Objective To investigate the effect of rosuvastatin on the morphine tolerance in rats and the underlying mechanism.Methods Forty-eight male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 6 groups (n =8 each):control group (group C),morphine tolerance group (group MT),rosuvastatin control group (group RC),rosuvastatin 0.4 mg/kg group (group R1),rosuvastatin 2.0 mg/kg group (group R2)and rosuvastatin 10.0 mg/kg group (group R3).Morphine tolerance was induced by subcutaneous injection of morphine 10.0 mg/kg at 8:00 and 16:00 everyday for 5 consecutive days.The equal volume of normal saline was given in groups C and RC.Normal saline 10 ml/kg was injected through a gastric tube into stomach everyday at 30 min after subcutaneous injection of normal saline or morphine for 5 consecutive days in groups C and MT.Rosuvastatin 10,0.4,2.0 and 10.0 mg/kg were injected through a gastric tube into stomach everyday at 30 min after subcutaneous injection of normal saline or morphine for 5 consecutive days in groups RC,R1,R2 and R3,respectively.The paw withdrawal latency to nociceptive thermal stimulation was measured 1 day before (T1) and 1 day after morphine tolerance was induced (T2).The percentage of maximal possible effect (MPE) was calculated.The rats were sacrificed after the last measurement of pain threshold and the L5 segment of the spinal cord was removed for determination of the expression of extracellular signal-regulated kinase (ERK) and phosphorylated ERK (p-ERK)(by Western blot) and contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) (by ELISA).Results Compared with group C,MPE was significantly decreased at T2 and the expression of p-ERK and contents of IL-1β and TNF-α were increased in groups MT and R1 (P ＜ 0.05).Compared with group MT,MPE was significantly increased at T2 and the expression of p-ERK and contents of IL-1β and TNF-α were decreased in groups RC,R2 and R3 (P ＜ 0.05).There was no significant difference in the indicators mentioned above between groups R2 and R3,and in the expression of ERK between the six groups (P ＞ 0.05).Conclusion Rosuvastatin can attenuate the morphine tolerance in rats by inhibiting the phosphorylation of ERK and decreasing the level of IL-1β and TNF-α.

Glucose transporter type 1 deficiency syndrome is a rare neurometabolic disorder caused by mutations of the solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) gene, characterized by complex manifestations including early onset epilepsy, motor and mental retardation, and movement disorders and so on. Ketogenic-diet is most suitable therapy and should be commenced as early as possible because timing the initiation of the diet may prevent seizure, movement disorder, and cognitive impairment. This review aims to improve the clinicians′ understanding of glucose transporter type 1 deficiency syndrome to ensure the diagnosis as early as possible.

As muscle activity during growth is considerably important for mandible quality and morphology,reducing dietary loading directly influences the development and metabolic activity of mandibular condylar cartilage (MCC).However,an overall investigation of changes in the protein composition of MCC has not been fully described in literature.To study the protein expression and putative signaling in vivo,we evaluated the structural changes of MCC and differentially expressed proteins induced by reducing functional loading in rat MCC at developmental stages.Isobaric tag for relative and absolute quantitation-based 2D nano-high performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight/ time-of-flight (MALDI-TOF/TOF) technologies were used.Global protein profiling,KEGG and PANTHER pathways,and functional categories were analyzed.Consequently,histological and tartrate-resistant acid phosphatase staining indicated the altered histological structure of condylar cartilage and increased bone remodeling activity in hard-diet group.A total of 805 differentially expressed proteins were then identified.GO analysis revealed a significant number of proteins involved in the metabolic process,cellular process,biological regulation,localization,developmental process,and response to stimulus.KEGG pathway analysis also suggested that these proteins participated in various signaling pathways,including calcium signaling pathway,gap junction,ErbB signaling pathway,and mitogen-activated protein kinase signaling pathway.Collagen types Ⅰ and Ⅱ were further validated by immunohistochemical staining and Western blot analysis.Taken together,the present study provides an insight into the molecular mechanism of regulating condylar growth and remodeling induced by reducing dietary loading at the protein level.

