Trend analysis and risk of gallbladder cancer mortality in China, 2013-2019.

OBJECTIVES: There is a lack of comprehensive analysis of recent gallbladder cancer (GBC) mortality trends in China. This study aims to analyse trends in GBC mortality in China, with a specific focus on urban and rural area differences, and to determine possible risk factors. STUDY DESIGN: This was a cross-sectional study. METHODS: Data were accessed through the Chinese Health Statistics Annual Report for 31 provinces from 2013 to 2019. Age-standardised mortality rate (ASMR) stratified by regions, gender and the years of diagnoses were analysed by Joinpoint regression analysis. RESULTS: The GBC ASMR was higher in females than in males and higher in urban areas than in rural areas. Mortality was primarily observed in individuals aged ≥65 years (in both sexes). A non-significant downward trend of GBC mortality was identified in urban areas from 2013 to 2019 (average annual percent change [AAPC] -1.50%; 95% confidence interval [CI]: -3.49, 0.53). However, in rural areas, the ASMR significantly increased with an AAPC of 2.64% (95% CI: 1.15, 4.15) in males and 3.85% (95% CI: 2.17, 5.56) in females. The GBC mortality rate was positively related to red meat consumption. CONCLUSIONS: The burden of GBC mortality in rural China cannot be ignored, as results from this study show significantly increasing trends in both females and males from 2013 to 2019. In addition, red meat consumption may play a vital role in the increasing GBC mortality rate.

[Analysis of influencing factors of shunt dysfunction after transjugular intrahepatic portosystemic shunt in liver cirrhosis accompanied with portal vein thrombosis].

Objective: To investigate the efficacy of shunt after transjugular intrahepatic portosystemic shunt (TIPS) in liver cirrhosis accompanied with portal vein thrombosis (PVT). Methods: Forty-four cases with liver cirrhosis accompanied with PVT who underwent TIPS treatment from January 2015 to May 2018 were retrospectively analyzed. Clinical baseline data of the patients were collected. Portal vein pressure gradient (PVPG) before and after the surgery was recorded. Shunt patency was observed at 3, 6, 12, 18 and 24 months after the surgery. The influencing factors were determined by univariate and multivariate analysis. Results: Transjugular intrahepatic portosystemic shunt was successfully established in all 44 cases. The postoperative PVPG was lower than preoperative (P < 0.01). The shunt patency rate after TIPS in PVT was 18.2% (n = 8). The cumulative shunt patency rates at 3, 6, 12, 18, and 24 months after surgery were 95.5%, 90.7%, 90.7%, 86.8% and 74.4%, respectively. Univariate analysis showed that diabetes history, platelet level and prothrombin time-international normalized ratio were associated with postoperative shunt dysfunction. Multivariate analysis showed that diabetes history (P = 0.007, OR = 28.606) was an independent risk factor for postoperative shunt dysfunction. Conclusion: TIPS is a safe and feasible procedure, which can effectively reduce the portal pressure in liver cirrhosis accompanied with PVT. Diabetic patients have a higher risk of postoperative shunt dysfunction. Therefore, clinical intervention should be strengthened for high-risk patients.

Single crystal Er3+ : YAG fibers with tailored refractive index profiles.

Erbium-doped yttrium aluminum garnet (Er3+:YAG) rods were inserted inside undoped tubes and grown into single-crystal fibers of a diameter of 300 µm using the laser-heated pedestal growth technique. Growth at various rates resulted in radially graded distributions of Er3+ dopant ions, as observed using laser-induced fluorescence imaging. Profiles of the refractive index were measured using cross-sectional reflectometry in a microscope. Dopant distributions and the corresponding index profiles were compared with thermal diffusion theory to determine the inter-diffusion coefficient of Y3+ and Er3+ ions at 2000°C, yielding an estimated value of D=(9.10±0.8)×10-11 m2/s. This work constitutes a step toward controlled growth of fibers with high thermal conductivities, low Brillouin gain, and waveguiding properties required for high-power optical amplifier and laser applications.

