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Ferroptosis is a novel iron-dependent mode of programmed cell death characterized by iron deposition and accumulation of lipid peroxidation. More and more studies have found that ferroptosis is closely related to the pathogenesis of type 2 diabetes mellitus （T2DM）. The yin-fire theory is an important part of LI Gao's spleen-stomach theory， and it is believed that qi-fire imblance and yin-fire internal generation is the main pathogenesis of T2DM. Abnormal iron metabolism may be an important prerequisite for T2DM yin-fire internal generation， while oxidative stress is the specific manifestation of T2DM qi-fire imbalance. Reactive oxygen species （ROS） is the end product of qi-fire imbalance， and lipid peroxide is the pathological products of T2DM yin-fire internal generation. This study intends to explore the pathological mechanism of qi-fire imbalance and yin-fire internal generation from the perspectives of iron metabolism， oxidative stress and lipid peroxidation， enriching the modern connotation of yin-fire theory， and benefiting traditional Chinese medicine to target against ferroptosis， and prevent and treat T2DM precisely.
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ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance （IR） by inhibiting the advanced glycation end product （AGE）/receptor for the advanced glycation end product （RAGE） signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group， a model group， high-， medium-， and low-dose Yitangkang-medicated serum groups （40， 20， and 10 g·kg-1）， and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted，the cell viability and glucose consumption level of each group were determined. In addition，the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， p53， cysteinyl aspartate-specific protease-3 （Caspase-3）， and cysteinyl aspartate-specific protease-9 （Caspase-9）］ were determined using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group， a model group， high-，medium-，and low-dose Yitangkang groups （40， 20， and 10 g·kg-1）， and a western medicine group （pioglitazone hydrochloride，1.35 mg·kg-1）. The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin （STZ） in animals and verified by the hyperinsulinemic-euglycemic clamp （HEC） test. After the model was determined successfully， the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group，while Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2， Bax， p53， Caspase-3， and Caspase-9. Result① In vitro experiments. compared with the blank group， the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group （P<0.01）. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. The medium-dose Yitangkang showed a similar effect as RAGE inhibitor， and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.
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@#Ferroptosis is a novel iron-dependent mode of programmed cell death characterized by iron deposition and accumulation of lipid peroxidation. More and more studies have found that ferroptosis is closely related to the pathogenesis of type 2 diabetes mellitus （T2DM）. The yin-fire theory is an important part of LI Gao's spleen-stomach theory， and it is believed that qi-fire imblance and yin-fire internal generation is the main pathogenesis of T2DM. Abnormal iron metabolism may be an important prerequisite for T2DM yin-fire internal generation， while oxidative stress is the specific manifestation of T2DM qi-fire imbalance. Reactive oxygen species （ROS） is the end product of qi-fire imbalance， and lipid peroxide is the pathological products of T2DM yin-fire internal generation. This study intends to explore the pathological mechanism of qi-fire imbalance and yin-fire internal generation from the perspectives of iron metabolism， oxidative stress and lipid peroxidation， enriching the modern connotation of yin-fire theory， and benefiting traditional Chinese medicine to target against ferroptosis， and prevent and treat T2DM precisely.
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ObjectiveTo compare the therapeutic effects of oral Chinese medicines （including Chinese patent medicines） on coronary artery disease （CAD） by the Bayesian network Meta-analysis. MethodThe randomized controlled trials of treating CAD with oral Chinese medicines were retrieved from the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， PubMed， Web of Science， Embase， and Cochrane Library from the inception to December 1， 2022. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included articles. The direct meta-analysis was performed to compare the performance of oral Chinese medicines alone and in combination with Western medicine in the treatment of CAD in terms of intima-media thickness （IMT）， vascular endothelial function， plaque score， hypersensitive C-reactive protein （hs-CRP）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and total response rate. Furthermore， the Bayesian network Meta-analysis was performed to compare the therapeutic effects of different Chinese medicines. ResultA total of 41 articles were included. The direct meta-analysis results showed that Chinese medicines combined with Western medicine outperformed Western medicine alone in recovering all the indicators of CAD. The Bayesian network meta-analysis yielded the following results. In terms of the total response rate， modified Huangqi Guizhi Wuwutang and Sanqi Huayu pills had obvious advantages over other Chinese medicines. In terms of IMT and plaque score， Xiaoban Huazhuo decoction， Yiqi Tongluo formula， Ruangan Jiangzhi capsules， and Guanxin Shutong capsules had obvious advantages over other Chinese medicines. In terms of blood lipid indicators， Shenqi Roumai mixture， Ruangan Jiangzhi capsules， Xiaoban Huazhuo decoction， Qiwei Sanxiong decoction， and Sanqi Huayu pills were superior to other Chinese medicines. The Chinese medicines above mainly had the functions of activating blood， resolving stasis， resolving phlegm， and dredging vessels. ConclusionThe combination of oral Chinese medicines and Western medicine is effective in treating CAD. Clinicians can use the drugs targeting abnormal indicators according to the results of this Bayesian network meta-analysis combined with the actual situation of patients to achieve better therapeutic effects.
