Objective:To study the anti-inflammatory mechanism of acupoint acupuncture combined with tetramethylpyrazine in regulating the nuclear factor kappa B (NF-κB)/NOD like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathway in a T-2 toxin induced rat model of Kashin-Beck disease.Methods:A total of 40 clean-grade Sprague-Dawley (SD) rats (half male and half female), weighing 180 - 220 g, were divided using a random number table method into model group, tetramethylpyrazine group, acupoint acupuncture combined with tetramethylpyrazine group, and control group, with 10 rats in each group. Rats in the model group, the tetramethylpyrazine group, and the acupoint acupuncture combined with tetramethylpyrazine group were intraperitoneally injected with 1.5 mg/kg of 0.1% T-2 toxin five times per week for 4 consecutive weeks. Rats in both the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group were intraperitoneally injected with 100 mg·kg -1·d -1 tetramethylpyrazine solution. Meanwhile, rats in the model group and the control group were administered an equivalent volume of physiological saline for consecutive 4 weeks. Acupoint acupuncture combined with tetramethylpyrazine group was used to needle the bilateral "Qu Chi" and "Wei Zhong" of rats with a diameter of 3 - 5 mm, leaving the needle for 20 minutes, once a day, for 4 weeks. After the last injection, the rats were euthanized to collect blood samples and knee joint cartilage. Hematoxylin and eosin staining was performed to observe the pathological changes in the knee joint cartilage of rats. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of osteocalcin (OC), alkaline phosphatase (ALP), β-carboxy-terminal cross-linked telopeptide of type Ⅰ collagen (β-CTX), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Western blot analysis was used to determine protein expression levels of NF-κB p65 and NLRP3. Results:In the control group, intact cartilage surface, middle, and deep structures were observed in the knee joint cartilage of rats. In the model group, pathological changes similar to adult Kashin-Beck disease were observed in the knee joint cartilage. The integrity of the knee joint cartilage of rats in the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group was significantly improved compared to the model group. Compared with the control group, the levels of OC and ALP in the serum of the model group rats were significantly reduced, while the level of β-CTX was significantly increased ( P < 0.05). Compared with the model group, the levels of OC and ALP in the serum of rats in the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group were significantly increased, while the levels of β-CTX were significantly decreased ( P < 0.05). The levels of OC and ALP in the serum of rats in the acupoint acupuncture combined with tetramethylpyrazine group were higher than those in the tetramethylpyrazine group, while the level of β-CTX was lower than that in the tetramethylpyrazine group ( P < 0.05). Compared with the control group, the levels of IL-1β, IL-6 and TNF-α in the serum of the model group rats were significantly increased ( P < 0.05). Compared with the model group, the levels of IL-1β, IL-6 and TNF-α in the serum of rats in the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group were significantly reduced ( P < 0.05). The levels of IL-1β, IL-6 and TNF-α in the serum of rats in the acupoint acupuncture combined with tetramethylpyrazine group were lower than those in the tetramethylpyrazine group ( P < 0.05). Compared with the control group, the expression levels of NF-κB p65 and NLRP3 proteins in the model group rats were significantly increased ( P < 0.05). Compared with the model group, the expression levels of NF-κB p65 and NLRP3 proteins were significantly reduced in the tetramethylpyrazine group and the acupoint acupuncture combined with tetramethylpyrazine group ( P < 0.05). The expression levels of NF-κB p65 and NLRP3 proteins in the acupoint acupuncture combined with tetramethylpyrazine group were significantly lower than those in the tetramethylpyrazine group ( P < 0.05). Conclusion:Acupoint acupuncture combined with tetramethylpyrazine has a good anti-inflammatory effect on T-2 toxin induced Kashin-Beck disease rats, and its mechanism may be related to the downregulation of NF-κB p65 and NLRP3 protein expression.

