Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca²⁺ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca²⁺ overload and fragmentation, and promoted intracellular Ca²⁺ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca²⁺ overload.
Male ; Mice ; Animals ; Heart Failure/drug therapy* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Berberine/therapeutic use* ; Disease Models, Animal ; Mitochondrial Dynamics ; Myocardium ; Homeostasis

Basophils, which are considered as redundant relatives of mast cells and the rarest granulocytes in peripheral circulation, have been neglected by researchers in the past decades. Previous studies have revealed their vital roles in allergic diseases and parasitic infections. Intriguingly, recent studies even reported that basophils might be associated with cancer development, as activated basophils synthesize and release a variety of cytokines and chemokines in response to cancers. However, it is still subject to debate whether basophils function as tumor-protecting or tumor-promoting components; the answer may depend on the tumor biology and the microenvironment. Herein, we reviewed the role of basophils in cancers, and highlighted some potential and promising therapeutic strategies.

OBJECTIVETo assess the clinical value of the diagnostic laparoscopy in choosing treatment strategies for patients with gastric cancer.

METHODSRetrospective analysis was performed on clinical and pathological data collected from 2 023 patients undergoing gastric cancer surgery in the Zhongshan Hospital of Fudan University from 2009 to 2014. All the patients were diagnosed as gastric cancer by endoscopic biopsy and staged by imaging examination before surgery. During the diagnostic laparoscopy procedure, a small periumbilical incision was made and a pneumoperitoneum with COunder 10-15 mmHg was established through a port. A 10 mm trocar was put in, and the camera was inserted. Two 5 mm trocars were put in two ports which located in midclavicular line two fingers under the left and right costal margin and then the instruments were inserted. A thorough inspection included ascites, the abdominal cavity, liver, diaphragm, spleen, greater omentum, colon, small intestine, mesentery, adnexa (female) and pelvic floor. If the tumor located at the posterior part of the stomach, the gastrocolic ligament was opened in order to look for carcinomatosis in the omental bursa. The accuracy rate of diagnostic laparoscopy in diagnosing adjacent organ invasion and intra-abdominal metastasis was calculated, and the rate of adjusting treatment plans after diagnostic laparoscopy was also calculated.

RESULTSThere were 52.7%(1 067/2 023) of patients underwent diagnostic laparoscopy. The accuracy rate of diagnostic laparoscopy in evaluating adjacent organ invasion and intra-abdominal metastasis were 98.3%(1 049/1 067) and 98.1%(1 047/1 067) respectively. Besides, 14 patients with stage T4b and 32 with intra-abdominal metastasis, which were missed by imaging examination, were diagnosed by diagnostic laparoscopy. The treatment plans of 9.3% (99/1 067) of patients were changed after diagnostic laparoscopy, and 65 (6.1%) cases of non-therapeutic laparotomy were avoided. However, 18 cases of adjacent organ invasion and 20 cases of intra-abdominal metastasis were still missed by diagnostic laparoscopy, and 12 cases received non-therapeutic laparotomy.

CONCLUSIONDiagnostic laparoscopy has considerable value in assessing adjacent organ invasion and intra-abdominal metastasis and has great clinical significance in making precise treatment plans.

Abdominal Neoplasms ; diagnostic imaging ; secondary ; Digestive System ; pathology ; Digestive System Surgical Procedures ; methods ; Female ; Humans ; Laparoscopes ; Laparoscopy ; instrumentation ; methods ; statistics & numerical data ; Laparotomy ; statistics & numerical data ; Male ; Neoplasm Invasiveness ; diagnostic imaging ; Patient Care Planning ; statistics & numerical data ; Retrospective Studies ; Stomach Neoplasms ; diagnostic imaging ; surgery ; Surgical Instruments ; Unnecessary Procedures ; statistics & numerical data

