Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking. AIM: To investigate the causal relationship between gut microbiota and CCA risk. METHODS: We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness. RESULTS: Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, genus Ruminococcustorques group, genus Coprococcus, genus Dorea, and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae, genus Alistipes, order Enterobacteriales, and phylum Firmicutes. Protective effects against CCA were suggested for genus Collinsella, genus Eisenbergiella, genus Anaerostipes, genus Paraprevotella, genus Parasutterella, and phylum Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy. CONCLUSION: This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

Mirizzi syndrome: Problems and strategies.

Mirizzi syndrome is a serious complication of gallstone disease. It is caused by the impacted stones in the gallbladder neck or cystic duct. One of the features of Mirizzi syndrome is severe inflammation or dense fibrosis at the Calot's triangle. In our clinical practice, bile duct, branches of right hepatic artery and right portal vein clinging to gallbladder infundibulum are often observed due to gallbladder infundibulum adhered to right hepatic hilum. The intraoperative damage of branches of right hepatic artery occurs more easily than that of bile duct, all of which are hidden pitfalls for surgeons. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) are the preferable tools for the diagnosis of Mirizzi syndrome. Anterograde cholecystectomy in Mirizzi syndrome is easy to damage branches of right hepatic artery and bile duct due to gallbladder infundibulum adhered to right hepatic hilum. Subtotal cholecystectomy is an easy, safe and definitive approach to Mirizzi syndrome. When combined with the application of ERCP, a laparoscopic management of Mirizzi syndrome by well-trained surgeons is feasible and safe. The objective of this review was to highlight its existing problems: (1) low preoperative diagnostic rate, (2) easy to damage bile duct and branches of right hepatic artery, and (3) high concomitant gallbladder carcinoma. Meanwhile, the review aimed to discuss the possible therapeutic strategies: (1) to enhance its preoperative recognition by imaging findings, and (2) to avoid potential pitfalls during surgery.

Three-dimensional versus two-dimensional laparoscopic surgery for rectal cancer: better promote postoperative sexual and urinary function of a propensity-matched study.

Laparoscopic total mesorectal excision (TME) with autonomic nerve preservation (ANP) is a common procedure for rectal cancer (RC), associated with a high prevalence of postoperative urogenital and anorectal dysfunctions. Compared to 2D laparoscopy, 3D laparoscopy provides better depth perception of the surgical field and hand-eye coordination to achieve better outcomes. We compared the performance of 2D and 3D laparoscopy on preserving urogenital and anorectal function in TME+ANP surgery for rectal cancer using propensity-score matching. Data were collected from consecutive male patients who underwent 3D or 2D laparoscopic TME+ANP for primary RC at our institution between March 2012 and December 2020. The primary outcome was sexual and urinary function 1 year after surgery. A total of 450 male patients were eligible. After 1:1 matching, 146 cases were included in each group for analysis. One year after surgery, the prevalence of sexual dysfunction (International Index of Erectile Function score <26) was 8.22% in the 3D laparoscopic group and 44.52% in the 2D laparoscopic group, respectively (P=0.000) and a significant difference in the incidence of urinary retention was observed (n=3 and 24, respectively (P=0.000)). Moreover, blood loss, operative time, duration of hospital stay, and the time to first flatus in the 3D laparoscopic group were significantly less than in the 2D laparoscopic group. In conclusion, 3D laparoscopic TME is associated with lower incidences of postoperative sexual and urinary dysfunction than 2D laparoscopic TME for rectal cancer in male patients.

The psychological impact of COVID-19 outbreak on medical staff and the general public.

To assess the psychological effects of the novel coronavirus disease (COVID-19) on medical staff and the general public. During the outbreak of COVID-19, an internet-based questionnaire included The Self-rating Depression Scale (SDS), Perceived Stress Scale (PSS-10), and Impact of Event Scale-Revised (IES-R) was used to assess the impact of the pandemic situation on the mental health of medical staff and general population in Wuhan and its surrounding areas. Among the 1493 questionnaires completed, 827 (55.39%) of these were men, and 422 (28.27%) of these were medical personnel. The results suggest that the outbreak of COVID-19 has affected individuals significantly, the degree of which is related to age, sex, occupation and mental illness. There was a significant difference in PSS-10 and IES-R scores between the medical staff and the general population. The medical staff showed higher PSS-10 scores (16.813 ± 4.87) and IES-R scores (22.40 ± 12.12) compared to members of the general population PSS-10 (14.80 ± 5.60) and IES-R scores (17.89 ± 13.08). However, there was no statistically significant difference between the SDS scores of medical staff (44.52 ± 12.36) and the general public (43.08 ± 11.42). In terms of the need for psychological assistance, 50.97% of interviewees responded that they needed psychological counseling, of which medical staff accounted for 65.87% and non-medical staff accounted for 45.10%. During the ongoing COVID-19 outbreak, great attention should be paid to the mental health of the population, especially medical staff, and measures such as psychological intervention should be actively carried out for reducing the psychosocial effects.