Vascular remodeling refers to a series of structural and functional abnormalities in the vascular wall,which is characterized by stenosis of the lumen,thickening of the vascular wall,reduction of vascular elasticity and compli-ance caused by changes in the microenvironment inside and outside the blood vessel,and ultimately the occurrence of car-diovascular events.Although the prevention,diagnosis and intervention of clinical cardiovascular diseases have improved,vascular dysfunction caused by vascular remodeling is still a huge problem and challenge that plagues clinical efficacy.N6-methyladenosine(m6A)modification is the most common and abundant post-transcriptional modification type in eukary-otic RNA.m6A methyltransferase,m6A demethylase and m6A reading protein are responsible for the occurrence,deletion and recognition of m6A modification,respectively.The m6A modification regulates the fate of important transcripts by participating in the splicing,degradation,translation,and subcellular translocation of RNA target molecules,thereby pla-ying a regulatory role in the maintenance of vascular physiological homeostasis and pathological remodeling.Studies have confirmed that m6 A modification-mediated vascular endothelial cell(EC)dysfunction,phenotypic transformation,abnormal proliferation,migration of medial vascular smooth muscle cell(VSMC),and aggregation and activation of monocytes/mac-rophages are involved in the occurrence and development of vascular remodeling diseases such as atherosclerosis and aneu-rysms.This article reviews the recent literatures on m6A modification in vascular remodeling,and discusses the effect of m6A methylation modification of important target molecules related to vascular remodeling on vascular cells function.Based on these,the intervention of m6A methylation may be a new target for clinical treatment and diagnosis in the future.

Vascular remodeling refers to a series of structural and functional abnormalities in the vascular wall,which is characterized by stenosis of the lumen,thickening of the vascular wall,reduction of vascular elasticity and compli-ance caused by changes in the microenvironment inside and outside the blood vessel,and ultimately the occurrence of car-diovascular events.Although the prevention,diagnosis and intervention of clinical cardiovascular diseases have improved,vascular dysfunction caused by vascular remodeling is still a huge problem and challenge that plagues clinical efficacy.N6-methyladenosine(m6A)modification is the most common and abundant post-transcriptional modification type in eukary-otic RNA.m6A methyltransferase,m6A demethylase and m6A reading protein are responsible for the occurrence,deletion and recognition of m6A modification,respectively.The m6A modification regulates the fate of important transcripts by participating in the splicing,degradation,translation,and subcellular translocation of RNA target molecules,thereby pla-ying a regulatory role in the maintenance of vascular physiological homeostasis and pathological remodeling.Studies have confirmed that m6 A modification-mediated vascular endothelial cell(EC)dysfunction,phenotypic transformation,abnormal proliferation,migration of medial vascular smooth muscle cell(VSMC),and aggregation and activation of monocytes/mac-rophages are involved in the occurrence and development of vascular remodeling diseases such as atherosclerosis and aneu-rysms.This article reviews the recent literatures on m6A modification in vascular remodeling,and discusses the effect of m6A methylation modification of important target molecules related to vascular remodeling on vascular cells function.Based on these,the intervention of m6A methylation may be a new target for clinical treatment and diagnosis in the future.

