Objective To explore the molecular mechanism of glucocorticoid (GC)-induced osteoporosis (GIOP). Methods Thirty-two female SD rats after matching body weight were divided randomly into three groups: baseline group (n = 10), control group (n = 11) and GC-treated group (n = 11). The administration time was 9 weeks. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry. A high resolution micro-CT was used to quantify the densitometric and microarchitectural properties of trabeculae in the proximal metaphysis of right tibia. In situ hybridization histochemistry and immunohistochemistry were used to detect the expression of cannabinoid type 1 receptor (CBI R) in the proximal metaphysis of left tibia. Results At the end of the experiment, whole-body BMD in vivo in the control group [(0. 156±0. 008) g/cm2]was higher than that in the baseline group [(0.147±0.006)g/cm2], while the whole-body BMD in vivo [(0.147±0.006) g/cm2]and total BMD in vitro at femurs in the GC-treated group [(0.220±0.011) g/cm2]was lower than those in the control group [(0. 240±0. 024)g/cm2]. Compared with the baseline group and control group, there was a remarkable decrease in the volumetric BMD, tissue BMD, trabecular number and trabecular connectivity (P<0.05) in the GC-treated group, while there was a significant increase in trabecular separation (P < 0. 05) and trabecular thickness also increased in the proximal metaphysis of tibiae in the GC-treated group. The expression level of CB1R mRNA and protein in osteoclasts in the GC-treated group was markedly higher than that in the baseline group and control group (P < 0. 05). There was a close correlation between the expression level of CB1R mRNA, protein in osteoclasts and some microarchitectural parameters in the proximal metaphysis in the GC-treated group (P<0.05). Conclusions The administration of GC is associated with a decrease in BMD and deterioration in microarchitecture of trabecular bone in rats tibiae. Glucocorticoid may up-regulate the CB1R expression level in osteoclasts and this may be a kind of molecular mechanism of GIOP.

ObjectiveTo investigate the relationships between traditional Chinese medicine(TCM) syndrome differentiation and serum cystatin C(Cys-C) and homocysteine(Hcy) in patients with chronic heart failure(CHF). Methods 115 cases with CHF admitted into the Department of Cardiology of the First Affiliated Hospital of Zhejiang Chinese Medical University were selected in the CHF group, and 30 cases who had taken health examination in the same period were chosen in the healthy control group. According to the TCM syndrome differentiation, the CHF cases were subdivided into four groups with different types of syndrome: 30 cases of deficiency of both Qi and Yin syndrome, 30 cases of Qi deficiency syndrome and blood stagnation syndrome, 30 cases of heart and kidney Yang deficiency syndrome and 25 casesof flooding due to Yang deficiency syndrome. The serum levels of Cys-C and Hcy in different groups were tested, and the relationships between TCM syndrome differentiation and serum Cys-C and Hcy were analyzed by using Spearman rank correlation analysis.Results The serum levels of Cys-C and Hcy in the patients with CHF were significantly higher than those in the healthy control group〔Cys-C(mg/L):1.24±0.34 vs. 0.77±0.22, Hcy(μmol/L):18.66±4.57 vs. 11.65±3.21,bothP<0.05〕. Compared with the healthy control group, the serum levels of Cys-C and Hcy in the above four groups of different syndromes had a tendency of gradual elevation in the sequence as follows: deficiency of both Qi and Yin, Qi deficiency and blood stagnation, heart and kidney Yang deficiency and flooding due to Yang deficiencygroups〔Cys-C(mg/L):1.02±0.27,1.09±0.31,1.32±0.22, 1.59±0.25; Hcy(μmol/L): 14.94±2.20, 17.66±3.04, 19.79±3.48, 22.96±5.31〕, and the elevation in levels of flooding due to Yang deficiency group was the most prominent compared with that in other groups(P<0.05). The correlation analyses showed that different types of TCM syndrome in patients with CHF were positively correlated with the levels of Cys-C and Hcy(r1=0.73,r2=0.79,bothP<0.05).ConclusionThe changes of serum Cys-C and Hcy levels are consistent with the evolution of regular pattern of TCM syndrome differentiation in patients with CHF, and these two markers can be regarded as the objective indicators of TCM syndrome differentiation of CHF.

