Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Klein-Levin syndrome is a chronic recurrent sleep disorder characterized by periodic excessive sleep, which can be accompanied by cognitive dysfunction, eating disorders, behavioral disorders, sensory disorders and emotional disorders, etc. During interval, individual′s daily functions are completely normal. Most of the KLS cases are sporadic. At present, only 17 familial cases of KLS have been reported abroad, while domestic reports in China are rare. We analyzed the detailed medical history, laboratory examinations, differential diagnosis, and the disease prevalence amongst family members of a patient with familial KLS, in order to provide reference for the follow-up study of familial cases of KLS.

Klein-Levin syndrome is a chronic recurrent sleep disorder characterized by periodic excessive sleep, which can be accompanied by cognitive dysfunction, eating disorders, behavioral disorders, sensory disorders and emotional disorders, etc. During interval, individual′s daily functions are completely normal. Most of the KLS cases are sporadic. At present, only 17 familial cases of KLS have been reported abroad, while domestic reports in China are rare. We analyzed the detailed medical history, laboratory examinations, differential diagnosis, and the disease prevalence amongst family members of a patient with familial KLS, in order to provide reference for the follow-up study of familial cases of KLS.

Objective To evaluate the efficacy and safety of oprinon hydrochloride in increasing cardiac pump function and stabilizing hemodynamics and preventing common complications after cardiac valve replacement. Methods Sixty-two patients were admitted to the First Affiliated Hospital of Zhengzhou University from January to August 2018 to undergo cardiac valve replacement operation, post-operatively, 32 patients using oprinon hydrochloride were in the observation group and 30 patients using milrinone were in the control group. Both groups received basic treatment, additionally the observation group was given oprinon hydrochloride intravenous pump injection for 48 hours and the control group was given milrinone intravenous pump injection for 48 hours. The changes of vital signs (blood pressure, heart rate, respiratory rate), cardiac function, hemodynamics, biochemical indexes, electrocardiogram, cardiac color Doppler ultrasound and adverse reactions were observed before and after treatment in the two groups. The incidence of cardiovascular events (worsening, re-hospitalization and death) was followed up 1 month after discharge. Results The left ventricular ejection fraction (LVEF), central venous pressure (CVP), arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2), N-terminal B-type natriuria (NT-proBNP), lactic acid, serum creatinine (SCr), blood sodium and potassium of the two groups after treatment were not statistically significant compared with those before treatment [LVEF: the control group was 0.52±0.09 vs. 0.60±0.09, the observation group was 0.62±0.12 vs. 0.50±0.11;CVP (mmHg, 1 mmHg = 0.133 kPa): the control group was 11.2±2.8 vs. 13.0±2.9, the observation group was 13.0±2.5 vs. 10.5±3.6; SaO2: the control group was 0.98 (0.90, 0.99) vs. 0.99 (0.98, 1.00), the observation group was 0.95 (0.94, 0.98) vs. 0.96 (0.90, 1.00); PaO2(mmHg): the control group was 100.5 (63.8, 135.3) vs. 99.5 (82.3, 179.5), the observation group was 95.0 (85.5, 129.0) vs. 75.5 (59.0, 138.3); NT-proBNP (pg/L): the control group was 1.45 (1.34, 3.31) vs. 0.92 (0.42, 1.81), the observation group was 0.47 (0.35, 1.37) vs. 2.07 (1.27, 4.44); lactic acid (mmol/L): the control group was 3.6 (2.4, 4.5) vs. 1.4 (1.2, 3.1), the observation group was 1.3 (1.1, 2.1) vs. 3.1 (1.4, 3.7); SCr (μmol/L): the control group was 106.7±35.9 vs. 84.4±20.3, the observation group was 96.5±40.7 vs. 77.1±23.1; sodium (mmol/L):the control group was 141.4±7.2 vs. 143.6±4.2, the observation group was 142.9±3.6 vs. 140.5±4.5; potassium (mmol/L): the control group was 4.6±0.9 vs. 4.8±0.6, the observation group was 4.8±0.6 vs. 4.1±0.6, all P > 0.05];the comparisons between the following indicators in levels before and after treatment in the two groups had statistical significant differences: the peripheral arterial pressure (PAP), white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), alanine aminotransferas (ALT) and aspartate aminotransferase (AST) [PAP (mmHg): the control group was 33.0 (24.0, 59.3) vs. 38.0 (34.8, 46.0), the observation group was 30.0 (25.0, 32.0) vs. 53.5 (29.3, 66.5); WBC (×109/L):the control group was 12.2 (10.4, 13.9) vs. 5.7 (4.4, 8.6), the observation group was: 8.4 (3.7, 11.8) vs. 8.6 (5.7, 12.4); Hb (g/L): the control group was 95.6±12.9 vs. 130.3±15.0, the observation group was 111.1±22.6 vs. 112.4±24.6; PLT (×109/L): the control group was 95.2±21.3 vs. 168.7±32.6, the observation group was 146.3±68.1 vs. 132.7±45.1;ALT (U/L): the control group was 36.5 (15.3, 80.5) vs. 14.0 (11.0, 19.0), the observation group was 15.0 (10.0, 32.3) vs. 20.3 (12.0, 35.8); AST (U/L): the control group was 33.0 (20.0, 83.0) vs. 16.5 (16.7, 28.8), the observation group was 35.5 (12.3, 56.8) vs. 75.5 (45.3, 140.3), all P < 0.05]; after treatment, the urea nitrogen (BUN) level in control group was higher than that before treatment (mmol/L: 11.4±4.7 vs. 7.1±2.5), while BUN in the observation group was decreased (mmol/L: 6.5 ±3.3 vs. 9.1±3.8), there was statistical significant difference in BUN level between the two groups after treatment (P < 0.05). The levels of systolic blood pressure and respiratory rate after treatment in the two groups were significantly higher than those before treatment (all P < 0.05). After treatment, the diastolic blood pressure in the observation group was increased, but there was no significant difference in the control group before and after treatment, and the diastolic blood pressure in the observation group after treatment was higher than that in the control group (mmHg: 67.8±9.9 vs. 62.0±10.5, P < 0.05). According to the New York Heart Association Heart (NYHA) function efficacy assessment score, the total effective rate of the observation group was higher than that of the control group [93.7% (30/32) vs. 83.3% (25/30), P > 0.05]. There was no statistical significant difference in the incidence of adverse reactions between the observation group and the control group [12.5% (4/32) vs. 30.0% (9/30), P > 0.05]. The patients in the two groups were followed up for one month after discharge, 9 cases (30.0%) in the control group were re-hospitalized due to heart failure, and 3 cases (9.4%) in the observation group were re-hospitalized due to heart failure, there was no statistical significant difference between the two groups in re-hospitalization rate (P > 0.05). Conclusion Oprinone hydrochloride can effectively improve cardiac function and maintain hemodynamic stability of patients after heart valve replacement surgery.

