1.Investigation of the Mechanism of Cold Hyperalgesia in KOA Mice Relieved by Shangke Lengtongtie Based on HMGB1/CX-CL12/CXCR4 Signaling Axis
Yibao WEI ; Li ZHANG ; Taiyang LIAO ; Lishi JIE ; Zhenyuan MA ; Peng WU ; Zhengquan HUANG ; Li ZHANG ; Liang DING ; Wei MEI ; Runlin XING ; Songjiang YIN ; Xiaochen LI ; Nongshan ZHANG ; Jun MAO ; Pei-min WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(2):195-202
OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.
2.A Randomized Controlled Clinical Study on the Treatment of Knee Osteoarthritis with Cold-Dampness Arthralgia Obstruc-tion by Shangke Lengtong Patch
Li ZHANG ; Liang DING ; Zhengquan HUANG ; Wei MEI ; Runlin XING ; Songjiang YIN ; Peng WU ; Xi-aochen LI ; Zhenyuan MA ; Nongshan ZHANG ; Jun MAO ; Peimin WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(3):393-398
OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.
3.A Randomized Controlled Clinical Study on the Treatment of Knee Osteoarthritis with Cold-Dampness Arthralgia Obstruc-tion by Shangke Lengtong Patch
Li ZHANG ; Liang DING ; Zhengquan HUANG ; Wei MEI ; Runlin XING ; Songjiang YIN ; Peng WU ; Xi-aochen LI ; Zhenyuan MA ; Nongshan ZHANG ; Jun MAO ; Peimin WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(3):393-398
OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.
4.Investigation of the Mechanism of Cold Hyperalgesia in KOA Mice Relieved by Shangke Lengtongtie Based on HMGB1/CX-CL12/CXCR4 Signaling Axis
Yibao WEI ; Li ZHANG ; Taiyang LIAO ; Lishi JIE ; Zhenyuan MA ; Peng WU ; Zhengquan HUANG ; Li ZHANG ; Liang DING ; Wei MEI ; Runlin XING ; Songjiang YIN ; Xiaochen LI ; Nongshan ZHANG ; Jun MAO ; Pei-min WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(2):195-202
OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.
5.Knockdown of nuclear protein 1 delays pathological pro-gression of osteoarthritis through inhibiting chondrocyte ferroptosis.
Taiyang LIAO ; Zhenyuan MA ; Deren LIU ; Lei SHI ; Jun MAO ; Peimin WANG ; Liang DING
Journal of Zhejiang University. Medical sciences 2024;53(6):669-679
OBJECTIVES:
To investigate the effect of nuclear protein (Nupr) 1 on the pathological progression of osteoarthritis and its relationship with ferroptosis of chondrocytes.
METHODS:
Chondrocytes from mouse knees were divided into small interfering RNA (siRNA) control group, small interfering RNA targeting Nupr1 (siNupr1) group, siRNA control+IL-1β group (siRNA control interference for 24 h followed by 10 ng/mL IL-1β) and siNupr1+IL-1β group (siNupr1 interference for 24 h followed by 10 ng/mL IL-1β). The protein and mRNA expressions of Nupr1 were detected by Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation viabilities were measured using the cell counting kit-8 method. The levels of ferrous ions were detected by FerroOrange staining. Lipid peroxidation levels were detected by C11-BODIPY-591 fluorescence imaging. The contents of malondialdehyde (MDA) and glutathione (GSH) were detected by enzyme-linked immunosorbent assay. The protein expressions of acyl-CoA synthetase long-chain family (ACSL) 4, P53, glutathione peroxidase (GPX) 4 and solute carrier family 7 member 11 gene (SLC7A11) were detected by Western blotting. The osteoarthritis model was constructed by destabilization of the medial meniscus (DMM) surgery in 7-week-old male C57BL/6J mice. The mice were randomly divided into four groups with 10 animals in each group: sham surgery (Sham)+adeno-associated virus serotype 5 (AAV5)-short hairpin RNA (shRNA) control group, Sham+AAV5-shRNA control targeting Nupr1 (shNupr1) group, DMM+AAV5-shRNA control group, and DMM+AAV5-shNupr1 group. Hematoxylin and eosin staining and Safranin O-Fast Green staining were used to observe the morphological changes in cartilage tissue. The Osteoarthritis Research Society International (OARSI) osteoarthritis cartilage histopathology assessment system was used to evaluate the degree of cartilage degeneration in mice. The mRNA expressions of matrix metallopeptidase (MMP) 13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5, cyclooxy-genase (COX) 2, and GPX4 were detected by qRT-PCR.
