Meta-analysis of infection and disease among household contacts of patients with drug-resistant tuberculosis / 中国热带医学

@#Abstract: Objective　To analyze the association between drug resistance and the risk of latent tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis, and to explore whether the compensatory mutation of drug-resistant Mycobacterium tuberculosis will enhance its pathogenicity or transmission ability. Methods　The English and Chinese databases, including PubMed, web of science, EMBASE, Cochrane library database, CNKI and Wanfang database, were searched by computer from the time of establishment of the database to January 2022. Cohort studies on the risk of infection and disease among household contacts of patients with drug-resistant and sensitive pulmonary tuberculosis were searched and screened according to the inclusion and exclusion criteria. The data were extracted and evaluated by NOS scale, using stata16.0 software meta-analysis to calculate the combined effect of tuberculosis infection and disease risk of family contacts, and carry out heterogeneity test, subgroup analysis and sensitivity analysis. Results　A total of 7 cohort studies involving 9653 TB index cases and 29, 734 house contacts were included. The results of meta-analysis showed that compared with drug-sensitive pulmonary tuberculosis patients, the risk of tuberculosis infection in house contacts of drug-resistant pulmonary tuberculosis patients was increased (OR=1.56, 95%CI=1.25-1.96, P<0.001), but there was no difference in the risk of incidence (RR=1.06, 95%CI=0.80-1.41, P=0.67>0.05). Subgroup analysis showed that the risk of latent tuberculosis infection in house contacts was affected by the study area, and the size of family contacts had an impact on the risk of TB . Sensitivity analysis showed that the results of meta-analysis were robust. Conclusion　Compared with drug sensitive TB patients, household contacts with drug-resistant TB patients had a higher risk of tuberculosis, but there was no difference in the risk of TB among the two groups.

Hypertension Prevalence, Awareness, Treatment, and Control and Their Associated Socioeconomic Factors in China: A Spatial Analysis of A National Representative Survey.

OBJECTIVE: We aimed to investigate and interpret the associations between socioeconomic factors and the prevalence, awareness, treatment, and control of hypertension at the provincial level in China. METHODS: A nationally and provincially representative sample of 179,059 adults from the China Chronic Disease and Nutrition Surveillance study in 2015-2016 was used to estimate hypertension burden. The spatial Durbin error model was fitted to investigate socioeconomic factors associated with hypertension indicators. RESULTS: Overall, it was estimated that 29.20% of the participants were hypertensive nationwide, among whom, 34.32% were aware of their condition, 27.69% had received antihypertensive treatment, and 7.81% had controlled their condition. Per capita gross domestic product (GDP) was associated with hypertension prevalence (coefficient: -2.95, 95% CI: -5.46, -0.45) and control (coefficient: 6.35, 95% CI: 1.36, 11.34) among adjacent provinces and was also associated with awareness (coefficient: 2.93, 95% CI: 1.12, 4.74) and treatment (coefficient: 2.67, 95% CI: 1.21, 4.14) in local province. Beds of internal medicine (coefficient: 2.66, 95% CI: 1.08, 4.23) was associated with control in local province. Old dependency ratio (coefficient: -3.58, 95% CI: -5.35, -1.81) was associated with treatment among adjacent provinces and with control (coefficient: -1.69, 95% CI: -2.42, -0.96) in local province. CONCLUSION: Hypertension indicators were not only directly influenced by socioeconomic factors of local area but also indirectly affected by characteristics of geographical neighbors. Population-level strategies should involve optimizing supportive socioeconomic environment by integrating clinical care and public health services to decrease hypertension burden.

Sodium butyrate enhances intestinal integrity, inhibits mast cell activation, inflammatory mediator production and JNK signaling pathway in weaned pigs.

The present study aimed to investigate the effects of sodium butyrate on the intestinal barrier and mast cell activation, as well as inflammatory mediator production, and determine whether mitogen-activated protein kinase signaling pathways are involved in these processes. A total of 72 piglets, weaned at 28 ± 1 d age, were allotted to two dietary treatments (control vs. 450 mg/kg sodium butyrate) for 2 wk. The results showed that supplemental sodium butyrate increased daily gain, improved intestinal morphology, as indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function reflected by increased transepithelial electrical resistance and decreased paracellular flux of dextran (4 kDa). Moreover, sodium butyrate reduced the percentage of degranulated mast cells and its inflammatory mediator content (histamine, tryptase, TNF-α and IL-6) in the jejunum mucosa. Sodium butyrate also decreased the expression of mast cell-specific tryptase, TNF-α and IL-6 mRNA. Sodium butyrate significantly decreased the phosphorylated ratio of JNK whereas not affecting the phosphorylated ratios of ERK and p38. The results indicated that the protective effects of sodium butyrate on intestinal integrity were closely related to inhibition of mast cell activation and inflammatory mediator production, and that the JNK signaling pathway was likely involved in this process.

Anemonin improves intestinal barrier restoration and influences TGF-ß1 and EGFR signaling pathways in LPS-challenged piglets.

