1.Tabersonine alleviates wear particle-induced inflammatory osteolysis by inhibiting osteoclast activation
Wei ZHANG ; Lei YU ; Peng YANG ; Dechun GENG
Chinese Journal of Tissue Engineering Research 2024;28(10):1519-1525
BACKGROUND:Tabersonine has shown good therapeutic effects in diseases such as myocardial remodeling,acute kidney injury and lung injury due to its anti-inflammatory biological activity.Prosthetic wear particles often lead to aseptic inflammation,and the massive release of inflammatory factors further promotes periprosthetic bone destruction and bone loss;however,there are no basic studies on the efficacy of tabersonine on periprosthetic osteolysis. OBJECTIVE:To investigate the effects of tabersonine on osteoclast activation,expression of inflammatory factors and inflammatory osteolysis induced by wear particles. METHODS:(1)Cell experiment:RAW264.7 cells were divided into four groups for culture.A complete medium was added in the control group.Osteoclast induction medium(50 ng/mL RANKL+complete medium)was added to the osteoclast induction group.1 and 5 μmol/L tabersonine was added for 4 hours,and then osteoclast induction medium was added to the low-and high-dose tabersonine groups,respectively.After 5 days of induction,tartrate-resistant acid phosphatase staining,F-actin staining and RT-PCR were performed.(2)Animal experiments:Twenty C57BL/6J mice were randomly divided into sham operation group,osteolysis group,low-dose tabersonine group and high-dose tabersonine group(n=5 per group).Skull osteolysis model of the skull was established by injecting titanium pellets on the skull surface in the osteolysis group,low-dose tabersonine group and high-dose tabersonine group.On day 2 after model establishment,mice in the low-dose and high-dose tabersonine groups received intraperitoneal injections of 10 and 20 mg/kg tabersonine every 2 days,respectively.2 weeks after surgery,mouse sera were collected for detecting inflammatory factors(interleukin 1β,interleukin 6,and tumor necrosis factor α),and cranial bones were collected for micro-CT scan and bone parameter analysis. RESULTS AND CONCLUSION:(1)Cellular experiments:Tartrate-resistant acid phosphatase staining and F-actin staining showed that compared with the osteoclast induction group,low-dose and high-dose tabersonine significantly inhibited osteoclast activation and bone resorption,and the inhibition was more significant in the high-dose tabersonine group.RT-PCR results showed that compared with the control group,the mRNA expressions of three kinds of inflammatory factors were increased in the osteoclast induction group(P<0.01).Compared with the osteoclast induction group,the mRNA expressions of three kinds of inflammatory factors were decreased in low-and high-dose tabersonine groups(P<0.01),and the decrease was more obvious in the high-dose tabersonine group.(2)Animal experiments:Compared with the sham operation group,the levels of three kinds of inflammatory factors were increased in the osteolysis group(P<0.01).Compared with the osteolysis group,the levels of three kinds of inflammatory factors were decreased in the low-and high-dose tabersonine groups(P<0.05,P<0.01),and the decrease was more obvious in the high-dose tabersonine group.The micro-CT scan results revealed that titanium particles caused the destruction of cranial osteolysis,and tabersonine could inhibit the osteolysis induced by titanium particles,especially in the high-dose tabersonine group.(3)The results confirm that tabersonine can enhance the osteolysis and bone destruction induced by titanium particles by inhibiting the release of inflammatory factors and down-regulating the bone absorption function of osteoclasts.