Endoscopy plays an important role in the diagnosis and treatment of postoperative complications of gastric cancer. Endoscopic intervention can avoid the second operation and has attracted wide attention. Early gastric anastomotic bleeding after gastrectomy is the most common. With the development of technology, emergency endoscopy and endoscopic hemostasis provide a new treatment approach. According to the specific circumstances, endoscopists can choose metal clamp to stop bleeding, electrocoagulation hemostasis, local injection of epinephrine or sclerotherapy agents, and spraying specific hemostatic agents. Anastomotic fistula is a serious postoperative complication. In addition to endoscopically placing the small intestine nutrition tube for early enteral nutrition support treatment, endoscopic treatment, including stent, metal clip, OTSC, and Over-stitch suture system, can be chosen to close fistula. For anastomotic obstruction or stricture, endoscopic balloon or probe expansion and stent placement can be chosen. For esophageal anastomotic intractable obstruction after gastroesophageal surgery, radial incision of obstruction by the hook knife or IT knife, a new method named ERI, is a good choice. Bile leakage caused by bile duct injury can be treated by placing the stent or nasal bile duct. In addition, endoscopic methods are widely used as follows: abdominal abscess can be treated by the direct intervention under endoscopy; adhesive ileus can be treated by placing the catheter under the guidance of endoscopy to attract pressure; alkaline reflux gastritis can be rapidly diagnosed by endoscopy; gastric outlet obstruction mainly caused by cancer recurrence can be relieved by metal stent placement and the combination of endoscopy and X-ray can increase success rate; pyloric dysfunction and spasm caused by the vagus nerve injury during proximal gastrectomy can be treated by endoscopic pyloromyotomy, a new method named G-POEM, and the short-term outcomes are significant. Endoscopic submucosal dissection (ESD) allows complete resection of residual gastric precancerous lesions, however it should be performed by the experienced endoscopists.
Anastomosis, Surgical ; adverse effects ; Bile Ducts ; injuries ; Constriction, Pathologic ; etiology ; therapy ; Digestive System Fistula ; etiology ; therapy ; Duodenogastric Reflux ; diagnostic imaging ; etiology ; Endoscopy, Gastrointestinal ; methods ; Enteral Nutrition ; instrumentation ; methods ; Female ; Gastrectomy ; adverse effects ; Gastric Outlet Obstruction ; surgery ; Gastritis ; diagnosis ; Gastrointestinal Hemorrhage ; etiology ; therapy ; Hemostasis, Endoscopic ; methods ; Hemostatics ; administration & dosage ; therapeutic use ; Humans ; Male ; Neoplasm Recurrence, Local ; surgery ; Postoperative Complications ; diagnosis ; therapy ; Precancerous Conditions ; surgery ; Pylorus ; innervation ; physiopathology ; surgery ; Stents ; Stomach Neoplasms ; complications ; surgery ; Treatment Outcome ; Vagus Nerve Injuries ; etiology ; surgery

OBJECTIVETo establish an evaluation model of peritoneal metastasis in gastric cancer, and to assess its clinical significance.

METHODSClinical and pathologic data of the consecutive cases of gastric cancer admitted between April 2015 and December 2015 in Department of General Surgery, Zhongshan Hospital of Fudan University were analyzed retrospectively. A total of 710 patients were enrolled in the study after 18 patients with other distant metastasis were excluded. The correlations between peritoneal metastasis and different factors were studied through univariate (Pearson's test or Fisher's exact test) and multivariate analyses (Binary Logistic regression). Independent predictable factors for peritoneal metastasis were combined to establish a risk evaluation model (nomogram). The nomogram was created with R software using the 'rms' package. In the nomogram, each factor had different scores, and every patient could have a total score by adding all the scores of each factor. A higher total score represented higher risk of peritoneal metastasis. Receiver operating characteristic (ROC) curve analysis was used to compare the sensitivity and specificity of the established nomogram. Delong. Delong. Clarke-Pearson test was used to compare the difference of the area under the curve (AUC). The cut-off value was determined by the AUC, when the ROC curve had the biggest AUC, the model had the best sensitivity and specificity.

RESULTSAmong 710 patients, 47 patients had peritoneal metastasis (6.6%), including 30 male (30/506, 5.9%) and 17 female (17/204, 8.3%); 31 were ≥ 60 years old (31/429, 7.2%); 38 had tumor ≥ 3 cm(38/461, 8.2%). Lauren classification indicated that 2 patients were intestinal type(2/245, 0.8%), 8 patients were mixed type(8/208, 3.8%), 11 patients were diffuse type(11/142, 7.7%), and others had no associated data. CA19-9 of 13 patients was ≥ 37 kU/L(13/61, 21.3%); CA125 of 11 patients was ≥ 35 kU/L(11/36, 30.6%); CA72-4 of 11 patients was ≥ 10 kU/L(11/39, 28.2%). Neutrophil/lymphocyte ratio (NLR) of 26 patients was ≥ 2.37(26/231, 11.3%). Multivariate analysis showed that Lauren classification (HR=8.95, 95%CI:1.32-60.59, P=0.025), CA125(HR=17.45, 95%CI:5.54-54.89, P=0.001), CA72-4(HR=20.06, 95%CI:5.05-79.68, P=0.001), and NLR (HR=4.16, 95%CI:1.17-14.75, P=0.032) were independent risk factors of peritoneal metastasis in gastric cancer. In the nomogram, the highest score was 241, including diffuse or mixed Lauren classification (54 score), CA125 ≥ 35 kU/L (66 score), CA72-4 ≥ 10 kU/L (100 score), and NLR ≥ 2.37 (21 score), which represented a highest risk of peritoneal metastasis (more than 90%). The AUC of nomogram was 0.912, which was superior than any single variable (AUC of Lauren classification: 0.678; AUC of CA125: 0.720; AUC of CA72-4: 0.792; AUC of NLR: 0.613, all P=0.000). The total score of nomogram increased according to the TNM stage, and was highest in the peritoneal metastasis group (F=49.1, P=0.000). When the cut-off value calculated by ROC analysis was set at 140, the model could best balanced the sensitivity (0.79) and the specificity (0.87). Only 5% of patients had peritoneal metastasis when their nomogram scores were lower than 140, while 58% of patients had peritoneal metastasis when their scores were ≥ 140(χ=69.1, P=0.000).

