Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19

BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.

Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma

Esophageal squamous cell carcinoma(ESCC)and esophagogastric junction adenocarcinoma(EGJA)are the two main types of gastrointestinal cancers that pose a huge threat to human health.ESCC remains one of the most common malignant diseases around the world.In contrast to the decreasing prevalence of ESCC,the incidence of EGJA is rising rapidly.Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers.Current approaches for early diagnosis mainly depend on invasive and costly endoscopy.Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients.Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis,making them promising biomarkers for early detection and monitoring of ESCC and EGJA.In this review,we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.

Clinical relevance of Helicobacter pylori babA2 and babA2/B in Costa Rica and Japan

AIM:To evaluate the prevalence of Helicobacter pylori(H.pylori ) babA2 ,babB and a recombinant gene between babA2 and babB(babA2/B ),and their role in the development of atrophic gastritis in Costa Rican and Japanese clinical isolates.METHODS:A total of 95 continuous H.pylori-positive Costa Rican(41 males and 54 females;mean age,50.65 years;SD,± 13.04 years) and 95 continuous H.pylori-positive Japanese(50 males and 45 females;mean age,63.43;SD,± 13.21 years) patients underwent upper endoscopy from October 2005 to July 2006.They were enrolled for the polymerase chain reaction(PCR)-based genotyping of the H.pylori babA2 ,babB and babA2/B genes.Statistical analysis was performed using the χ2 test and the Fisher's exact probability test and multivariate analysis was performed by logistic regression adjusting for gender and age.P < 0.05 was regarded as statistically significant.RESULTS:The PCR-based genotyping of 95 Costa Rican and 95 Japanese isolates showed a higher prevalence of babA2 in Japan(96.8%) than in Costa Rica(73.7%),while that of babA2/B was higher in Costa Rica(11.6%) than in Japan(1.1%).In Costa Rican isolates only,babA2 was significantly associated with atrophic gastritis(P = 0.01).CONCLUSION:These results suggest that the status of babA2 and babA2/B shows geographic differences,and that babA2 has clinical relevance in Costa Rica.

High Blood Pressure Increases the Risk of Cerebral Microbleeds in Hypertensive Individuals

Introduction: Hypertension is the leading preventable risk factor for major cardiovascular diseases worldwide. Recently, compelling evidence has emerged associating hypertension with cerebral microbleeds (CMBs), which are subclinical hemorrhages in the brain resulting from structural abnormalities in the small vessels that supply the brain. In addition to overall elevated blood pressure (BP), elevation in individual parameters such as systolic BP, diastolic BP, pulse pressure and mean arterial pressure could also individually be important risk factors for CMBs. This study aimed to assess the association between CMBs and blood pressure, and assess blood pressure parameters that could be possible risk factors for CMB. Methods: A retrospective case-control study was conducted from August 2021 to September 2022 on patients who underwent MRI due to primary complaints of limb disorders, loss of consciousness, persistent dizziness, and intermittent headaches. The patients were divided according to MRI results into 52 cases (those who had CMBs) and 52 controls (those who had no CMBs). Extracted data were analyzed in SPSS. Chi-square test, binary logistic regression, and Spearman’s correlation analysis were conducted. Results: In total, 104 cases and control patients were assessed, with mean (±SD) age 70.6 ± 8.56 vs 68.9 ± 8.93 years respectively (p > 0.05). CMB patients had more cases of stroke, hyperlipidemia and diabetes than non-CMB patients. Systolic blood pressure (SBP), diastolic blood pressure, pulse pressure (PP) and mean arterial pressure (MAP) were all considerably raised in CMB patients than non-CMBs patients. Blood pressure grades were positively correlated with the severity of CMBs (r = 0.22;p = 0.044). Logistic regression analysis showed that SBP and MAP were independent risk factors for CMBs (age and sex adjusted odds ratio = 1.420;95% CI: 1.030 - 1.851, and 1.310;95% CI: 1.011 - 1.631 respectively). Conclusions: In summary, this study found that hypertension was positively correlated with CMBs severity, and that SBP and MAP are independent risk factors for CMBs in patients with hypertension.