Association of CD226 polymorphisms with the susceptibility to type 1 diabetes in Chinese children.

Polymorphisms in the CD226 gene have been reported to be associated with autoimmune diseases. The aim of our study was to investigate the association between two single nucleotide polymorphisms (SNPs) (rs763361 and rs727088) in the CD226 gene and the risk for developing type 1 diabetes (T1D) in Chinese Han children. This case-control study included a total of 152 Chinese children with T1D and 304 matched-pair, healthy controls based on age and gender. The genetic variants of the rs763361 and rs727088 SNPs in the CD226 gene were determined using the polymerase chain reaction and restriction fragment length polymorphism method. The CD226 rs763361 polymorphism increased the risk of T1D in the genotype [P < 0.001, odds ratio (OR) = 3.9, 95% confidence interval (CI) = 2.24-6.76], dominant (P < 0.001, OR = 2.1, 95%CI = 1.40-3.14), and recessive (P < 0.001, OR = 0.5, 95%CI = 0.30-0.84) models. Additionally, the carriers of the T allele were more susceptible to T1D (P < 0.001, OR = 2.1, 95%CI = 1.58-2.79). Carriers of the T allele who were younger than 10 years of age at disease onset had an increased risk of T1D than those who were older at the disease onset. However, there was no association between the CD226 rs727088 SNP and risk for developing T1D. These findings revealed that CD226 rs763361 polymorphism was significantly associated with susceptibility to T1D and that the presence of the T allele might be a genetic factor for susceptibility to T1D.

Circulating miR-125b as a biomarker of Ewing's sarcoma in Chinese children.

Previous studies indicated that microRNA-125b (miR-125b) has an important role in the progression of Ewing's sarcoma (ES). The purpose of the current study was to examine expression changes of miR-125b in the serum of ES patients and evaluate if the expression level of miR-125b could serve as a new biomarker for ES. This study was performed on patients who underwent surgical resection at our hospital between 2005 and 2013 after an initial diagnosis of ES. We measured serum miR-125b levels in 63 patients with ES and 126 healthy control patients using a real-time quantitative reverse transcriptase-PCR (qRT-PCR) method. Expression levels of serum miR-125b were distinctly decreased in ES patients when compared with healthy controls (P < 0.001). ES cases that had a poor response to chemotherapy presented a significant down-regulation of miR-125b (P = 0.001). The ROC curve showed that the serum miR-125b could serve as a valuable biomarker for differentiating ES patients from healthy controls with an AUC of 0.879 (95%CI = 0.817-0.924; P < 0.001). At a cut-off value of 2.203 for miR-125b, the sensitivity was 72.8% and the specificity was 87.2% in discriminating ES from the controls. Our results indicate that serum miR- 125b may serve as a useful noninvasive biomarker for ES.

Non-invasive determination of the immune physiological state of reindeer (Rangifer tarandus) in the Greater Khingan Mountains, China.

Immunoglobulin and cortisol levels are good indicators of well-being and living status in animals. In this study, the concentrations of fecal immunoglobulins A ([IgAF]), G ([IgGF]), and M ([IgMF]), and cortisol ([cortisolF]) were examined by enzyme-linked immunosorbent assay in reindeer of the Greater Khingan Mountains of Inner Mongolia, China. [IgAF] was significantly higher than [IgGF] and [IgMF], and [IgGF] was significantly higher than [IgMF] (P < 0.05). Both [IgAF] and [IgGF] were higher in the Adult group than in Aged or Infant groups, and higher in the Young than Infant group (P < 0.05). The four age group [IgMF]s were not significantly different (P > 0.05). [IgAF], [IgGF], and [IgMF] in each age group were higher in females than in males, with a significant difference in the Young group (P < 0.05). The Infant group had the highest [cortisolF], and the Adult group the lowest; [cortisolF] was significantly higher in the Infant group than in other age groups (P < 0.05). In each age group, [cortisolF] was higher in females than males, and there were significant differences among the Infant, Young, and Aged groups (P < 0.05). A significant negative correlation was observed between [cortisolF] and [IgAF] and [IgGF] (P > 0.05). Overall physical condition was better in the Adult and Young groups than in the Aged and Infant groups as determined by the comprehensive analysis of fecal Ig levels in the four age groups, with the Infant group the worst.