CONCLUSIONThe risk evaluation model established with Lauren classification, CA125, CA72-4 and NLR can effectively predict the risk of peritoneal metastasis in gastric cancer, and provide the reference to preoperative staging and choice of therapeutic strategy.

Antigens, Tumor-Associated, Carbohydrate ; blood ; Area Under Curve ; CA-125 Antigen ; blood ; CA-19-9 Antigen ; blood ; Female ; Humans ; Leukocyte Count ; statistics & numerical data ; Logistic Models ; Lymphocytes ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; diagnosis ; Neutrophils ; pathology ; Nomograms ; Peritoneal Neoplasms ; secondary ; Prognosis ; ROC Curve ; Retrospective Studies ; Risk Assessment ; methods ; Risk Factors ; Sensitivity and Specificity ; Stomach Neoplasms ; blood ; classification ; diagnosis ; pathology

With the introduction and promotion of "precision medicine" conception, the history of disease occurrence, progression and prognosis has been deeply investigated with more accuracy, and the surgical treatment concept has become more precise and minimally invasive. With the rapid development of minimally invasive technique, laparoscopic gastrectomy has become an important part for treatment of gastric cancer. A number of randomized controlled clinical trials, such as KLASS-01 and CLASS-01, have demonstrated that laparoscopic gastrectomy is safe and feasible for treatment of early and locally advanced gastric cancer, respectively. Endoscopic treatment would also be considered with strict indications. The surgical safety is identical between standard laparoscopy surgery and open surgery for local advanced gastric cancer. Radical cure, organ function preservation and reduced surgical trauma are the basic rules for minimally invasive treatment for gastric cancer. Specialized treatment mode, which consists of precise evaluation of tumor location, gastrectomy and lymph node resection, reduced surgical trauma and control of postsurgical complications, is the premise for implementation of minimally invasive surgery. Accurate preoperative staging, strict indication of operation, accurate quality control and postoperative management are important warrants for the effect of minimally invasive treatment in patients with gastric cancer. With standard diagnosis and treatment procedures, the specialized treatment mode for gastric cancer combined with standard surgical resection is an important force to promote the development of minimally invasive surgery. And what should we do to train and promote gastric cancer treatment in primary medical care centers is an urgent problem. With the development of equipment, minimally invasive treatment will be more professional, more precise, safer and less invasive. In the era of precision medicine, with deeper exploring the pathogenesis of gastric cancer, promoting the development of specialized treatment mode and strengthened surgical team training could meet the demand for minimally invasive treatment of gastric cancer. Therefore, specialized minimally invasive treatment is the trend of minimally invasive treatment for gastric cancer in the new era.

Objectives: Intracranial atherosclerosis, especially the middle cerebral artery (MCA), is the commonestvascular lesion for ischemic stroke the Chinese population. We explored the association of geneticpolymorphism and environmental factors in MCA atherosclerosis in the Chinese population. Methods:One hundred fifty-six ischemic stroke patients with MCA stenosis and 181 well-matched ischemicstroke patients without MCA stenosis were examined by polymerase chain reaction (PCR). ThePCR products were analyzed for lipoprotein lipase (LPL) S447X and paraoxonase1 (PON1) Q192Rpolymorphisms by restriction enzyme digestion. Medical history documentation and investigationof biochemical markers were performed for each subject. Results: Univariate analysis showed thatthe levels of systolic blood pressure (SBP) were higher in the MCA stenosis group. There were nosignificant differences in the genotype and allele frequencies of the LPL S447X and PON1 Q192Rpolymorphism observed between the two groups. But, in the patients above 60 years of age with andwithout MCA stenosis, LPL X carriers have higher level of SBP than the LPL SS genotype carriers.Multivariate logistic regression found that SBP was the significant, independent predictor of thepresence of MCA stenosis patients above 60 years of age (P < 0.001, OR=1.206, 95% confidenceintervals: 1.014-1.032).Conclusions: SBP appears to contribute to the pathogenesis of MCA stenosis among Chinese. Thegene polymorphism of LPL S447X may be associated with atherosclerotic MCA stenosis in Chinesepopulation.