Risk of Autism Spectrum Disorder According to the Dose and Trimester of Exposure to Antiseizure Medications: A Systematic Review and Meta-Analysis

Background: The association between prenatal exposure to antiseizure medications (ASM) and autism spectrum disorder has been documented. This study sought to examine and synthesize evidence from studies that have evaluated these associations, with particular focus on the trimester of pregnancy and dosage of exposure. Methodology: PubMed, Embase, and PsycINFO databases were searched following strict inclusion/exclusion criteria. 10 studies were recruited involving children born to mothers with epilepsy who took ASM during pregnancy as cases, and those with epilepsy who did not take any ASM in pregnancy. Results: The relative risk of developing ASD among children exposed to valproic acid (RR, 3.90 [95% CI: 2.36 - 6.44], p < 0.006), was twice higher than that of carbamazepine (RR, 1.65 [95% CI: 0.62 - 4.37], p < 0.0001), or lamotrigine (RR, 1.60 [95% CI: 0.77 - 3.32], p = 0.006). The trimester of exposure and dosage of ASM administered were not significant. Conclusion: In summary, prenatal exposure to ASM increased the risk of developing ASD in children. The relative risk was twice as high in those exposed to valproic acid compared to those exposed to carbamazepine or lamotrigine. Trimester of pregnancy and dosage of ASM used by the mothers were not significant.

Establishment of a rapid detection method of Ureaplasma urealyticum based on recombinant polymerase amplification

Ureaplasma urealyticum(UU),is one of the most vital pathogens causing genitourinary tract infections of the body,and it can result in poor maternal and perinatal outcomes.The aim of this study was to establish a method to detect Ureaplasma urealyticum based on recombinant polymerase amplification(RPA)technique.Specific primers and probes were designed according to the 16sRNA gene sequence of Ureaplasma urealyticum.Six pathogens were detected for real-time fluorescence RPA specificity verification,including Mycoplasma hominis(MH),Chlamydia trachomatis(CT),Neisseria gonorrhoeae(NG),Staphylococcus aureus,Escherichia coli,and Lactobacillus vaginalis.The sensitivity of the method was performed by gradient dilution of the extracted template.A total of 60 clinical samples were detected by the established real-time fluorescence RPA.Detection of Ureaplasma urealyticum can be completed within 20 minutes at 39°C using established RPA method.The minimum detection limit of Ureaplasma urealyticum by real-time fluorescence RPA was 3 pg.The evaluation of 60 clinical samples proved that RPA method was feasible.A high specificity,sensitivity,simplicity and rapidity method for Ureaplasma urealyticum detection was successfully established based on the real-time fluorescence RPA method.

Blood-based biomarkers for early detection of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor of the digestive system worldwide,especially in China.Due to the lack of effective early detection methods,ESCC patients often present at an advanced stage at the time of diagnosis,which seriously affects the prognosis of patients.At present,early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy.Therefore,there is an unmet need for a noninvasive method to detect ESCC in the early stages.With the emergence of a large class of non-invasive diagnostic tools,serum tumor markers have attracted much attention because of their potential for detection of early tumors.Therefore,the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC.This article reviews the recent advances in the discovery of blood-based ESCC biomarkers,and discusses the origins,clinical applications,and technical challenges of clinical validation of various types of biomarkers.

A rare case of primary choriocarcinoma in the sigmoid colon

Primary colorectal choriocarcinoma is an extremely rare neoplasm and is usually associated with a poor prognosis.Only 13 cases of colorectal choriocarcinoma have previously been reported.There is no standard chemotherapeutic regimen for this tumor type.A 68-year-old man presented with melena and was diagnosed with sigmoid colonic adenocarcinoma with multiple liver metastases.He underwent a laparoscopic sigmoidectomy.Pathology revealed choriocarcinoma with a focal component of moderately differentiated adenocarcinoma of colon origin.Based on the collagen gel droplet-embedded culture drug sensitivity test(CD-DST)results,mFOLFOX6 and bevacizumab were administered,which suppressed aggressive tumor growth for 4 mo.The patient died 9 mo after the initial diagnosis.Our study results suggest that the standard chemotherapy regimen for colorectal cancer might have suppressive effects against primary colorectal choriocarcinoma.Moreover,CD-DST may provide,at least in part,therapeutic insight for the selection of appropriate antitumor agents for such patients.

