Objective:To investigate the value of CT radiomic model based on analysis of primary gastric cancer and the adipose tissue outside the gastric wall beside cancer in differentiating stage T1-2 from stage T3-4 gastric cancer.Methods:This study was a case-control study. Totally 465 patients with gastric cancer treated in Affiliated People′s Hospital of Jiangsu University from December 2011 to December 2019 were retrospectively collected. According to postoperative pathology, they were divided into 2 groups, one with 150 cases of T1-2 tumors and another with 315 cases of T3-4 tumors. The cases were divided into a training set (326 cases) and a test set (139 cases) by stratified sampling method at 7∶3. There were 104 cases of T1-2 stage and 222 cases of T3-4 stage in the training set, 46 cases of T1-2 stage and 93 cases of T3-4 stage in the test set. The axial CT images in the venous phase during one week before surgery were selected to delineate the region of interest (ROI) at the primary lesion and the extramural gastric adipose tissue adjacent to the cancer areas. The radiomic features of the ROIs were extracted by Pyradiomics software. The least absolute shrinkage and selection operator was used to screen features related to T stage to establish the radiomic models of primary gastric cancer and the adipose tissue outside the gastric wall beside cancer. Independent sample t test or χ2 test were used to compare the differences in clinical features between T1-2 and T3-4 patients in the training set, and the features with statistical significance were combined to establish a clinical model. Two radiomic signatures and clinical features were combined to construct a clinical-radiomics model and generate a nomogram. The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of each model in differentiating stage T1-2 from stage T3-4 gastric cancer. The calibration curve was used to evaluate the consistency between the T stage predicted by the nomogram and the actual T stage of gastric cancer. And the decision curve analysis was used to evaluate the clinical net benefit of treatment guided by the nomogram and by the clinical model. Results:There were significant differences in CT-T stage and CT-N stage between T1-2 and T3-4 patients in the training set ( χ2=10.59, 15.92, P=0.014, 0.001) and the clinical model was established. After screening and dimensionality reduction, the 5 features from primary gastric cancer and the 6 features from the adipose tissue outside the gastric wall beside cancer established the radiomic models respectively. In the training set and the test set, the AUC values of the primary gastric cancer radiomic model were 0.864 (95% CI 0.820-0.908) and 0.836 (95% CI 0.762-0.910), and the adipose tissue outside the gastric wall beside cancer radiomic model were 0.782 (95% CI 0.731-0.833) and 0.784 (95% CI 0.702-0.866). The AUC values of the clinical model were 0.761 (95% CI 0.705-0.817) and 0.758 (95% CI 0.671-0.845), and the nomogram were 0.876 (95% CI 0.835-0.917) and 0.851 (95% CI 0.781-0.921). The calibration curve reflected that there was a high consistency between the T stage predicted by the nomogram and the actual T stage in the training set ( χ2=1.70, P=0.989). And the decision curve showed that at the risk threshold 0.01-0.74, a higher clinical net benefit could be obtained by using a nomogram to guide treatment. Conclusions:The CT radiomics features of primary gastric cancer lesions and the adipose tissue outside the gastric wall beside cancer can effectively distinguish T1-2 from T3-4 gastric cancer, and the combination of CT radiomic features and clinical features can further improve the prediction accuracy.

Objective To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer.Methods Tumor associated fibroblasts(CAFs)co-cultured with breast cancer cells were treated with metformin,and the changes in expressions of hypoxia-inducible factor-1α(HIF-1α),p-AMPK,stroma-derived factor-1(SDF-1)and interleukin-8(IL-8)in the CAFs were detected using ELISA,RT-qPCR or Western blotting;Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1,IL-8 and TGF-β1.The effects of HIF-1α shRNA or overexpression plasmid,AMPK shRNA,and treatment with OG(a proline hydroxylase inhibitor)or 2-OXO(a proline hydroxylase activator)were examined on p-AMPK,HIF-1α,SDF-1 and IL-8 expressions and invasiveness of the CAFs.Results Metformin treatment significantly increased the expression levels of p-AMPK,SDF-1 and IL-8(P<0.05)and decreased HIF-1α expression(P<0.05)without affecting AMPK expression level(P>0.05)in the CAFs.The invasion ability of metformin-treated breast cancer cells was significantly decreased(P<0.05).Exogenous SDF-1 and IL-8,HIF-1α overexpression,and OG-induced upregulation of HIF-1α all significantly attenuated the inhibitory effects of metformin on breast cancer cell invasion(P<0.05)and HIF-1α,SDF-1 and IL-8 expressions in CAFs(P<0.05).Transfection with HIF-1α shRNA or treatment with 2-OXO significantly decreased the invasiveness of breast cancer cells(P<0.05).P-AMPK knockdown significantly suppressed the inhibitory effect of metformin on HIF-1α expression in CAFs and on invasion of breast cancer cells(P<0.05).Treatment with TGF-β1 partially decreased the inhibitory effect of metformin on HIF-1α expression in CAFs and invasiveness of the breast cancer cells(P<0.05).Conclusion Metformin suppresses HIF-1α expression in CAFs to block tumor-stromal cross talk in breast cancer.

