Background and purpose: Increasing evidence has indicated that polymorphisms in the microRNA (miRNA, miR) binding site of target gene can alter the ability of miRNA and modulate the risk of cancer. We aimed to investigate the association between a miR-520a binding site single nucleotide polymorphism (SNP) rs141178472 in the PIK3CA 3’UTR and the risk of colorectal cancer in a Chinese Han population. Methods:The polymorphism rs141178472 was analyzed in a case-control study, including 386 colorectal cancer patients and 394 age-and sex-matched controls. The relationship between the polymorphism and the risk of colorectal cancer was examined by statistical methods. Results:Individuals carrying the rs141178472 CC genotype or C allele had an increased risk of developing colorectal cancer (CC vs TT, OR=1.716, 95%CI:1.084-2.716, P=0.022;C vs T, OR=1.258, 95%CI:1.021-1.551, P=0.033). Furthermore, the expression of PIK3CA was detected in the peripheral blood mononucleated cell of colorectal cancer patients, suggesting that mRNA levels of PIK3CA might be associated with SNP rs141178472. Conclusion:These ifndings provide evidence that a miR-520a binding site polymorphism rs141178472 in the PIK3CA 3’UTR may play crucial roles in the etiology of colorectal cancer.

Objective To evaluate the effect of pretreatment with botulinum toxin A injected intrath?ecally or locally at the incision site on the neurokinin?1 ( NK?1) receptor internalization in the spinal dorsal horn in a rat model of incisional pain. Methods Male Sprague?Dawley rats, weighing 280-300 g, aged 6-8 weeks, were used in the study. The experiment was performed in two parts. ExperimentⅠ Twenty?seven rats with no sign of nerve injury at day 7 after successful catheterization were selected and divided into 3 groups (n=9 each) using a random number table: control group (C1 group), incisional pain group (IP1 group) and intrathecal botulinum toxin A group (BoNT∕A1 group). At 24 h before operation, botulinum tox?in A 0.5 U ( in 10μl of normal saline) was injected intrathecally in group BoNT∕A1, and normal saline 10μl was injected intrathecally in group IP1. ExperimentⅡ Twenty?seven rats were selected and divided into 3 groups (n=9 each) using a random number table: control group (group C2), incisional pain group (IP2 group) and locally injected botulinum toxin A at the incision site group (BoNT∕A2 group). At 24 h before op?eration, botulinum toxin A 2 U ( in 0.4 ml of normal saline) was injected subcutaneously at the incision site and into the plantar surface, and normal saline 0.4 ml was injected subcutaneously at the incision site and into the plantar surface in group IP2. Six rats in each group were selected, and the cumulative pain score (CPS) was recorded, and the mechanical paw withdrawal threshold ( MWT) in the right hindpaw was measured be?fore administration, before operation, and at 3 h and 1, 3, 5 and 7 days after operation. At 3 h after opera?tion, 3 rats in each group were selected and sacrificed, and the lumbar segment ( L4,5 ) of the spinal cord was removed for determination of the expression of NK?1 receptors in the spinal dorsal horn by immunofluores?cence. Results ExperimentⅠ Compared with group C1, the CPS was significantly increased at 3 h and 1, 3, 5 and 7 days after operation, the MWT was significantly decreased at 3 h and 1 and 3 days after opera?tion, and the expression of NK?1 receptors in the spinal dorsal horn was significantly up?regulated in group IP1, and the CPS was significantly increased at 3 h and 1, 3 and 5 days after operation, the MWT was sig?nificantly decreased at 3 h after operation ( P<0.05) , and no significant change was found in the expression of NK?1 receptors in the spinal dorsal horn in group BoNT∕A1 (P>0.05). Compared with group IP1, the CPS was significantly decreased, and the MWT was significantly increased at 3 h and 1, 3, and 5 days after oper?ation, and the expression of NK?1 receptors in the spinal dorsal horn was significantly down?regulated in group BoNT∕A1 (P<0.05). ExperimentⅡ Compared with group C2, the CPS was significantly increased at 3 h and 1, 3, 5 and 7 days after operation, the MWT was significantly decreased at 3 h and 1, 3, 5 and 7 days after operation, and the expression of NK?1 receptors in the spinal dorsal horn was significantly up?regu?lated in group IP2, and the CPS was significantly increased at 3 h and 1, 3, 5 and 7 days after operation, the MWT was significantly decreased at 3 h after operation ( P<0.05) , and no significant change was found in the expression of NK?1 receptors in the spinal dorsal horn in group BoNT∕A2 ( P>0.05) . Compared with group IP2, the CPS was significantly decreased at 3 h and 1, 3, and 5 days after operation, the MWT was signifi?cantly increased at 3 h and 1 and 3 days after operation, and the expression of NK?1 receptors in the spinal dorsal horn was significantly down?regulated in group BoNT∕A2 (P<0.05). Conclusion Pretreatment with botulinum toxin A injected intrathecally or locally at the incision site can inhibit the internalization of NK?1 re?ceptors in the spinal dorsal horn in a rat model of incisional pain.

