Objective:To analyse the differences of related genes between serum alpha-fetoprotein (AFP) positive gastric cancer and AFP negative gastric cancer, and the relationship between related genes and prognosis of serum AFP positive gastric cancer.Methods:A total of 1 144 gastric cancer patients undergoing surgery at the 940th Hospital , Joint Logistic Support Force, People's Liberation Army from Jan 2013 to Dec 2018 were retrospectively analyzed. Of them, 47 cases were of AFP positive gastric cancer, and 47 serum AFP negative case were obtained by proper matching method.Results:Forty-seven patients with serum AFP positive gastric cancer, accounting for 4.1% of all gastric cancer patients during the same period. The prognosis of serum AFP negative gastric cancer is better than that of serum AFP positive gastric cancer. The 1-, 3- and 5-year cumulative survival rates were 95.6% vs. 63.8%, 48.9% vs. 23.4% and 26.7% vs. 14.9%, respectively. There were statistical differences in the immunohistochemistry of AFP, HER2, VEGF, GPC3, SALL4, P53 and Ki67 between the two groups ( χ2=67.758, P<0.001; χ2=4.004, P=0.044; χ2=19.299, P<0.001; χ2=5.232, P=0.022; χ2=6.359, P=0.012; χ2=6.224, P=0.013; χ2=5.232, P=0.022). The more co-positive expressions of AFP, GPC3, VEGF and SALL4, the more likely they were to affect pTNM stage, vascular invasion and liver metastasis ( χ2=5.328, P=0.021; P=0.013; χ2=5.887, P=0.015; χ2=3.923, P=0.048). Univariate and multivariate survival analysis of serum AFP positive gastric cancer showed:AFP, GPC3, VEGF and SALL4 were risk factors for AFP positive gastric cancer ( HR=3.700, P=0.036; HR=4.237, P=0.003; HR=3.916, P=0.004; HR=3.412, P=0.001). Conclusions:Serum AFP positive gastric cancer is a rare and highly invasive special type of gastric cancer. AFP, GPC3, VEGF and SALL4 are overexpressed in serum AFP positive gastric cancer, which is correlated with tumor stage, vascular invasion and liver metastasis. The final diagnosis of serum AFP positive gastric cancer still needs immunohistochemical examination. Preoperative serum AFP level is an important basis for AFP positive gastric cancer screening and AFP immunohistochemical examination.

In order to standardize the postoperative pain management in adults in China, the Chinese Society of Anesthesiology formulated the "Clinical practice guidelines for postoperative pain management in adults (2024 edition)" according to the methods and steps of the "Principles for Formulation/Revision of Clinical Diagnosis and Treatment Guidelines in China (2022 Edition)". This protocol mainly introduced the purpose of guideline formulation, the formation and responsibilities of the working group, the collection and selection of clinical questions, the evaluation and synthesis of evidence, the formation of recommendations and other processes.

Objective    To evaluate the efficacy and safety of modified maze Ⅳ (Cox-maze Ⅳ) in hypertrophic obstructive cardiomyopathy (HOCM) patients. Methods    From June 2016 to June 2019, 30 HOCM and persistent atrial fibrillation (pAF) patients received Cox-maze Ⅳ operation with modified extended Morrow operation, including 21 males and 9 females. The average age was 51.36±10.27 years and the average weight was 72.48±11.29 kg. All patients underwent left atrial appendectomy. Recurrence of AF, improvement of symptoms, cardiac function (NYHA) were assessed during follow-up. Results    There was no death during the perioperative period. Postoperative left ventricular outflow tract gradient was significantly decreased compared with that before operation (P<0.01), and all systolic anterior motion (SAM) signs disappeared after operation. Thirty patients were all effectively followed up for 3-40 (16.24±8.26) months. During the follow-up period, there was no death, and the cardiac function (NYHA) of all patients recovered to gradeⅠ-Ⅱ. At the end of follow-up, twenty-four patients (80.00%) maintained sinus rhythm, and twenty-seven patients (90.00%) maintained sinus rhythm after amiodarone conversion. Univariate analysis showed that the smoking history (P=0.04), left atrial diameter≥55 mm before operation (P=0.03), left atrial diameter≥50 mm after operation (P=0.02), postoperative tricuspid regurgitation (P=0.02) were closely related to postoperative AF recurrence. The increase of left atrial diameter after operation was an independent risk factor for AF recurrence (P=0.02). Conclusion    Morrow/Cox-maze Ⅳ procedure is safe and effective in treatment of patients with HOCM complicated with pAF, which helps to maintain postoperative sinus rhythm, and to improve the cardiac function. The increase of left atrial diameter after operation is an independent risk factor for AF recurrence.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable malignancy, with an only 6% 5-year relative survival rate. The dismal therapeutic effect is attributed to the chemotherapy resistance and unique pathophysiology with abundant inflammatory cytokines and abnormal hyperplasia of extracellular matrix (ECM). Based on the theory that bone marrow mesenchymal stem cells (BM-MSCs) can influence the tumorous microenvironment and malignant growth of PDAC, we employed exosomes (Exos) derived from BM-MSCs as PDAC-homing vehicles to surpass the restrictions of pathological ECM and increase the accumulation of therapeutics in tumor site. To overcome chemoresistance of PDAC, paclitaxel (PTX) and gemcitabine monophosphate (GEMP)-an intermediate product of gemcitabine metabolism-were loaded in/on the purified Exos. In this work, the Exo delivery platform showed superiorities in homing and penetrating abilities, which were performed on tumor spheroids and PDAC orthotopic models. Meanwhile, the favorable anti-tumor efficacy and , plus relatively mild systemic toxicity, was found. Loading GEMP and PTX, benefitting from the naturally PDAC selectivity, the Exo platform we constructed performs combined functions on excellent penetrating, anti-matrix and overcoming chemoresistance (Scheme 1). Worth expectantly, the Exo platform may provide a prospective approach for targeted therapies of PDAC.