The present study was aimed at investigating whether dietary anemonin could alleviate LPS-induced intestinal injury and improve intestinal barrier restoration in a piglet model. Eighteen 35-d-old pigs were randomly assigned to three treatment groups (control, LPS and LPS+anemonin). The control and LPS groups were fed a basal diet, and the LPS + anemonin group received the basal diet + 100 mg anemonin/kg diet. After 21 d of feeding, the LPS- and anemonin-treated piglets received i.p. administration of LPS; the control group received saline. At 4 h post-injection, jejunum samples were collected. The results showed that supplemental anemonin increased villus height and transepithelial electrical resistance, and decreased crypt depth and paracellular flux of dextran (4 kDa) compared with the LPS group. Moreover, anemonin increased tight junction claudin-1, occludin and ZO-1 expression in the jejunal mucosa, compared with LPS group. Anemonin also decreased TNF-α, IL-6, IL-8 and IL-1ß mRNA expression. Supplementation with anemonin also increased TGF-ß1 mRNA and protein expression, Smad4 and Smad7 mRNA expressions, and epidermal growth factor and epidermal growth factor receptor (EGFR) mRNA expression in the jejunal mucosa. These findings suggest that dietary anemonin attenuates LPS-induced intestinal injury by improving mucosa restoration, alleviating intestinal inflammation and influencing TGF-ß1 canonical Smads and EGFR signaling pathways.

L-cysteine protects intestinal integrity, attenuates intestinal inflammation and oxidant stress, and modulates NF-κB and Nrf2 pathways in weaned piglets after LPS challenge.

In this study we investigated whetherL-cysteine (L-cys) could alleviate LPS-induced intestinal disruption and its underlying mechanism. Piglets fed with anL-cys-supplemented diet had higher average daily gain.L-cys alleviated LPS-induced structural and functional disruption of intestine in weanling piglets, as demonstrated by higher villus height, villus height (VH) to crypt depth (CD) ratio, and transepithelial electrical resistance (TER) and lower FITC-dextran 4 (FD4) kDa flux in jejunum and ileum. Supplementation withL-cys up-regulated occludin and claudin-1 expression, reduced caspase-3 activity and enhanced proliferating cell nuclear antigen expression of jejunum and ileum relative to LPS group. Additionally,L-cys suppressed the LPS-induced intestinal inflammation and oxidative stress, as demonstrated by down-regulated TNF-α, IL-6 and IL-8 mRNA levels, increased catalase, superoxide dismutase, glutathione peroxidase activity, glutathione (GSH) contents and the ratio of GSH and oxidized glutathione in jejunum and ileum. Finally, a diet supplemented withL-cys inhibited NF-κB(p65) nuclear translocation and elevated NF erythroid 2-related factor 2 (Nrf2) translocation compared with the LPS group. Collectively, our results indicated the protective function ofL-cys on intestinal mucosa barrier may closely associated with its anti-inflammation, antioxidant and regulating effect on the NF-κB and Nrf2 signaling pathways.

[Scale invariance analysis of the ten-day sunshine duration in Henan Province, China].

Using the ten-day sunshine duration data of 107 meteorological stations in Henan Province from 1961 to 2012, spatial-temporal variation characteristics of ten-day sunshine duration were analyzed, and the scale invariance analysis of ten-day sunshine duration was studied by using the method of detrended fluctuation analysis. The results showed that the means of ten-day sunshine duration and its standardized error among stations were 57.90 and 9.18 h, respectively, and their probability distributions were not subject to normal distribution. The cumulative abnormal of sunshine duration had a distinct linear increasing trend, however, its square deviation among the stations was of phase characteristics. The scale index of ten-day sunshine of each station was above 0.5, indicated that time series of scale index was of permanence. Variation of scale index among stations was small, which obeyed the normal distribution.

Zinc oxide influences mitogen-activated protein kinase and TGF-ß1 signaling pathways, and enhances intestinal barrier integrity in weaned pigs.

Weaning is the most significant event in the life of pigs and is always related with intestinal disruption. Although it is well known that zinc oxide (ZnO) exerts beneficial effects on the intestinal barrier, the mechanisms underlying these effects have not yet been fully elucidated. We examined whether ZnO protects the intestinal barrier via mitogen-activated protein kinases and TGF-ß1 signaling pathways. Twelve barrows weaned at 21 d of age were randomly assigned to two treatments (0 verus 2200 mg Zn/kg from ZnO) for 1 wk. The results showed that supplementation with ZnO increased daily gain and feed intake, and decreased postweaning scour scores. ZnO improved intestinal morphology, as indicated by increased villus height and villus height:crypt depth ratio, and intestinal barrier function, indicated by increased transepithelial electrical resistance and decreased mucosal-to-serosal permeability to 4-ku FITC dextran. ZnO decreased the ratios of the phosphorylated to total JNK and p38 (p-JNK/JNK and p-p38/p38), while it increased the ratio of ERK (p-ERK/ERK). Supplementation with ZnO increased intestinal TGF-ß1 expression. The results indicate that supplementation with ZnO activates ERK ½, and inhibits JNK and p38 signaling pathways, and increases intestinal TGF-ß1 expression in weaned pigs.