Inflammatory myofibroblastic tumor of the pancreatic neck: A case report and review of literature.

BACKGROUND: Pancreatic inflammatory myofibroblastic tumor (IMT) is a relatively rare disease that is often confused with pancreatic cancer or pancreatic neuroendocrine tumors. The histological features of IMTs show that tissue from this type of tumor contains an intermingling of fibroblast and myofibroblast proliferation, accompanied by a varying degree of inflammatory cell infiltration. CASE SUMMARY: The management of an IMT occurring at the neck of the pancreas is presented in this paper. A 66-year-old female patient was diagnosed with a pancreatic neck mass after a series of tests. The patient underwent enucleation of the pancreatic neck tumor after a pathological diagnosis of IMT. Previous research on the clinical features, pathological diagnosis and treatment of pancreatic IMTs was reviewed. Compared with previous reports, this is a unique case of enucleation of a pancreatic IMT. CONCLUSION: The enucleation of pancreatic IMTs may be a safe and efficient surgical method for managing such tumors with a better prognosis. Further cases are required to explore surgical measures for pancreatic IMTs.

Study of aerodynamic focusing lens stacks (ALS) for long focal length aerosol-assisted focused chemical vapor deposition (AAFCVD).

Mask-free direct printing can alleviate the high cost and high consumption involved in photo-lithography for chip processing. Most of their technical routes are based on the traditional short focal length nozzles, which is suffered from higher probability of nozzle retardation or clogging as well as the higher mechanical burdens. While aerosol-assisted chemical vapor deposition (AACVD) has better deposition adaptability but usually lack of focused printing. In this study, a system that combines of long focal length ALS with AACVD, so called AAFCVD printing system has been developed. The single-point printing capability and aerosol precursor adaptability were verified, and the relationship between the single spot printing performance and the chemical reaction mechanisms were studied. Furthermore, a unique carbon injection effect brought by ALS was discovered. Finally, the linear graphics printing performances of the system were evaluated. This system is expected to become a new generation of high-performance mask-free printing system for chip manufacturing.

Small bowel perforation caused by pancreaticojejunal anastomotic stent migration after pancreaticoduodenectomy: A case report.

INTRODUCTION: Pancreaticoduodenectomy (PD) has been widely applied as a standard surgical procedure to treat periampullary diseases. The placement of a pancreaticojejunal anastomotic stent is considered an effective and safe method for preventing pancreatic fistula after PD. Recently, the role of pancreaticojejunal anastomotic stents has been challenged, as gradually increasing complications have been observed. Stent-related small bowel perforation has only occurred in 2 cases as long-term complications but has not been reported to occur within 1 week after surgery. PATIENT CONCERNS: Here, we report the case of a 71-year-old female patient complaining of painless jaundice who underwent PD with a pancreaticojejunal anastomotic stent for a duodenal papillary adenocarcinoma (T4N1M0). Four days after surgery, she had a sudden rise in temperature, high white blood cell count, significantly elevated C-reactive protein and 400 ml green-brown drainage fluid. Enhanced computed tomography showed hydrops abdominis. DIAGNOSIS: Small bowel perforation caused by stent migration was considered first. INTERVENTIONS: An emergency exploratory laparotomy was performed. We located the pancreaticojejunal anastomotic stent, which extended 2 cm from the small bowel, and sutured the jejunum hole after cutting away the protruding part of the stent. OUTCOMES: The patient recovered smoothly and was discharged on the 7th day after the second surgery. After more than 12 months of follow-up, the patient is doing well and is free of any symptoms related to the procedure. CONCLUSION: We caution that stent-related complications can occur when perioperative patients suffer from unexplained or sudden changes in vital signs after PD. In addition, the function of the pancreaticojejunal anastomotic stent needs to be reevaluated by future studies.