Role of bacterial and genetic factors in gastric cancer in Costa Rica

AIM: To evaluate several risk factors for gastric cancer (GC) in Costa Rican regions with contrasting GC incidence rate (GCIR). METHODS: According to GCIR, 191 Helicobacter pylori (H pylori)-positive patients were classified into groups A (high GCIR, n = 101) and B (low GCIR, n = 90). Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin (IL)-1β and IL-10 by PCR-RFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS: Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach (mixed strain infection) were more frequently found in group A than in group B, and cagA and vacA s1b were signif icantly associated with high GCIR (P = 0.026 and 0.041, respectively). IL- 1β+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4). CONCLUSION: Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of H pylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica.

Non-Epstein-Barr virus associated lymphoepithelioma-like carcinoma of the inferior common bile duct

A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma(LEC),and some of LEC is associated with Epstein-Barr virus(EBV).All of the 13 previously reported cases of LEC of the biliary system were intrahepatic in location.Herein,we describe the first case of LEC of the inferior common bile duct.A 68-year-old Japanese man,who had been previously treated for hepatocellular carcinoma using microwave coagulation therapy,was found to have tumors of the common bile duct and pancreas head.Histopathological study of the resected tumor showed solid or cohesive nests of large undifferentiated cells with irregular large vesicular nuclei and nucleoli.Around the tumor cell nests,dense lymphoplasmacytic infiltration was observed.Focal glandular differentiation(approximately 5%) was also present.These histopathological features corresponded morphologically to LEC.Immunohistochemically,the tumor cells were positive for cytokeratin(CK) 7,CK 19 and CA19-9,but negative for CK 20 and Hep Par 1.In situ hybridization for Epstein Barr virus early small RNAs disclosed no nuclear signal in tumor cells.Therefore,a diagnosis of non-EBV-associated LEC of the inferior common bile duct was made.Although the prognosis of the biliary LEC is thought to be better than that of conventional cholangiocarcinoma,the differences in prognosis between EBV-positive and-negative cases have not yet been established.Therefore,additional case studies will be needed to clarify the clinicopathological features of LEC of the biliary tract.

Activation of AMPK/MnSOD signaling mediates anti-apoptotic effect of hepatitis B virus in hepatoma cells

AIM: To investigate the anti-apoptotic capability of the hepatitis B virus(HBV) in the HepG2 hepatoma cell line and the underlying mechanisms.METHODS: Cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Targeted knockdown of manganese superoxide dismutase(Mn SOD), AMP-activated protein kinase(AMPK) and hepatitis B virus X protein(HBx) genes as well as AMPK agonist AICAR and antagonist compound C were employed to determine the correlations of expression of these genes.RESULTS: HBV markedly protected the hepatoma cells from growth suppression and cell death in the condition of serum deprivation. A decrease of superoxide anion production accompanied with an increase of Mn SOD expression and activity was found in Hep G2.215 cells. Moreover, AMPK activation contributed to the up-regulation of Mn SOD. HBx protein was identified to induce the expression of AMPK and Mn SOD. CONCLUSION: Our results suggest that HBV suppresses mitochondrial superoxide level and exerts an antiapoptotic effect by activating AMPK/Mn SOD signaling pathway, which may provide a novel pharmacological strategy to prevent HCC.