2.Ferroptosis in bone diseases:therapeutic targets of osteoporosis
Heng XIE ; Ye GU ; Yingchu GU ; Zerui WU ; Tao FANG ; Qiufei WANG ; Yuqin PENG ; Dechun GENG ; Yaozeng XU
Chinese Journal of Tissue Engineering Research 2024;28(16):2613-2618
BACKGROUND:With the aging of the global population,the incidence rate of osteoporosis is also increasing.It is very important to further understand its pathogenesis and propose new therapeutic targets.Recent studies have shown that ferroptosis is closely related to the pathogenesis of some bone diseases,such as inflammatory arthritis,osteoporosis and osteoarthritis. OBJECTIVE:To summarize the previous studies on the mechanism of ferroptosis in osteoporosis,so as to provide new therapeutic ideas and potential therapeutic targets for osteoporosis. METHODS:The first author used the computer to search the documents published from 2000 to 2022 in CNKI,WanFang,VIP,PubMed and Web of Science with the key words of"ferroptosis,osteoporosis,osteoblasts,osteoclasts,iron chelators,reactive oxygen species,nuclear factor erythroid 2-related factor 2,heme oxygenase-1,glutathione peroxidase 4,review"in Chinese and English.A total of 70 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:Ferroptosis is significantly different from necrosis,apoptosis and autophagy.In terms of cell morphology and function,it does not have the morphological characteristics of typical necrosis,nor does it have the characteristics of traditional apoptosis,such as cell contraction,chromatin condensation,the formation of apoptotic bodies and the disintegration of cytoskeleton.Contrary to autophagy,ferroptosis does not form a classical closed bilayer membrane structure(autophagic vacuole).Morphologically,ferroptosis is mainly manifested by obvious contraction of mitochondria,increased membrane density,and reduction or disappearance of mitochondrial cristae,which are different from other cell death modes.Iron overload can destroy bone homeostasis by significantly inhibiting osteogenic differentiation and stimulating osteoclast formation,leading to osteoporosis.Iron overload interferes with the differentiation of stem cells to osteoblasts,leading to a weakened osteoblast function and further imbalance of bone metabolism in the body,which eventually leads to osteoporosis.Stimulated by iron overload,osteoclast bone resorption is enhanced and bone loss exceeds new bone formation.Iron chelators have been proved to have osteoprotective effects by inhibiting osteoclast activity and stimulating osteogenic differentiation of osteoblasts.Its potential mechanism is related to inhibiting osteoclast differentiation and promoting osteoblast differentiation.Antioxidants can prevent reactive oxygen species production and inhibit bone absorption,thus improving bone metabolism and effectively preventing osteoporosis.
3.Novel programmed cell death in periprosthetic osteolysis
Xiaolong LIANG ; Kai ZHENG ; Dechun GENG ; Yaozeng XU
Chinese Journal of Tissue Engineering Research 2024;28(21):3393-3399
BACKGROUND:In addition to apoptosis,recent studies have discovered novel forms of programmed cell death in periprosthetic osteolysis,which is involved in regulating local chronic inflammation and the outcome of osteoblast and osteoclast under pathological conditions.This has an important value for the treatment and prognosis of periprosthetic osteolysis. OBJECTIVE:To provide new ideas and strategies for the prevention and treatment of periprosthetic osteolysis by summarizing studies on the novel forms of programmed cell death. METHODS:The first author used the computer to search the articles published from 2005 to 2022.Chinese search terms"wear particles,periprosthetic osteolysis,programmed cell death,apoptosis,autophagy,pyroptosis,necrotizing apoptosis,iron death"were used to search the databases of CNKI,WanFang and VIP.English search terms"osteolysis,wear debris,wear particles,peri*prosthetic osteolysis,PPOL,aseptic loosening,autophagy,regulated cell death,programmed cell death,apoptosis,pyroptosis,autophagic cell death,autophagy,necroptosis,ferroptosis"were used for search in PubMed and Web of Science databases.A total of 68 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:(1)Inadequate or excessive activation of autophagy can cause cell death,inhibit bone formation,and promote bone resorption,leading to bone metabolism disorders and osteolysis.(2)Recent studies have paid close attention to pyroptosis in periprosthetic osteolysis,where the Nod-like receptor,pyrin containing 3 inflammasome plays an important role in local inflammation.Inhibiting pyroptosis can effectively alleviate osteolysis.(3)In vitro studies have shown that necroptosis can inhibit the formation and function of osteoblasts and osteoclasts,affecting the process of osteolysis and destruction.(4)Ferroptosis is the newest form of programmed cell death,which is regulated by complex signaling pathways and mechanisms,but is not yet fully understood.(5)Autophagy,pyroptosis,necroptosis,and ferroptosis play important roles in the development of periprosthetic osteolysis,and their associated signaling pathways and genes require further investigation.
4.Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis
CHU MIAO ; CHEN GUANGDONG ; CHEN KAI ; ZHU PENGFEI ; WANG ZHEN ; QIAN ZHONGLAI ; TAO HUAQIANG ; XU YAOZENG ; GENG DECHUN
Journal of Zhejiang University. Science. B 2024;25(6):513-528,中插3-中插9
Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.