RESULTS:
In vitro experiments showed that knocking down Nupr1 alleviated the decrease of chondrocyte proliferation activity induced by IL-1β, reduced iron accumulation in mouse chondrocytes, lowered lipid peroxidation, downregulated ACSL4 and P53 protein expression and upregulated GPX4 and SLC7A11 protein expression (all P<0.01), thereby inhibiting ferroptosis in mouse chondrocytes. Meanwhile, in vivo animal experiments demonstrated that knocking down Nupr1 delayed the degeneration of articular cartilage in osteoarthritis mice, improved the OARSI score, slowed down the degradation of the extracellular matrix in osteoarthritis cartilage, and reduced the expression of the key ferroptosis regulator GPX4 (all P<0.01).
CONCLUSIONS
Knockdown of Nupr1 can delay the pathological progression of osteoarthritis through inhibiting ferroptosis in mouse chondrocytes.
Animals
;
Ferroptosis
;
Mice
;
Chondrocytes/metabolism*
;
Osteoarthritis/pathology*
;
RNA, Small Interfering/genetics*
;
Basic Helix-Loop-Helix Transcription Factors/genetics*
;
Interleukin-1beta/metabolism*
;
Phospholipid Hydroperoxide Glutathione Peroxidase/genetics*
;
Coenzyme A Ligases/genetics*
;
Tumor Suppressor Protein p53/metabolism*
;
Mice, Inbred C57BL
;
DNA-Binding Proteins
;
Neoplasm Proteins
;
Amino Acid Transport System y+
;
Nuclear Receptor Subfamily 1, Group D, Member 1
6.Study on the role of changing lifestyle and diet in in the treatment of laryngopharyngeal reflux disease
Ming LU ; Jiyi CAI ; Zesheng HONG ; Yuming HONG ; Chaohui ZHENG ; Zhenyuan LIANG ; Yahong LI ; Xiaofang CHEN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(4):255-259
OBJECTIVE To explore the effect of changing lifestyle diet in the treatment of laryngeal reflux disease(LRPD).METHODS A total of 92 patients with LRPD who received outpatient treatment in the Second Affiliated Hospital of Fujian Medical University from January 2022 to June 2023 were selected as the study control,divided into control group(46 cases)and treatment group(46 cases).The control group was treated with conventional acid suppression and gastric motogenic therapy.The treatment group was treated on the basis of the control group with giving guidance on lifestyle and diet.The changes of reflux symptom index scale(RSI)and reflux sign score scale(RFS)and the clinical efficacy of the two groups were compared 8 weeks and 12 weeks after treatment.RESULTS RSI total score was improved 8 weeks after treatment compared with before treatment in both RSI control group and treatment group(P<0.05).The total RSI score of 12 weeks after treatment was improved compared with that of 8 weeks after treatment in both control and treatment groups(P<0.05).The total RFS score at 8 weeks after treatment was improved in both control group and treatment group compared with before treatment(P<0.05).Compared with 8 weeks after treatment,the total RFS score in both control group and treatment group was improved(P<0.05).After 8 weeks of treatment,the total effective rate of the control group(60.9%)was compared with that of the treatment group(71.7%),and there was no significant difference between the two groups(χ2=1.335,P=0.513).After 12 weeks of treatment,the total effective rate of the control group(73.9%)was compared with the total effective rate of the treatment group(91.3%),and the difference between the two groups was statistically significant(χ2=6.226,P=0.044).CONCLUSION The change of lifestyle and diet should become an important part of the treatment of LRPD.By adjusting the unhealthy lifestyle and diet,the symptoms of patients can be significantly reduced and better clinical efficacy can be obtained.