Objective:To analyze the efficacy of phantom-less quantitative computer tomography (PL-QCT) for the diagnosis of osteoporosis in patients with lumbar degenerative diseases.Methods:From October 2021 to October 2023, a total of 1 248 patients with lumbar degenerative disease who did not receive anti-osteoporosis treatment in the Department of Spine Surgery, Tianjin Hospital were retrospectively analyzed. There were 520 males and 728 females, aged 62.31±9.37 years (range, 40-87 years), height 1.66±0.08 m (range, 1.43-1.89 m), weight 69.04±8.27 kg (range, 49-93 kg). The mean body mass index was 26.11±3.67 kg/m 2 (range, 14.40-37.11 kg/m 2). Dual-energy X-ray absorptiometry (DXA) and PL-QCT were used to diagnose osteoporosis, and the detection rates of the two diagnostic methods were compared. The receiver operating characteristic (ROC) curve of PL-QCT for the diagnosis of osteoporosis was drawn, the area under the curve (AUC) and 95% confidence interval (CI), sensitivity and specificity were calculated. Results:Among 1 248 patients with lumbar degenerative diseases, 626 (50.2%) were diagnosed as osteoporosis by PL-QCT, 423(33.9%) were diagnosed by spine DXA, 488(39.1%) were diagnosed by hip DXA and 539 patients(43.2%) were diagnosed by dual-site DXA. The detection rate of osteoporosis of PL-QCT was higher than that of spine DXA (χ 2=193.557, P<0.001), hip DXA (χ 2=322.201, P<0.001) and dual-site DXA (χ 2=94.683, P<0.001), and the difference was statistically significant. Taking the diagnostic results of spinal DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 79%, a specificity of 81%, and an AUC and 95% CI of 0.82(0.79, 0.85). Taking the diagnostic results of hip DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 85%, a specificity of 55%, and an AUC and 95% CI of 0.75(0.71, 0.78). Taking the diagnostic results of two-site DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 72%, a specificity of 75%, and an AUC and 95% CI of 0.81(0.78, 0.83). Conclusion:Compared with DXA, PL-QCT has a higher detection rate of osteoporosis in patients with degenerative lumbar spine disease and good diagnostic efficacy.

Objective:To investigate the clinical efficacy of lumbar lateral interbody fusion (LLIF) versus posterior lumbar interbody fusion (PLIF) in the treatment of severe lumbar spinal stenosis.Methods:The data of patients with severe lumbar spinal stenosis who underwent LLIF or PLIF from February 2019 to December 2023 were retrospectively analyzed. There were 30 patients in the LLIF group, 10 males and 20 females, aged 62.7±5.6 years (range, 53-74 years), including 21 cases of single segment and 9 cases of double segment. There were 46 patients in the PLIF group, including 20 males and 26 females, aged 63.2±8.4 years (range, 43-75 years), 40 cases of single segment and 6 cases of double segment. The visual analogue scale (VAS), Oswestry disability index (ODI), intervertebral space height, intervertebral foramen height and postoperative complications were compared between the two groups.Results:All patients were followed up for an average of 21.3±6.4 months (range, 12-32 months). The intraoperative blood loss in the LLIF group was 112.2±76.9 ml, which was significantly lower than 193.9±88.2 ml in the PLIF group ( P<0.05). The VAS scores of back pain and leg pain after operation were significantly lower than those before operation in the two groups ( P<0.05). There was no statistically significant difference between groups in back pain VAS scores at preoperative, 6 months postoperative, and final follow-up ( P>0.05); the back pain VAS score at 1 month postoperatively in the LLIF group was 1.6±1.2, which was less than 2.8±0.7 in the PLIF group ( P<0.05). There was no statistically significant difference between groups in leg pain VAS scores at preoperative, 1 month postoperative, and 6 months postoperative ( P>0.05); the leg pain VAS score at the final follow-up in the LLIF group was 1.2±1.5, which was smaller than 1.8±1.0 in the PLIF group ( P<0.05). The postoperative ODI was smaller than the preoperative one in both groups, and the difference was statistically significant ( P<0.05); the preoperative, 1-month postoperative, 6-month postoperative, and final follow-up ODIs in the LLIF group were 45.7%±16.0%, 17.9%±12.0%, 16.2%±11.6%, and 15.7%±11.7%, and those in the PLIF