Cross-sectional and dynamic change of serum metabolite profiling for Hepatitis B-related acute-on-chronic liver failure by UPLC/MS.

Summary Acute-on-chronic liver failure(ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function and results in the failure of one or more organs with high short-term mortality. The focus of this study was to discover noninvasive and reliable biomarkers for the diagnosis and prognosis of hepatitis B-related ACLF. Ultra-performance liquid chromatography-mass spectrometry (UPLC/MS) was used to analyse serum metabolites of 28 patients with hepatitis B-related ACLF, 35 patients with Child-Pugh A cirrhosis, 30 patients with chronic hepatitis B and 35 healthy volunteers (HS). Characteristic metabolites were screened, identified and dynamically tracked to investigate their value for diagnosis and prognosis. After comparing serum metabolic profile of hepatitis B-related ACLF and Child-Pugh A cirrhosis, 99 characteristic metabolites were selected, and 38 of them were identified. Dynamic tracking model demonstrated that 17 metabolites were related to prognosis of hepatitis B-related ACLF, and there were also 11 metabolites which improved with treatment in the survival group. The correlations between these characteristic metabolites and the model for end-stage liver disease score were strong. These observations contributed to the investigation of the mechanisms of hepatitis B-related ACLF manifestation and progression on the metabolic level, and they provided information for the identification of biomarkers for the diagnosis and prognosis of hepatitis B-related ACLF.

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes.

AIMS/HYPOTHESIS: Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. METHODS: The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. RESULTS: Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). CONCLUSIONS/INTERPRETATION: We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

[HIV infection status and related factors in men who have sex with men in sentinel surveillance in Shanxi province, 2010, 2015 and 2020].

Objective: To understand the infection status of HIV and related factors in men who have sex with men (MSM) in Shanxi province in 2010, 2015 and 2020. Methods: According to the sentinel surveillance protocol, continuous cross-sectional survey were conducted to collect the information about basic characteristics, general demographic characteristics, AIDS knowledge awareness, high-risk sexual behavior, sexually transmitted diseases, intervention services and HIV infection rate of the MSM in Shanxi in 2010, 2015 and 2020. Results: In 2010, 2015 and 2020, a total of 2 708 MSM were included in this study. There were significant differences in HIV infection rate among three years (χ2=23.76, P<0.001) with an increasing trend with year (trend χ2 =17.34, P<0.001). The rates of anal sex, commercial sex and heterosexual behavior in the past 6 months were 77.62% (2 102/2 708), 5.91% (160/2 708) and 28.14% (762/2 708) respectively, and the rates of consistent use of condom were 52.52% (1 104/2 102), 63.13% (101/160) and 23.49%(179/762) respectively, and the rate of consistent condom use was low. Results from multivariate logistic regression analysis showed that different cities, having educational level of junior high school or below, being recruited through internet, voluntary counseling and testing, suffering from sexually transmitted diseases, occasional condom use in anal sex in the past 6 months were the correlative factors of HIV infection of MSM. Conclusions: The HIV infection rate of MSM in Shanxi increased year by year from 2010, 2015 to 2020. The HIV/AIDS-related risk behavior persisted, and the proportion of condomuse adherence was low, and the HIV detection rate was low in the MSM, so targeted and effective measures should be taken to promote the condom use adherence and regular HIV testing in MSM.

Vitamin D: a novel therapeutic approach for keloid, an in vitro analysis.