5.MicroRNA-145-5p Regulates the Epithelial-Mesenchymal Transition in Nasal Polyps by Targeting Smad3
Mengyu ZHANG ; Xiaole PENG ; Xiaolong LIANG ; Wentao WANG ; Yuqing YANG ; Fan XU ; Xiaomin LU ; Dechun GENG ; Manyi LI
Clinical and Experimental Otorhinolaryngology 2024;17(2):122-136
Objectives:
. The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear.
Methods:
. The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays.
Results:
. miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression.
Conclusion
. Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.
6.Surgical technique of lateral unicompartmental knee arthroplasty and discussion of the maximum correction value in the treatment of knee valgus deformity.
Xin LIU ; Kai ZHENG ; Feng ZHU ; Yijun WANG ; Lianfang ZHANG ; Weicheng ZHANG ; Dechun GENG ; Jun ZHOU ; Yaozeng XU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(10):1238-1245
OBJECTIVE:
To investigate the surgical technique and the short-term effectivenss of lateral unicompartmental knee arthroplasty (LUKA) through lateral approach in the treatment of valgus knee and to calculate the maximum value of the theoretical correction of knee valgus deformity.
METHODS:
A retrospective analysis was performed on 16 patients (20 knees) who underwent LUKA and met the selection criteria between April 2021 and July 2022. There were 2 males and 14 females, aged 57-85 years (mean, 71.5 years). The disease duration ranged from 1 to 18 years, with an average of 11.9 years. Knee valgus was staged according to Ranawat classification, there were 6 knees of type Ⅰ, 13 knees of type Ⅱ, and 1 knee of type Ⅲ. All patients were assigned the expected correction value of genu valgus deformity by preoperative planning, including the correction value of lateral approach, intra-articular correction value, and residual knee valgus deformity value. The actual postoperative corrected values of the above indicators were recorded and the theoretical maximum correctable knee valgus deformity values were extrapolated. The operation time, intraoperative blood loss, incision length, hospital stay, hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibia angle (mMPTA), joint line convergence angle (JLCA), posterior tibial slope (PTS), range of motion (ROM), Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were also recorded for effectiveness evaluation.
RESULTS:
The patients' incision length averaged 13.83 cm, operation time averaged 85.8 minutes, intraoperative blood loss averaged 74.9 mL, and hospital stay averaged 6.7 days. None of the patients suffered any significant intraoperative neurological or vascular injuries. All patients were followed up 10-27 months, with a mean of 17.9 months. One patient with bilateral knee valgus deformities had intra-articular infection in the left knee at 1 month after operation and the remaining patients had no complication such as prosthesis loosening, dislocation, and infection. The ROM, HSS score, and WOMAC score of knee joint significantly improved at each time point after operation when compared to those before operation, and the indicators further improved with time after operation, the differences were all significant ( P<0.05). Imaging measurement showed that HKA, mLDFA, JLCA, and PTS significantly improved at 3 days after operation ( P<0.05) except for mMPTA ( P>0.05). Postoperative evaluation of the knee valgus deformity correction values showed that the actual intra-articular correction values ranged from 0.54° to 10.97°, with a mean of 3.84°. The postoperative residual knee valgus deformity values ranged from 0.42° to 5.30°, with a mean of 3.59°. The actual correction values of lateral approach ranged from 0.21° to 12.73°, with a mean of 4.26°.
CONCLUSION
LUKA through lateral approach for knee valgus deformity can achieve good early effectiveness. Preoperative planning can help surgeons rationally allocate the correction value of knee valgus deformity, provide corresponding treatment strategies, and the maximum theoretical correction value of knee valgus deformity can reach 25°.