Objective To summarize the perioperative management strategies and early results of modified Morrow expanded operation and coronary artery bypass grafting (CABG) in patients with hypertrophic obstructive cardiomyopathy (HOCM) and coronary atherosclerotic heart disease. Methods Between January 2012 and December 2017, in the Second Inpatient Department of Fuwai Hospital, 32 patients (20 females and 12 males) underwent modified expanded Morrow operation and CABG. The median age was 53.7±8.7 years (interquartile range 37 to 67 years). Preoperative chest distress symptom was found in 24 patients, chest pain symptom was found in 14 patients, history of syncope in 6 patients. Cardiac echocardiography, electrocardiogram, chest X-ray, magnectic resonance imaging (MRI) were performed routinely after operation and follow-up to analyze structure and function of heart and mitral valve. Results All patients underwent modified and expanded Morrow combined with CABG. The preoperative left ventricular outflow tract peak pressure difference (LVOTG) was 40 to 152 (79.6±28.7) mm Hg. Four patients underwent myocardial bridge releasing in the same period, mitral valve replacement in 2 patients, mitral valve angioplasty in 3 patients, Maze operation in 2 patients and tricuspid valveoplasty in 3 patients. There was no hospital mortality. CABG surgery in patients with branches included anterior descending artery in 26 patients, diagonal branch in 16 patients, left circumflex in 8 patients, right coronary artery in 11 patients. There were 15 patients with one coronary artery (CA) bypass graft, 5 patients with two CA bypass grafts, and 12 patients with 3 CA bypass grafts. The average of CA bypass grafts was 1.9±0.6. The postoperative ICU time ranged from 1–13 (4.1±2.8) days and postoperative hospital stay ranged from 7 to 30 (12.6±5.5) days. No severe postoperative complications were found and 1 patient had postoperative incision healing. The postoperative new arrhythmia included left bundle branch block in 6 patients. Compared with the preoperative values, postoperative left ventricular outflow tract peak pressure (79.6±28.7 mm Hg vs. 10.8±5.9 mm Hg, P<0.001), interventricular septum thickness (1.9±0.4 cmvs. 1.3±0.5 cm, P<0.001) were decreased obviously. Mitral valve closure is good or only mild reflux, mitral valve forward movement (SAM sign) disappeared. The patients were followed up for 6-68 months, with an average of 38.8±20.6 months. All patients were followed up with symptoms disappeared or only mild symptoms. NYHA classification decreased Ⅰ to Ⅱ grade after surgery, without long-term mortality, complications or reoperation. Conclusion For patients with hypertrophic obstructive cardiomyopathy with coronary atherosclerotic heart disease, the application of improved expand morrow operation at the same time undergoing coronary artery bypass grafting is safe. It can significantly improve patients' survival and reduce symptoms, play a synergistic effect, and do not increase the patient's surgical complications.

Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them. The purpose of this work is to construct a self-assembled glutathione (GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription (RCT) method. GSH-responsive cationic polymer polyethyleneimine (pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid (DHA), a targeting molecule, which is a substrate of glucose transporter 1 (GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.

The blood-brain barrier (BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme (GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel (PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles (NPs). Here we characterize PTX-loaded human serum albumin (HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P (SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content (7.89%) and entrapment efficiency (85.7%) with a spherical structure (about 150 nm) and zeta potential of -12.0 mV. The drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells (BCECs) and U87 cells was greatly improved. The low IC, prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.