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Objective To study mechanical properties of the novel micro-movement elastic implant of distal tibiofibular syndesmosis in dorsiflexion position.Methods A combination of simulation and experiment was used. The normal ankle dorsiflexion model, the bone nail repaired model and the micro-movement elastic implant repaired model were established by using Mimics and CT data. Besides, ANSYS Workbench was used for finite element analysis. Mechanical experiments on lower limb specimens were conducted on Instron E10000 mechanical test instrument, and five sets of experimental data were measured and analyzed.Results Mechanical properties of the micro-movement elastic implant repaired model were closer to those of the normal ankle dorsiflexion model, but stress of the micro-movement elastic implant repaired mode was greater than that of the bone nail repaired model. The results of two-sample heteroscedasticity t test indicated that there was no significant difference in resistance torque between the micro-movement elastic implant repaired model and the normal ankle dorsiflexion model.Conclusions For dorsiflexion position, repairing mechanical properties of the novel micro-movement elastic implant are much better than those of the bone nail, and there is still room for optimizing the micro-movement elastic implant.
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Objective: To investigate the effectiveness of two surgical approaches in the treatment of type Ⅳ Pipkin fracture. Methods: The clinical data of 15 patients with type Ⅳ Pipkin fracture treated surgically between July 2013 and June 2018 were retrospectively analyzed. According to different surgical approaches, they were divided into group A (8 cases, using K-L posterior approach) and group B (7 cases, using greater trochanter osteotomy approach). There was no significant difference in gender, age, cause of injury, and interval from injury to operation between the two groups ( P>0.05). The incision length, operation time, intraoperative blood loss, hospital stay, fracture healing time, and complications of the two groups were recorded. Hip joint function recovery was evaluated according to Thompson-Epstein functional evaluation system. Results: All the 15 patients were followed up 1-5 years, with an average of 2.5 years. There was no significant difference in operation time between the two groups ( t=14.681, P=0.100); the incision length, intraoperative blood loss, and fracture healing time in group A were all greater than those in group B, and the hospital stay was shorter than that in group B, showing significant differences ( P<0.05). In group A, 1 patient presented hip pain, clasthenia, and limited mobility after operation, 1 patient presented ossifying myositis, 1 patient presented osteonecrosis of the femoral head, 1 patient presented fat liquefaction of incision, and 1 patient presented sciatica, with a complication incidence of 62.5%. Postoperative hip pain occurred in 1 patient and ossifying myositis in 2 patients in group B, with a complication incidence of 42.9%. There was no significant difference in the incidence of complications between the two groups ( χ2=-0.735, P=0.462). At last follow-up, according to Thompson-Epstein functional evaluation system, the results in group A were excellent in 3 cases, good in 2 cases, fair in 2 cases, and poor in 1 case, with an excellent and good rate of 62.5%; in group B, the results were excellent in 4 cases, good in 2 cases, and fair in 1 case, and the excellent and good rate was 85.7%. There was no significant difference in good and fair rate between the two groups ( χ2=-0.990, P=0.322). Conclusion: K-L posterior approach is more convenient in the fracture treatment during operation, but it has greater trauma, greater vascular damage, and more blood loss. The greater trochanter osteotomy approach can better protect the blood supply of femoral head, shorten the operation time, reduce intraoperative blood loss, and reduce postoperative complications. It is an ideal way in the surgical treatment of type Ⅳ Pipkin fracture.
