Pharmacological and toxicological studies of a novel goserelin acetate extended-release microspheres in rats.

LY01005 is an investigational new drug product of goserelin acetate which is formulated as extended-release microspheres for intramuscular injection. To support the proposed clinical trials and marketing application of LY01005, pharmacodynamics, pharmacokinetics and toxicity studies were performed in rats. In the pharmacological study in rats, LY01005 induced an initial supra-physiological level increase of testosterone at 24 h post-dosing which then rapidly fell to castration level. The potency of LY01005 was comparable to the comparator Zoladex® but its effect lasted longer and more stable. A single-dose pharmacokinetics study in rats demonstrated that the Cmax and AUClast of LY01005 increased in a dose-proportional manner in the range of 0.45-1.80 mg/kg and the relative bioavailability was 101.0% between LY01005 and Zoladex®. In the toxicity study, almost all of the positive findings of LY01005 in rats including the changes in hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, progestin) and in reproductive system (uterus, ovary, vagina, cervix uteri, mammary gland, testis, epididymis and prostate) were related to the direct pharmacological effects of goserelin. Mild histopathological changes in foreign body removal reaction induced by excipient were also observed. In conclusion, LY01005 displayed a sustained-release profile of goserelin, and exerted a continuous efficacy in vivo in animal models, which had a comparable potency but with a more sustained effect than that of Zoladex®. The safety profile of LY01005 was largely the same with Zoladex®. These results strongly support the planned LY01005 clinical trials.

Non-clinical pharmacology and toxicology studies of bevacizumab biosimilar LY01008.

LY01008 was a biosimilar of Avastin® developed by Shandong Boan Biotechnology. To support the clinical trial and marketing application of LY01008 as a biosimilar, a series of non-clinical pharmacodynamics (PD), pharmacokinetics (PK), and toxicological studies have been conducted. The PD study results showed that LY01008 had similar pharmacodynamic effects with Avastin in VEGF (vascular endothelial growth factor) binding activity, inhibitory effect on angiogenesis and vascular permeability, and anti-tumor activities in nude mouse models alone or combined with chemotherapeutic agents. PK study showed that LY01008 had similar PK parameters with Avastin at the same doses, and the relative bioavailability of LY01008 was 111.4%. The maximum tolerated dose of LY01008 in the single-dose toxicity study of cynomolgus monkeys was greater than 258 mg/kg. LY01008 had no effects on central nervous system, cardiovascular system and respiratory system in cynomolgus monkeys. LY01008 had no hemolytic effect in vitro and no local irritation in cynomolgus monkeys. The immunogenicity of LY01008 was no higher than that of Avastin in cynomolgus monkeys. In the one-month multiple-dose toxicity study in cynomolgus monkeys, the toxicokinetics profiles of LY01008 was similar with Avastin, the characteristics of the toxic reactions were the same and the extent was similar between LY01008 and Avastin, and no new toxic reactions were observed on LY01008. In conclusion, LY01008 had a good safety profile, and was biosimilar with Avastin in the comparative studies of pharmacodynamics, pharmacokinetics, toxicokinetics and toxicology, which supported the clinical trial and marketing application of LY01008 as a biosimilar of Avastin.

Evaluation of antibody kinetics and durability in health subjects vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China

BackgroundAlthough inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed. MethodsWe enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests. ResultsOur results revealed that binding antibody IgM peaked 14-28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The NAb inhibition rate subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89) to 17.8% (16/90). ConclusionsTwo doses of CoronaVac vaccine resulted in limited protection over a short duration. The homologous booster slightly increased antibody responses to the Delta and Omicron variants; therefore, the optimization of booster procedures is vital. FundingKey Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation.