Objective To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer.Methods Tumor associated fibroblasts(CAFs)co-cultured with breast cancer cells were treated with metformin,and the changes in expressions of hypoxia-inducible factor-1α(HIF-1α),p-AMPK,stroma-derived factor-1(SDF-1)and interleukin-8(IL-8)in the CAFs were detected using ELISA,RT-qPCR or Western blotting;Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1,IL-8 and TGF-β1.The effects of HIF-1α shRNA or overexpression plasmid,AMPK shRNA,and treatment with OG(a proline hydroxylase inhibitor)or 2-OXO(a proline hydroxylase activator)were examined on p-AMPK,HIF-1α,SDF-1 and IL-8 expressions and invasiveness of the CAFs.Results Metformin treatment significantly increased the expression levels of p-AMPK,SDF-1 and IL-8(P<0.05)and decreased HIF-1α expression(P<0.05)without affecting AMPK expression level(P>0.05)in the CAFs.The invasion ability of metformin-treated breast cancer cells was significantly decreased(P<0.05).Exogenous SDF-1 and IL-8,HIF-1α overexpression,and OG-induced upregulation of HIF-1α all significantly attenuated the inhibitory effects of metformin on breast cancer cell invasion(P<0.05)and HIF-1α,SDF-1 and IL-8 expressions in CAFs(P<0.05).Transfection with HIF-1α shRNA or treatment with 2-OXO significantly decreased the invasiveness of breast cancer cells(P<0.05).P-AMPK knockdown significantly suppressed the inhibitory effect of metformin on HIF-1α expression in CAFs and on invasion of breast cancer cells(P<0.05).Treatment with TGF-β1 partially decreased the inhibitory effect of metformin on HIF-1α expression in CAFs and invasiveness of the breast cancer cells(P<0.05).Conclusion Metformin suppresses HIF-1α expression in CAFs to block tumor-stromal cross talk in breast cancer.

Objective:To investigate the early- and mid-term clinical, functional and radiographic outcomes of patellofemoral arthroplasty (PFA).Methods:A retrospective analysis was conducted in 64 patients (80 knees) who suffered from severe patellofemoral osteoarthritis (PFOA) and underwent PFA from January 2013 to December 2020. These patients were aged 60.50±8.82 (range from 27 to 82) years, including 9 males (12 knees) and 55 females (68 knees). All enrolled individuals presented typical PFOA. Unilateral PFA was performed in 48 cases, bilateral PFA in 16 cases, including one-stage PFA in 9 cases and two-stage PFA in 7 cases. The visual analogue scale (VAS), Hospital for Special Surgery (HSS) knee score and Oxford knee score (OKS) of patients with more than 5 years' follow-up were assessed to evaluate the clinical effects of PFA at the time before surgery, 1 year and 5 years after surgery. In addition, the patellar tilt angle (PTA) and hip-knee-ankle (HKA) angle were measured and analyzed to evaluate the improvement of patellar tracking and progression of tibiofemoral osteoarthritis, based on axial X-ray imaging (skyline view) of knee and the full length standing X-ray imaging of the lower limbs at before surgery and 5 years after surgery. Meanwhile, the complications of all patients that related to the operation were recorded.Results:A total of 64 patients were followed up for 4.31±1.79 (range, 1.5 to 8.2) years. Twenty-five patients (32 knees) who followed up more than 5 years were analyzed. The VAS, HSS and OKS improved from 5.91±0.82, 68.06±6.03 and 21.22±3.46 preoperatively to 0.88±1.01, 90.09±3.30 and 39.06±3.37 at 1 year after surgery, and to 0.41±0.76, 94.53±2.99 and 42.13±3.17 at 5 years after surgery, respectively ( F=89.38, 81.47, 56.73, P<0.001). Additionally, comparing to the preoperative radiological data, the patellar tract was improved with the PTA decreased from 8.21°±3.14° preoperatively to 3.58°±4.48°at 5 years after surgery ( t=4.96, P<0.001). The HKA angle changed from 179.01°±1.43° preoperatively to 178.77°±1.67° at 5 years follow up ( t=1.71, P=0.096). There was no case of prosthesis loosening or wear and no case of obvious progression of tibiofemoral osteoarthritis that needed revision in all patients. Conclusion:Satisfied early- and mid-term clinical outcomes could be achieved by PFA in treating severe PFOA patients. PFA could relieve pain and improve function of knee joint.