7.Coiled tube of femoral anterolateral flap for repair of circumferential defect after operation of advanced hypopharyngeal carcinoma
Xiaofang CHEN ; Ming LU ; Yuming HONG ; Chaohui ZHENG ; Zhenyuan LIANG ; Yahong LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(10):998-1004
Objective:To investigate the clinical application value of coiled tube of femoral anterolateral flap in the repair of circumferential defect after resection of advanced hypopharyngeal carcinoma.Methods:Clinical data of 42 patients with advanced hypopharyngeal cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to April 2022 were retrospectively analyzed, including 41 males and 1 female, aged from 33 to 82 years old. All patients received surgical treatment, including total laryngectomy plus total laryngopharyngectomy in 20 cases, total laryngectomy, total laryngopharyngectomy and resection of partial tongue base in 8 cases, total laryngectomy, total laryngopharyngectomy and resection of cervical esophagus in 9 cases, total laryngectomy, total laryngopharyngectomy, and resection of partial tongue base and cervical esophagus in 5 cases. The postoperative circumferential defects were repaired with the coil tube of anterolateral femoral skin flap in phase Ⅰ, and the healing status of the flap, wound healing and swallowing function were observed. All cases were followed up.Results:The lengths of the hypopharyngeal defects were 7-18 cm and the sizes of the harvested flaps were 6 cm×9.5 cm-10 cm×20 cm. Flaps survived in 41 cases, flap necrosis occurred in one case, and the survival rate of flaps was 97.6%. One artery and one vein were anastomosed in 40 cases, and one artery and two veins were anastomosed in 2 cases. Postoperative cervical wound infection occurred in 5 cases, and pharyngeal fistula occurred in 2 cases. Three months of follow-up after surgery, 31 cases had normal diet, 9 cases presented with semi-liquid diet and 2 cases with liquid diet. Following up for 6-65 months, recurrence and metastasis occurred in 14 patients (33.3%), including primary site recurrence in 4 cases (9.5%), cervical lymph node recurrence in 6 cases (14.3%), and distant metastasis in 4 cases (9.5%). The 1-year and 3-year overall survival rates were respectively 79.4% and 60.5%.Conclusion:Coiled tube of femoral anterolateral flap is an ideal skin flap for repair of circumferential defects after resection of advanced hypopharyngeal carcinoma.
8.Analyzing the efficiency of increasing blood pressure before the end of the operation to reduce post coblation assisted tonsillectomy hemorrhage
Rongzhi LIN ; Yuming HONG ; Zhenyuan LIANG ; Chaohui ZHENG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2017;24(1):39-40
OBJECTIVE To explore the efficiency of reducing post-tonsillectomy hemorrhage by increasing blood pressure before the end of the coblation operation.METHODS Clinical data of 1069 patients with coblation assisted tonsillectomy under general anesthesia between January 2008 and January 2016 were retrospectively reviewed.The treatment group were 546 patients checked the operation cavity after increasing blood pressure before the end of tonsillectomy,while the control group were 523 patients checked the operation cavity with routine procedure without increasing the blood pressure.Post-tonsillectomy hemorrhage incidence and postoperative bleeding volume were compared between the two groups.RESULTS Checking the operation cavity after increasing blood pressure before the end of tonsillectomy can reduce the incidence of postoperative primary hemorrhage (P<0.05),but cannot reduce the incidence of postoperative secondary hemorrhage (P>0.05).CONCLUSION Increasing blood pressure before the end of tonsillectomy can effectively reduce the incidence of postoperative primary hemorrhage.