Male
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Female
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Humans
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Arthroplasty, Replacement, Knee/methods*
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Retrospective Studies
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Blood Loss, Surgical
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Osteoarthritis, Knee/surgery*
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Knee Joint/surgery*
7.Clinical effects and prognostic analysis of radical surgery for primary gallbladder cancer
Chen CHEN ; Dong ZHANG ; Lin WANG ; Zuoren WANG ; Lei SHI ; Jie TAO ; Jigang BAI ; Rui ZHANG ; Qi LI ; Wenzhi LI ; Dechun LIU ; Qingguang LIU ; Zhimin GENG
Chinese Journal of Digestive Surgery 2019;18(2):128-134
Objective To investigate the clinical effects and prognostic factors of radical surgery for primary gallbladder cancer (GBC).Methods The retrospective case-control study was conducted.The clinicopathological data of 305 patients with primary GBC who underwent radical Ro resection in the First Affiliated Hospital of Xi'an Jiaotong University from 2013 to 2017 were collected,including 108 males and 197 females,aged from 30 to 88 years,with a median age of 62 years.According to the different tumor staging,patients underwent corresponding operation and adjuvant treatment based on the postoperative indication of chemotherapy.Observation indicators:(1) results of imaging and laboratory examinations;(2) treatment situations:① surgical situations,② postoperative adjuvant treatment;(3) results of postoperative pathological examination;(4) followup;(5) prognostic factors analysis.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 5,2018,and death was used as the end point.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Count data were represented as percentage.The survival curve and survival rate were respectively drawn and calculated using the Kaplan-Meier method.The univariate analysis and multivariate analysis were respectively done using the Log-rank test and COX regression model.Results (1) Results of imaging and laboratory examinations:results of imaging examination showed that diagnostic rates of ultrasound,CT and MRI examination were respectively 84.06% (174/207),85.71% (168/196) and 63.11% (65/103).Results of laboratory examination showed that the positive rates of CA19-9,CA125 and carcinoembryonic antigen (CEA) were respectively 55.34% (145/262),48.06% (124/258) and 46.15% (126/273).(2) Treatment situations:① surgical situations:305 patients underwent radical R0 resection for primary GBC,including 145 undergoing liver wedge resection + D2 lymph node dissection,61 undergoing liver wedge resection + D1 lymph node dissection,55 undergoing liver Ⅳ B and Ⅴ segmentectomy + D2 lymph node dissection,11 undergoing liver Ⅳ B and Ⅴ segrnentectomy + D1 lymph node dissection,9 undergoing right hepatectomy + D2 lymph node dissection,5 undergoing liver wedge resection + D2 lymph node dissection + partial colectomy,4 undergoing pancreaticoduodenectomy,3 undergoing simple cholecystectomy in Tis stage,3 undergoing right hepatectomy + D1 lymph node dissection,2 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial colectomy,1 undergoing liver Ⅳ B and Ⅴ segmentectomy + resection and reconstruction of portal vein + D2 lymph node dissection,1 undergoing liver ⅣB and Ⅴ segmentectomy + D2 lymph node dissection + partial resection of the stomach or duodenum,1 undergoing pancreaticoduodenectomy + resection and reconstruction of portal vein,1 undergoing right hepatectomy + pancreaticoduodenectomy,1 undergoing right hepatic lobectomy + partial gastrectomy + D2 lymph node dissection,1 undergoing right hepatic lobectomy + D1 lymph node dissection and 1 undergoing right hepatic trilobectomy + D2 lymph node dissection.Of 94 patients with unsuspected GBC,78 who were diagnosed in the other hospitals received salvage surgery in the authors' center.Twenty-one patients had postoperative surgery-related complications,including 11 with bile leakage,8 with pulmonary infection and 2 with abdominal bleeding.Two patients died in the perioperative period.② Postoperative adjuvant treatment:26 patients underwent postoperative adjuvant chemotherapy.Chemotherapy regimen:gemcitabine + oxaliplatin were used in 12 patients,gemcitabine + tegafur in 7 patients,gemcitabine + cisplatin in 6 patients,oxaliplatin + tegafur in 1 patient.