Association between SNP rs10569304 on the Second Expressed Region of Hole Gene and the Congenital Heart Disease

The correlation of single nucleotide polymorphism (SNP) rs10569304 on the second expressed region of hole gene and congenital heart disease (CHD) of human being, and the effect of hole gene on CHD were investigated. 179 patients with CHD as CHD group and 183 healthy people as control group were selected in the case-control study. DNA was abstracted from the peripheral blood by phenol-chloroform method. Primer was designed for the flanking sequence of SNP rs10569304 on the second expressed region of hole gene. The genotype was identified by PCR degenerative acrylamide electrophoresis with amplification products. Then the three amplification products received sequencing. By chi-square test, the genotype frequency and allele frequency in CHD group and control group were analyzed. There was insertion-deletion (GCC/-) of SNP rs10569304 which corresponded to alleles of A and B in Southern Chinese people. The genotype frequency and allele frequency in control group and CHD group were met the Hardy-Weinberg equilibrium. By chi-square test, in control group and CHD group, the genotype frequency of AA (insertion homozygous), AB (insertion-deletion heterozygous) and BB (deletion homozygous) was 21.31%, 54.09%, 24.59% and 16.75%, 46.36%, 36.87%, respectively. The distributional difference of genotype frequency had statistical significance (χ2=6.51, P<0.05); The allele frequency of A and B was 48.36% and 51.64% in control group, 39.94% and 60.06% in CHD group, respectively. The distribu- tional difference of allele frequency had statistical significance (χ2=5.20, P<0.05). Meanwhile, by contrast with the control group, the BB genotype frequency and B allele frequency in CHD group was higher, but the AA and AB frequency was lower. There was higher risk to suffer from CHD involving B allele. BB genotype had 1.907-fold increased risk of developing CHD according to AA genotype (P<0.05). It is concluded that there is insertion-deletion (GCC/-) of SNP rs10569304 in the Southern Chinese people, and the people whose hole gene involving BB genotype have higher risk to suffering from CHD.

Effect of Helicobacter pylori cdrA on interleukin-8 secretions and nuclear factor kappa B activation

AIM:To investigate genetic diversity of Helicobacter pylori (H.pylori) cell division-related gene A (cdrA) and its effect on the host response.METHODS:Inactivation of H.pylori cdrA,which is involved in cell division and morphological elongation,has a role in chronic persistent infections.Genetic property of H.pylori cdrA was evaluated using polymerase chain reaction and sequencing in 128 (77 American and 51 Japanese) clinical isolates obtained from 48 and 51 patients,respectively.Enzyme-linked immunosorbent assay was performed to measure interleukin-8 (IL-8) secretion with gastric biopsy specimens obtained from American patients colonized with cdrA-positive or-negative strains and AGS cells cocultured with wild-type HPK5 (cdrA-positive) or its derivative HPKT510 (cdrA-disruptant).Furthermore,the cytotoxin-associated gene A (cagA) status (translocation and phosphorylation) and kinetics of transcription factors [nuclear factor-kappa B (NF-κB) and inhibition kappa B] were investigated in AGS cells co-cultured with HPK5,HPKT510 and its derivative HPK5CA (cagA disruptant) by western blotting analysis with immunoprecipitation.RESULTS:Genetic diversity of the H.pylori cdrA gene demonstrated that the cdrA status segregated into two categories including four allele types,cdrA-positive (allele types;Ⅰand Ⅱ) and cdrA-negative (allele types;Ⅲ and Ⅳ) categories,respectively.Almost all Japanese isolates were cdrA-positive (Ⅰ:7.8% and Ⅱ:90.2%),whereas 16.9% of American isolates were cdrA-positive (Ⅱ) and 83.1% were cdrA-negative (Ⅲ:37.7% and Ⅳ:45.5%),indicating extended diversity of cdrA in individual American isolates.Comparison of each isolate from different regions (antrum and corpus) in the stomach of 29 Americans revealed that cdrA status was identical in both isolates from different regions in 17 cases.However,12 cases had a different cdrA allele and 6 of them exhibited a different cdrA category between two regions in the stomach.Furthermore,in 5 of the 6 cases possessing a different cdrA category,cdrA-negative isolate existed in the corpus,suggesting that cdrA-negative strain is more adaptable to colonization in the corpus.IL-8 secretions from AGS revealed that IL-8 levels induced by a cdrA-disrupted HPKT510 was significantly lower (P < 0.01) compared to wildtype HPK5:corresponding to 50%-60% of those of wild-type HPK5.These data coincided with in vivo data that an average value of IL-8 in biopsy specimens from cdrA-positive and cdrA-negative groups was 215.6 and 135.9 pg/mL,respectively.Western blotting analysis documented that HPKT510 had no effect on CagA translocation and phosphorylation,however,nuclear accumulation of NF-κB was lower by HPKT510 compared to HPK5.CONCLUSION:Colonization by a cdrA-negative or cdrA-dysfunctional strain resulted in decreased IL-8 production and repression of NF-κB,and hence,attenuate the host immunity leading to persistent infection.