Abstract: Objective　To explore the correlation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and insulin resistance (IR) in male patients with type 2 diabetes mellitus (T2DM) combined with metabolic-related fatty liver disease (MAFLD). Methods A total of 454 male patients with T2DM combined with MAFLD in National Metabolic Management Center (MMC) of the Affiliated Hospital of Jiangsu University from May 2018 to July 2020 were enrolled. The general clinical data of subjects were collected, blood routine and biochemical indexes were tested, homeostasis model insulin resistance index (HOMA-IR) was calculated, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured. Accordingtothe MHR quartile, patients were divided into group Q1 (MHR≤0.38), group Q2 (0.380.64) to compare the differences in measured indicators above. In addition, patients were divided into two groups according to HOMA-IR, HOMA-IR<2.5 and HOMA-IR≥2.5, and the differences in MHR were compared. Results The patients were divided into four groups according to MHR:group Q1 (n=115), group Q2 (n=110), group Q3 (n=120) and group Q4 (n=109). Fasting insulin (FINS) were respectively 6.17(4.20,9.76), 7.73(4.94,10.66), 8.92(5.32,11.33) and 9.13(5.25,12.27) mU/L, 2-hour postprandial insulin were 22.75(12.87,39.59), 27.55(16.44,39.77), 30.98(17.46,43.11) and 31.28(18.54,45.92) U/L. HOMA-IR were 3.12(1.63,4.25), 3.72(2.26,4.66), 3.87(2.48,5.44) and 3.95(2.42,5.31). Neutrophil (Neu) were 3.10(2.60,3.70), 3.20(2.50,3.93), 3.60(2.80,4.28), 4.20(3.30,5.00)×109/L. Subcutaneous fat area (SFA) were (181.27±53.60), (192.64±62.41), (199.53±61.40) and (203.69±71.51) cm2. They all increased gradually. However, the levels of high-density lipoprotein cholesterol (HDL-c) [1.18(1.06,1.35), 1.02(0.86,1.17), 0.96(0.80,1.03) and 0.80(0.69,0.92) mmol/L] and low-density lipoprotein cholesterol (LDL-c) [(3.00±0.79), (2.76±0.83), (2.67±0.85) and (2.59±0.92) mmol/L] decreased gradually. Pearson's or Spearman's correlation analysis showed that MHR was positively correlated with FINS, 2-hour postprandial insulin (2hINS), HOMA-IR, VFA and SFA (r=0.190, 0.153, 0.184, 0.114, 0.127, P<0.05). The coronary heart disease history, systolic blood pressure,diastolic blood pressure,fasting plasmaglucose (FPG), FINS, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood uric acid (Ur), body mass index (BMI), VFA, SFA and MHR of patients in group HOMA-IR≥2.5 were higher than group HOMA-IR<2.5 (P<0.05). Conclusion　MHR is positively correlated with IR in male patients with T2DM combined with MAFLD, and as MHR increases, the degree of IR is higher.