Neuro-osteological interactions have an important role in the regulation of bone metabolism and regeneration. Neuropeptides combined with porous biphasic calcium phosphates (BCP) using protein adsorption may contribute to the acceleration of bone formation. In the present study, we investigated the effect of BCP combined with nerve growth factor (NGF) on the growth of osteoblasts in vitro and the combinational therapeutic effect on the repair of calvarial defects in vivo. NGF was separated and purified from Chinese cobra venom using a simplified three-step chromatography method. BCP combined with NGF exerted a potent effect on osteoblast differentiation, as evidenced by enhanced cell proliferation, increased ALP activity and the up-regulated expression of osteogenesis-related genes and proteins. Further, combinational therapy with BCP and NGF improved calvarial regeneration, which was superior to treatment with therapy alone, as observed using imageological and morphological examination and histological and immunohistochemical staining. The results confirmed the effect of neuro-osteological interactions through combinatorial treatment with NGF and BCP to promote osteogenesis and bone formation, which may provide an effective and economical strategy for clinical application.
Acceleration ; Adsorption ; Asian Continental Ancestry Group ; Calcium Phosphates ; Cell Proliferation ; Ceramics* ; Chromatography ; Cobra Venoms ; Elapidae* ; Humans ; In Vitro Techniques ; Metabolism ; Methods ; Nerve Growth Factor* ; Neuropeptides ; Osteoblasts ; Osteogenesis ; Regeneration ; Therapeutic Uses*