OBJECTIVETo investigate the impact of additional gastrectomy after endoscopic submucosal dissection(ESD) on the prognosis of early gastric cancer.

METHODSClinical data of 107 early gastric cancer patients undergoing additional gastrectomy after ESD (research group, n=44) or radical surgery (control group, n=63) from January 2008 to December 2014 in Zhongshan Hospital were retrospectively analyzed. The reasons for additional gastrectomy after ESD included positive resection margin (n=10), lymphovascular invasion (n=5), well-differentiated mucosal tumor with a diameter >3 cm (n=10), poor-differentiated mucosal tumor with a diameter >2 cm (n=4), submucosal tumor(sm1) with a diameter >3 cm (n=10), and submucosal tumor(sm2) (n=9). Operation time, length of stay, lymph node metastasis, tumor recurrence and disease-free survival rate were compared between two groups.

RESULTSBaseline data of two groups were not significantly different (all P>0.05). After evaluation, absolute and relative indications were identified in 19 cases (43.2%) and 25 cases (56.8%) of research group, and in 28 cases (44.4%) and 35 cases(55.6%) of control group without significant difference (P=0.897). Lymph node metastasis occurred in 6 patients (4.5%) after surgery in research group and 6.3% in control group (P=0.690). Operation time was (218.5±74.3) minutes in research group and (219.8±81.8) minutes in control group (P=0.932). Length of stay was (10.0±12.3) days in research group and (10.8±9.9) days in control group (P=0.687). Follow-up time was (35.5±15.0) months in research group and (29.5±18.1) months in control group (P=0.072). Tumor recurrence rate was 4.5% in research group and 9.5% in control group (χ(2)=0.928, P=0.229). Mortality was 4.5% in research group and 7.9% in control group (χ(2)=0.487, P=0.485). Besides, no significant differences of operation mode (P=0.164), lymphatic clearance mode (P=0.330), number of harvested lymph node (P=0.467), morbidity of postoperative infection or fever (P=0.923) were found. Three-year tumor-free survival rate was 95.5% and 89.2% in research and control group respectively without significant differences (P=0.571).

CONCLUSIONAdditional gastrectomy after endoscopic submucosal dissection has no negative influence on the prognosis of patients with early gastric cancer, whose efficacy is similar to simple radical gastrectomy.

Aged ; Disease-Free Survival ; Early Detection of Cancer ; Endoscopic Mucosal Resection ; Female ; Gastrectomy ; methods ; Gastric Mucosa ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Lymphatic Vessels ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Operative Time ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Survival Rate

OBJECTIVETo evaluate the safety and short-term outcomes of laparoscopic-assisted surgery for rectal cancer by comparing the efficacy of laparoscopy and open surgery.

METHODSClinical data of patients with rectal cancer treated by laparoscopy or open surgery in Zhongshan Hospital from April 2011 to June 2012 were analyzed retrospectively, and the clinical outcomes between the two groups were compared.

RESULTSNinety-six rectal cancer patients undergoing laparoscopic surgery(LS) were enrolled. A total of 216 rectal cancer patients underwent open surgery(OS). There was no operative death in both groups. In LS and OS group, the overall completion rates of TME were 86.4%(83/96) vs. 89.3%(193/216)(P>0.05) respectively, and the overall anal reservation rates were 78.1%(75/96) vs. 75.0%(162/216)(P>0.05) respectively. The mean distance to proximal resection margin and distal resection margin respectively were (10.3±4.1) cm vs.(10.0±4.3) cm(P>0.05) and (3.4±0.9) cm vs. (3.6±1.4) cm(P>0.05) respectively. The mean number of harvested lymph nodes respectively were (12.8±5.2) vs.(13.7±6.4)(P>0.05). Compared to OS, LS presented less blood loss [(98.0±28.7) ml vs. (175.0±41.0) ml, P<0.05], shorter postoperative hospital stay [(9.4±4.9) d vs.(11.6±6.2) d, P<0.05], quicker postoperative recovery of bowel function[(2.7±0.9) d vs. (3.4±0.9) d, P<0.05], shorter postoperative time to intake semi-solid[(3.7±1.2) d vs. (4.4±1.5) d, P<0.05], less postoperative complications(15.6% vs. 25.9%, P<0.05), but longer operative time[(155.7±48.4) min vs. (120.0±26.7) min, P<0.05]. Postoperative follow-up was 6 to 24 months, and the local recurrence of LS and OS was 2.1% and 2.3%(P>0.05).

CONCLUSIONLaparoscopic surgery can obtain the same radical efficacy for rectal cancer as compared to open surgery.

Anal Canal ; Digestive System Surgical Procedures ; Humans ; Laparoscopy ; Lymph Nodes ; Neoplasm Recurrence, Local ; Operative Time ; Postoperative Complications ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Treatment Outcome