Deregulated mTOR signaling pathway is associated closely with variety of human cancers. Preclinical and clinical studies of both classical and newly developed mTOR inhibitors in digestive system cancers show that these drugs not only have anti-tumor properties, but also can enhance tumor cells sensitivity to standard chemotherapy agents.

AIM:To study the purified factors of Guanxinning for Injection(Radix et Rhizoma salviae miltiorrhizae,Rhizoma Chuanxiong,etc). METHODS: The total of salvianolic acid B、protocatchuci aldehyde and ferulic acid were used to evaluate for the study of type of macroporous adsorption resin,sample volume,the ratio of diameter to height,pH value and sample consistency etc. RESULTS: pH value Guanxinning extract was adjusted to 3.0,through D101 resin finally reached the ratio of diameter to height 1∶2,4 times of water was applied to elution and then 3 times of 70% ethanol for re-elution and collected. CONCLUSION: These factors are approprite for purifying Guanxinning for Injection.

Cyclosporine A( CsA) , as an immune inhibitor, is commonly used after organ transplantation.It has been found that the long-term use of CsA produced serious testicular toxicity and affected the fertility of organ transplantation patients.In order to investigate male reproductive damage induced by CsA, this article reviews its impact on reproductive organ development, its damage mechanism on the male reproductive system and drug research for alleviating its reproductive toxicity.It helps to make medical workers pay more attention to reproductive toxicity produced by CsA and make their efforts to develop some special drugs to lessen CsA reproductive toxicity.

Objective To explore the experimental conditions of labeling rabbit bone marrow mesenchymal stem cells (Rb-MSCs) with 5,6-carboxyfluorescein diacetic succinimidyl ester (CFSE) and to investigate the impact on the biological characteristics of Rb-MSCs in vitro.Methods Rb-MSCs were separated and purified by whole bone marrow adherent culture and then were identified by morphology and surface markers.Rb-MSCs were labeled with CFSE and the labeling effect was measured by flow cytometer.The proliferation capacity of labeled cells was detected with CCK-8.The differentiation capacity of labeled cells was investigated by being induced to osteoblasts and lipoblasts.The capacity of labeled cells to secret vascular endothelial growth factor (VEGF) was detected by VEGF ELISA kits.Results The primary Rb-MSCs adhered in 48 h,being fusiform and colony-like growth.Subculture cells became fibroblast-like cells in order with uniform configuration.Most (above 98％) cultured cells expressed the surface markers CD29 and CD44 except for CD45.Compared with other labeling conditions,10μmol/L final concentration of CFSE and 10 min was the best one with a 100％ labeling rate and high fluorescence intensity.Compared with unlabeled cells,the ability of the labeled cells to proliferate and to secrete VEGF was not significantly decreased (P ＞ 0.05).Moreover,the labeled cells had osteogenic and adipogenic differentiation capacity.Conclusions It was a simple and efficient method to label Rb-MSCs with CFSE,especially in a short-term.The capacity of cell proliferation,differentiation,and secretion were not affected.

AIM:Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation ( AF) .Al-though tumor necrosis factor ( TNF)-αlevels are increased in patients with AF , the role of TNF-αin the pathogenesis of AF remains unclear.Recent research has revealed that T-type Ca2+currents ( ICa,T ) play an important role in the pathogenesis of AF .METH-ODS:In this study , we used the whole-cell voltage-clamp technique and biochemical assays to explore the role of TNF-αin the regula-tion of ICa,T in atrial myocytes.RESULTS:We found that compared with sinus rhythm (SR) controls, T-type calcium channel (TCC) subunit mRNA levels were decreased , while TNF-αexpression levels were increased , in human atrial tissue from patients with AF .In murine atrial myocyte HL-1 cells, after cultured for 24 h, 12.5, 25 and 50 μg/L TNF-αsignificantly reduced the protein expression levels of the TCC α1G subunit in a concentration-dependent manner .The peak current was reduced by the application of 12.5 or 25μg/L TNF-αin a concentration-dependent manner [from ( -15.08 ±1.11) pA/pF in controls to ( -11.89 ±0.83) pA/pF and (-8.54 ±1.55) pA/pF in 12.5 and 25 μg/L TNF-αgroups, respectively].TNF-αapplication also inhibited voltage-dependent inactivation of ICa,T shifted the inactivation curve to the left .CONCLUSION:These results suggest that TNF-αis involved in the path-ogenesis of AF, probably via decreasing ICa,T function in atrium-derived myocytes through impaired channel function and down -regula-tion of channel protein expression .This pathway thus represents a potential pathogenic mechanism in AF .