Efficacy of additional treatment with azathioprine in a patient with prednisolone-dependent gastric sarcoidosis

Gastric sarcoidosis with noncaseating granuloma is rare. Although corticosteroid produces a dramatic clinical response, it is unknown whether azathioprine show efficacy in prednisolone-dependent cases. Here, we report a case of gastric sarcoidosis in a 25-year-old man with severe epigastlargia. Gastroendoscopy revealed multiple map-like ulcerations. Histological examination showed multiple noncaseating granulomatous lesions in gastric mucosa, which were incompatible with diagnoses of Crohn's disease or tuberculosis. He was started on prednisolone at 30 mg/d, and his symptoms improved within 7-d. The prednisolone was gradually tapered by 5 mg every 2-wk, but oral azathioprine at 50 mg was added after symptoms recurred at tapered dose of 10 mg. Endoscopy 4-wk later showed healing ulcers, and, lymphocytic infiltration was absent. The efficacy of additional azathioprine in gastric sarcoidosis is not well defined. Here, we report a case of prednisolone-dependent gastric sarcoidosis that improved after additional azathioprine, and also review the literature concerning the treatment, especially for prednisolone-dependent cases.

Application of novel magnified single balloon enteroscopy for a patient with Cronkhite-Canada syndrome

We present a case of Cronkhite-Canada syndrome(CCS) in which the entire intestine was observed using a prototype of magnifying single-balloon enteroscope(SIF Y-0007, Olympus). CCS is a rare, non-familial gastrointestinal polyposis with ectodermal abnormalities. To our knowledge, this is the first report showing magnified intestinal lesions of CCS. A 73-year-old female visited our hospital with complaints of diarrhea and dysgeusia. The blood test showed mild anemia and hypoalbuminemia. The esophagogastroduodenoscopy and colonoscopy revealed diffuse and reddened sessile to semi-pedunculated polyps, resulting in the diagnosis of CCS. In addition to the findings of conventional balloon-assisted enteroscopy or capsule endoscopy, magnifying observation revealed tiny granular structures, non-uniformity of the villus, irregular caliber of the loop-like capillaries, scattered white spots in the villous tip, and patchy redness of the villus. Histologically, the scattered white spots and patchy redness of the villus reflect lymphangiectasia and bleeding to interstitium, respectively.

Micro RNA-378a-3p Downregulation as a Novel Biomarker with Poor Clinical Outcomes in Cervical Cancer

Objective Cervical cancer(CC)is one of the most common malignant tumors in gynecology.This study aimed to investigate the prognostic significance of serum micro RNA(mi R)-378 a-3 p in CC and the effect of mi R-378 a-3 p on tumor growth.Methods Real-time quantitative polymerase chain reaction analysis was used to measure the expression of mi R-378 a-3 p in serum from patients with CC and healthy control subjects as well as from CC tissues and adjacent normal tissues.The association between serum mi R-378 a-3 p levels and clinicopathological factors was analyzed.The correlation between mi R-378 a-3 p levels and overall survival(OS)of CC patients was determined by Kaplan-Meier analysis.The CC cell proliferation and migration abilities after transfection of mi R-378 a-3 p mimics were detected by Cell Counting Kit-8 and scratch wound healing assays,respectively.Tumor volume and weight in mice treated with mi R-378 a-3 p were measured using a caliper and an electronic balance.Results Mi R-378 a-3 p expression was downregulated in the serum and tissues of CC patients compared to that in healthy control subjects and normal tissues,respectively.Low expression of mi R-378 a-3 p was positively correlated with large tumor size,advanced tumor stage,and lymph node metastasis.The OS of patients with low expression of mi R-378 a-3 p was significantly lower than that of patients with high expression.Overexpression of mi R-378 a-3 p suppressed the proliferation and migration of CC cells.In vivo studies indicated that overexpression of mi R-378 a-3 p was associated with decreased tumor volume and weight in mice.Conclusion Mi R-378 a-3 p downregulation is associated with the development and prognosis of CC,suggesting that it may be a potential biomarker for CC.