(3) Results of postoperative pathological examination.The postoperative pathological type of 305 patients:257,23,6,5,4,3,3,2,1 and 1 patients were respectively confirmed as pure adenocarcinoma,adenocarcinoma combined with squamous cell carcinoma,adenocarcinoma combined with neuroendocrine carcinoma,mucinous adenocarcinoma,neuroendocrine carcinoma,adenocarcinoma combined with mucinous carcinoma,squamous cell carcinoma,sarcomatoid carcinoma,adenocarcinoma combined with sarcomatoid carcinoma,adenocarcinoma combined with signet-ring cell carcinoma.Degree of tumor differentiation:highdifferentiated,moderate-differentiated and low-differentiated tumors were detected in 37,130 and 121 patients,respectively,17 with unknown differentiated degree.Of 305 patients,16 and 32 patients had respectively vascular invasion and nerve invasion.The number of lymph node dissected of 305 patients was 8±5,with positive lymph node of 0 (range,0-9),including 121 with lymphatic metastasis (26 with jumping lymphatic metastasis).TNM staging of 305 patients:stage 0,Ⅰ,Ⅱ,ⅢA,ⅢB,ⅣA and ⅣB were detected in 7,18,13,137,57,11 and 62 patients,respectively.(4) Follow-up:245 of 305 patients were followed up for 18.0 months (range,6.0-70.0 months).The survival time,1-and 3-year survival rates were respectively 29.5 months (range,0.5-69.9 months),71.6% and 45.8%.One hundred and twenty-two patients died during the follow-up.(5) Prognostic factors analysis:the results of univariate analysis showed that preoperative level of bilirubin,pathological type,degree of tumor differentiation,liver invasion,vascular invasion,nerve invasion,T staging,N staging and postoperative chemotherapy were factors affecting prognosis of patients with primary GBC (x2 =10.26,3.96,45.89,34.64,12.75,27.05,35.09,39.44,4.40,P<0.05).The results of multivariate analysis showed that low-differentiated tumor,liver invasion and N2 staging were independent risk factors affecting prognosis of patients with primary GBC [odds ratio (OR)=1.90,1.71,1.46,95% confidence interval (CI):1.34-2.70,1.15-2.52,1.17-1.82,P<0.05],and postoperative chemotherapy was a protective factor affecting prognosis of patients with primary GBC (OR=0.35,95% CI:0.15-0.82,P<0.05).Conclusions For patients with primary GBC undergoing radical resection,D2 lymph node dissection should be performed routinely.The low-differentiated tumor,liver invasion and N2 staging are independent risk factors affecting prognosis of patients,and postoperative chemotherapy is a protective factor.
8.Application value of the different lymph node staging system predicting prognosis of advanced gallbladder carcinoma
Chen CHEN ; Dechun LIU ; Zhen ZHANG ; Qianglao MENG ; Huiqiang CAI ; Rui ZHANG ; Dong ZHANG ; Lin WANG ; Zhimin GENG
Chinese Journal of Digestive Surgery 2018;17(3):244-251
Objective To investigate the application value of the anatomical location of positive nodes (N staging) from TNM staging systems published by American Joint Committee on Cancer (AJCC) (7th edition),number of metastatic lymph nodes (NMLN),lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS) as prognostic predictors in advanced gallbladder carcinoma(GBC).Methods The retrospective crosssectional study was conducted.The clinicopathological data of 176 patients who underwent radical resection of advanced GBC in the First Affiliated Hospital of Xi'an Jiaotong University between January 2008 and December 2014 were collected.According to preoperative assessment,intraoperative exploration and frozen section biopsy,staging and surgical procedure were confirmed.Observation indicators and evaluation criteria:(1) surgical and postoperative situations;(2) follow-up and survival situations;(3) N staging related indicators based on TNM staging systems of AJCC (7th edition):LNR =NMLN / total number of lymph node dissection,LODDS =Log (NMLN+0.5) / (total number of lymph node dissection-NMLN+0.5);(4) lymph node staging based on NMLN,LNR and LODDS:LODDS <-1.0 as LODDS 1 staging,-1.0 ≤ LODDS < 0 as LODDS 2 staging,LODDS ≥0 as LODDS 3 staging;(5) prognostic comparisons of patients with different lymph node staging;(6) accuracy of 4 different types of lymph node staging predicting the prognosis of patients.