OBJECTIVE CYP2D is one of the most abundant subfamily of CYPs in the brain, especially in the cerebellum. Brain CYP2D is responsible for the metabolism of endogenous neurotransmitters such as tyramine and serotonin. Our previous studies have shown brain CYP2D can be regulated by exogenous and endogenous substances with tissue- specificity. The purpose of this study is to examine the effects of cerebral CYP2D on the mice behavior and the regulatory mechanism of brain CYP2D by growth hormone. METHODS Mice received the stereotaxic injection with CYP2D inhibitor quinine in deep cerebellar nuclei of cerebellum. The animals were tested with rotarod apparatus, balance beam, water maze, elevated plus maze and open field. The changes in CYP2D22, PPARαand PPARγ in brain regions and liver were assayed in male growth hormone receptor knockout mice, SH-SY5Y cells and HepG2 cells. RESULTS The inhibition of cerebellum CYP2D significantly affected the spatial learning and exploring ability of mice. Compared with WT mice, CYP2D expression was lower in brain regions from GHR(-/- ) male mice; however, hepatic CYP2D level was similar. Pulsatile GH decreased PPARα mRNA level, and increased mRNA levels of CYP2D6 and PPARα in SH- SY5Y cells. In HepG2 cells, pulsatile GH resulted in decreases in PPARα and PPARγ mRNA levels, but not CYP2D6. PPARα inhibitor induced CYP2D6 mRNA and protein by 1.32-fold and 1.43-fold in SH-SY5Y cells. PPARγ inhibitor decreased CYP2D6 mRNA and protein by 74.76% and 40.93%. PPARα agonist decreased the level of CYP2D22 mRNA in liver and cerebellum, while PPARγ agonist rosiglitazone resulted in diametrically increases. The luciferase assay showed that PPARγ actived the CYP2D6 gene promoter while PPARα inhibited its function. Pulsatile GH declined the binding of PPARα with CYP2D6 promoter by 40%, promoted the binding of PPARγ with CYP2D6 promoter by approximate 60%. The levels of brain and liver PPARα expression in male GHR(-/- ) mice is obviously higher than those in WT mice. The level of PPARγ in male GHR(-/- ) mice was decreased in the frontal cortex and hippocampus, while remained stable in the cerebellum and striatum; meanwhile, PPARγ was increased in the liver. CONCLUSION Brain CYP2D may be involved in learning and memory functions of central system. Masculine GH secretion altered the PPARs expression and the binding of PPARs to CYP2D promoter, leading to the elevated brain CYP2D in a tissue- specific manner. Growth hormone may specifically alter the metabolic and synthetic of important endogenous substances in the central nervous system (such as serotonin) through the specific regulation of brain CYP2D expression.

BACKGROUND: Pancreatic damage in critically ill patients is associated with the progressive failure of multiple organs, but little is known about its clinical characteristics. At present, no guidelines are available for the diagnosis and management of pancreatic damage. This study was undertaken to analyze the clinical and pathologic characteristics of pancreatic necrosis in critically ill children, and to find some biological markers of pancreatic damage or pancreatic necrosis. METHODS: We retrospectively reviewed the clinical data, laboratory results, and autopsy findings of 25 children, who were admitted to Hunan Children's Hospital, China from 2003 to 2009, and died of multiple organ failure. The autopsy revealed pancreatic necrosis in 5 children, in whom sectional or gross autopsy was performed. RESULTS: The 5 children had acute onset and a fever. Two children had abdominal pain and 2 had abdominal bulging, flatulence and gastrointestinal bleeding. Four children had abnormal liver function, characterized by decreased albumin and 3 children had elevated level of C-reactive protein (CRP). B-ultrasonography revealed abnormal acoustic image of the pancreas in all children, and autopsy confirmed pancreatic necrosis, which may be associated with the damage of the adrenal gland, liver, lung, heart, spleen, kidney, intestine, thymus, mediastinal and mesenteric lymph nodes and other organs. Children 1 and 2 died of acute hemorrhagic necrotizing pancreatitis (AHNP);children 3-5 died of multiple organ dysfunction syndrome (MODS) due to pancreatic necrosis. CONCLUSION: Pancreatic damage or pancreatic necrosis in critically ill children is characterized by acute onset, severity, short course, multiple organ damage or failure. It may be asymptomatic in early stage, and easy to be ignored.