BACKGROUND: Vitamin D and its metabolites play an important role in calcium homeostasis, bone remodelling, hormone secretion, cell proliferation and differentiation. Recent studies also suggest a beneficial role of vitamin D in slowing the progression of tissue fibrosis. However, their effects on dermal fibrosis and keloids are unknown. Objectives To investigate the effect of 1,25-dihydroxyvitamin D3 (1,25D) in the pathogenesis of tissue fibrosis by keloid fibroblasts (KFs). METHODS: KFs were cultured and exposed to different concentrations of 1,25D in the presence or absence of transforming growth factor (TGF)-ß1. KF phenotypes and protein production were analysed by real-time reverse transcriptase-polymerase chain reaction, Western blot, immunofluorescence and multiplex enzyme-linked immunosorbent assay techniques. Collagen synthesis was evaluated by measuring (3) H-proline incorporation. The effect of 1,25D on cell proliferation and viability was evaluated by Formazan assay, proliferating cell nuclear antigen expression and the colorimetric conversion of 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide. RESULTS: We confirmed the presence of vitamin D receptors (VDRs) in cultured keloid fibroblasts. Fibroblasts transfected with a vitamin D response element reporter construct and exposed to the active vitamin D metabolite 1,25D showed increased promoter activity indicating VDR functionality in these cells. Incubation of KFs with 1,25D suppressed TGF-ß1-induced collagen type I, fibronectin and α-smooth muscle actin expression. 1,25D also modulated plasminogen activator inhibitor-1 and matrix metalloproteinase-9 expression induced by TGF-ß1. Interestingly, 1,25D induced hepatocyte growth factor mRNA expression and protein secretion in keloid fibroblasts. CONCLUSIONS: This study highlights key mechanistic pathways through which vitamin D decreases fibrosis, and provides a rationale for studies to test vitamin D supplementation as a preventive and/or early treatment strategy for keloid and related fibrotic disorders.

Role of caveolin-1 in the pathogenesis of tissue fibrosis by keloid-derived fibroblasts in vitro.

BACKGROUND: Recent studies have suggested that caveolin-1 (cav-1) plays an important role in the regulation of transforming growth factor (TGF)-ß1 signalling and participates in the pathogenesis of tissue fibrosis. However, its effects on dermal fibrosis keloids are unknown. OBJECTIVES: To investigate the effect of cav-1 in the pathogenesis of tissue fibrosis by keloid fibroblasts. METHODS: Keloid fibroblasts were cultured and exposed to different concentrations of cav-1 cell-permeable peptides (cav-1p) in the presence of TGF-ß1. Keloid fibroblast phenotypes and protein production were analysed by real-time reverse transcriptase-polymerase chain reaction, Western blot, and multiplex enzyme-linked immunosorbent assay techniques. The effect of cav-1p on cell viability was evaluated by MTT assay. RESULTS: Cav-1 was markedly decreased in the keloid-derived fibroblasts. Moreover, cav-1p significantly reduced TGF-ß receptor type I levels and Smad2/3 phosphorylation in response to added TGF-ß1. Additionally, TGF-ß1 decreased cav-1 expression in human skin fibroblasts. Cav-1 was able to suppress TGF-ß1-induced extracellular matrix production in cultured keloid fibroblasts through regulation of the mitogen-activated protein kinase pathway. CONCLUSIONS: Cav-1 appears to participate in the pathogenesis of tissue fibrosis in keloid. Restoration of cav-1 function by treatment with a cell-permeable peptide corresponding to the cav-1 scaffolding domain may be a novel therapeutic approach in keloid.

Caspase-3 feedback loop enhances Bid-induced AIF/endoG and Bak activation in Bax and p53-independent manner.

