[Expression and clinical significance of plasma methylated SEPT 9 gene in patients with primary liver cancer].

Objective: To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer. Methods: 393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests. Results: 367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant (χ (2) = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant (χ (2) = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant (χ (2) = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion: In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.

Metformin Hydrochloride and Sitagliptin Phosphate Fixed-Dose Combination Product Prepared Using Melt Granulation Continuous Processing Technology.

The development of oral solid dosage forms, such as tablets that contain a high dose of drug(s), requires polymers and other additives to be incorporated at low levels as possible, to keep the final tablet weight low, and, correspondingly, the dosage form size small enough to be acceptable from a patient perspective. Additionally, a multi-step batch-based manufacturing process is usually required for production of solid dosage forms. This study presents the development and production, by twin-screw melt granulation technology, of a high-dose immediate-release fixed-dose combination (FDC) product of metformin hydrochloride (MET) and sitagliptin phosphate (SIT), with drug loads of 80% w/w and 6% w/w, respectively. For an 850/63 mg dose of MET/SIT, the final weight of the caplets was approximately 1063 mg compared with 1143 mg for the equivalent dose in Janumet®, the marketed product. Mixtures of the two drugs and polymers were melt-granulated at temperatures below the individual melting temperatures of MET and SIT (231.65 and 213.89°C, respectively) but above the glass transition temperature or melting temperature of the binder(s) used. By careful selection of binders, and processing conditions, direct compressed immediate-release caplets with desired product profiles were successfully produced. The melt granule formulations before compression showed good flow properties, were larger in particle size than individual starting API materials and were easily compressible. Melt granulation is a suitable platform for developing direct compressible high-dose immediate-release solid dosage forms of FDC products.

[Observation on the efficacy of modified Appleby operation for carcinoma of the body and tail of the pancreas].

OBJECTIVE: To evaluate the security, feasibility and therapeutic efficacy of modified Appleby operation for carcinoma of the body and tail of pancreas. METHODS: From March 2010 to February 2015 modified Appleby operation was performed in 17 patients with carcinoma of the body and tail of the pancreas. The biochemical indices of fasting plasma blood (FPB), body weight (BW), visual analogue pain intensity scale (VAS score) and the quality of life index were evaluated before and 1 day , 1, 2, 6weeks after surgery. Survival time, tumor recurrence time, hospitalization time and treatment-related complications were analyzed. RESULTS: There was no hospital mortality in this study. Pancreatic fistula and diarrhea were the major complications. The overall complication rate was 47.1%. The liver function index of ALT and AST were increased on postoperative day 1, and they were restored to normal after one week. Blood glucose has no obvious abnormal increase and abdominal pain was completely relieved. The VAS score decreased after surgery comparing with before (1.9±3.6 vs 83.2±8.5, P<0.05). Life quality assessment was significantly higher. The body weight of patients after surgery has a mean increment of (4.1±1.3)kg than that before surgery (68.1±4.3 vs 64.0±6.7, P<0.05). A significant rise of the overall quality of life index was observed after surgery (93.8±9.7 vs 68.6±6.7, P<0.05). The recurrence rates of 1, 2, 3 and 5 years were 22.9%, 58.9%, 72.6% and 72.6%, respectively. Median recurrence time was (20.0±3.8 m) (95%CI: 12.6-27.4 m). The survival rates of 1, 2, 3 and 5 years were 80.4%, 54.2%, 32.5% and 16.3%, respectively. The median survival time was (26.0±6.0)m (95%CI: 14.2-37.8 m). CONCLUSIONS: Modified Appleby operation for pancreatic cancer is safe and feasible. It can relieve abdominal pain, improve the quality of life, improve the survival rate and prolong the survival time.

The oval-shaped cell as a candidate for a liver stem cell in embryonic, neonatal and precancerous liver: identification based on morphology and immunohistochemical staining for albumin and pyruvate kinase isoenzyme expression.