Background and objective Paclitaxol (PTX) resistance is one of main factors which affect the outcome of chemotherapy of lung adenocarcinoma. The aim of this study is to compare the secreted protein expression profiles between Paditaxol (PTX) resistant and sensitive lung adenocarcinoma cells by proteomic research method, so as to provide evidence of choosing individual chemotherapy drugs in clinical treatment. Methods Total secreted proteins extracted from a PTX sensitive cell line A549 and a PTX resistant cell line A549-Taxol were separated by fluorscent differential gel electrophoresis (DIGE). High quality 2-DE profiles were obtained and analyzed by Decyder 6.5 analysis software to screen differentially expressed protein spots. Those spots were identified by mass spectrometry. Results 2-DE patterns of lung adenocarcinoma cells with high-reso-lution and reproducibility were obtained. 76 significantly differentially expressed protein spots were screened, 19 proteins were identified by mass spectrometry. The identified proteins could be classified into different catogories: metabolic enzyme, extracel-lular matrix (ECM) degradation enzyme, cytokine, signal transducer, cell adhesion, and so on. Conclusion Multiple secreted proteins related to chemoresistance of A549-Taxol cells were identified in this study for the first time. The results presented here would provide dues to identify new serologic chemoresistant biomarkers of NSCLC.

Acute symptomatic seizures secondary to autoimmune encephalitis refers to seizures that occur during the active stage of immune-mediated encephalitis,and autoimmune-related epilepsy refers to disorders with an immune etiol-ogy and a long-term predisposition to unprovoked seizures.Both diseases often have poor response to antiepileptic drugs,and early identification of immune etiology and initiation of immunotherapy may help patients achieve a good prognosis.However,there are no guidelines for the use of drugs in patients with different types of symptomatic seizures,and there is also a lack of diagnostic criteria and treatment principles for autoimmune-related epilepsy.This article reviews and dis-cusses the two diseases from the aspects of possible pathogenesis,clinical manifestations,and recommended treatment methods,so as to provide a theoretical basis for diagnosis and treatment and help to determine future research directions.

Objective To compare the clinical outcomes of endoscopic nasobiliary drainage (ENBD) versus percutaneous transhepatic biliary drainage (PTBD) in patients with perihilar cholangiocarcinoma.Methods This retrospective case-control study was conducted on 55 patients with perihilar cholangiocarcinoma who were treated by of hepatobiliary and pancreatic surgeons at the Nanjing Drum Tower Hospital between December 2010 and August 2017.Results There was no significant difference in the effectiveness of the two drainage methods (P＞0.05).Morbidity after drainage was significantly higher in the ENBD group than the PTBD group (86.7％ vs 28.0％,P＜0.05).24 patients in the ENBD group developed postERCP pancreatic complications which included hyperamylasemia (n =20) and pancreatitis (n =4).All these patients responded well to conservative treatment.A patient in the PTBD group developed catheter tract tumor implantation.There were no significant differences in the surgical outcomes and in the different Clavien-Dindo grades of complications (P＞0.05).Abdominal infection after surgery was more common in the PTBD group than the ENBD group (64.3％ vs 26.3％,P＜0.05).Conclusion As PTBD caused catheter tract tumor implantation and increased the incidence of abdominal infection after surgery,ENBD was recommended for patients with perihilar cholangiocarcinoma treated in a tertiary medical center.