Chemoresistance in cancer has previously been attributed to gene mutations or deficiencies. Bax or p53 deficiency can lead to resistance to cancer drugs. We aimed to find an agent to overcome chemoresistance induced by Bax or p53 deficiency. Here, we used immunoblot, flow-cytometry analysis, gene interference, etc. to show that genistein, a major component of isoflavone that is known to have anti-tumor activities in a variety of models, induces Bax/p53-independent cell death in HCT116 Bax knockout (KO), HCT116 p53 KO, DU145 Bax KO, or DU145 p53 KO cells that express wild-type (WT) Bak. Bak knockdown (KD) only partially attenuated genistein-induced apoptosis. Further results indicated that the release of AIF and endoG also contributes to genistein-induced cell death, which is independent of Bak activation. Conversely, AIF and endoG knockdown had little effect on Bak activation. Knockdown of either AIF or endoG alone could not efficiently inhibit apoptosis in cells treated with genistein, whereas an AIF, endoG, and Bak triple knockdown almost completely attenuated apoptosis. Next, we found that the Akt-Bid pathway mediates Bak-induced caspase-dependent and AIF- and endoG-induced caspase-independent cell death. Moreover, downstream caspase-3 could enhance the release of AIF and endoG as well as Bak activation via a positive feedback loop. Taken together, our data elaborate the detailed mechanisms of genistein in Bax/p53-independent apoptosis and indicate that caspase-3-enhanced Bid activation initiates the cell death pathway. Our results also suggest that genistein may be an effective agent for overcoming chemoresistance in cancers with dysfunctional Bax and p53.

Microdetermination of G6PD isoenzyme activity in human erythrocytes by thin-layer PAG-IEF.

An improved method of microdetermination of G6PD isoenzyme activity in human erythrocytes was developed by modification of previously reported procedures. The volume of blood samples was reduced from 2 ml to 20 microliters. After hemolysis in 2% Triton X-100 and 0.1% beta-mercaptoethanol, the samples were subjected to centrifugation and thin-layer isoelectric focusing in polyacrylamide gel (PAG-IEF). By comparison with the original method, excellent resolution was obtained by this more rapid and simple procedure.

Determination of glucose-6-phosphate dehydrogenase isoenzymes of human erythrocytes by a thin-layer PAG-IEF procedure.

A procedure of thin-layer PAG-IEF was employed to separate glucose-6-phosphate dehydrogenase (G6PD) isoenzymes of human erythrocytes into 15-16 bands in a pH range between 4.7 and 6.5. The G6PD isoenzymes were scanned with a dual-wavelength thin-layer chromatoscanner and the relative enzyme content of each band was calculated. The method possesses the merits of simplicity, high sensitivity, rapidity and high reproducibility.

Suppression of natural killer cell activity in biliary obstruction.

Prior studies regarding immune function in bile-duct ligated rats have illustrated blunted immune function. The present study measures natural killer (NK) cell activity. Rats underwent bile duct ligation (BDL) or sham celiotomy (SC) and were sacrificed at 1, 2, and 3 weeks after surgery. Ficoll-Hypaque density centrifugation was used to obtain a purified preparation of splenocytes. NK cell activity was determined by incubating varying concentrations of splenocytes with chromium-labelled YAC-1 tumor cells for 4 hours. Chromium release was measured by a gamma counter and expressed as per cent activity (compared with 100 per cent activity obtained by complete lysis with detergent). The experiments were repeated after preincubation in tissue culture flasks to remove an adherent cell population. NK cell activity was decreased at all spleen cell:target cell ratios studies at 1 week after BDL. At 2 weeks after BDL, NK cell activity was decreased at all but the lowest two concentrations; and 3 weeks after BDL, NK cell activity was decreased only at the highest concentrations used. Separation of an adherent cell fraction restored NK cell activity. This suppression in NK cell activity one week after BDL may account, in part, for the poor response of BDL animals to bacterial and immune challenge. Restoration of activity after removal of an adherent cell fraction suggests that macrophages may be at least partly responsible for this inhibition.

Splenocytes from bile duct ligated rats do not elicit a normal immune response in the intact host.