Mechanism of Ganshuang granule extract in alleviating N-acetyl-p-aminophenol-induced hepatocellular injury / 临床肝胆病杂志

ObjectiveTo investigate the ability of Ganshuang granule (a liver-protecting drug widely used in clinical practice) extract to reduce N-acetyl-p-aminophenol (APAP)-induced hepatotoxicity and possible mechanisms. MethodsA total of five cell culture groups were set up in this experiment, i.e., normal control group, APAP injury group, and three injury protection groups treated with different concentrations of Ganshuang granule extract. Then 20 mmol/L APAP was added to the cell culture medium and incubated for 24 hours to establish an in vitro model of drug-induced liver injury, and the injury protection groups were treated with different concentrations of Ganshuang granule extract (0.2, 1, and 5 μg/ml) in advance for 8 hours of incubation before APAP were added for 24 hours. Related markers were measured, including the markers for hepatocellular injury ［alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)］, the markers for mitochondrial injury ［mitochondrial membrane potential, and glutamate dehydrogenase (GDH)］, and antioxidant and oxidative stress markers ［glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS)］. Related mechanism was discussed based on the experimental results. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsGanshuang granule extract alleviated APAP-induced hepatotoxicity, improved cell viability (P＜0001), and reduced the levels of AST, ALT, and LDH in supernatant (P＜0.001, P＜0.001, and P＜0.05). Ganshuang granule extract inhibited APAP-induced hepatocellular oxidative stress, and compared with the APAP group, the Ganshuang granule extract groups had significant reductions in the oxidative stress indicators ROS and MDA (both P＜0.01). Ganshuang granule extract alleviated the loss of mitochondrial membrane potential induced by APAP (P＜0.05) and reduced the content of the mitochondrial injury marker GDH in supernatant (P＜0.001) in a dose-dependent manner. Ganshuang granule extract inhibited the expression of CYP2E1/1A2 (both P＜0.05) and increased the expression of phase Ⅱ enzymes in hepatocytes. Ganshuang granule extract induced the expression of Nrf2 and its downstream genes NQO-1 and GCLC (all P＜0.05). ConclusionGanshuang granule extract can prevent APAP-induced hepatocellular injury through two ways. The first way is that Ganshuang granule extract downregulates the expression of CYP2E1/1A2 and thus reduces the production of NAPQI, a toxic product of APAP; the second way is that Ganshuang granule extract upregulates the expression of the detoxification pathway, which can activate Nrf2 to increase the expression of antioxidant enzymes (SOD and GSH) and phase Ⅱ enzymes and thus accelerate the harmless metabolism of APAP.

The outcome predicted value of enhanced MRI for prolapsed or sequestrated lumbar disc herniation / 中华骨科杂志