Objective To investigate the relationship between the incipient serum C-reactive protein (CRP) and clinicopathologic features in anti-neutrophil cytoplasmic antibody associated vasculitis (AAV).Methods Data of 138 consecutive AAV patients were collected.According to their serum CRP levels,patients were divided into group 1 with normal CRP,group 2 with slightly increased CRP and group 3 with severely increased CRP.Clinical features of AAV and histopathologic features of the kidney injury were compared among groups.Results CRP levels increased in 77.53％ AAV patients on admission.Patients in the group of severely increased CRP had the highest levels of BVAS,serum C3,serum ANCA titer,leukocyte counts and the lowest levels of hemoglobin and albumin among the 3 groups (all P ＜ 0.05).The mortality during the stage of therapy was highest in patients with severely increased CRP (P ＜ 0.05).The focal kidney damage was more obvious in patients with severely increased CRP.There was no significant difference in renal prognosis among patients with different CRP levels.Conclusion The levels of incipient serum C-reactive protein of AAV vary in different patients and are positively correlated with patients' inflammation status as well as the disease activity,but are not correlated with the severity of kidney injury.

Objective To investigate the outcome of a new designed extramedullary femoral osteotomy module and to compare with conventional intramedullary system in clinical study.Methods The extramedullary femoral osteotomy module was designed with the extramedullary alignment rod connecting with the T type rod at right angle,and it had a 5°-7° adjustable valgus design.The positioning module fixation screw was parallel with the epicondylar axis.The coronal plane of the distal femur bone cut was orientated by the extramedullary alignment rod pointing to the inguinal midpoint,and the sagittal plane was orientated by the extramedullary alignment rod keeping parallel with the distal femoral medullary cavity.The terminal distal femoral bone cut was conducted with suitable osteotomy after the orientation.Sixty patients who underwent unilateral total knee arthroplasty (TKA) from October 2015 to March 2016 were randomly divided into intramedullary and extramedullary group for prospective controlled study.Blood loss,drainage and the incidence of deep vein thrombosis (DVT) were evaluated at one week postoperatively.Knee valgus angle and femoral prosthesis flexion angle were analyzed at two weeks postoperatively.Moreover,the extramedullary femoral osteotomy module was used in 273 patients (78 males and 195 females) with an average age of 68.7 (range,57-82 years old) who underwent unilateral TKA from April 2016 to January 2017.Blood loss,operation duration and lower limb ultrasonography preoperatively and at one week postoperatively were recorded.Knee valgus angle and femoral prosthesis flexion angle were measured at 2 weeks postoperatively.Range of knee motion and Hospital for Special Surgery (HSS) knee score at six weeks postoperatively were also reported.Results In the randomized controlled trial,blood loss and drainage in extramedullary group was less than that in intramedullary group (t=-3.330,P=0.004).There was no significant difference in the incidence of DVT at 1 week postoperatively (x2=2.269,P=0.132) and the knee valgus angle and femoral prosthesis flexion angle at 2 weeks postoperatively within the two groups.In the clinical application,operation time was 60.13± 13.69 min,and blood loss and drainage was 109.11±70.73 ml.There were four cases of popliteal vein thrombosis,nine cases of posterior tibial vein thrombosis,and seventeen cases of muscular venous thrombosis at one week postoperatively.The incidence rate of DVT was 11.0％.There was no symptomatic pulmonary embolism at three months postoperatively.Knee valgus angle was 7.34°±0.69°,and 211 knees accounting for 77.3％ were in the range of ±3° error.Femoral prosthesis flexion angle was 6.43°±1.59°,and 273 knees were all in the range of ±10° error.Range of knee motion improved from 54.52±5.96 preoperative to 86.20±4.92 at six weeks postoperative.HSS knee score improved from 100.88°±7.51° preoperative to 110.42°±7.08° at six weeks postoperative.Conclusion The new designed extramedullary femoral osteotomy module used in distal femoral osteotomy during TKA can significantly reduce the risk of bleeding and the incidence rate of DVT postoperatively.Furthermore,patients can obtain as excellent prosthesis position and limb alignment as conventional intramedullary system.

