Objective:To investigate effect of trimetazidine(TMZ)on immune function of Streptococcus pneumoniae(SP)pneumonia rats through cyclic guanylate adenylate synthase(cGAS)-stimulator of interferon gene(STING)pathway.Methods:Rats were randomly separated into model group,TMZ group and DMXAA group(cGAS-STING signaling pathway activator).SP pneumonia rat model was replicated by intranasal instillation of SP,while rats in control group were infused with an equal amount of physiological saline.ELISA was applied to detect IL-1β and IL-10 levels.Flow cytometry was applied to detect CD4+T and CD8+T levels.Spleen and thymus indexes of rats in each group were compared.Transmission turbidity method was applied to detect IgG and IgA levels.HE staining was applied to observe pathological changes in lung tissue.Western blot was applied to detect cGAS-STING pathway proteins expressions.Results:Compared with control group,rats in model group showed an increase in alveolar wall and lung interstitium,accompanied by edema,bleeding and inflammatory cell infiltration,IL-1β,CD8+T cells levels,lung tissue pathological injury score,cGAS,STING expressions were increased,IL-10,CD4+T cells levels,CD4+T/CD8+T,spleen and thymus indexes,IgG,IgA levels were decreased(P<0.05).Compared with model group,rats in TMZ group showed reduced thickening of alveolar walls,great improve-ment in alveolar structure,and less infiltration of inflammatory cells,IL-1β,CD8+T cells levels,lung tissue pathological injury score,cGAS,STING expressions were decreased,IL-10,CD4+T cells levels,CD4+T/CD8+T,spleen and thymus indexes,IgG,IgA levels were increased(P<0.05).Compared with TMZ group,IL-1β,CD8+T levels,pathological injury score of lung tissue,cGAS and STING expressions in DMXAA group were increased,while IL-10,CD4+T cells levels,CD4+T/CD8+T,spleen and thymus index,IgG and IgA levels were decreased(P<0.05).Conclusion:TMZ may inhibit inflammation by inhibiting cGAS-STING signaling pathway,and enhance immune function of rats with SP pneumonia.

Objective:To observe any effect of ankle dorsiflexion angle on the gait of children with cerebral palsy (CP) after Achilles tendon lengthening surgery.Methods:Nine children with CP and equinus foot deformity were given Achilles tendon lengthening surgery. Reconstruction images of their pelvises and lower limbs were collected before the surgery and used to construct OpenSim simulations. Gait analysis data were also recorded before the surgery. The curve of changes to the Achilles tendon insertion was simulated in the software to determine the optimum angle of ankle dorsiflexion, and that guided the Achilles tendon extension surgery. The 3D gait analysis was repeated 12 months after the surgery to compare the spatiotemporal, kinematic and dynamic parameters (especially maximum ground reaction force on the affected side). The maximum dorsiflexion angles of the ankle joint before and after surgery were also recorded.Results:Before the surgery the dorsiflexion angles ranged from 8 to 12°, with an average of (10.1±1.2)°. After the surgery, significant changes were observed in the stride length, rhythm, speed and stride time of the affected side, as well as the maximum forward angle of the supported pelvis, the maximum dorsiflexion angle of the supported ankle and the maximum plantar flexion angle of the swinging ankle. Twelve months after the surgery, no recurrence of horseshoe malformation or over-correction complications were found in any of the 9 patients.Conclusions:3D gait analysis technology combined with OpenSim software can simulate the changes in Achilles tendon length needed by children with cerebral palsy. The optimum ankle dorsiflexion angle can be predicted pre-operatively and the simulation can also guide the operation. This technique also offers pre-and post-operative quantitative evaluation to provide references for subsequent rehabilitation treatment.