Objective:To analyze the predictive value of enhanced MRI in the outcome of prolapsed and sequestrated lumbar disc herniation through a retrospective analysis.Methods:A retrospective analysis of the data of 64 patients with prolapsed and sequestrated lumbar disc herniation from January 2015 to December 2018, including 38 males and 26 females; age 35.72±12.44 years (range, 22-64 years) ; 43 cases of prolapsed type, 21 cases of sequestrated type. Conservative treatment was the first choice for all patients, in case of surgical indications during the treatment, percutaneous endoscopic lumbar discectomy or fenestration discectomy will be performed. Enhanced MRI was performed at the first and last inspections, the volume of the protrusion, the thickness of rim enhancement (Tr), and the extent of rim enhancement (Er) were measured and calculated at the same time. According to the ring around the protrusion, the size of the rim-enhancement area was divided into type I-III; then compared the relationship between the rim-enhancement signal differentiation and the resorption rate of protrusions, and the correlation between Tr, Er values and the resorption rate of protrusions during the initial inspection.Results:Among the 64 patients, 42 patients completed conservative treatment, and 22 received surgical treatment. According to the rim-enhancement signal differentiation, 23 cases were treated conservatively for type I, 3 cases were treated by surgery; 16 cases were treated for type II conservatively, 7 cases were treated by surgery; 3 cases were treated for type III conservatively, and 12 cases were treated by surgery. All patients were followed up for 12 to 34 months. Among 42 conservatively treated patients, The volume of the protrusion before treatment was 2 645.67±690.86 mm 3, and the volume of the protrusion after treatment was 842.76±573.35 mm 3. The volume of protrusions before and after treatment was statistical significance ( t=11.897, P<0.001), Tr was 1.38±0.83 mm, and Er was 73.08%±34.39%, the resorption rate of protrusions was 65.10%±24.50%, and 39 cases (92.86%, 39/42) reached the standard for protrusion resorption (resorption rate ≥30%); 23 cases of type I , the resorption rate was 76.54%±18.62%; 16 cases of type II had an resorption rate of 56.81%±21.44%; 3 cases of type III had an resorption rate of 21.58%±12.19%. The resorption rate of type III were compared by single factor analysis of variance, and the difference was statistically significant ( F=12.885, P<0.001); 32 cases of both type I and II (82.05%, 32/39) had significant resorption (resorption rate ≥50%), and no case of type Ⅲ had significant resorption, comparing with type I and II, the difference was statistically significant ( P=0.010); Tr was positively correlated with resorption rate ( r=0.569, P<0.001), Er was positively correlated with resorption rate ( r=0.677, P<0.001). Conclusion:Under close clinical observation, parts of the prolapsed or sequestrated lumbar disc herniations can be conservatively treated, and the herniated disc can be resorption in many people and the clinical symptoms were alleviated. Rim-enhancement signal differentiation by enhanced MR has a better predictive value for the outcome of the herniation, type I is more prone to resorption, preferred conservative treatment, type Ⅲ is not easy to resorption, preferred surgery treatment, and the higher thickness of rim enhancement, the greater extend the rim-enhancement, the more prone to resorption phenomenon.

Application of PBL combined with video teaching mode in the standardized residency training of digestive operating room / 中华医学教育探索杂志

Objective:To explore the effect of problem-based learning (PBL) combined with video teaching mode on the standardized residency training of digestive operating room.Methods:The study selected 52 digestive operating room residents who participated in the standardized residency training in The First Affiliated Hospital of Air Force Medical University from December, 2019 to March, 2020 as research subjects and they were randomized into the routine group and the observation group, with 26 residents in each group. The routine group only issued the standardized training materials for learning, and the observation group introduced PBL combined with video teaching mode on this basis, with 1 month of learning time for both group. The scores of theory and practice, the scores of core competence before and after learning and the satisfaction with teaching mode were compared between the two groups. SPSS 24.0 was used for t test, rank sum test and chi-square test. Results:The results of theory and practice, excellent and good rate of observation group were higher than those of routine group ( P<0.05). After learning, the scores of basic knowledge reserve, emergency identification ability, event handling ability, field investigation ability and safety protection ability of the two groups were higher than those before learning, of which the observation group were significantly higher than the routine group, with statistical differences ( P<0.05). The satisfaction of the observation group was higher than that of the routine group. Conclusion:PBL combined with video teaching mode can improve the performance and core competence of digestive operating room residents, thus reaching their satisfaction.

The level of plasma C-reactive protein is closely related to the liver injury in patients with COVID-19

AimsCorona virus disease 2019 (COVID-19) has rapidly become the most severe public health issue all over the world. Despite respiratory symptoms, hepatic injury has also been observed in clinical settings. This study aimed to investigate the risk factors involved with hepatic injury in the patients with COVID-19. MethodsA total of 85 hospitalized patients who were diagnosed with COVID-19 in Beijing Youan Hospital were retrospectively analyzed. According to liver function, they were divided into ALT normal group (n=52) and ALT elevation group (n=33). Clinical features and laboratory data were compared between the two groups. The independent risk factors for liver injury were analyzed. ResultsThere were 33 patients with hepatic injury in our study, accounting for 38.8% (33/85). The patients in ALT elevation group were older than those in ALT normal group. The levels of lactic acid, CRP, myoglobin, and neutrophils were significantly higher in ALT elevation group. The lymphocytes and albumin were significantly lower in ALT elevation group. The proportion of severe and critical patients in ALT elevation group was significantly higher. Multivariate logistic regression analysis showed CRP [≥]20 mg/L and lymphocyte count< 1.1x10^9/L were independently related to hepatic injury. ConclusionsLymphopenia and CRP may serve as the risk factors related to hepatic injury in patients with COVID-19, which might be related to inflammatory cytokine storm in liver injury. Early detection and timely treatment of hepatic injury in patients with COVID-19 are necessary.