Objective To determine whether thyroid hormone (TH) level could also be an independent and incremental predictor of adverse events in patients with hypertrophic cardiomyopathy (HCM).Methods A total of 982 consecutive patients with HCM at the National Center for Cardiovascular Diseases (China) from October 2009 to December 2013 were included in the present study,and followed up till the end of December 2016.The patients were divided into three groups according to the levels of free triiodothyronine (FT3):the group 1 (FT3≤4.28 pmol/L,n=335),the group 2 (FT3＞4.28-＜4.79 pmol/L,n=310),and the group 3 (FT34.79-6.30 pmol/L,n=337).Results After a follow-up period of (53.8 ± 14.1) months,39 patients (4.0％) either suffered death with all causes or received a cardiac transplantation (7.8％,2.9％ and 1.2％ of the patients in the group 1,group 2 and group 3,respectively).A multivariable Cox regression analysis revealed that FT3≤4.28 pmol/L was associated with a significantly higher risk of all-cause mortality or cardiac transplantation (HR 8.83,95％ CI 1.115-69.905,P=0.039) in HCM patients.Conclusions Low levels of FT3 is a risk factor of adverse events for patients with HCM,indicting a role of FT3 as a marker for assessing the risk of long-term adverse events in these patients.

Objective: To determine the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the long-term outcome of patients with hypertrophic cardiomyopathy (HCM) . Methods: NT-proBNP was measured in 831 consecutive patients with HCM at Fuwai Hospital from October 2009 to December 2013 and patients were followed up clinically for (53.3±15.4) months. Patients were divided into 3 groups according to NT-proBNP values: NT-proBNP<860 pmol/L (n=276) , 860 pmol/L≤NT-proBNP≤1 905 pmol/L (n=278) , NT-proBNP>1 905 pmol/L (n=277) . The related baseline data, laboratory examination and echocardiographic results were compared among groups. The primary endpoints of this study were all-cause mortality and cardiac transplantation. Cox proportional hazards model was used to estimate hazard ratio (HR) . Kaplan-Meier analysis was used to evaluate the survival status of patients among the 3 groups. Results: During a median follow-up of (53.3±15.4) months, all-cause mortality or cardiac transplantation occurred in 37 patients (4.5%) , event rate was 1.4% (4/276) , 4.0% (11/278) and 7.9% (22/277) in patients with NT-proBNP<860 pmol/L, 860 pmol/L≤NT-proBNP≤1 905 pmol/L and NT-proBNP>1 905 pmol/L, respectively. Multivariable Cox regression analysis identified that age (HR 1.066, 95%CI 1.027-1.107) and NT-proBNP (HR 1.026, 95% CI 1.010-1.042) were independent predictors of all-cause mortality or cardiac transplantation. Among the 3 groups, the survival rate of the NT-proBNP<860 pmol/L group was the highest,and that of the NT-proBNP>1 905 pmol/L group was the lowest (P<0.01) . Conclusions The level of NT-proBNP provides clinically relevant information for long-term adverse events risk stratification in patients with HCM.

Objective: To evaluate the efifcacy of modiifed extended Morrow procedure on hypertrophic obstructive cardiomyopathy (HOCM) in adolescent patients. Methods: We retrospectively studied 29 consecutive HOCM patients at the age≤21 years who received modiifed extended Morrow procedure in our hospital from 2011 to 2015 for their clinical conditions to assess surgical efifcacy. Echocardiography was performed to compare left atrial size, left ventricular end diastolic diameter, left ventricular ejection fraction, left ventricular outlfow tract peak pressure, ventricular septal thickness, mitral systolic anterior motion and mitral regurgitation grade before and after operation. Moreover, pre-operative and post-operative plasma NT-proBNP levels were determined. Cardiac function was evaluated by New York Heart Association functional class. Results: There were 17 (58.6%) patients received isolated modiifed extended Morrow procedure and 12 patients had concomitant operation including 8 (27.6%) with coronary artery bypass grafting. Compared with pre-operation, the post-operative thickness of ventricular septum decreased from (24.6 ± 6.8) mm to (16.9 ± 7.1) mm, left ventricular outlfow tract gradient decreased from (68.8 ± 15.7) mmHg to (10.7 ± 4.2) mmHg, bothP<0.001; mitral regurgitation degree reduced from (1.7 ± 1.3) to (0.2 ± 0.4),P<0.01; NYHA classification improved from (3.4 ± 0.8) to (1.4 ± 0.5),P<0.01; plasma level of NT-proBNP reduced from (1957.6 ± 392.5) ng/ml to (458.7 ± 161.0) ng/ml,P<0.01. There was no peri-operative death, the survival rates at 12, 24 and 36 months post-operation were 100%, 86.7% and 86.7% respectively. Conclusion: Modiifed extended Morrow procedure has been a safe and effective method for treating adolescent HOCM patients, adequate exposure is the key point to assure surgical efifcacy.