OBJECTIVETo investigate polymorphisms in the coding exons and their splicing areas of caspase10 gene (CASP10) in Chinese of Han nationality.

METHODSPolymerase chain reaction (PCR), denaturing high-performance liquid chromatography (DHPLC), direct sequencing and clonal sequencing were used to analyze the exon 9 and its flanking sequences.

RESULTSIn 70 blood samples of Chinese subjects researched the known single nucleotide polymorphisms (SNPs) in the exon 9 of CASP10 gene published in dbSNP of NCBI were not identified. We found a short sequence with more than ten continuous and repeated T nucleotides within the intron 8 near the exon 9 and the length of repeated sequence nucleotides T was different in samples. Clonal sequencing analysis indicated that it was a microsatellite of single nucleotide-repeated sequence. The recurrence and specificity of same result was further confirmed by PCR with high fidelity polymerase and sequencing. Furthermore all of 70 blood samples detected by DHPLC showed heterozygous profiles. We named it as IVS8-13(T)n temperately.

CONCLUSIONOur research suggested that the site be a microsatellite of single nucleotide-repeated sequence. Meanwhile, our data further showed that it was quite different from that by querying SNP database of non-Chinese population in NCBI, in the same region a SNP of type of insertion deletion existed. It could be inferred that the difference between the populations might be associated with the genetic characteristics of ethnics. The significance of the microsatellite in CASP10 gene in Chinese of Han nationality remains to be elucidated.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Caspase 10 ; Caspases ; genetics ; China ; ethnology ; Ethnic Groups ; Genetics, Population ; Humans ; Introns ; genetics ; Microsatellite Repeats ; genetics ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA

OBJECTIVETo investigate the expression profiles of serum Golgi protein-73 (GP73) in liver cirrhosis and primary hepatic carcinoma (PHC) and determine its clinical value for differential diagnosis.

METHODSSerum protein expressions of GP73 and alpha-fetoprotein (AFP) were detected by enzyme-linked immunosorbent assay and chemiluminescence assay, respectively, in patients with PHC (n=80), liver cirrhosis (n=65), and healthy controls (n=50). Inter-group changes were assessed by Kruskal-Wallis test, and significance of these differences was assessed by Mann-Whitney test. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency and determine the cut-off values for GP73 and AFP. Sensitivity and specificity were compared by the Chi-squared test. Correlation between serum GP73 expression and clinical parameters was determined by Spearman's rank correlation analysis.

RESULTSThe PHC group showed significantly higher serum GP73 (282.0 mug/L) than the liver cirrhosis group (211.8 mug/L) and control group (58.3 mug/L) (H = 93.30, P less than 0.01). For differential diagnosis of PHC and liver cirrhosis, the cut-off value was 318.1 mug/L for GP73 and 13.4 mug/L for AFP. Sensitivity of GP73 was lower than AFP (45% (36/80) vs. 65% (52/80); X2 = 8.02, P less than 0.05). Specificity of GP73 was lower than AFP but no significance was found (83.1% (54/65) vs. 87.7% (57/65); X2=0.27, P more than 0.05). The areas under the ROC curves were not significantly different between GP73 and AFP (0.65 (95% confidence interval (CI): 0.54~0.72) vs. 0.75 (95% CI: 0.67~0.83); Z = 1.88, P more than 0.05). The area under the ROC curves increased but not significantly (0.80 (95% CI: 0.73~0.88) vs. 0.75 (95% CI: 0.67~0.83); Z=2.61, P more than 0.05). Serum GP73 was correlated with liver cirrhosis (r=0.27), vascular invasion (r=0.29), and TNM staging (r=0.27) (all P less than 0.05), but not with sex (r=0.13), age (r=0.10), enhanced AFP (> 13.4 mug/L; r=0.03), tumor size (r=0.18), or distant metastasis (r=0.04), all P less than 0.05.