Objective To investigate the effect of vascular endothelial function on restenosis after carotid artery stenting(CAS).Methods A total of 236 patients with carotid artery stenosis who received CAS in Jinhua People's Hospital from January 2019 to December 2022 were selected as study objects.According to whether in-stent restenosis(ISR)occurred during follow-up,they were divided into ISR group(n=41)and non-ISR group(n=195).Blood lipid indexes[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)],vascular endothelial indexes[endothelin-1(ET-1),von Willebrand factor(vWF),vascular endothelial growth factor(VEGF),vascular cell adhesion molecule 1(VCAM-1),thromboxane B2(TXB2),endothelial nitric oxide synthase(eNOS),nitric oxide(NO)],inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),C-reactive protein(CRP)]and oxidative stress indexes[malondialdehyde(MDA),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)]were collected and compared between two groups.Transcriptome sequencing was performed on peripheral blood of ISR group and non-ISR group.Multivariate Logistic regression was used to analyze the independent influencing factors of ISR after CAS.Results The levels of TC,TNF-α,CRP,IL-6,MDA,ET-1,vWF,TXB2 and VCAM-1 in ISR group were significantly higher than those in non-ISR group(P＜0.01),and the levels of HDL-C,SOD,GSH-Px,NO,eNOS and VEGF in ISR group were significantly lower than those in non-ISR group(P＜0.01).Transcriptome differential gene enrichment analysis showed that the signaling pathways such as inflammatory response activation,oxidative stress response,and endothelial cell dysfunction were significantly enhanced in ISR group.Multivariate Logistic regression analysis showed that TNF-α,IL-6,ET-1,vWF,VEGF,SOD,and GSH-Px were independent influencing factors for ISR after CAS(P＜0.05).Conclusion Inflammatory factors,oxidative stress indexes and vascular endothelial function jointly promoted the occurrence and development of ISR after CAS in patients with carotid artery stenosis.TNF-α,IL-6,ET-1,vWF,VEGF,SOD,GSH-Px were independent risk factors for ISR after CAS.

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

Objective:To retrospectively study the curative effect of Vbeam 595nm pulsed dye laser(PDL)in treating the mid-term infantile hemangiomas(IHs),and analyze and explore the possible influencing factors of that.Methods:A total of 219 IHs patients who underwent PDL treatment in Tangshan Maternal and Child Health Care Hospital from January 2020 to December 2022 were selected,and they received follow-up at least 6 months.The relationship between the treatment effect and the month age,location,thickness of hemangioma and the number of treatments was analyzed.Results:The median month age of the 219 pediatric children was 7 months,and the average month age of them was(4-10)months,and there was a total of 219 lesions.There were no statistically significant differences in the general data such as month age and the characteristics of lesion between different genders(P＞0.05).The overall effective rate of treatment was 92.7%,and the median number of treatments was 3 times,and the average number of treatments was(2-4)times.There were no statistically significant differences in the comparisons of gender,the number of treatments and the treatment outcome(P＞0.05).The curative effects of 6 pediatric children were poor,whose month age was 13(8,19)months.The curative effects of 10 pediatric children were general,whose month age was 13(8,14)months.The curative effects of 31 pediatric children were favorable,whose month age was 8(4,10)months.The curative effects of 172 pediatric children were excellent,whose month age was 6(4,9)months.The difference of month age of pediatric children among different curative effect was significant(Z=24.863,P＜0.001),and the pediatric children with better curative effect had smaller month age.The treatment outcome of pediatric children with hemangioma was correlated with the thickness of lesion,the area size of lesion and the number of treatment(r=-0.32,-0.46,-0.46,P＜0.05),respectively.The effective treatment mainly focused on the treatments of the 2nd-4th times.The adverse reaction caused by treatment was skin erythema,and the rate of the total residual after six months of the complication was 5.48%.Conclusion:The treatment of 595nm PDL combined with dynamic cooling device(DCD)can provide a safe and effective treatment for IHs.Early intervention for IHs can improve the curative effect,and reduce the course of treatment,and further reduce the possibility of corresponding complications.