Objective: To investigate the clinical effect of bile reinfusion combined with enteral nutrition support before surgery for hilar cholangiocarcinoma. Methods: A retrospective analysis of patients with hilar cholangiocarcinoma who underwent surgical treatment at Nanjing Drum Tower Hospital Hepato-biliary-pancreatic Surgery Department from July 2010 to August 2017 was completed.A total of 52 cases were finally enrolled in our study.All the patients included, on the basis of whether they received preoperative drainage and bile reinfusion, were divided into non-drainage group(n=15) and drainage group(n=37). Differences of clinical indicators, including operation time, intraoperative bleeding and serum liver function index levels at day 1, 3, 7 postoperative, postoperative complications(liver failure, biliary fistula, pleural effusion, peritoneal effusion, abdominal cavity infection, death in hospital), tumor classification, R0 resection, postoperative hospitalization time between the 2 groups were analyzed. At the same time, in the drainage group, patients were divided into non-enteral nutrition subgroup(n=13) and enteral nutrition subgroup(n=24) according to whether they received enteral nutrition before operation. The normal distribution data of the group was statistically analyzed by independent sample t test, the non-normal distribution data of the group was statistically analyzed by rank-sum test. The count data was statistically analyzed by non-calibration and correction of the square test. Results: There was no statistically significant difference in general infomation such as age, gender, and serum liver function between non-drainage group and drainage group(P>0.05). There was no statistically significant difference in general information such as age, gender, and serum liver function between non-enteral nutrition group and enteral nutrition group(P>0.05). The rate of vascular resection and reconstruction(33.3%) and operating time(10.8(2.2)h) in drainage group were both higher than those in non-drainage group(6.7% and 8.3(3.0)h), the differences were both statistically significant(χ²=4.397, Z=1.595; both P<0.05). The level of AST at the 7th day after surgery in drainage group(32.8(17.3)U/L) was significantly lower than that in non-drainage group(55.0(64.7)U/L), the difference was statistically significant(Z=-2.212, P<0.05). The level of TBil at 1st day after surgery in drainage group(43.6(91.2)μmol/L) was lower than that in non-drainage group(91.2(188.4)μmol/L), the difference was statistically significant(Z=-2.150, P<0.05). The rate of pancreatoduodenectomy(25.0%) and average operating time(11.1(1.3)h) in the enteral nutrition group were both higher than those in the non-enteral nutrition group(0, 9.0(2.6)h). The differences were both statistically significant(χ²=3.879, Z=-2.693; P<0.05). The average level of AST at the 1st day after surgery in enteral nutrition group(396.4(268.3)U/L) was significantly lower than that in non-enteral nutrition group(642.5(341.1)U/L), the difference was statistically significant(Z=-2.483, P<0.05). The average level of TBil at the 1st, 3th day after surgery in enteral nutrition group(38.8(21.5)μmol/L and 30.0(25.6)μmol/L) were both lower than those in non-enteral nutrition group(60.9(75.2)μmol/L and 46.5(50.0)μmol/L), the differences were both statistically significant(Z=-2.416, -2.026; P<0.05). The level of CRP at 1st, 3th day after surgery((41.9±31.1)mg/L, (50.8±31.4)mg/L)in enteral nutrition subgroup was lower than that in non-enteral nutrition subgroup((64.4±33.6)mg/L, (74.1±35.3)mg/L), the differences were both statistically significant(t=1.456, 1.675; P<0.05). Conclusion Based on the present study , there is no effective improvement on postoperative recovery using bile reinfusion combined with nutrition support before R0 resection of hilar cholangiocarcinoma.

Clinical data of 15 patients diagnosed with acute renal infarction (ARI) in Affiliated Zhongshan Hospital of Dalian University from Jan 2011 to Dec 2021 were retrospectively analyzed. Of the included 15 patients, there were 14 cases of cardiac origin and 1 case of antiphospholipid syndrome. We found that there were 12 cases of atrial fibrillation, 2 cases of atrial premature beats, 12 cases of elevated level of D-dimer, 15 cases of elevated level of LDH, 11 cases of positive urine occult blood and positive urine protein. Among the 15 patients, catheter-directed thrombolysis was performed in 4 cases, of which 3 cases were revascularized successfully, intravenous thrombolysis in 2 cases and alone anticoagulation therapy in 9 cases. It is suggested that CECT or CTA can assist the early diagnosis of ARI especially in patients with acute onset and persistent abdominal pain with high risk factors of thromboembolism, high levels of LDH, microscopic hematuria and/or proteinuria. Despite prolonged embolic ischemia, try to reconstruct blood flow to save the kidney as much as possible. Late standardized anticoagulant therapy is of critical importance to prevent recurrent embolic episodes.