9.Analysis of clinical diagnosis and treatment of 112 cases of parapharyngeal space tumors.
Yuming HONG ; Juanjuan HU ; Zhenyuan LIANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2015;29(11):994-997
OBJECTIVE:
To explore the diagnosis, treatment and surgical approaches of parapharyngeal space tumors.
METHOD:
This retrospective study consisted of 112 patients with parapharyngeal space tumors underwent surgeries. The data included clinical symptoms and signs, pathological types, imaging examinations, surgical approaches and postoperative complications.
RESULT:
Computerized tomography (CT), magnetic resonance imaging (MRD and digital subtraction angiography (DSA) made clear the tumor size, localization and its relation to adjacent structures. The postoperative histopathology varied and showed benign in 98 cases consisting of salivary gland tumors (52 cases), neurogenic tumors(33 cases) and other types (13 cases). During the 3 years follow-up period, local recurrence appeared in 3 patients with salivary pleomorphic adenoma and 1 patient with neurofibromatosis. These recurrent tumor cases were cured with second surgery. In 14 patients with malignant tumors reported, 8 cases survived for 5 years, 2 cases (1 adenoid cystic carcinoma and 1 carcinoma in pleornorphic adenoma) recurred in the two and a half years cured with second surgery affiliated radiation therapy through 3 years follow-up time and the rest were followed up 1 to 3 years without recurrence. Peripheral facial paralysis was observed in 25 patients, and 3 patients experienced hypoglossal nerve palsy. Only 1 patient encountered vagus nerve injury, and 2 patients appeared Horner's syndrome, and 4 patients endured Frey syndrome. Gills leakage was discovered in 3 cases and cavity infection was noted in 1 patient.
CONCLUSION
CT, MRI and DSA were important in the diagnosis and differential diagnosis of parapharyngeal space tumors. The key to successful treatment is knowing the anatomy of the parapharyngeal space, preoperative assessment and appropriate surgical approach.
Adenoma, Pleomorphic
;
complications
;
Carcinoma, Adenoid Cystic
;
complications
;
Diagnosis, Differential
;
Facial Paralysis
;
complications
;
Horner Syndrome
;
complications
;
Humans
;
Magnetic Resonance Imaging
;
Neoplasm Recurrence, Local
;
Pharyngeal Neoplasms
;
diagnosis
;
therapy
;
Pharynx
;
pathology
;
Postoperative Complications
;
Postoperative Period
;
Retrospective Studies
;
Salivary Gland Neoplasms
;
complications
;
Tomography, X-Ray Computed
10.The application of decompression in the treatment of gnathous cystic lesions.
Yuming HONG ; Zhihui XU ; Wenyuan WU ; Zhenyuan LIANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2013;27(16):908-910
OBJECTIVE:
To explore the application of decompression in the treatment of ganthous cystic lesions.
METHOD:
Decompression surgery were performed on 32 patients with gnathous cystic lesions, the cavities of cysts were open and the cysts pressure was relieved. The cavities of cysts were flushed after the operation and the prognosis were assessed in the regular follow-up.
RESULT:
All cysts cavities were shrinks afer decompression operation. Through the X-line and/or CT scans, we could observe that the new bones formed around cysts cavities, tilt shift teeth were gradually corrected and the permanent tooth germs of pediatric patients almost returned to the right places and erupted; There were the only remaining small bone indentations in the 18 cases, which do not need the Phase II surgery. Eight cases of cysts cavities shrinks more than 50%, which needed cystectomy. Six cases of cysts cavities shrinks less than 50%, which were still in the follow-up treatment.
CONCLUSION
The decompression surgery is a simple, economical and effective method for the treatment of gnathous cystic lesions.
Adolescent
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Adult
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Bone Diseases
;
surgery
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Child
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Cysts
;
surgery
;
Decompression, Surgical
;
methods
;
Female
;
Humans
;
Jaw
;
Male
;
Young Adult

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