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 31,2017.Measurement data with normal distribution were represented as x-±s.Measurement data with skewed distribution were described as M (range),and comparisons were done using the nonparametric test.The survival rate was calculated by the Kaplan-Meier method,and the Log-rank test was used for survival comparison.Correlation analysis was done using the Spearman correlation analysis,r ≥ 0.800 as a high correlation,0.500 ≤ r < 0.800 as a moderate correlation and 0.300 ≤ r < 0.500 as a low correlation.The receiver operating characteristic (ROC) curve and area under the curve (AUC) were respectively drawn and calculated based on 4 kinds of binary logistic regression model.Akaike information criterion (AIC) and Harrell concordance index (Harrell c-index) were respectively calculated based on 4 kinds of COX proportional hazard regression model.The larger values of AUC and Harrell c-index caused a smaller value of AIC,but a lymph node staging standard correlated with greater prognostic accuracy.Harrell c-index < 0.50 was no prediction,and 0.50 ≤ Harrell c-index ≤ 1.00 was an obvious prediction.Results (1) Surgical and postoperative situations:176 patients underwent successful radical resection of GBC,including 161 in R0 resection and 15 in R1 resection,99 with D1 lymph node dissection and 77 with D2 lymph node dissection.Of 176 patients,9 with postoperative complications were improved by symptomatic treatment,including 6 with bile leakage,2 with hepatic dysfunction and 1 with intra-abdominal hemorrhage.Results of postoperative pathological examination:total number of lymph node dissection,NMLN and LNR were respectively 6.7±4.4,0 (range,0-12.0) and 0 (range,0-1.00);high-differentiated,moderate-differentiated and low-differentiated tumors were respectively detected in 16,81 and 79 patients;162 and 14 patients were in T3 and T4 stages;60 patients were combined with infiltration of the liver.(2) Follow-up and survival situations:176 patients were followed up for l-118 months,with a median time of 33 months.The 1-,3-and 5-year overall survival rates were respectively 63.1%,42.0% and 32.0%.(3) N staging related indicators based on TNM staging systems ofAJCC (7th edition):95,45 and 36 patients were respectively detected in staging N0,N1 and N2.NMLN,LNR and LODDS were respectively 2.0 (range,1.0-7.0),0.40 (range,0.08-1.00),-0.15 (range,-0.99-1.04) in staging N1 and 4.0 (range,1.0-12.0),0.57 (range,0.13-1.00),0.11 (range,-0.70-1.04) in staging N2,with a statistically significant difference in NMLN (Z=-3.888,P<0.05) and with no statistically significant difference in LNR and LODDS (Z=-1.492,-1.689,P>0.05).(4) Lymph node staging based on NMLN,LNR and LODDS:NMLN and LNR as a cut-off point were respectively 4.0 and 0.70,NMLN 1 staging (NMLN=0) was detected in 95 patients,NMLN 2 staging (1.0 ≤ NMLN ≤ 4.0) in 61 patients and NMLN 3 staging (NMLN>4.0) in 20 patients;LNR 1 staging (LNR=0) was detected in 95 patients,LNR 2 staging (0 < LNR ≤ 0.70) in 58 patients and LNR 3 staging (LNR>0.70) in 23 patients.LODDS 1,2 and 3 stagings was detected in 61,70 and 45 patients,respectively.The lymph node staging based on NMLN and LNR was significantly correlated with based on N staging of TNM staging systems of AJCC (7th edition) (r =0.949,0.922,P<0.05);the lymph node staging based on LODDS was moderately correlated with based on N staging of TNM staging systems of AJCC (7th edition) (r =0.758,P< 0.05).(5) Prognostic comparisons of patients with different lymph node staging:1-,3-and 5-year overall survival rates were respectively 86.3%,65.3%,52.2% in N0 staging patients and 44.4%,22.2%,13.3% in N1 staging patients and 25.0%,5.6%,2.8% in N2 staging patients,with a statistically significant difference (x2=88.895,P<0.05).The 1-,3-and 5-year overall survival rates were respectively 86.3%,65.3%,52.2% in NMLN 1 staging patients and 47.5%,19.7%,11.1% in NMLN 2 staging patients and 0,0,0 in NMLN 3 staging patients,with a statistically significant difference (x2=121.086,P<0.05).The 1-,3-and 5-year overall survival rates were respectively 86.3%,65.3%,52.2% in LNR 1 staging patients and 41.4%,17.2%,11.8% in LNR 2 staging patients and 17.4%,8.7%,0 in LNR 3 staging patients,with a statistically significant difference (x2 =86.503,P< 0.05).The 1-,3-and 5-year overall survival rates were respectively 85.2%,65.5%,51.8% in LODDS 1 staging patients and 65.7%,40.0%,31.3% in LODDS 2 staging patients and 28.9%,13.3%,5.9% in LODDS 3 staging patients,with a statistically significant difference (x2=59.195,P<0.05).(6) Accuracy of 4 different types of lymph node staging predicting the prognosis of patients:according to N staging of TNM staging systems of AJCC (7th edition),NMLN,LNR and LODDS,AUC,AIC and Harrell c-index of lymph node staging were respectively 0.878,0.881,0.870,0.864 and 1 047.5,1 026.4,1 044.2,1 063.6 and 0.77,0.78,0.77,0.76.AIC value was smaller with increased values of AUC and Harrell c-index based on NMLN,showing a greatest accuracy predicting the prognosis of patients.Conclusion Among N staging of TNM staging system of AJCC (7 edition),NMLN,LNR and LODDS as prognostic predictors,NMLN can more precisely predict radical resection of advanced GBC.