group were 47.9%±15.4%, 20.1%±9.3%, 16.9%±10.6%, and 14.6%±11.0% in the PLIF group, and the difference between the groups was not statistically significant ( P>0.05). The preoperative intervertebral space height in the LLIF group was 10.6±2.0 mm, which was smaller than that in the PLIF group 11.8±2.2 mm ( P<0.05). The intervertebral space heights in the immediate postoperative period and at the final follow-up were 13.3±2.3 mm and 12.3±2.2 mm in the LLIF group and 13.7±1.7 mm and 13.0±1.9 mm in the PLIF group ( P>0.05). The preoperative intervertebral foraminal height in the LLIF group was 18.0±3.2 mm, which was smaller than that of 19.7±2.4 mm in the PLIF group ( P<0.05); the intervertebral foraminal heights in the immediate postoperative period and at the final follow-up were 21.4±2.5 mm and 20.2±2.4 mm in the LLIF group, and in the PLIF group were 20.7±2.4 mm and 19.7±2.6 mm in the PLIF group ( P>0.05). In the LLIF group, 2 cases had femoral nerve injury and 2 cases had transient back pain after operation. There were 2 cases of cerebrospinal fluid leakage, 1 case of screw loosening, and 2 cases of deep vein thrombosis in the PLIF group. In the PLIF group, 2 patients underwent revision, including 1 case due to cage displacement and 1 case due to screw malposition. The fusion settling rate was 21% (8/39) in the LLIF group and 12% (6/52) in the PLIF group ( P>0.05). Conclusion:Both LLIF and PLIF can effectively restore the intervertebral height, improve the lumbar function and the symptoms of back and leg pain in the treatment of severe lumbar spinal stenosis.

Objective:To investigate the risk factors for complications following lateral lumbar interbody fusion (LLIF) surgery.Methods:A retrospective analysis was conducted on 196 patients who underwent LLIF surgery via the psoas major muscle approach in the Department of Spinal Surgery, Tianjin Hospital, Tianjin University, from October 2018 to July 2024. The age, gender, body mass index (BMI), presence of hypertension, type 2 diabetes, heart disease, osteoporosis, history of lumbar surgery, history of abdominal surgery, history of abdominal inflammation, smoking status, operative time, surgical segments (whether the surgery was single-segment or multi-segments), and use of internal fixation or not were compared between patients with and without postoperative complications, the indicators with P<0.10 were included in the binary variable logistic regression analysis, and determine the independent risk factors for complications after LLIF surgery. Complications included anterior thigh symptoms (pain, numbness, weakness), cage subsidence, surgery-related complications (nerve injury, surgical site infection, postoperative buttock pain, urinary and fecal incontinence, etc.), and medical complications (cerebrovascular accident, deep vein thrombosis, urinary tract infection, etc.). Results:All 196 patients were followed up for 27.02 (12.6, 40.69) months. Postoperative complications occurred in 71 cases (96 times), and no complications occurred in 125 cases. In the complication group, there were 15 males and 56 females with a mean age of 61.82±7.57 years; in the non-complication group, there were 43 males and 82 females with a mean age of 62.00± 8.39 years. In the complication group, there were 43 cases of anterior thigh symptoms, 38 cases of cage subsidence, 11 cases of surgical operation-related complications, and 4 cases of medical complications. There were statistically significant differences in gender (χ 2=3.829, P=0.051), operation time ( t=2.391, P=0.018), and surgical segment (χ 2=4.245, P=0.039) between the complication group and the non-complication group. No statistically significant differences were found in age, gender, BMI, presence of hypertension, type 2 diabetes, heart disease, osteoporosis, history of lumbar surgery, history of abdominal surgery, history of abdominal inflammation, smoking status, or use of internal fixation ( P>0.10). Binary variable logistic regression analysis indicated that prolonged operative time [ OR=1.007, 95% CI(1.001, 1.013), P=0.019] and multilevel surgery [ OR=2.099, 95% CI(1.095, 4.025), P=0.026] were independent risk factors for complications following LLIF. Conclusion:Prolonged operative time and multi-segments surgery are independent risk factors for complications following LLIF.