Preliminary efficacy analysis of Cheng's Giraffe reconstruction after proximal gastrectomy in adenocarcinoma of esophagogastric junction / 中华胃肠外科杂志

Objective@#To investigate the safety and feasibility of proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction for the treatment of early Siewert II adenocarcinoma of esophagogastric junction (AEG).@*Methods@#Indication of Cheng's Giraffe esophagogastric reconstruction: (1) Siewert II AEG or Siewert III AEG with diameter < 4 cm; (2) preoperative staging as cT1-2N0M0. A descriptive case series study was carried out. Clinical data of 34 patients with Siewert II AEG undergoing proximal partial gastrectomy and Cheng's Giraffe esophagogastric reconstruction at Department of Abdominal Surgery of Zhejiang Cancer Hospital and Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from February to July 2018 were retrospectively collected and analyzed, including 14 cases in IA stage, 11 cases in IIA stage and 8 cases in IIB stage. Brief procedure of Cheng's Giraffe esophagogastric reconstruction was as follows: Firstly, 12 cm long tubular stomach was formed by longitudinal incision 4 cm away from the great curvature of the stomach. Secondly, the gastric fundus and His angle were formed. Finally, the distance from His angle to esophagal-tubular gastric anastomosis should be more than 5 cm. The reflux disease questionare (RDQ) scores, radionuclide gastric emptying scintigraphy, and 24-hour multichannel intraluminal (MII)-pH monitoring technology were used to evaluate postoperative gastric emptying and gastroesophageal reflux.@*Result@#All 34 patients successfully completed proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction, including 13 cases by open surgery and 21 cases by laparoscopic surgery. The operation time was (144.6±39.8) minutes, the blood loss during operation was (35.4±17.2) ml. No laparoscopic case was converted to open surgery and no postoperative complication was observed. The postoperative hospital stay was (8.4±2.5) days. The postoperative RDQ score was 4.4±3.1 one month after operation, and 3.3±2.5 six months after operation. Gastric-half emptying time was (67.0±21.5) minutes, and the residual ratio was (52.2±7.7)% in 1 hour, (36.4±3.1)% in 2 hours and (28.8±3.6)% in 3 hours at postoperative 1-month. The 24-hour MII-pH monitoring at postoperative 2-month revealed the frequency of acid reflux was (12.6±7.9) times, frequency of non-acid reflux was (19.6±9.7) times, DeMeester score was 5.8±2.9.@*Conclusion@#Cheng's Giraffe esophagogastric reconstruction is safe and feasible in the treatment of Siewert type II AEG, and has good dynamic and anti-reflux effects.

Systematic review and Meta-analysis of incidence of oral feeding intolerance in acute pancreatitis / 国际外科学杂志

Objective To systemically review andquantify the incidence of oral feeding intolerance in acute pancreatitis. Methods Randomized controlled trials that reported the oral feeding intolerance rates of acute pancreatitis were searchedfrom PubMed, EMBASE, Medline, Cochrane Library, WanFang, CNKI, CMCC and VIP dal,abase wilh the" Acute pancreatitis " " Feeding intolerance" " Incidence" " Meta- analysis "from January 2002 to May 2017. Date were analyzed by using R 3. 4. 0 software. The heterogeneity of data were analyzed using 12test. Results Eleven randomized controlled trials including 658 cases were enrolled in Meta-analysis. The incidence of oral feeding of intolerance was 12. 2% . The result of subgroup analysis showed that there were no significant difference in the incidence of oral feeding intolerance when region, sample size and published year were taken into analysis (P > 0. 05). The oral feeding intolerance rate of mild acute pancreatitis was lower than that when moderately severe acute pancreatitis and severe acute pancreatitis were, included (8. 2% and 19. 9% , respectively; P = 0. 002 7). Conclusion Oral feeding intolerance affects approximately l in 8 patients with acute pancreatitis. The incidence of oral feeding intolerance of patients with severe acute pancreatitis is higher than that of patients with mild acute pancreatitis