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Objective@#To analyze the risk factors of implant-related complications in adult patients with adult degenerative scoliosis (ADS) who underwent long-level internal fixation.@*Methods@#This was a retrospective study that analyzed 99 cases of adult degeneration scoliosis patients who underwent long level posterior pedicle screw fixation in our hospital between June 2013 and January 2016. The internal fixation and related complications were evaluated by measuring and analyzing the radiographic data of the postoperative X-ray films. The timepoints of measurement were pre-operation, before discharge, half a year, 1 year, when complications occur and the final follow-up after operation. Implant-related complications included proximal junctional kyphosis (PJK), proximal junctional failure (PJF), distal junctional kyphosis/failure (DJK/DJF), rod breakage in addition to other radiographic implant-related complications (that were not related to PJF) such as screw loosening, breakage or pullout, or interbody graft and hook or set screw dislodgements seen on follow-up radiographs. The incidence of postoperative implant-related complications was counted. All the cases included in the study were divided into the complication group and the non-complication group. Statistical difference between groups at different follow-up time point was analyzed. Potential risk factors were identified using univariate testing. Multivariate Logistics regression was used to analyze the independent risk factors for implant-related complications. The postoperative functional scores were assessed using the Oswestry Disability Index (ODI), Japanese Orthopaedic Association Scores (JOA), Visual Analogue Scale (VAS), and Lumbar Stiffness Disability Index (LSDI). Functional scores were tested using group t tests. Patients were divided into groups according to PI-LL <10 °, 10°-20 ° and > 20 °. The preoperative and postoperative radiographical parameters and clinical function score among each groupwere compared.The best PI-LL matching value was verified by analyzing the effect of long-segment fusion orthopedics on ADS.@*Results@#Ninety-nine ADS patients who underwent long level posterior fixation were included. The incidence of patients with mechanical complications was 30.3%. Univariate analysis showed that chronic risk factors of postoperative implant-related complications after surgery of ASD included diabetes (OR=3.52, P=0.001) and blood transfusion (OR=2.61, P=0.030); surgical risk factor isosteotomy (OR=4.33, P=0.000); preoperative imaging risk factor was preoperative SVA (OR=1.03, P=0.000); the risk factors for increased risk of the implant-related complications included anemia (OR=1.17, P=0.810), cardiac complications (OR=1.80, P=0.290) and hospital stay (OR=1.11, P=0.110). Independent predictors identified on multivariate Logistics regression modeling included osteotomy (OR=3.05, P=0.032), and preoperative SVA (OR=1.03, P=0.007). The radiographical parameters and clinical function scores of the PI-LL 10°-20° group were better than or partially superior to those of the PI-LL<10° group and the PI-LL>20° group. The postoperative SVA of the PI-LL 10°-20° group was significantly lower than that of the PI-LL<10° group (t=2.399, P=0.020) and the PI-LL>20° group (t=-3.074, P=0.005). The incidence of implant-related complications in the PI-LL 10°-20° group was significantly lower than that in the PI-LL<10° group (t=1.584, P=0.003). Survival analysis showed that the PI-LL 10°-20° group was significantly better than the PI-LL<10° group (χ2=7.782, P=0.005), while the PI-LL 10°-20° group had better survival than PI-LL>20° group, althoughthatwas not statistically significant (χ2=2.542, P=0.111).@*Conclusion@#Risk factors of postoperative implant-related complications after surgery of ASD included osteotomy and preoperative SVA. Patients with one or more of these risk factors should be informed of the risk increase with informed consent. Patients with PI-LL between 10 ° and 20 ° had better postoperative radiographical parameters and clinical functional scores. They should be optimized preoperatively and followed up closely during the postoperative period.