CONCLUSIONSerum GP73 and AFP have comparable diagnostic efficiency, but the sensitivity of AFP is superior for differential diagnosis of liver cirrhosis and primary hepatic carcinoma. Elevated serum GP73 may be correlated with liver tumor load and aggressiveness.

Adult ; Aged ; Carcinoma, Hepatocellular ; diagnosis ; Case-Control Studies ; Diagnosis, Differential ; Female ; Humans ; Liver Cirrhosis ; diagnosis ; Liver Neoplasms ; diagnosis ; Male ; Membrane Proteins ; blood ; Middle Aged ; Sensitivity and Specificity ; Transcriptome ; alpha-Fetoproteins ; metabolism

OBJECTIVETo evaluate the efficacy and safety of hydrochloride valacyclovir in treatment of varicella in pediatric patients between April 2006 and March 2007.

METHODSA randomized controlled multi-center clinical trial was conducted in 5 pediatric centers, i.e., Children's Hospital of Fudan University, Children's Hospital of Zhejiang University, Children's Hospital of Nanjing Medical University, Pediatric Department of Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology and Children's Hospital, Chongqing University of Medical Sciences. Patients who were clinically diagnosed as varicella without any complications and were beyond 3 years of age were enrolled into the study from the out-patient clinics. The subjects were divided into two groups randomly, one was treated with hydrochloride valacyclovir, the other with ribavirin. There were 128 cases in the group treated with hydrochloride valacyclovir and 132 cases in control group treated with ribavirin. The treatment duration of two groups was five days. The clinical efficacy and safety were evaluated after the first day and the fourth day of the treatment and within three days after the end of the treatment. The clinical efficacy was assessed by efficacy index.

RESULTS(1) The efficacy index on the fourth day of the therapy (0.80 +/- 0.24) in the valacyclovir group was significantly higher than that of ribavirin control group (0.59 +/- 0.37) (t = 5.42, P < 0.01). The efficacy index at the end of the treatment (0.86 +/- 0.14) in the hydrochloride valacyclovir group was also significantly higher than that (0.70 +/- 0.30) of the ribavirin control group (t = 5.43, P < 0.01). (2) In the valacyclovir and ribavirin groups, the effective rates on the fourth day of the therapy were 94.53% and 72.7% respectively (chi2) = 22.38, P < 0.01). The effective rates at the end of the therapy were 99.2% and 88.6%, respectively (chi(2) = 12.60, P < 0.01). The rates of cure of the two groups were 33.6% and 25.0% (chi2) = 2.32, P > 0.05). (3) No severe adverse drug reactions were observed in any of the two groups.

CONCLUSIONSThe hydrochloride valacyclovir was safe, reliable and convenient in treatment of uncomplicated varicella in children.

Acyclovir ; adverse effects ; analogs & derivatives ; therapeutic use ; Antiviral Agents ; adverse effects ; therapeutic use ; Chickenpox ; drug therapy ; Child ; Child, Preschool ; Female ; Humans ; Male ; Valine ; adverse effects ; analogs & derivatives ; therapeutic use

OBJECTIVETo observe the effect of Chuanhuang No.1 Recipe (CHR) on renal function and micro-inflammation in phase 3 chronic kidney disease (CKD) patients.