Objective To explore the prognostic value of early relevant clinical indicators in hemoperfusion patients with severe acute organophosphorus poisoning(AOPP).Methods The clinical data of 91 patients with severe AOPP admitted to Baoding NO.2 Central Hospital from March 2018 to October 2022 were retrospectively analyzed,including gender,age,comorbidities,body mass index(BMI),amount of drug taken,time from drug taking to gastric lavage,number of hemoperfusion,white blood cell count(WBC),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),blood urea nitrogen(BUN),serum cholinesterase(ChE)activity,lymphocyte count,pH value,arterial partial pressure of carbon dioxide(PaCO2),arterial partial pressure of oxygen(PaO2),blood K+,Na+,Cl-and inflammatory cytokine levels,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ),Glasgow coma scale(GCS),the occurrence of complications.The patients were divided into the death group and the survival group according to the prognosis within 72 hours.Differences in early clinical indicators between the two groups were compared,independent risk factors affecting the short-term prognosis of AOPP patients were analyzed by multivariate Logistic regression,and the predictive efficacy of each risk factor on the prognosis of patients was analyzed by plotting the receiver operator characteristic curve(ROC curve).Results The age of the death group was significantly higher than that of the survival group,the proportion of complicated with coronary heart disease,patients with dose of poison,time from poison to gastric perfusion,WBC,ALT,TNF-α,IL-1β and IL-6 levels at admission were significantly higher than those in survival group,and the number of hemoperfusion,TBil,ChE activity,PaCO2 were significantly lower than those in survival group(all P<0.05).Multivariate Logistic regression analysis showed that dose of poison,number of hemoperfusion,ALT,ChE activity and TNF-α were independent risk factors for poor prognosis in AOPP patients[odds ratio(OR)and 95％confidence interval(95％CI)were 1.865(1.032-3.370),2.282(1.406-3.703),2.522(1.258-5.057),2.843(1.036-7.802),2.077(1.107-3.897),respectively,all P<0.05];ROC curve analysis showed that dose of poison,number of hemoperfusion,ALT,ChE activity,TNF-α and the above combined indicators had certain predictive value for the prognosis of AOPP patients,and the combined detection had the highest predictive value,area under the ROC curve(AUC)=0.976,95％CI was 0.919-0.996.AOPP exhibited a sensitivity of 100.0％and a specificity of 85.7％,all P<0.05.With the increase of hemoperfusion times,compared with admission,the levels of WBC,ALT,AST,TBil,serum creatinine(SCr),ChE activity,TNF-α,IL-1β and IL-6 showed a significant decrease trend,while the levels of PaCO2 and PaO2 showed a significant increase trend(all P<0.05).Conclusion The early dose of poison,number of hemoperfusion,ALT,ChE activity,and TNF-α in severe AOPP patients can help predict short-term prognosis.

Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P＜0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P＜0.05),sIL-2R was positively correlated with TNF-α(P＜0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P＜0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P＜0.05),and CD4+/CD8+was positively correlated with the efficacy(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P＜0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P＜0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.

BACKGROUND:Bushen Yiqi Huayu granule has the effect of replenishing qi and eliminating blood stasis,tonifying kidney and smoothing collages,and is often used in the treatment of osteoporosis.At present,there are few studies on the effect of Bushen Yiqi Huayu granule on the callus angiogenesis of osteoporotic fractures. OBJECTIVE:To explore the mechanism of Bushen Yiqi Huayu granule by up-regulating extracellular signal-regulated kinase/mitogen-activated protein kinases(ERK/MAPK)signaling pathway to improve callus angiogenesis after fracturing in osteoporotic rats. METHODS:(1)Bone marrow mesenchymal stem cells from osteoporotic SD rats and bone marrow monocytes from C57BL/6 mice were collected.MTT assay was used to detect different doses of Bushen Yiqi Huayu granule on bone mesenchymal stem cell toxicity.Bone mesenchymal stem cells and bone marrow monocytes were cultured in the medium supplemented with 0 and 1.5 mg/mL Bushen Yiqi Huayu granules,respectively,and osteogenic differentiation and osteoclast differentiation were carried out in vitro.(2)144 SD rats were randomly divided into sham operation group,model group,granule group and granule+PD98059 group with 36 rats in each group.The osteoporotic model was established in the model group,granule group and granule+PD98059 group,and only part of the adipose tissue near the ovary was removed in the sham operation group.8 weeks later,all rats received left tibial osteotomy.In the granule+PD98059 group,5 g/kg Bushen Yiqi Huayu granule was given intragastrically,and 0.3 mg/kg PD98059 was injected into the tail vein.The granule group was given 5 g/kg Bushen Yiqi Huayu granule,and the same volume of normal saline was injected into the tail vein.The sham operation group and model group were given an equal volume of normal saline,and the caudal vein was injected with an equal volume of normal saline.Drug administration was conducted once a day for 8 weeks.Fracture healing and callus angiogenesis were observed by X-ray,micro-computed tomography and microvascular perfusion angiography.Bone mineral density and mechanical strength of the callus were measured.The tibia was observed by hematoxylin-eosin staining and Masson staining.Western blot assay and immunohistochemistry were used to examine the expression of ERK/MAPK signaling pathway-related molecules. RESULTS AND CONCLUSION:(1)Compared with the 0 mg/mL group,the alkaline phosphatase activity,mineralization level,p-ERK1/2 and p-p38 MAPK expression levels of osteocytes increased(P<0.05),while the density and volume of osteoclasts decreased in the 1.5 mg/mL group(P<0.05).(2)Compared with the sham operation group,the fracture healing degree of the granule group was similar at 4 and 8 weeks,but there was no significant difference in Lane-Sandhu score,total callus volume,mineralized callus volume,mineralized callus volume/total callus volume,trabecular thickness,vascular number,spacing,thickness,vascular volume/total volume,bone mineral density,ultimate load of callus,stiffness,p-ERK1/2,p-p38 MAPK,p-IκB-α,and p-p65 expression levels(P>0.05).In the model group and granule+PD98059 group,fracture healing was slow,Lane-Sandhu score,total callus volume,mineralized callus volume,mineralized callus volume/total callus volume,trabecular thickness,vascular number,thickness,vascular volume/total volume,bone mineral density,ultimate load of callus,stiffness,p-ERK1/2,p-p38 MAPK,p-IκB-α,and p-p65 expression levels decreased(P<0.05),and vascular spacing increased(P<0.05),compared with the sham operation group.(3)It is indicated that Bushen Yiqi Huayu granule can improve fracture healing,promote callus angiogenesis and alleviate the symptoms of osteoporosis by enhancing the expression of the ERK/MAPK signaling pathway-related molecules in osteoporotic rats.

