],P＞0.05).Conclusion:China-made Toumai? Robot surgical system is safe and reliable for laparoscopic radical prosta-tectomy,with satisfactory postoperative recovery of urinary continence.