METHODSTotally 60 phase 3 CKD patients were randomly assigned to the treatment group (treated by CHR) and the control group (treated by Losartan Potassium), 30 in each group. All patients received basic treatment. Patients in the treatment group took CHR decoction, 400 mL each time, one dose per day, while those in the control group took Losartan Potassium, 50-100 mg per day. All medication lasted for 24 weeks. Changes of serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), serum uric acid (UA), 24 h urinary protein excretion (24 h U-pro), urinary microalbumin (U-Alb), high-sensitivity C-reactive protein (hs-CRP), serum tumor necrosis factor (TNF)-alpha, and serum IL-6 were detected and compared before and after treatment. Efficacy was also compared.

RESULTSCompared with before treatment, SCr and BUN significantly decreased in the treatment group (P<0.05, P<0.01); eGFR in- creased (P<0.05). Only UA obviously decreased in the control group (P<0.05), but with no obvious change in SCr, BUN, or eGFR. Compared with before treatment, 24 h U-pro decreased after treatment in the treatment group (P<0.05), but with less decreased level when compared with the control group. U- Alb was also significantly decreased in the control group (P<0.01). There was statistical difference in 24 h U-pro and U-Alb between the two groups after treatment (P<0.05). Compared with before treatment, hs-CRP obviously decreased after treatment in the two groups, but serum levels of TNF-alpha and IL-6 obviously decreased only in the treatment group (P<0.05). The total effective rate was obviously higher in the treatment group than in the control group (70.00% vs. 43.33%, P<0.01).

CONCLUSIONCHR could efficiently improve the renal function of phase 3 CKD patients and alleviate the micro-inflammation.

Adult ; Blood Urea Nitrogen ; C-Reactive Protein ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Inflammation ; Interleukin-6 ; metabolism ; Losartan ; therapeutic use ; Male ; Middle Aged ; Phytotherapy ; Renal Insufficiency, Chronic ; drug therapy ; Tumor Necrosis Factor-alpha ; metabolism ; Urea

Objective To construct the molecular transmission networks of HIV-1 CRF01 AE strains circulating in China and to analyze their characteristics. Methods Sequences of the pol genes of Chinese CRF01 AE strains were downloaded from Los Alamos database and the related demographic informa-tion was checked. Transmission networks were created by four steps,including phylogenetic tree construc-tion,transmission cluster extraction,minimum genetic distance identification and network visualization. Chi-square test was performed to analyze the differences in the distribution of different populations in the networks and the differences in the distribution of subjects with different degrees among different sub-populations. De-scriptive analysis was used to investigate the transmission links between sub-populations and various regions. Results The 2 419 sequences constituted 250 separate networks including 847 nodes and 610 edges. The number of subjects covered by different networks ranged from 2 to 25. Subjects with degree ≥2 represented only 26. 4%(224 / 847)of network-individuals,but were connected with 66. 5%(563 / 847)of all network-individuals. There were 37. 6%(669 / 1 781)of men who have sex with men(MSM),28. 4%(102 / 359) of heterosexual men,16. 1%(10 / 62)of intravenous drug users(IDUs)and 30. 4%(66 / 217)of hetero-sexual women involved in the networks(χ2 =23. 774,P﹤0. 001). The percentage of subjects with degree ≥2 was high in MSM(10. 8% ,193 / 1 781)compared to that in heterosexual men(5. 6% ,20 / 359)(P =0. 002)and heterosexual women(4. 6% ,10 / 217)(P=0. 004). Of the 669 MSM in the networks,95. 5%(639 / 669)linked to other MSM and only 2. 4% (16 / 669)linked to heterosexual women. However, 15. 1%(10 / 66)of the heterosexual women in the networks linked to MSM. Of the heterosexual men in the networks,35. 3%(36 / 102)linked to heterosexual women,9. 8%(10 / 102)linked to MSM. Of the sub-jects in the networks,20. 9%(177 / 847)linked to other regions' individuals. Conclusion The super-spreaders played an important role in the molecular transmission networks of HIV-1 CRF01 AE strains even though they were in a minority. The transmission of HIV-1 CRF01 AE strains between sub-populations and various regions was complicated and active.