To introduce the surgical procedure of orthopaedic robot-assisted vascularised fibular grafting for the treatment of ANFH and report the short-term result. Methods From September, 2016 to November, 2018, 17 patients (21 hips) with ANFH had undergone robot-assisted free fibular grafting. There were 14 males and 3 females, of which, 8 cases were associated with the right side, 5 cases the left side, and 4 cases with both sides. The average age was 35 (ranged from 17 to 55) years. There were 7 patients suffered from idiopathic ischemic necrosis of femoral head, 4 patients who had cannulated screws fixed after a femoral neck fracture, 4 patients who had a history of alcohol consumption, 1 patient who had taken corticosteroids for 6 months to treat nephritis, and 1 patient who had a history of alcohol consumption and had also taken corticosteroids. Seventeen hips were in Ficat stage II, and 4 hips were in Ficat stage III. The orthopaedic surgical robot workstation was used to plan the entry point and target of the guide pin during the operation, to place a cannula in the optimal position. Then a bone window was created and the fibula was placed into the bone tunnel.Using fluoroscopy to monitor each step of the procedure and verify the position of the fibula. Finally, the vessels were anastomosed. The patient remain in bed completely for a week with the use of vasodilator. The follow-up was accomplished with phone call and outpatient clinic, and Harris score was evaluated. Results All 21 surgical procedures were successful. The guide pins and fibula were accurately placed according to the robot’s plan, and the tips of the fibula were placed at the centre of the load-bearing region of the femoral heads, 4 to 6 mm from the articular surface. Conventional anticoagulant, anti-infective therapy was performed after the pro-cedure. Ten patients were followed-up postoperatively more than 1 year, with an average of 15 (from 12 to 24) months. The function of the hip joint recovered smoothly for 9 patients.Frontal and lateral X-ray and CT scans showed that the tips of the fibula were placed at the centre of the load-bearing region, 4 to 6 mm from the articular surface.One patient suffered from bilateral femoral head necrosis and the right side recovered smoothly after operation.However, joint move-ment was restricted for the left hip and the pain was significant.An arthroscopic examination was performed 1 month after the operation and did not identify any problems such as intraarticular incular infection or articular surface of the femoral head was protruded by the tip of the fibula.The symptoms were alleviated after removing the osteophytes at the rim of the acetabulum.The Harris score was 62.4±13.6 before operation, and 84.5±4.5 at the last time of followed-up after opera-tion.The difference in Harris scores was statisticly significant (P＜0.05). Conclusion With the assistance of an or-thopaedic robot system, the guide pin can be accurately positioned, thereby allowing the tip of the fibula to be inserted in-to the optimal anatomical position and maximising its mechanical efficacy.In theory, it is the best choice for performing fibular bone transplantation in ANFH.And the early effect of treatment is good.

Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca²⁺ homeostasis. The store-operated calcium (SOC) channel is the primary Ca²⁺ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on Ca²⁺ influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM. The effect of tunicamycin on the expression of the unfolded protein response (UPR)-related proteins BiP and CHOP was assayed by western blotting with or without inhibition of Orai1. Tunicamycin induced endothelial dysfunction by activating ER stress. Orai1 expression and the influx of extracellular Ca²⁺ in HUVECs were both upregulated during ER stress. The SOC channel inhibitor SKF96365 reversed tunicamycin-induced endothelial cell dysfunction by inhibiting ER stress. Regulation of tunicamycin-induced ER stress by Orai1 indicates that modification of Orai1 activity may have therapeutic value for conditions with ER stress-induced endothelial dysfunction.
Blotting, Western ; Calcium ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Endothelial Cells ; Homeostasis ; Human Umbilical Vein Endothelial Cells ; Tunicamycin ; Unfolded Protein Response

Objective:To investigate the factors affecting the application of systemic glucocorticoids in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with carbon dioxide (CO 2) retention, and to guide the formulation of a strategy to reduce systemic glucocorticoid exposure. Methods:The AECOPD patients with CO 2 retention admitted to the Ningde Municipal Hospital of Fujian Medical University from January 2017 to December 2019 were enrolled. The general information, past history, times of acute exacerbations within 1 year, pneumonia on admission, causes of COPD, heart failure, blood gas analysis, eosinophil count (EOS), albumin (Alb) and apolipoprotein E (ApoE) levels, exhaled nitric oxide (FeNO) level, inhaled glucocorticoid and non-invasive mechanical ventilation treatment at acute exacerbation were collected. The patients were divided into recommended dosage group (exposure levels in the recommended dosage range, cumulative prednisone dosage ≤ 200 mg) and exceeded group (exposure levels exceeded the recommended dose, cumulative prednisone dosage > 200 mg) according to cumulative systemic glucocorticoid exposure dosage of the patients during hospitalization. The clinical data of patients between the two groups were compared, and possible factors with P < 0.1 in univariate analysis were included in multivariate Logistic regression analysis to screen the related factors of systemic glucocorticoid exposure level in AECOPD patients with CO 2 retention. Results:According to the order of hospitalization, 151 AECOPD patients with CO 2 retention were enrolled, 8 patients were excluded, and 143 patients were enrolled in the analysis. Of the 143 patients, 68 received the recommended dose of systemic glucocorticoid, and 75 received excessive systemic glucocorticoid. Age, percentage of forced expiratory volume in 1 second (FEV1%) at stable phase, frequency of acute exacerbation within 1 year, heart failure ratio, oxygen index (PaO 2/FiO 2), arterial partial pressure of carbon dioxide (PaCO 2), serum EOS and ApoE levels at admission, the ratio of aerosolized inhaled glucocorticoids and non-invasive mechanical ventilation showed statistical differences between the two groups. Multivariate Logistic regression analysis showed that related factors affecting systemic glucocorticoid exposure levels of AECOPD patients with CO 2 retention were FEV1% at stable phase [odds ratio ( OR) = 0.957, 95% confidence interval (95% CI) was 0.921-0.994, P = 0.023], acute exacerbation frequency within 1 year ( OR = 1.530, 95% CI was 1.121-2.088, P = 0.007), heart failure ( OR = 3.022, 95% CI was 1.263-7.231, P = 0.013), PaCO 2 ( OR = 1.062, 95% CI was 1.010-1.115, P = 0.018) and EOS at admission ( OR = 0.103, 95% CI was 0.016-0.684, P = 0.019), aerosolized inhaled glucocorticoids ( OR = 0.337, 95% CI was 0.145-0.783, P = 0.011) and non-invasive mechanical ventilation at acute exacerbation ( OR = 0.422, 95% CI was 0.188-0.948, P = 0.037), of which high FEV1% at stable phase, high EOS at admission, aerosolized inhaled glucocorticoid and non-invasive mechanical ventilation at acute exacerbation were protective factors, while high frequency of acute exacerbation within 1 year, heart failure and high PaCO 2 were risk factors. Conclusions:For AECOPD patients with CO 2 retention, high FEV1% at stable phase, high EOS level at admission, aerosolized inhaled glucocorticoid and non-invasive mechanical ventilation at acute exacerbation can reduce systemic glucocorticoid exposure. In addition, high frequency of acute exacerbation within 1 year, heart failure, and high PaCO 2 can increase systemic glucocorticoid exposure.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.