ObjectiveTo determine the changes in tumor necrosis factor-α (TNF-α) and interleukin-lβ (IL-1β)expression after bone marrow mesenchymal stem cells (BMSCs) transplantation in a rat pup model of hypoxic-ischemic brain damage (HIBD) and discuss the anti-inflammatory mechanism of BMSCs transplantation in the repair of HIBD.MethodsThree-day-old Sprague-Dawley rat pups were randomly divided into three groups: the transplantation group, in which a model of HIBD was established by ligation of left common carotid artery and hypoxia for two hours followed by the injection of 2μl BMSCs (2×105 cells) into the lateral ventricle; the HIBD model group, in which HIBD model was established and 2μl phosphate saline buffer was injected into the lateral ventricle; and the sham-operation group, in which no intervention was given. Histological changes in the brain were detected by HE staining and the number of cells positive for ectodermal dysplasia-1 (ED-1) staining, which is a specific marker for activated microglia, was detected by immunohistochemistry. The protein and mRNA levels of TNF-α and IL-1β were determined by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. One-way analysis of variance and LSD test were applied for statistical analysis.ResultsHE staining showed that cellular edema and necrocytosis was not observed in cerebral white matter on the 7th post-transplantation day in the transplantation group, but observed in the HIBD model group. In the sham-operation group, cerebral white matter was normal. The number of ED-1 positive cells in the transplantation group (26.3±2.5) was significantly lower than that in the HIBD model group (33.0±4.0), but higher than that in the sham-operation group (2.3±0.6) (LSD test, allP<0.05). The contents of TNF-α and IL-1β both in the transplantation group and the HIBD model group increased and peaked 24 h after transplantation, then gradually decreased, but did not reach normal levels (sham-operation group) on the 7th day. The contents of TNF-α and IL-1β in brain tissue in the HIBD model group [TNF-α: (3.03±0.10), (5.57±0.19), (7.78±0.19), (4.39±0.20), (2.70±019)μg/L; IL-1β:(293.1±7.9), (369.8±17.5), (303.6±23.9), (226.7±21.6), (183.9±33.4) ng/L] were significantly higher than those in the transplantation group [TNF-α: (2.84±0.20), (3.80±0.14), (4.63±0.17), (3.56±0.03), (1.99± 0.17)μg/L; IL-1β: (267.6±14.5), (323.5±26.9), (211.2±24.9), (140.8±7.4), (100.2±8.3) ng/L] at 6, 12, 24, 48 h and 7 days after BMSCs transplantation, respectively. The contents of TNF-α and IL-1β in the sham-operation group [TNF-α:(1.03±0.02), (1.13±0.03), (1.05±0.02), (1.09±0.02), (1.07±0.02)μg/L; IL-1β:(63.6±13.0), (64.0±11.3), (60.8±10.0), (67.9±13.5), (66.2±11.7) ng/L] were significantly lower than those in the transplantation group and HIBD model group (LSD test, allP<0.05). TNF-α and IL-1β mRNA at 24 h after transplantation in the HIBD model group (TNF-α: 2.69±0.43; IL-1β: 3.07±0.38) were significantly higher than those in the transplantation group (TNF-α: 1.61±0.29; IL-1β: 1.08±0.11) and those in the sham-operation group (TNF-α: 0.94±0.16; IL-1β: 1.08±0.11) (LSD test, allP<0.05).ConclusionsBMSCs may play an important role in the recovery of preterm HIBD and the mechanism may involve the inhibition of microglia activation and down-regulation of the expression of inflammatory factors.

Objective To evaluate the efficacy of double filtration plasmapheresis (DFPP) combined with immunosuppressive agents (leflunomide plus methotrexate) on synovitis in magnetic resonance imaging (MRI) in patients with high active rheumatoid arthritis (RA). Methods Fifty eight patients with RA (disease duration 6 months to 12 years) were randomly divided. Thirty-one were randomized to the treatment group and 27 were randomized to the control group. All patients received leflunomide 10 mg, two times daily; plus methotrexate 15 mg orally once weekly. DFPP was performed in the treatment group once 1-2 weeks for 3-4 sessions. Control patients did not receive DFPP. All patients underwent contrast-enhanced MRI of the right wrist at the baseline and 6 months, 1 month in the treatment group. The signs including synovitis pannus, bone marrow edema and effusion were observed on MRI. The scoring of synovial hypertrophy, pannus, bone marrow edema were measured according to the outcome measures in RA MRI scoring system. Comparisons between groups were performed with paired-samples t test and independent-sample t test. Results The MRI synovitis score, MRI pannus score and MRI bone marrow edema in the treatment group was (1.4±1.6), (0.13± 0.35) and (5±4) respectively,so was significantly lower than that of the control group [respectively for (7.9± 1.3), (2.76±0.43), (16±12),P<0.01]. 53% of the treatment group satisfied both the disease activity score 28-joint assessment and MRI synovitis assessment (no enhancement of synovium or pannus, no effusion), but none in the control group (P<0.01). Significant changes at 1 month was observed in DAS28 and HAQ scores (P<0.01), but not in the MRI synovitis score, MRI pannus score, MRI bone marrow edema score and effusion in the treatment group (P>0.05). Conclusion DFPP combined with immunosuppressive agents can significantly improve synovitis in MRI in patients with high active RA. Improvement of the signs of MRI is later than that in the clinic. So imaging assessment may be necessary for accurate evaluation of disease status and selection of therapy.