Research progress of the open abdomen in the treatment of gastrointestinal fistula with complicated intra-abdominal infection / 中华胃肠外科杂志

Gastrointestinal fistula patients may suffer from complicated intra-abdominal infection and sepsis with improper treatment, which is characterized by high mortality ranging from 20% to 60%, as well as high medical costs. Gastrointestinal fistula patients with complicated intra-abdominal infections are not often diagnosed early, and proper treatment remains an unsolved problem. Therefore it is a great challenge for surgeons to repair broken intestines under complicated intra-abdominal infection conditions and to repair ruptured intestines under conditions of severe abdominal adhesions and swelling of the intestinal wall and mesentery. After the open abdominal approach was first adopted to treat complicated intra-abdominal infection patients by Duff and Moffat in 1981, it gradually began to be used more widely. However, some investigators have reported that the open abdomen approach has not been effective in controlling controlled mortality, instead, it may even increase mortality. For this reason, the approach has only been used in large medical centers rather than having been widely popularized. In this review, the effect, timing, indications of open abdomen approach and the principles for the open abdominal wound management are summarized, and the reason for the various efficacy among different centers is also analyzed. We provide a new perspective for clinicians to manage the gastrointestinal fistula patients with complicated intra-abdominal infection.

Construction of a model predicting the risk of tube feeding intolerance after gastrectomy for gastric cancer based on 225 cases from a single Chinese center.

Identifying patients at high risk of tube feeding intolerance (TFI) after gastric cancer surgery may prevent the occurrence of TFI; however, a predictive model is lacking. We therefore analyzed the incidence of TFI and its associated risk factors after gastric cancer surgery in 225 gastric cancer patients divided into without-TFI (n = 114) and with-TFI (n = 111) groups. A total of 49.3% of patients experienced TFI after gastric cancer. Multivariate analysis identified a history of functional constipation (FC), a preoperative American Society of Anesthesiologists (ASA) score of III, a high pain score at 6-hour postoperation, and a high white blood cell (WBC) count on the first day after surgery as independent risk factors for TFI. The area under the curve (AUC) was 0.756, with an optimal cut-off value of 0.5410. In order to identify patients at high risk of TFI after gastric cancer surgery, we constructed a predictive nomogram model based on the selected independent risk factors to indicate the probability of developing TFI. Use of our predictive nomogram model in screening, if a probability > 0.5410, indicated a high-risk patients would with a 70.1% likelihood of developing TFI. These high-risk individuals should take measures to prevent TFI before feeding with enteral nutrition.

Expression of microRNA-210 in gastric cancer and its relationship with clinicopathological factors and prognosis / 中国癌症杂志

Background and purpose: miR-210 was closely related to the occurrence and development of gastric cancer, but its mechanism and clinical significance were still not clear. The purpose of this study was to explore the expression of miR-210 in gastric cancer tissues and its clinical significance. Methods: The expression of miR-210 was detected in gastric cancer tissues and the corresponding adjacent tissues. The relationship between the expression of miR-210 and clinical pathological factors and prognosis was analyzed. Results: Real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) showed that the expression of miR-210 in gastric cancer was higher than that in adjacent tissues, and there was a significant difference between the two groups (P<0.05). The expression of miR-210 was closely related to tumor size, lymph node metastasis and TNM stage, but was not related to age, gender, tumor dif-ferentiation and depth of invasion. The 5-year survival rate of patients with low miR-210 expression was 48.2%, where-as the 5-year survival rate of patients with high miR-210 expression was 30.4% (χ2=4.216, P=0.040). Conclusion: The expression of miR-210 in gastric cancer was higher than that in adjacent tissues, and maybe related to the development and prognosis of gastric cancer. miR-210 is expected to be a new diagnostic marker and therapeutic target for gastric cancer.