Objective:To investigate the risk factors for complications following lateral lumbar interbody fusion (LLIF) surgery.Methods:A retrospective analysis was conducted on 196 patients who underwent LLIF surgery via the psoas major muscle approach in the Department of Spinal Surgery, Tianjin Hospital, Tianjin University, from October 2018 to July 2024. The age, gender, body mass index (BMI), presence of hypertension, type 2 diabetes, heart disease, osteoporosis, history of lumbar surgery, history of abdominal surgery, history of abdominal inflammation, smoking status, operative time, surgical segments (whether the surgery was single-segment or multi-segments), and use of internal fixation or not were compared between patients with and without postoperative complications, the indicators with P<0.10 were included in the binary variable logistic regression analysis, and determine the independent risk factors for complications after LLIF surgery. Complications included anterior thigh symptoms (pain, numbness, weakness), cage subsidence, surgery-related complications (nerve injury, surgical site infection, postoperative buttock pain, urinary and fecal incontinence, etc.), and medical complications (cerebrovascular accident, deep vein thrombosis, urinary tract infection, etc.). Results:All 196 patients were followed up for 27.02 (12.6, 40.69) months. Postoperative complications occurred in 71 cases (96 times), and no complications occurred in 125 cases. In the complication group, there were 15 males and 56 females with a mean age of 61.82±7.57 years; in the non-complication group, there were 43 males and 82 females with a mean age of 62.00± 8.39 years. In the complication group, there were 43 cases of anterior thigh symptoms, 38 cases of cage subsidence, 11 cases of surgical operation-related complications, and 4 cases of medical complications. There were statistically significant differences in gender (χ 2=3.829, P=0.051), operation time ( t=2.391, P=0.018), and surgical segment (χ 2=4.245, P=0.039) between the complication group and the non-complication group. No statistically significant differences were found in age, gender, BMI, presence of hypertension, type 2 diabetes, heart disease, osteoporosis, history of lumbar surgery, history of abdominal surgery, history of abdominal inflammation, smoking status, or use of internal fixation ( P>0.10). Binary variable logistic regression analysis indicated that prolonged operative time [ OR=1.007, 95% CI(1.001, 1.013), P=0.019] and multilevel surgery [ OR=2.099, 95% CI(1.095, 4.025), P=0.026] were independent risk factors for complications following LLIF. Conclusion:Prolonged operative time and multi-segments surgery are independent risk factors for complications following LLIF.

Objective To evaluate the protective effect of Schistosoma japonicum cystatin(rSj-Cystatin)in a mouse mode of"two-hit"sepsis.Methods Sixty male C57BL/6 mice randomized equally into sham-operated group,protein group,"two-hit"modeling group,and protein intervention group.In the former two groups,the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later;In the latter two groups,100 μL PBS containing LPS(5 mg/kg)was injected intraperitoneally 24 h before cecal ligation and puncture(CLP),and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP.At 12 h after rSj-Cystatin treatment,6 mice from each group were sacrificed for detection of TNF-α,IL-6,IL-10,TGF-β,iNOS and Arg-1 in the serum,spleen,liver,lung and kidney tissues using ELISA,for examinations of liver,lung and kidney pathologies with HE staining,and for analysis of CD3+CD4+CD25+Foxp3+T cell percentage in the spleen using flow cytometry.The remaining mice were observed for general condition and 72-h survival.Results The 72-h survival rates in the 4 groups were 100％,100％,0％and 20％,respectively,showing significant differences between the latter two groups.The mouse models of"two-hit"sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate,which were significantly ameliorated by rSj-Cystatin treatment.Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3+CD4+CD25+Foxp3+T cell percentage.The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney,and these changes were obviously improved by rSj-Cystatin treatment.Conclusion rSj-Cystatin has a protective effect against"two-hit"sepsis in mice by regulating the inflammatory microenvironment.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

OBJECTIVES: To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis. METHODS: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival. RESULTS: The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment. CONCLUSIONS rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals ; Mice ; Sepsis/drug therapy* ; Male ; Schistosoma japonicum/chemistry* ; Mice, Inbred C57BL ; Cystatins/therapeutic use* ; Interleukin-10/metabolism* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Transforming Growth Factor beta/metabolism*