Objective:The diagnostic values of urine free and fractionated catecholamine metabolites (including metanephrine MN and normetanephrine NMN, usually known as MNs) were established and their clinical value was evaluated.Methods:Using high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS), urine free MNs (f-MN, f-NMN) and fractionated MNs(t-MN, t-NMN) from 180 cases of non-pheochromocytoma and 54 cases of pheochromocytoma (PCC)patients were detected respectively.Receiver operating characteristic curve (ROC) was used to establish clinical reference cut-off value for different forms of MNs, and diagnostic efficacy of free, fractionated and total MNs was evaluated.Results:(1) The cut-off values of f-MN, f-NMN, t-MN and t-NMN were 47.8 μg/24 h, 52.3 μg/24 h, 224.9 μg/24 h and 664 μg/24 h, respectively. The cut-off values of total f-MNs and total t-MNs were 126 μg/24 h and 1 070 μg/24 h, respectively. (2) The correlation between f-MN and t-MN ( r=0.976, P<0.001), f-NMN and t-NMN ( r=0.940, P<0.001) was good. The area under ROC curve(AUC)of f-MN was lower than that of t-MN(0.579 vs 0.730, P<0.001), the sensitivity was slightly lower than that of t-MN((37.01% vs 51.85%, P=0.036), and the specificity was similar (99.44% vs 96.67%, P>0.05). There was no significant difference in sensitivity (90.74% vs 92.59%, P>0.05), specificity (99.44% vs 96.67%, P>0.05) and AUC (0.944 vs 0.959, P>0.05) between f-NMN and t-NMN. The combined diagnostic value of MN and NMN (total MNs) was higher than MN (free type:0.932>0.579, fractionation type: 0.960>0.730), which was similar to NMN. Conclusions:The diagnostic performance of urine free NMN or total MNs for PCC is similar to that of fractionated typewhich can meet the clinical needs.With few influencing factors, free type MNs may be used as an alternative indicator for PCC screening in the future.

BACKGROUND: Da Vinci Surgical System is one of the greatest inventions of the 20th century, which represents the development direction of the precise minimally invasive surgical techniques, the aim of this study was to comparing the short-term outcomes between da Vinci robot-assisted lobectomy and video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer. METHODS: 45 pairs of non-small cell lung cancer patients underwent pulmonary lobectomy with da Vinci Robotic assisted thoracoscopic (RATS) and VATS approach during the same period from January 2014 to January 2017. The operative time, estimated blood loss (EBL), total number and total groups of dissected lymph nodes, postoperative duration of drainage, the first day volume of drainage, total volume of drainage were compared. RESULTS: No perioperative death and convertion to thoracotomy occured in both groups. There were significant difference between RATS group and VATS group in EBL [(50.30±32.33) mL vs (208.60±132.63) mL], the first day volume of drainage [(275.00±145.42) mL vs (347.60±125.80) mL], the dissected total number [(22.67±9.67) vs (15.51±5.41)] and total team [(6.31±1.43) vs (4.91±1.04)] of lymph node. There were no significant difference in other outcomes. CONCLUSIONS RATS is safe and effective and took better short-outcomes than VATS in non-small cell lung cancer.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; surgery ; Case-Control Studies ; Female ; Humans ; Lung Neoplasms ; surgery ; Lymph Node Excision ; Lymph Nodes ; surgery ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; Operative Time ; Retrospective Studies ; Robotics ; methods ; Thoracic Surgery, Video-Assisted ; instrumentation ; methods ; Thoracoscopy ; instrumentation ; methods

Objective To analyze the feasibility of totally no tube (TNT) in da Vinci robotic mediastinal mass surgery and its significance for fast track surgery. Methods A total of 79 patients receiving robotic mediastinal TNT surgery in the General Hospital of Shenyang Military Command from January 2016 to December 2017 were enrolled as a TNT group; 35 patients receiving robotic mediastinal surgery in General Hospital of Shenyang Military Command from January 2014 to December 2017 and 54 patients receiving thoracoscopic mediastinal surgery during the same period were enrolled as a non-TNT group and a video-assisted thoracoscopic surgery (VATS) group. The muscle relaxation and tracheal intubation/laryngeal masking time, operation time, intraoperative blood loss, postoperative ICU stay, postoperative hospital stay, postoperative visual analogue scale (VAS), hospitalization costs and postoperative complications and other related indicators were retrospectively analyzed among the three groups. Results Surgeries were successfully completed in 168 patients with no transfer to thoracotomy, serious complications (postoperative complications in 9 patients) or death during the perioperative period. All patients were discharged. Compared with the non-TNT group, the TNT group had significantly less muscle relaxation-tracheal intubation/laryngeal masking time, operation time, intraoperative blood loss, VAS pain score, ICU stay, postoperative hospital stay (P<0.01); there was no significant difference in the total cost of hospitalization between the two groups (P>0.05). Between the non-TNT group and the VATS group, there was no significant difference in time of muscle relaxation and tracheal intubation, operation time and ICU stay (P>0.05). The non-TNT group was superior to the VATS group in terms of intraoperative blood loss, VAS pain scores on the following day after operation, chest drainage volume 1-3 days postoperatively, postoperative catheterization time and postoperative hospital stay (P<0.05); but the cost of hospitalization in the non-TNT group was significantly higher (P=0.000). Conclusion The da Vinci robot is safe and feasible for the treatment of mediastinal masses. At the same time, TNT is also safe and reliable on the basis of robotic surgery which has many advantages such as better comfort, less pain, ICU stay and hospital stay as well as faster recovery.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.