Oval cells observed in some experimental models of hepatocarcinogenesis can function as stem cells capable of differentiating into hepatocytes and bile ductular cells. Using markers which characterise embryonic hepatocytes, we showed that oval cells display different patterns of gene expression, suggesting some are more mature than others. In this study we looked for oval cells in developing liver, predicting that they are abundant in embryonic liver and decline in number during development. Albumin (ALB) serves as a liver-specific marker, and the isoenzymes of pyruvate kinase, M2-PK and L-PK, are used to identify immature and mature hepatocytes, respectively. Small oval-shaped cells expressing ALB, M2-PK and L-PK are found near the vascular spaces and portal areas in 20-day gestation (E20), E21, newborn, 3-day and 1-week-old rat liver. Similar cells expressing ALB and M2-PK, but not L-PK are seen only periportally in adult liver. These are abundant in early embryonic liver and decrease in number during development until only a few, located periportally, persist in the adult. Oval cells, located periportally a few days after commencing a choline-deficient, ethionine-supplemented diet, co-express ALB and M2-PK. Their similarity with respect to markers, morphology and location suggests that oval-shaped cells may be the progenitors of oval cells.

Assessment of autopsic samples of carotid atherosclerosis in the aged by intravascular ultrasound.

To assess the value of intravascular ultrasound in detecting carotid atherosclerosis, we compared the ultrasound images of 48 carotid artery segments from autopsies with their histological findings. The results showed that by intravascular ultrasonography one could distinguish between elastic and muscular tissues of arteries, determine the lesions of fibroelastosis and calcified plaques on arterial wall, and precisely measure the wall thickness, inner and outer diameter, luminal area and cross-sectional area of arteries with a high correlation between the data measured from ultrasonography and histological study (r values were 0.98, 0.97, 0.97, 0.96 and 0.96, respectively). This study suggests that intravascular ultrasound might be effectively used for morphological study and detection of atherosclerotic lesions in vivo.

Genetic polymorphisms of HLA class III and GLO1 in Chinese Yao nationality.

Yao is one of the minority nationalities located mainly in the South of China (Guang Xi province). The purpose of this study was to examine HLA class III and GLO1 in Yao nationality to identify the difference between Yao and Han. Han is the major nationality in China. Yao has the lowest C2*C frequency (0.9336) in the world. Before this study the lowest C2*C frequency known was that of the Japanese (0.9386). Gene frequencies in Yao are the following: C2*C = 0.9336, C2*B = 0.0664; BF*S = 0.9071, BF*F = 0.0929; C4A*4 = 0.0253, C4A*3 = 0.6061, C4A*2 = 0.2121, C4A*1 = 0.0152, C4A*Q0 = 0.1414; C4B*3 = 0.0051, C4B*2 = 0.0657, C4B*1 = 0.7071, C4B*92 = 0.0455, C4B*95 = 0.0253, C4B*96 = 0.0253, C4B*12 = 0.0051, C4B*Q0 = 0.1212; GLO1*1 = 0.1161, GLO1*2 = 0.8839. We have compared these data with those reported for Han.

Genetic polymorphism of MHC class III and GLO in Chinese Yao nationality.

Yao nationality is one of the minority nationalities living mainly in South China (Guangxi Province). The purpose of this study was to provide data of MHC class III and GLO in Chinese Yao nationality and the different genetic background of Yao and Han nationality, the latter representing the major nationality in China. The genetic polymorphism of MHC class III and GLO in Chinese Yao nationality was determined. Previously the Japanese were considered to have the lowest C2*C frequencies (0.9386), but now we ascertained that the Yao have the lowest C2*C frequencies (0.9336). The data concerning gene frequencies of Yao are presented. They were also compared with the available data of Han.

[Genetic polymorphism of the second component of human complement (C2) in the Han Nationality in Wuhan district of China].

A total number of 231 unrelated Chinese (Han Nationality) were investigated for C2 polymorphism by hemolytic overlay technique after polyacrylamide gel isoelectric focusing on plasmas. The following phenotype distributions were observed: C2C, 216; C2BC, 9; C2AC, 5; and C2A, 1. The gene frequencies calculated from these phenotypes were as follows: C2*A, 0.015; C2*B, 0.019; C2*C, 0.965. The C2 phenotypic frequency distributions were in agreement with those expected from Hardy-Weinberg equilibrium.