Mucin 1 and interleukin-11 protein expression and inflammatory reactions in the intestinal mucosa of necrotizing enterocolitis children after surgery

BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.

Expression of Survivin and Its Splice Variants in Gastric Cancer

Survivin variants specific real time quantitative RT-PCR was developed to analyze their expression in 53 paired cancer and para-cancerous tissues, and the expression of the wild-type survivin protein was detected by immunohistochemistry. The results showed that survivin mRNA and protein were expressed in gastric cancer and para-cancerous tissues, The survivin-2B was dominantly expressed in para-cancerous tissues, whereas the survivin-△Ex3 was more frequently detected in cancer tissues. The positive rate of survivin-2a was 100% in both cancer and para-cancerous tissues, but its relative transcript expression level was not significantly increased in cancer tissues in comparison with para-cancerous tissues. The correlation analysis revealed that the expression of survivin-2a mRNA was significantly associated with that of total survivin （rs=0.4178, P=0.0018）, whereas inversely to that of survivin-△EX3 （rs=-0.4506, P=0.0007）. It was suggested that survivin-2a may act as an antagonist of survivin-△EX3. The balance between antiapoptotic survivin iso-forms and nonantiapoptotic ones may play an important role in tumorigenesis and tumor progression, Promising value is hinted to analyze survivin and its variants in tumor early diagnosis and distinguishing malignant tumors from benign ones.

Correlation of serum vitamin E content with insulin resistance and oxidative stress response in patients with type 2 diabetes mellitus

Objective: To study the correlation of serum vitamin E content with insulin resistance and oxidative stress response in patients with type 2 diabetes mellitus. Methods: Patients who were diagnosed with type 2 diabetes mellitus in Xining Second People's Hospital between February 2016 and February 2017 were selected as T2DM group, healthy volunteers who received physical examination during the same period were selected as control group, oral glucose tolerance test was conducted to detect insulin resistance indexes, and fasting venous blood was collected to detect oxidative stress indicators. Results: Serum VitE, 2 h-Ins, 2 h-CP, Trx, Txnip, SOD and GSH-Px levels of T2DM group were significantly lower than those of control group while F-Ins, F-CP, MDA, AOPP, 8-OHdG, AGEs and LOX-1 levels were significantly higher than those of control group;serum VitE level in T2DM patients was positively correlated with serum 2 h-Ins, 2 h-CP, Trx, Txnip, SOD and GSH-Px levels, and negatively correlated with serum F-Ins, F-CP, MDA, AOPP, 8-OHdG, AGEs and LOX-1 levels. Conclusion: The decrease of serum vitamin E in patients with type 2 diabetes mellitus can lead to the aggravation of insulin resistance and the activation of oxidative stress response.

Examination of Huntington's disease in a Chinese family

We report brain imaging and genetic diagnosis in a family from Wuhan, China, with a history of Huntington＇s disease. Among 17 family members across three generations, four patients （Ⅱ2, Ⅱ6, Ⅲ5, and Ⅲ9） show typical Huntington＇s disease, involuntary dance-like movements. Magnetic resonance imaging found lateral ventricular atrophy in three members （Ⅱ2, Ⅱ6, and Ⅲ5）. Moreover, genetic analysis identified abnormally amplified CAG sequence repeats （〉 40） in two members （Ⅲ5 and Ⅲ9）. Among borderline cases, with clinical symptoms and brain imaging features of Huntington＇s disease, two cases were identified （Ⅱ2 and Ⅱ6）, but shown by mutation analysis for CAG expansions in the important transcript 15 gene, to be non-Huntington＇s disease. Our findings suggest that clinical diagnosis of Huntington＇s disease requires a combination of clinical symptoms, radiological changes, and genetic diagnosis.