Long Non-Coding RNA STARD13-AS Suppresses Cell Proliferation And Metastasis In Colorectal Cancer.

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is closely related with the progression of cancer in humans. The functional and regulatory roles of lncRNAs in colorectal cancer (CRC) are still largely unclear. The purpose of this study is to explore the function of lncRNA STARD13-AS in CRC. METHODS: The bioinformatics tool "GEPIA" was used to predict the potential expression of STARD13-AS in CRC. qRT-PCR was used to evaluate the relative expression level of STARD13-AS in CRC cells lines and tissues samples. The functional involvement of STARD13-AS in the CRC cells was assessed using MTT assay, flow cytometry, and Transwell assay. The expression levels of cyclin D, cyclin E, E-cadherin, N-cadherin, and vimentin were assessed using Western blot. RESULTS: Bioinformatics prediction and qRT-PCR results showed that STARD13-AS expression was decreased in CRC tissues. Patients with low STARD13-AS expression exhibited distant and lymphatic metastasis as well as enhancement in tumor size. STARD13-AS expression was downregulated in CRC cell lines compared to normal human colon mucosal epithelial cell line NCM460 and STARD13-AS expression in SW620 and LoVo cell lines was lowest. Moreover, we observed that while STARD13-AS overexpression suppressed the cell cycle, proliferation, migration, and invasion, while promoted apoptosis both in LoVo and SW620 cells. In addition, STARD13-AS overexpression inhibited Cyclin E, Cyclin D, N-cadherin and vimentin expression, and promoted E-cadherin expression both in LoVo and SW620 cells. CONCLUSION: Expression of STARD13-AS suppresses cell proliferation and metastasis in CRC, suggesting that STARD13-AS might act as a potential target for CRC treatment.

Circulating miR-125a but not miR-125b is decreased in active disease status and negatively correlates with disease severity as well as inflammatory cytokines in patients with Crohn's disease.

AIM: To determine the association of circulating miR-125a/b expression with the risk and disease severity of Crohn's disease (CD), and with inflammatory cytokines. METHODS: Plasma samples were collected from patients with active CD (A-CD), or CD in remission (R-CD) and from healthy controls (HCs). The levels of the inflammatory cytokines interleukin-17 (IL-17), tumour necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay. The expression of miR-125a/b was assessed by quantitative polymerase chain reaction (qPCR). RESULTS: Twenty-nine A-CD patients, 37 R-CD patients, and 37 HCs were included in the study. Plasma miR-125a expression was decreased in A-CD patients compared with that in R-CD patients (P < 0.001) and HCs (P < 0.001). miR-125a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve (AUC) = 0.854] and from HCs (AUC = 0.780), whereas miR-125b expression did not. miR-125a was negatively correlated with C-reaction protein (CRP) (P = 0.017), erythrocyte sedimentation rate (ESR) (P = 0.026), Crohn's disease activity index (CDAI) (P = 0.003), IL-17 (P = 0.015), and TNF-α (P = 0.004) in A-CD patients. Furthermore, miR-125a was negatively associated with CRP (P = 0.038) and CDAI (P = 0.021) in R-CD patients. Regarding miR-125b, no association with CRP, CDAI, IL-17, TNF-α, or IFN-γ was found in A-CD or in R-CD patients. miR-125a levels gradually increased in A-CD patients who achieved clinical remission (P = 0.009) after 3-mo treatment, whereas they remained unchanged among patients who failed to achieve remission. No changes in miR-125b expression were detected in remission or non-remission patients after treatment. CONCLUSION: Circulating miR-125a but not miR-125b is decreased in patients with active disease status and negatively correlates with disease severity and inflammatory cytokines in patients with CD.

Formal total synthesis of the akuammiline alkaloid (+)-strictamine.

An asymmetric formal total synthesis of the akuammiline alkaloid (+)-strictamine is reported. The key features of the synthesis include a Friedel-Crafts cyclization to form the D-ring and the critical C7 all-carbon quaternary carbon centre, as well as an aza-1,6-conjugate addition to assemble the 2-azabicyclo[3.3.1]nonane system.

DEC2 suppresses tumor proliferation and metastasis by regulating ERK/NF-κB pathway in gastric cancer.