Objective Cervical disc herniation(CDH)is one of the common orthopaedic diseases.With the in-depth study of it and the development of cervical implants,the establishment of cervical fusion animal models has become an indispensable part.Notably however,studies of the establishment and evaluation of cervical fusion animal models in China are currently lacking.This study aimed to provide a suitable animal model and evaluation scheme for implants for cervical spine-related research.Methods Small-tailed Han sheep were chosen for anterior cervical discectomy fusion(ACDF)after modified surgery,and a polyetheretherketone(PEEK)interbody fusion cage(Cage)(control group),3D-printed Ti6Al4V Cage(group 1),and new method Ti6Al4V Cage(group 2)were implanted in different cervical segments(C2/3～C4/5)in each sheep,respectively.Hematology and histopathological analyses were carried out after surgery to evaluate recovery of sheep and the biosafety of the materials.Bone in-growth and bone fusion were assessed by X-ray,computed tomography(CT),Micro-CT and quantitative analysis,hard tissue section staining,and biomechanical tests.Results The modified ACDF ovine model was established successfully.There were no significant differences in important hematology indexes(P＞0.05)and histopathological analysis showed no pathological changes,such as inflammatory cell infiltration.The implants had good biosafety.Furthermore,X-ray and CT examinations showed that the position of internal fixation and the interbody fusion were good.Micro-CT and quantitative analysis at 3 and 6 months after operation showed that compared with PEEK Cage group,the bone volume/total volume and trabecular number were significantly increased(P＜0.01)while the trabecular spacing was significantly decreased in the new method Ti6Al4V and 3D-printed Ti6Al4V groups compared with the PEEK Cage group(P＜0.01).Moreover,the new method new method Ti6Al4V Cage group had more bone growth(P＜0.01).Hard tissue section staining demonstrated that the pores of the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage had obvious bone growth and relatively dense pores in the new method Ti6Al4V and 3D-printed Ti6Al4V groups,and the combination was slightly better than that of PEEK Cage.Biomechanical evaluation indicated that the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cage reduced the range of cervical flexion-extension,lateral bending,and axial rotation(P＜0.05)compared with the PEEK cage,as well as enhancing the stability of the cervical vertebra,and the new method Ti6Al4 V Cage was more advantageous(P＜0.05).Conclusions After the establishment of the modified ACDF ovine model,reasonable and effective assessment method were used to demonstrate the suitability and effectiveness of the model and the good biosecurity of all three Cage materials.Compared with the PEEK Cage,the new method Ti6Al4V Cage and 3D-printed Ti6Al4V Cages showed better performances in terms of bone growth and bone fusion,which could enhance the stability of the cervical vertebrae.The new method Ti6Al4V Cage was particularly advantageous.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.