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Objective To analyze the risk factors of implant?related complications in adult patients with adult degenera?tive scoliosis (ADS) who underwent long?level internal fixation. Methods This was a retrospective study that analyzed 99 cases of adult degeneration scoliosis patients who underwent long level posterior pedicle screw fixation in our hospital between June 2013 and January 2016. The internal fixation and related complications were evaluated by measuring and analyzing the radiograph?ic data of the postoperative X?ray films. The timepoints of measurement were pre?operation, before discharge, half a year, 1 year, when complications occur and the final follow?up after operation. Implant?related complications included proximal junctional ky?phosis (PJK), proximal junctional failure (PJF), distal junctional kyphosis/failure (DJK/DJF), rod breakage in addition to other ra?diographic implant?related complications (that were not related to PJF) such as screw loosening, breakage or pullout, or interbody graft and hook or set screw dislodgements seen on follow?up radiographs. The incidence of postoperative implant?related complica?tions was counted. All the cases included in the study were divided into the complication group and the non?complication group. Statistical difference between groups at different follow?up time point was analyzed. Potential risk factors were identified using uni?variate testing. Multivariate Logistics regression was used to analyze the independent risk factors for implant?related complica?tions. The postoperative functional scores were assessed using the Oswestry Disability Index (ODI), Japanese Orthopaedic Associa? tion Scores (JOA), Visual Analogue Scale (VAS), and Lumbar Stiffness Disability Index (LSDI). Functional scores were tested us?ing group t tests. Patients were divided into groups according to PI-LL<10°, 10°-20°and>20°. The preoperative and postoper?ative radiographical parameters and clinical function score among each groupwere compared.The best PI-LL matching value was verified by analyzing the effect of long?segment fusion orthopedics on ADS. Results Ninety?nine ADS patients who underwent long level posterior fixation were included. The incidence of patients with mechanical complications was 30.3%. Univariate analy?sis showed that chronic risk factors of postoperative implant?related complications after surgery of ASD included diabetes ( OR=3.52, P=0.001) and blood transfusion ( OR=2.61, P=0.030); surgical risk factor isosteotomy ( OR=4.33, P=0.000); preoperative im?aging risk factor was preoperative SVA ( OR=1.03, P=0.000); the risk factors for increased risk of the implant?related complications included anemia ( OR=1.17, P=0.810), cardiac complications ( OR=1.80, P=0.290) and hospital stay ( OR=1.11, P=0.110). Indepen?dent predictors identified on multivariate Logistics regression modeling included osteotomy ( OR=3.05,P=0.032), and preoperative SVA ( OR=1.03,P=0.007). The radiographical parameters and clinical function scores of the PI-LL 10°-20° group were better than or partially superior to those of the PI-LL<10°group and the PI-LL>20°group. The postoperative SVA of the PI-LL 10°-20°group was significantly lower than that of the PI-LL<10°group (t=2.399, P=0.020) and the PI-LL>20°group (t=-3.074, P=0.005). The incidence of implant?related complications in the PI-LL 10°-20°group was significantly lower than that in the PI-LL<10°group (t=1.584, P=0.003). Survival analysis showed that the PI-LL 10°-20°group was significantly better than the PI-LL<10°group (χ2=7.782, P=0.005), while the PI-LL 10°-20°group had better survival than PI-LL>20°group, althoughthatwas not statistically significant (χ2=2.542, P=0.111). Conclusion Risk factors of postoperative implant?related complications after sur?gery of ASD included osteotomy and preoperative SVA. Patients with one or more of these risk factors should be informed of the risk increase with informed consent. Patients with PI-LL between 10°and 20°had better postoperative radiographical parame?ters and clinical functional scores. They should be optimized preoperatively and followed up closely during the postoperative period.
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Objective To explore the expressions and significances of p 53、bcl-2、Ki-67 and apopto-sis in keratoacanthoma(KA)and well differentiated squamous cell carcinoma (WDSCC).Methods The expres-sions of p53、bcl-2、Ki-67 were detected by immunohistochemical technique in 44 cases of KA and 20 cases of WDSCC.Apoptosis was identified by using terminal deoxynucleotidyl transfers ( TdT) -mediated dUTP -biotin nick and labelling(TUNEL)method.Results The positive expressive rates of p53 in proliferative、mature and re-gressive of KA were 22.23%、26.18% and 6.52%, which was lower than the positive rate of WDSCC (41.82%).Significant differences were found between every period of KA with WDSCC in p 53 expression;The intensity of expression and pattern were similar in KA of Ki -67 and p53.There were a positive correlation be-tween p53 and Ki-67 expression rate(r=0.986,P<0.001).The bcl-2 staining showed weak expression in 1 case in WDSCC and 2 cases in KA ,but only a few positive tumor cells was limited to basal cell layer in KA .The average apoptosis rate in KA was 21.72%,which was apparently higher than in WDSCC (9.925%).There were a negative correlation between the apoptosis rate and proliferation rate of Ki -67(r=-0.824,P<0.001).Con-clusion The proliferation and apoptosis in KA can coexist .However ,the apoptosis will occupy a dominance posi-tion in regressive phase ,which results in the regression of tumor .The expressions of p53、Ki-67 and apoptosis would be a certain significance in differentiated KA and WDSCC .