Differentiated embryonic chondrocyte expressed gene 2 (DEC2; BHLHE41/Sharp1) is a helix-loop-helix (bHLH) transcription factor, and its deregulation has been observed in several tumors. However, this gene's effects on tumor progression are controversial, and its roles in gastric cancer (GC) remain unclear. In the present study, we found that DEC2 expression level is lower in GC tissues compared with adjacent non-tumor tissues, and negatively correlated with tumor invasion, lymph node metastasis, TNM stage, and poor survival of GC patients. Positive clinical correlations of DEC2 with EMT regulator, E-cadherin, were also observed in the tissue sections. Overexpression of DEC2 inhibits cell proliferation and EMT in vitro, as well as tumor growth and metastasis in vivo. DEC2 expression also induces cell apoptosis. Furthermore, the anti-metastatic effect of DEC2 was mediated by inhibiting ERK/NF-κB/EMT axis. After treatment with ERK1/2 chemical inhibitor (U0126), DEC2's inhibitory effect on ERK/NF-κB/EMT was further decreased. Collectively, these data helped to characterize DEC2, which might be a potential molecular target for diagnostic and therapeutic approaches for GC.

Expression and clinical significance of IL-17 and IL-17 receptor in ulcerative colitis.

The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor (IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis (UC) and controls, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein (CRP) levels were determined by ELISA and immunonephelometry, respectively. The IL-17R mRNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls (P<0.05). Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase (P<0.05), and correlated with CRP levels (r=0.578, P<0.01). IL-17R expression levels were higher in active UC patients than in healthy controls (P<0.05). It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.

Glutathione-functionalized graphene quantum dots as selective fluorescent probes for phosphate-containing metabolites.

Bright blue fluorescent glutathione-functionalized graphene quantum dots (GQDs@GSH) were prepared by a one-step pyrolysis method with a fluorescence quantum yield as high as 33.6%. Futhermore, the obtained GQDs@GSH can be used as a probe to estimate the ATP level in cell lysates and human blood serum.

Clinical pathology and recent follow-up study on gastric intraepithelial neoplasia and gastric mucosal lesions.

BACKGROUND/AIMS: To explore the correlations between endoscopic gastric mucosal lesions and pathological gastric intraepithelial neoplasia (GIN), and to investigate outcomes of gastric intraepithelial neoplasia after treatments. METHODOLOGY: Biopsies of 18,566 Chinese patients undergoing diagnostic gastroscopy were included. Among them, 130 patients were given various treatments, including medication, endoscopic treatment and surgery. RESULTS: There were 433 patients with GIN by initial pathological diagnosis. Among them, 367 low-grade GIN and 66 high-grade GIN, 348 cases accompanied with chronic gastritis, and 85 cases accompanied with localized foci. Eighty cases of Hp-positive patients with low-grade GIN were given anti-Hp therapy. Our results showed that 45 cases of intraepithelial neoplasia disappeared when chronic inflammation left, and 33 cases were given the original diagnoses and two cases developed into high-grade GIN. Surgery was then performed, after which one case was confirmed to have early gastric carcinoma, and the other was diagnosed as advanced gastric carcinoma. Pathological examinations were carried out undergoing EMR or ESD treatment for 18 patients with localized foci accompanied with low-grade GIN. Results showed four cases of chronic inflammation, 11 cases with original diagnoses maintained, and three cases of high-grade GIN. CONCLUSIONS: GIN occurred frequently in patients with more severe pathological inflammations under endoscope, which also had certain correlations with intestinal metaplasia. After treatment, parts of low-grade GIN could be reserved. The effect of endoscopic resection on localized foci accompanied with low-grade GIN was affirmative. However, the limitation of endoscopic biopsy should be fully understood.

Overexpression of metastasis-associated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer.