Objective To study the effects and mechanism of p-hydroxyacetophenone (PHA ) on bile secretion ,choles-terol metabolism and blood lipids .Methods Cystic duct cannula was cannulated and bile were collected in SD rats .PHA was administrated in the high cholesterol rats .The activity of HMG-CoA reductase was determined by spectrophotometry in reac-tion system .Samples of liver were obtained in experiment hypercholesterolemia rats and Real-time PCR test was conducted for AQP8 ,CYP7A1 ,OATP and NTCP .Results Secretion of bile were increased ,cholesterol in bile were reduced and secretion of total bile acid were increased in rats by PHA .The level of serum cholesterol in hyperglycemia rat model was reduced signifi-cantly and inhibitory ability had been limited in the activity of HMG-CoA reeducates by PHA ,but the gene transcription inclu-ding AQP8 ,CYP7A1 ,OATP ,and NTCP were promoted ,which are related to function of excretion of biliary acid and trans-formation of cholesterol .Conclusion These results suggest that PHA ,as a lead compound ,might be of significance for fur-ther development for a bile secretory and lipid lowering agent .

Objective To detect the plasma level of tissue factor (TF) in non-small cell lung cancer (NSCLC) patients,and to discuss its association with hypercoagulation,venous thromboembolism and prognosis of lung cancer.Methods Sixty-one impatients in our hospital with confirmed lung cancer were enrolled as the study group.Thirteen patients with benign pulmonary diseases and 14 healthy volunteers were selected as the control groups.Bseline and follow-up clinical data were collected from participants.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TF in plasma of all subjects.Results The levels of TF in plasma from NSCLC patients and participants with benign pulmonary diseases was significantly higher than that in healthy controls((550.88 ± 201.58) ng/L vs (510.77 ± 201.20) ng/L vs (178.34 ±66.73) ng/L,P ＜0.05).According to the plasma levels of TF,which have been detected in all subjects,the patients were divided into two groups:low level group (range from 103.73 ng/L to 476.22 ng/L) and high level group (range from 476.221 ng/L to 1003.00 ng/L).Statistical analysis showed that there was a positive correlation between plasma TF levels and TNM stages in NSCLC patients (P =0.026).Patient with metastasis had a higher plasma TF level than other patients (P =0.020).The log-rank test revealed that there was no significant difference in survival between the high level group and low level group (x2 =0.145,P =0.704).Multivariate Cox proportional hazards regression analysis indicated that plasma TF levels did not predicted for death(RR =1.001,95％CI0.998-1.004,P=0.452).Conclusion The plasma TF level in NSCLC patients was correlated with TNM stages;it had no significant relationship with hypercoagulation state and survival rate in NSCLC patients.Limitations should be aware of while evaluating the clinical course and prediction of prognosis of NSCLC patients using plasma TF levels.

Objective To investigate the effect of anomalous pancreaticobiliary ductal union on the injuries of pancreas.Methods 10 health cats were treated by a 4～6 cm incision in biliary and pancreatic duct adjacent to duodenum, and interrupted suture was made to induce the model of anomalous pancreaticobiliary ductal union.The pancreatic tissues were harvested during model induction and 6 months after model induction,and histopathological changes were evaluated by electron microscopic examination and the level of maleic dialdehyde (MDA) were determined.Results Seven out of 10 cats survived surgery and remained alive for 6 months.6 months later,the pancreas appeared to be in the color of dark red and hyperemia,edema was present.Dilated pancreatic duct could be found in three of them.Light microscopic examination suggested there was inflammatory cell infiltration in the pancreas in 3 cats;mesenchymal vascular proliferation and white cell adhesion was present in the pancreas in 4 cats.Electron microscopic examination suggested rough endoplasmic reticulum expanding in the shape of pool,swelling mitochondria disaggregated and increased in number,Golgi complex became well developed.The preoperative level of MDA in pancreatic tissue was (1.23±0.7 ) nmol/mg prot,which increased to (2.90±1.9 ) nmol/mg prot 6 months later with statistically significant difference (F=4.80,P=0.0215 ).Conclusions This animal model demonstrated that anomalous pancreaticobiliary ductal union may cause injury to the pancreas,and antioxidant treatment may alleviate this injury.