Patients with severe tumors do not refer to the patients with end-stage tumors,but rather to the patients with a performance status(PS)score between 2 and 4 in certain stages due to various reasons,such as acute or chronic comorbidities,tumor itself,or treatment-related adverse events.To these patients,there is a high probability of achieving survival benefit and/or improvement in PS scores after synergistic management of available life-support technologies and anti-tumor therapies based on dynamic and precise testing.Elderly patients with tumors frequently present with one or more chronic illnesses and have poor toler-ance and compliance to treatment.Moreover,their treatment regimens often lack high-quality clinical evidence,making them more susceptible to developing severe tumors.The management of severe tumors in the elderly is based on three basic diagnosis and treatment technologies:dynamic and precise detection,powerful life support technologies,and skillful application of current anti-tumor treatments.In specific clinical practice,the following 7 flexible and individualized treatment strategies should be adopted for different tumor types:1.concurrent management of cancer and comorbidities,2.upgrading and downgrading of anti-tumor drugs based on PS score,3.dynamic accurate detection,4.skillful combinations for increasing efficacy and reducing toxicity,5.complete overview,paying equal attention to systemic therapy and local therapy,6.safety first in medication for the elderly,7.multi-discipli-nary participation,individualized and comprehensive treatment.This article introduced the concept of severe tumors in the elderly and the associated management strategies,to increase awareness and provide feasible guidance for clinical practice.

Objective: To analyze the treatment of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4, in order to improve the diagnosis and treatment of these patients. Methods: A total of 36 patients with advanced NSCLC with hypoxemia were reviewed. The clinical data of disease characteristics, etiology, complications, manifestation, therapy, progression, and secondary biopsy were collected. The clinical efficacy was graded according to the Response Evaluation Criteria In Solid Tumors (RECIST): complete response (CR), partial response (PR), stable disease (SD) and disease progression (PD). Results: All patients had hypoxemia, of whom 86.1% (31 patients) had complications and 55.6% (20 patients) had noninvasive ventilator for respiratory support. 77.8% (28 cases) received broad-spectrum antibiotic treatment, and 78.6% of them got lung osmotic relief after the anti-infection treatment. 15 cases received bedside fiberoptic bronchoscopy suction, of whom two cases were treated with airway stent deposition due to airway obstruction, four cases with thoracic drainage, four cases with anticoagulation, and one with thrombolytic therapy. After these supportive treatment, the PS score of these patients decreased from 3.4±0.5 to 2.5±0.7, while SPO₂ improved from (89.0±5.2)% to (95.0±3.5)%. As first-ling anti-cancer treatment, nine patients were administrated with targeted medicine orally, 13 patients with a combined chemotherapy of pemetrexed plus bevacizumab or carboplatin, eight patients with paclitaxel plus carboplatin, four patients with gemcitabine plus carboplatin, and two patients with docetaxel plus gemcitabine. In the first response evaluation, there were one case of CR, 23 cases of PR, four cases of SD, and eight cases of PD, with a clinical benefit rate of 66.7% and a disease control rate of 77.8%. A total of 22 patients experienced disease progression, of whom eight cases had a secondary biopsy and six cases had gene sequencing. Of these 36 patients, 10 (27.8%) patients survived at the last follow-up, with a progression-free survival of (10.0±6.5) months. Conclusion Besides prompt anti-cancer treatment and best supportive treatment should be incorporated to improve PS and improve outcome.