Cell apoptosis pathway in the development of alcoholic pancreatitis in mice / 中华胰腺病杂志

Objective To explore the role of cell apoptosis pathway in alcoholic pancreatitis.Methods C57BL/J mice were divided into control group (NC) and Alcohol group (AC),Acute pancreatitis group (AP) and Alcoholic acute pancreatitis group(AAP).Alcohol treatment was 10％ w/v ethanol feeding for 2 d,15％ w/v ethanol for 5 d,and then 20％ w/v ethanol until 13 weeks.AP model was established by the intraperitoneal injection of 50μg caerulein/kg body weight once an hour for a total of 7 times.Blood samples were collected for detecting serum amylase and lipase activity.Part pancreatic tissue was collected and the wet and dry weight were both measured to calculate the water content.The routine pathological exanination of the pancreatic tissues were conducted.The expression of apoptosis associated protein caspase3 and caspase8 was determined by Western blot.And cell apoptosis was determined using TUNNEL method.Results The level of serum amylase in NC group,AC group,AP group and AAP group were(3 630 ± 259),(3 196 ± 187),(35 955 ± 4607) and (53 607 ± 3 848) U/L;the level of serum lipase were (502 ± 41),(745 ± 42),(7 346 ± 665) and(12 764 ± 2 544) U/L;the water content were (70.2 ± 3.1) ％,(69.6 ± 2.0) ％,(78.2 ± 1.5) ％ and(85.0 ± 3.0) ％ and (12.75 ± 0.25);the expression of caspase3 were (1.017 ± 0.0784),(1.287 ± 0.097),(178 ± 0.07785) and (0.2443 ± 0.0243);the expression of caspase8 were (0.8289 ± 0.0096),(0.5985 ±0.0735),(1.27 ±0.08) and (0.145 ±0.015);the number of apoptotic cells were 1,6,214,97/10 high power field.The pathological score of pancreas injure in NC group,AC group,AP group and AAP group were 0,0,(7 ± 0.4) and (12.8 ± 0.3),respectively.Serum anylase,lipase,water content and pathological scores in AP group were obviously higher than those in NC group (P ＜ 0.05),which in AAP group were also obviously higher than those in AP group,and all the differences were statistically significant (all P ＜0.05).Compared with NC group,the expressions of apoptosis associated protein caspase3 and caspase8 and the number of apoptotic cells were obviously increased in AP group,which were obviously higher than those in AAP group,but the expression of caspase3 and caspase8 in AAP group were decreased compared with NC group,and all the differences were statistically significant (all P ＜ 0.05).Conclusions Chronic alcohol exposure may aggravate the severity of pancreatitis,and the inhibition of apoptosis pathway and the enhancement of acinar cell necrosis may be involved in this process.