BACKGROUND: The aims of this work are to detect the expression levels of metastasis-associated protein 1 (MTA1) in patients with early-stage non-small cell lung cancer (NSCLC), and to investigate the relationship of MTA1 protein with clinicopathologic factors, tumor angiogenesis, and prognosis. METHODS: One hundred and two patients with pathologic stage I NSCLC who successfully underwent curative surgical resection were enrolled in this study. Immunohistochemical staining for MTA1 and CD34 was performed using the streptavidin-peroxidase method, and intratumoral microvessel density (MVD) was recorded by counting CD34-positive immunostained endothelial cells. All statistical analyses were performed with SPSS statistical software to determine the effects of MTA1 protein on clinicopathologic factors, tumor angiogenesis, and prognosis. RESULTS: MTA1 protein overexpression was detected in 41 cases and was significantly associated with MVD (P = 0.008). MTA1 protein overexpression and high MVD were significantly associated with tumor relapse (P = 0.004 and 0.007) and poor 5-year disease-free survival (P = 0.001 and 0.004). Patients with MTA1 protein overexpression and high MVD had significantly poor overall survival (P = 0.005 and 0.043) and disease-specific survival (P = 0.006 and 0.031) at 5 years after operation. Multivariate analysis demonstrated that MTA1 protein overexpression was an independent prognosticator for unfavorable disease-free, overall, and disease-specific survival (P = 0.011, 0.024, and 0.046). CONCLUSIONS: MTA1 protein overexpression is common in early-stage NSCLC and is significantly associated with tumor angiogenesis and poor survival. These findings suggest that MTA1 may have clinical potential as a promising predictor to identify individuals with poor prognostic potential and as a possible novel target molecule of antiangiogenic therapy for patients with early-stage NSCLC.

Upregulated mRNA expression of major histocompatibility complex class I chain-related gene A in colon and activated natural killer cells of Chinese patients with ulcerative colitis.

OBJECTIVE: To explore the expression of major histocompatibility complex class I chain-related gene A (MICA) and its ligand in colonic mucosa and the role of MICA-natural killer (NK) group 2D (NKG2D) interaction in activating NK cells in ulcerative colitis (UC) patients. METHODS: Intestinal mucosal biopsies were obtained from patients with UC and the controls. The expression of major histocompatibility complex class I-related gene (MIC) genes was determined by a reverse transcription polymerase chain reaction (RT-PCR) and the imaging of MICA expressed on colonic mucosa was measured by confocal microscopy resonance scanning. NKG2D and intracellular interferon (IFN)-γ expressions on NK cells were assayed by flow cytometry. RESULTS: The relative amount of MICA mRNA in the colonic mucosa of UC patients was significantly higher than in that of the controls (3.5408 ± 2.6658 vs 1.0477 ± 0.7201, P = 0.001), as were the major histocompatibility complex class I chain-related gene B (MICB) (8.9879 ± 3.2893 vs 4.6293 ± 1.2616, P < 0.001) and NKG2D mRNA expression (2.4395 ± 0.8147 vs 1.1624 ± 0.3954, P < 0.001). Confocal microscopy resonance scanning had shown that MICA was localized predominantly on the basolateral membranes of the epithelium. Further flow cytometry confirmed that the percentage of IFN-γ producer NK cells that expressed NKG2D in peripheral blood lymphocytes was higher in UC patients than in the healthy controls (45.36% ± 12.47% vs 27.45% ± 9.30%, P < 0.001). CONCLUSION: MICA, MICB and NKG2D were upregulated in the colonic mucosa of UC and were associated with activating NK cells with promoted NKG2D and IFN-γ production.

[CTLA-4 gene polymorphism regulates CTLA-4 mRNA stability and protein level in patients with ulcerative colitis].

OBJECTIVE: To investigate the effect of (AT)n repeat polymorphism of the 3'untranslated region in cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) gene on CTLA-4 mRNA stability and full length (flCTLA-4) and soluble CTLA4 (sCTLA-4) expression in ulcerative colitis (UC). METHODS: flCTLA-4 mRNA in colonic biopsies and sCTLA-4 mRNA stability in peripheral blood mononuclear cells of UC patients were measured by quantitative PCR and half-life, respectively. The protein expression of flCTLA-4 in colonic biopsies and sCTLA-4 in sera of UC patients were determined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The polymorphism of CTLA-4 (AT)n repeats in 300 UC and 700 age and sex matched healthy controls was genotyped by fluorescent PCR. RESULTS: Among the UC patients, sCTLA-4 mRNA expression levels were decreased in active disease compared to non-active disease (P= 0.004). Carriers of the longer alleles of the (AT)n repeats expressed lower levels of flCTLA-4 and sCTLA-4 mRNA and sCTLA-4 protein than those of the shorter alleles in UC (all P< 0.01), and mRNA with long (AT)n repeat alleles has shorter half-life than mRNA with short alleles and, hence, are unstable. The frequency of long allele carriers of CTLA-4 (AT)n repeats was significantly higher in UC patients than in the healthy controls (22.0% vs. 6.3%, P< 0.01, OR= 4.21, 95% CI: 2.79-6.33), and associated with extensive colitis (P= 0.008). CONCLUSION: CTLA-4 gene expression levels were associated with (AT)n repeat polymorphisms in UC patients. The expression of CTLA-4 mRNA and protein were decreased in carriers of the longer alleles of the (AT)n repeats of CTLA-4 gene. This study suggests that CTLA-4 plays an important role in genetic risk and pathophysiology for UC in central China.