Aim Paclitaxel(PTX)has shown an effect against human cancer. However, serious drawbacks hamper PTX clinical use.Overcoming paclitaxel limi-tations is one of the best approaches to enhance water solubility.Methods In this study,water-soluble pa-clitaxel prodrug was prepared,folic acid-polyethylene glycol-glutamic-paclitaxel (FA-PEG-Glu-PTX ) com-posed of folic acid (FA,target),amino acids (Glu, linker),and polyethylene glycol(PEG)in order to im-prove the solubilization and stability. The chemical structure and physicochemical property of prodrug were measured by LC-MS,solubility,drug release rate to e-valuate the antitumor activity and cytotoxicity of FA-PEG-Glu-PTX.MTT assays were conducted on MDA-MB-231,MCF-7,A549 and HELF cell lines.FA-PEG-Glu-PTX prodrugs were labeled with 5 amino flu-orescence visible fluorescent dye (5 AF ) for fluores-cence microscopy.Results The successful conjugation of FA-PEG-Glu-PTX was confirmed by LC-MS,and had better water solubility,release rate curve.In vitro studies indicated that foliate receptor(FR-α)mediated uptake of PTX-conjugated multi-small molecules carri-ers induced highly targeting ability,and antitumor ac-tivity,as well as reduced side toxicity effects of PTX. Conclusion FA-PEG-Glu-PTX has a good antitumor activity.

BACKGROUND:Col agen type II and proteoglycan loss are two most obvious manifestations of cartilage damage in the onset of osteoarthritis. Changes in col agen type II and proteoglycan as the main components of cartilage matrix directly lead to cartilage degeneration and subsequently result in osteoarthritis. How to reverse or prevent the development of this process becomes the focus of medical research. OBJECTIVE:To observe the effect of warming yang and benefiting marrow recipe on the expression of col agen type II and proteoglycan in the articular cartilage of knee osteoarthritis rabbits as wel as to further explore the mechanism underlying chondrocyte protection. METHODS:Ninety-six New Zealand rabbits, aged 9 months old, male and female, were selected to prepare osteoarthritis models in extension position using cast immobilization method, and were randomly divided into four groups:blank group (untreated), model group (simple modeling), Chinese medicine group (intragastric administration of extracts of warming yang and benefiting marrow recipe, 24 mL/kg/d) and western medicine group (intragastric administration of glucosamine hydrochloride, 24 mL/kg/d). Intragastric administration was done once a day for 6 weeks. RT-PCR technology was used to observe the effect of warming yang and benefiting marrow recipe on the expression of col agen type II and proteoglycans in the articular cartilage, and pathological examination was also done. RESULTS AND CONCLUSION:The cartilage surface was smooth in the blank group and Chinese medicine group, with uniform toluidine blue staining, but in the model group and western medicine group, the cartilage surface was rough and the toluidine blue staining was extremely uneven with obvious loss of surface and middle layer dying. The expressions of cartilage proteoglycan and col agen type II in the model group were significantly lower than those in the blank group (P<0.01) as wel as in the Chinese medicine group and western medicine group (P<0.05). In addition, the expressions of cartilage proteoglycan and col agen type II in the Chinese medicine group were higher than those in the western medicine group (P<0.05). These findings indicate that the recipe of warming yang and benefiting marrow can enhance the expressions of col agen type II and proteoglycan, which can maintain the normal col agen phenotype and protect the articular cartilage.

BACKGROUND:There are few reports concerning effects of warming the yang and benefiting the marrow for the knee osteoarthritis on the expression of matrix metal oproteinase.
OBJECTIVE:To observe the effect of warming the yang and benefiting the marrow on the expression of matrix metal oproteinase in rabbit models of knee osteoarthritis.
METHODS:Of 96 healthy adult New Zealand rabbits, 72 rabbits were randomly selected for making rabbit models of knee osteoarthritis using plaster external fixation. After success model establishment, the rabbits were randomly assigned to three groups. Model group was left intact. Chinese medicine group received daily intragastric administration of drug extract 24 mL/kg. Drug control group was daily intragastrical y administered Puli Capsule (glucosamine hydrochloride) 24 mg/kg, once a day, until the eighth week of success model induction. An additional 24 New Zealand rabbits served as blank controls.
RESULTS AND CONCLUSION:Using quantitative PCR, matrix metal oproteinase-1, matrix metal oproteinase-3 and matrix metal oproteinase-13 expression was significantly higher in the model group than that in the other three groups. Matrix metal oproteinase-1, matrix metal oproteinase-3 and matrix metal oproteinase-13 expression was significantly lower in the Chinese medicine group and drug control group than that in the model group. These results indicated that warming the yang and benefiting the marrow for knee osteoarthritis in rabbits could effectively inhibit the expression of matrix metal oproteinase in rabbits.

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