Correlation of MRI apparent diffusion coeffcient with molecular marker Ki-67 in gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVES</b>To study the correlation between MRI apparent diffusion coefficient (ADC) and expression of Ki-67 in gastric cancers, and to investigate the application of ADC value in diagnosing the malignance of gastric cancer.</p><p><b>METHODS</b>A retrospective cohort analysis was performed on 87 gastric cancer patients who received MRI examination and radical resection at Zhejiang Provincial Hospital of Traditional Chinese Medicine from November 2014 to August 2015. All the postoperative resected samples were confirmed as gastric cancer. Preoperative MRI examination was performed by using Siemens 3.0-T Verio MRI with following parameters: section thickness 3 mm, gap 1 mm, matrix 182×320, field of view 40 cm. Plain scan was followed by T1-weighted fat suppression technique VIBE 3D(TR3.92/TE1.39,90degree) scans at arterial phase (the 30th second), portal venous phase (the 60th second), lag period (the 90th second), axial planes and coronal planes (the 180th second), and sagittal planes (the 210th second), respectively. ADC value of tumor was measured at b-factor of 800 s/mmand ADC map was generated from DWI data on the work station. The expression of Ki-67 in cancer tissue was detected by routine immunohistochemical (SP) staining after surgery. Correlation between ADC value and the expression of Ki-67 in gastric cancer was analyzed.</p><p><b>RESULTS</b>Irregular thickening of the gastric wall and inhomogeneous enhancement of the tumor after injection of the contrast material appeared in gastric cancer. Gastric cancer tissue presented hyperintensity and normal gastric wall presented isointensity in DWI image (b=800 s/mm). Compared with normal gastric tissue, mean ADC value of gastric cancer tissue was significant lower [(1.114±0.265)×10mm/s vs. (2.032±0.202)×10mm/s, t=26.209, P=0.000]. The ADC values of high-middle differentiation group, middle-low differentiation group, low differentiation group and signet ring cell carcinoma/mucinous adenocarcinoma group were (1.347±0.234)×10mm/s, (1.179±0.257)×10mm/s, (0.996±0.185)×10mm/s and (1.082±0.230)×10mm/s, respectively. The difference of mean ADC value among different tumor stages was significant(F=8.498, P=0.000). Along with the Ki-67 expression up-regulated, the ADC value decreased in cancer tissue. The Ki-67 expressions in cancer tissue was negatively correlated with cancer ADC values (r=-0.570, P=0.000). Furthermore, negative correlations of Ki-67 expressions with ADC values of high-middle differentiation group (r=-0.627, P=0.016), low differentiation group (r=-0.787, P=0.000) and signet ring cell carcinoma/mucinous adenocarcinoma group (r=-0.792, P=0.000) were observed respectively, while Ki-67 expression was not correlated with ADC value of middle-low differentiation group.</p><p><b>CONCLUSION</b>The ADC value of gastric cancer can reflect the level of tumor differentiation, and is negatively correlated with Ki-67 expression in cancer tissues.</p>

Intestinal microbiota dysbiosis associated with the development of colon cancer：progress and prospects / 中国药理学通报

Intestinal microflora is an important part of the organ-ism, promoting digestion and absorption of nutrients, maintaining intestinal normal physiological function, regulating immune sys-tem. Intestinal microflora maintains steady state under normal conditions, but intestinal microbiota dysbiosis occurs when surrounding environment c hanges, such as age, diet, obesity and other metabolic diseases as well as antibiotics. Many recent studies have found intestinal flora could cause a variety of disea-ses, and colon cancer is closely related with intestinal microbiota dysbiosis. Some researches suggest improving the intestinal flora dysbiosis can reduce the incidence of colon cancer and inhibit the growth and the worsening of colon cancer. However, under-lying mechanisms remain unknown. So this article summarizes the research progress on the development of colon cancer and in-testinal microbiota dysbiosis, in order to provide reference for re-search on intestinal flora and colon cancer treatment.

Detecting the intrarenal arteries hemodynamics indexes in patients with systemic lupus erythematosus by enhance-lfow / 中华医学超声杂志（电子版）