Effect of cytotoxic T lymphocyte-associated molecule 4 1661 gene polymorphism on its expression and transcription in ulcerative colitis.

OBJECTIVE: Our aim was to investigate the expression of cytotoxic T lymphocyte-associated molecule 4 (CTLA-4) in ulcerative colitis (UC) and to evaluate the effect of CTLA-4 gene -1661A/G polymorphism on CTLA-4 expression and transcription. METHODS: A total of 20 UC patients and 22 healthy controls matched by age and sex were enrolled at Zhongnan Hospital of Wuhan University in central China. The CTLA-4 -1661A/G polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. A Western blot analysis was performed to determine the full length CTLA-4 (flCTLA-4) protein expression in the peripheral blood of the UC patients. Serum-soluble CTLA-4 (sCTLA-4) levels were measured by enzyme-linked immunosorbent assay. CTLA-4-1661G mutant promoter transcription function was analyzed by site-directed PCR-based mutagenesis. RESULTS: CTLA-4 protein expression on CD4(+) T cells in UC patients was lower than that in the healthy controls (P < 0.001) while serum sCTLA-4 in the UC patients was significantly higher than that in the healthy controls (P < 0.001). No correlation was found between flCTLA-4 and sCTLA-4 expression levels and the -1661 A/G polymorphism of the CTLA-4 gene. Meanwhile, CTLA-4 -1661 allele A had no significant impact on the promoter activity compared with allele G (P > 0.05). CONCLUSION: CTLA-4 expressions were aberrant in UC patients compared with the healthy controls. CTLA-4 -1661A/G polymorphism had no significant impact on CTLA-4 expression and transcription in the peripheral CD4 T cells of UC patients.

[Association of cytotoxic T lymphocyte antigen-4 promoter C-658T polymorphism with ulcerative colitis in Chinese].

OBJECTIVE: To investigate the association of gene polymorphism of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) with ulcerative colitis (UC) in Chinese. METHODS: One hundred and seventeen patients with UC and 246 healthy controls were genotyped for the polymorphisms of C-658T in the promoter and C61T at the 3' untranslated region of the CTLA-4 gene using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), respectively. The genotype and allele frequencies of the two groups were calculated and compared by chi square test. RESULTS: The frequency of TT+CT genotype at the CTLA-4 gene C-658T in the promoter was significantly higher in UC patients than that in healthy controls (P=0.015). The frequency of the T allele at this locus was also significantly higher in UC patients than that in the controls (P=0.033). The frequencies of TT genotype and T allele at the C-658T locus were highly associated with extensive colitis in UC patients (P=0.037, and P=0.0067, respectively). CONCLUSION: The T allele of CTLA-4 promoter C-658T locus was highly associated with UC in Chinese Han of central China.

[A novel microemulsion electrokinetic chromatography for measuring lipid-water partition coefficients of pharmaceuticals].

AIMS: To establish a novel microemulsion electrokinetic chromatography (MEEKC) method for measuring lipid-water partition coefficients ( logP(ow)) of pharmaceuticals without using microemulsion phase marker in order to avoid the error from tracing the migration time of microemulsion phase. METHODS: The migration time of microemulsion phase (t(me)) was obtained by non-linearity fitting with logP(ow) values from literature and measured migration time (t(m)) of a series of organic compounds, a calibration curve for estimating logP(ow) of pharmaceuticals was thus obtained. In addition, the accuracy of the values measured by MEEKC was evaluated. RESULTS: The logP(ow) values of 4 pharmaceuticals measured by MEEKC method presented in this paper were close to those determined by shake-flask method, and the average error between values from two methods was 0.15 logarithm units. Furthermore, according to the suggested theory, the measurement accuracy of logP(ow) is correlated with different t(m) in MEEKC. CONCLUSION: The proposed method is simple, rapid, reproducible, and reliable with high measurement accuracy, which can be useful to estimate lipid-water partition coefficients of pharmaceuticals.