Previous studies have shown impaired immune function in biliary obstruction, and our earlier investigations have demonstrated impaired response to alloantigens in the jaundiced rat host. The present study uses the graft versus host (GVH) popliteal lymph node assay to assess the ability of lymphocytes from bile duct ligated animals to elicit an immune response in normal rats. Female Lewis rats underwent bile duct ligation and transection (BDL) or sham celiotomy. A third group of rats served as normal controls. The animals were killed at intervals from 1 to 6 weeks after surgery, and spleen cell preparations were made. Splenocytes (5 x 10(6) from BDL, sham celiotomy, or normal control rats were injected into the hind footpads of LBNF1 hybrid rats. The contralateral hind footpads were injected with media as controls. The popliteal lymph nodes were removed and weighted 7 days after injection. The BDL rats were clinically jaundiced. GVH response was normal at 1 week and decreased at 2 weeks, remaining depressed through 6 weeks. Contralateral control lymph node weights were similar in all groups. Obstructive jaundice not only impairs host immune defense, but also significantly decreases splenocyte GVH capability.

New perspectives in fetal surgery: the chicken embryo.

After a short literature a review a comparison is made between the development of the human digestive tract during the second trimester of gestation and that of the chick embryo (Gallus domesticus) during the last week of incubation. The surgical procedure for chick embryosis is discussed in connection with the the study of the pathogenesis of small bowel atresia and meconium peritonitis. The results corroborate that the chick embryo is a valuable laboratory animal in experimental fetal surgery.

The effects of temporary general hypoxia and local ischemia on the development of the intestines: an experimental study.

It is generally accepted that a circulatory disorder of the bowel during the embryonic stage of development plays an important part in the occurrence of atresias of the small bowel and colon, with the exception of the septal types of atresia. In most cases, the cause of this disorder is not known. An experimental study, making use of chick embryos, is presented and the results are discussed. Two sets of experiments were conducted. In the first set the bowel of the chick embryo was subjected to temporary ischemia. In the second one the chick embryo was subjected to a period of general hypoxia. Temporary ischemia of the bowel frequently resulted in stenosis or atresia. The duration of the vascular occlusion was significant factor. Temporary general hypoxia resulted in serious morphologic changes of the bowel and the liver. Stenosis or atresia did not occur in this case, but there was a strong resemblance to the histopathological picture of neonatal necrotizing enterocolitis.

A diagnostic kit to screen individuals with glucose-6-phosphate dehydrogenase defect and its application on anti-malaria spot in the countryside.

OBJECTIVE: To prepare a kit for screening individuals with glucose-6-phosphate dehydrogenase (G6PD) defect. The kit is easy to use and to get the fast as well as reliable results. Especially it is suitable for the anti-malaria spots usually located in the remote countryside where no electricity is available. METHODS: The double filter paper method and other 2 techniques, the quantitative method and the single filter paper method, were used to determine G6PD activity in 70 samples of human erythrocytes. It was found that the results of the double filter paper method and those of the single filter paper method in the first 8 hours after the drying of the blood-soaked filter paper were consistent with those of the quantitative method. When a piece of blood-soaked paper is left under room temperature more than 24 hours, G6PD in the erythrocytes deteriorated spontaneously and consequently the number of positive cases increased along with the elapse of time. RESULTS: Satisfactory results were achieved when the kit was used to screen cases of G6PD defect from 151 farmers who were receiving anti-malaria therapy. The kit was made according to a technique named "double filter paper" method. CONCLUSIONS: These findings suggest that the double filter paper method can reveal the level of G6PD activity and the results are rapidly obtained when the method is used on the anti-malaria spot.

Coarctatio aortae in pigs: a morphological approach.

Two types of coarctatio aortae in pigs are described. In the juvenile type the, funnel-shaped, narrowing in the arcus aortae was located between the origin of the a. subclavia sinistra and the aortic end of the ductus arteriosus or ligamentum arteriosum. Until now, this type has been observed only in animals with other heart anomalies. In the adult type, the narrowing of the arcus aortae was crescent-shaped and was located at the aortic end of the ductus arteriosus or ligamentum arteriosum. Histologic examination of parts of the funnel-shaped and the crescent-shaped narrowing revealed that the two types of coarctatio aortae develop differently.