Objective To explore the reliability of assessing the renal damage and prognosis with enhance-lfow (E-Flow) in patients with systemic lupus erythematosus (SLE) by detecting hemodynamics indexes of intrarenal arteries. Methods There were 50 SLE patients who were treated in the Second Hospital Afifliated to Harbin Medical University from May 2012 to March 2013. The 50 SLE patients were divided into 2 groups:28 patients with LN and 22 ones without LN, and 30 healthy persons were served as the control group who were from the health check centre. All patients underwent renal ultrasonic examination, and two-dimensional images were observed. E-Flow technique were used to measure the peak systolic velocity (PSV), end-diastolic velocity (EDV) and vascular resistance indexes (RI) of the segmental, interlobar, arcuate and interlobular arteries. ANOV was used to compare the PSV, EDV and RI of segmental, interlobar, arcuate and interlobular arteries in the three groups, and LSD-t was used to compare the indexes between the two groups. A linear correlation analysis was used to determine the correlation between the RI of the intrarenal arteries in patients with LN and the levels of serum creatinine. Results The two-dimensional images of kidneys in patients without LN were normal. There were 8 cases with renal parenchymal diffused change in patients with LN. The spectrums of interlobular arteries in patients without LN were similar with those of control subjects, and the turgor curve of diastolic phase reduced slightly. The spectrums of interlobular arteries in patients with LN were blunt, with high resistance and hypoperfusion. Compared with the control subjects, PSV of the interlobar, arcuate and interlobular arteries in patients with LN decreased statistically (t=-2.46,-2.40,-3.49, P<0.05 or 0.01). EDV of the intrarenal arteries in patients with or without LN decreased statistically (patients with LN:t=-5.50,-5.95,-5.83,-5.01, all P<0.01;patients without LN:t=-3.41,-3.69,-3.29,-2.49, P<0.05 or 0.01). Compared with patients without LN, PSV and EDV of the arcuate and interlobular arteries in patients with LN all decreased statistically (PSV:t=-2.00,-2.16, both P<0.05;EDV:t=-2.13,-2.16, both P<0.05). Compared with the control subjects, RI of the intrarenal arteries in all SLE patients increased signiifcantly (patients with LN:t=12.78, 13.30, 11.95, 9.52, all P<0.01;patients without LN:t=9.88, 10.05, 8.71, 5.30, all P<0.01). Compared with patients without LN, RI of the the intrarenal arteries in patients with LN increased signiifcantly (t=2.05, 2.38, 2.43, 3.57, P<0.05 or 0.01). There were positive correlations between the RI of the intrarenal arteries in patients with LN and the level of serum creatinine (r=0.684, 0.752, 0.755, 0.851, all P<0.01). Conclusions E-Flow could clearly display the branches of intrarenal arteries and assess the progress and prognosis of the patients with SLE by measuring intrarenal arteries hemodynamics.

mTOR and its signaling pathway in gastric cancer / 国际肿瘤学杂志

Mammalian target of rapamycin (mTOR) and its signaling pathway regulate protein synthesis, cell growth and metabolism, and angiogenesis. This pathway is highly activated in gastric cancer and closely related to the progression and prognosis of the cancer. Blocking the mTOR signaling pathway by rapamycin and its derivatives can inhibit gastric cancer cell growth and promote tumor necrosis and such effects can be synergistically improved by combined use of other chemotherapeutic agents. Thus, rapamycin and its derivatives may be effective in the prevention and treatment of gastric cancer.

Clinical features and ageing-related changes in patients with venous thromboembolism / 中华老年医学杂志

Objective To investigate the clinical and epidemiological characteristics of pulmonary thromboembolism (PTE) and deep venous thrombosis (DVT). Methods The clinical data of 114 200 inpatients from June 2002 to June 2008, including gender, age, smoking history, primary disease and risk factors, were reviewed. Results There were 1445(1.27%) cases with venous thromboembolism (VTE), while 1433(1. 25%) patients suffered from DVT and 153(0. 13%) patients suffered from PTE, 16(11. 11 %) patients were dead of PTE. Of all the DVT patients, there were 1348(94. 1%) cases with DVT of lower limbs with no significant difference between left or right lower limb (P>0. 05). There were 49(3.4%) cases with inferior vena cava, 23(1.6%) cases with cavitas pelvis veins and 13(0. 9%) cases with upper extremity veins. The peak ages of morbidity were between 51 to 60 years. Conclusions The incidence of VTE is increasing with ageing and there is no significant difference between males and females. The most common risk factors for thromboembolism include trauma, surgery, cardiac and pulmonary disease, age over 50 years, deep phlebitis, long-term smoking, cancer, pregnancy, childbirth, braking, history of VTE, etc. We may lower the incidence and mortality of VTE by strengthening prevention work according to the high risk factors.