9.Multiple linear regression analysis of hip function and vitamin D levels before and after hip arthroplasty
Wei ZHANG ; Zaixiang TANG ; Dechun GENG ; Feng ZHU ; Hanqing DONG ; Yijun WANG ; Yaozeng XU
Chinese Journal of Tissue Engineering Research 2016;20(44):6557-6563
BACKGROUND:The incidence of low serum level of vitamin D in patients undergoing hip arthroplasty and its impact has not been reported in China, indicating that it has not been brought to the forefront. OBJECTIVE:To determine the prevalence of low serum level of vitamin D in patients before total hip arthroplasty and its relationship with the hip function scores. METHODS:Forty-eight hips from 48 patients undergoing primary hip arthroplasty from July 2013 to August 2014 in the First Affiliated Hospital of Suzhou University were enrol ed. According to the serum level of vitamin D, patients were assigned to low-level (<20μg/L) and high-level (20≥μg/L) groups. The general information of patients, the hip function scores before and after replacement at the last fol ow-up in the two groups were observed and compared. The relationship between the serum level of vitamin D and the hip function scores before and after replacement was analyzed by multiple linear regression analysis. And the average fol ow-up was 12 months (11-14 months). RESULTS AND CONCLUSION:(1) The incidence of low vitamin D level was 82%(20 ng/mL serving as standard). (2) Compared with patients with high vitamin D level, patients with low level of vitamin D had lower preoperative Harris scores and Merle D′Aubigne-Postel score (P<0.05), and also at the last fol ow-up (P<0.05. (3) Based on the preoperative and postoperative Harris, the multiple linear regression analysis showed that there was a positive correlation between the level of vitamin D and Harris score both preoperatively and postoperatively (P<0.05). (4) These results suggest that there is a higher incidence of low level of vitamin D in patients undergoing arthroplasty, and hip function scores before and after replacement in patients with low level of vitamin D are lower than the high level patients. Moreover, there is a positive correlation between the level of vitamin D and the hip joint function scores. Therefore, it is advisable to supplement vitamin D and calcium preoperatively, and the level of vitamin D wil be helpful for disease assessment and prognosis.
10.Intervention of inflammatory cell infiltration and cartilage destruction of the knee joints in mouse models of collagen-induced arthritis by small molecule tyrosine kinase inhibitors
Wei LIU ; Yong ZHANG ; Dechun GENG ; Lixin HUANG ; Jian LI
Chinese Journal of Tissue Engineering Research 2015;(24):3783-3787
BACKGROUND:At present, spleen tyrosine kinase is the new target of studying and treating rheumatoid arthritis. OBJECTIVE:To study the influence of smal molecule tyrosine kinase inhibitor HL131078 on the inflammatory cel infiltration and cartilage destruction of the knee joint of mice with col agen-induced arthritis. METHODS:Forty DBA/1 mice were randomly and evenly divided into blank, model, positive and experimental groups. Col agen type II (CII) solution and Freund’s complete adjuvant (including mycobacterium tuberculosis) were injected into the mice of the latter three groups through the tail to establish mouse models of col agen-induced arthritis. At 2 weeks after the the first immunization with CII, the mice in the positive group were intragastrical y given R406 (10 mg/kg), once a day, for 28 consecutive days. The mice in the experimental group were intragastrical y given HL131078 (10 mg/kg), once per day, for 28 consecutive days. RESULTS AND CONCLUSION:Compared with the model group, the mean arthritis indexes of mice in the experimental and positive groups started to decline at 29 and 26 days. In the experimental group, the cartilage destruction of mouse knee joint was obviously reduced and the inflammatory cel infiltration in the knee joints was obviously reduced, which was close to that in the positive group. The results demonstrate that the smal molecule tyrosine kinase inhibitor HL131078 can effectively reduce inflammatory cel infiltration and cartilage destruction in the knee joints of mice with col agen-induced arthritis.

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