Developmental changes of TGF-ß1 and Smads signaling pathway in intestinal adaption of weaned pigs.

Weaning stress caused marked changes in intestinal structure and function. Transforming growth factor-ß1 (TGF-ß1) and canonical Smads signaling pathway are suspected to play an important regulatory role in post-weaning adaptation of the small intestine. In the present study, the intestinal morphology and permeability, developmental expressions of tight junction proteins and TGF-ß1 in the intestine of piglets during the 2 weeks after weaning were assessed. The expressions of TGF-ß receptor I/II (TßRI, TßRII), smad2/3, smad4 and smad7 were determined to investigate whether canonical smads signaling pathways were involved in early weaning adaption process. The results showed that a shorter villus and deeper crypt were observed on d 3 and d 7 postweaning and intestinal morphology recovered to preweaning values on d 14 postweaning. Early weaning increased (P<0.05) plasma level of diamine oxidase (DAO) and decreased DAO activities (P<0.05) in intestinal mucosa on d 3 and d 7 post-weaning. Compared with the pre-weaning stage (d 0), tight junction proteins level of occludin and claudin-1 were reduced (P<0.05) on d 3, 7 and 14 post-weaning, and ZO-1 protein was reduced (P<0.05) on d 3 and d 7 post-weaning. An increase (P<0.05) of TGF-ß1 in intestinal mucosa was observed on d 3 and d 7 and then level down on d 14 post-weaning. Although there was an increase (P<0.05) of TßR II protein expression in the intestinal mucosa on d3 and d 7, no significant increase of mRNA of TßRI, TßRII, smad2/3, smad4 and smad7 was observed during postweaning. The results indicated that TGF-ß1 was associated with the restoration of intestinal morphology and barrier function following weaning stress. The increased intestinal endogenous TGF-ß1 didn't activate the canonical Smads signaling pathway.

Zinc oxide influences intestinal integrity, the expressions of genes associated with inflammation and TLR4-myeloid differentiation factor 88 signaling pathways in weanling pigs.

This study explored whether zinc oxide (ZnO) supplementation could alleviate weanling-induced intestinal injury through TLR and NOD-like receptor signaling pathways. Twelve early-weanling piglets were allotted to two dietary treatments (control vs 2200 mg Zn/kg from ZnO) for 1 wk. The results showed that supplemental ZnO improved daily gain and feed intake, decreased post weaning scour scores, increased villus height and villus height:crypt depth ratio at the jejunal mucosa, and decreased diamine oxidase activity and endotoxin concentration in plasma. The intestinal mRNA levels of TLR4 and its downstream signals, including MyD88, IL-1 receptor-associated kinase 1 and TNF-α receptor-associated factor 6, were decreased, and the expressions of intestinal pro-inflammatory cytokines and chemokines were decreased simultaneously in the ZnO-supplemented piglets. Although NF-κB p65 mRNA abundance was not affected by ZnO supplementation, NF-κB p65 protein expression was down-regulated by ZnO. However, ZnO supplementation had no effect on intestinal expressions of NOD1 and NOD2, and their adaptor molecule receptor-interacting serine/threonine-protein kinase 2, as well as protein expressions of caspase-3 and heat shock protein 70. The results indicated that the protective effects of ZnO on intestinal integrity were closely related to decreasing the expressions of genes associated with inflammation through inhibiting the TLR4-MyD88 signaling pathways.

[Biological characteristics of hematopoietic progenitor cells at different stages of hematopoietic development].

The aim of the present paper is to better understand the mechanism of hematopoietic development through studying the biological characteristics of hematopoietic progenitor cells at different stages of development. Firstly, the c-kit expression levels of the mononuclear cells from murine embryonic aorta-gonad-mesonephros (AGM) region at embryonic day (E)10.5 and E11.5, fetal liver (FL) at E12.5, E14.5, E16.5, E18 and bone marrow (BM) were assayed with fluorescence activated cell sorting (FACS). Secondly, hematopoietic progenitor cells derived from AGM at E10.5, FL at E14.5 and BM were isolated by using c-kit microbeads. Isolated c-kit(+) population cells from AGM, FL and BM were then co-cultured with E14.5 FL-derived stromal cells in transwell co-culture system in vitro. After 3, 7, 10 days of co-culture, numerous floating cells were generated. The floating cells generated in transwell inserts were collected for FACS cell count, migration activity detection and colony forming unit (CFU) formation assay. The results showed that the c-kit was highly expressed in E10.5 AGM, with the percentage of c-kit(+) cells declining during AGM development. c-kit expression was highly expressed again in E12.5 FL, declining along with the progressive development of the FL region. Co-cultured with FL-derived stromal cells, E10.5 AGM-derived c-kit(+) cells produced the highest number of hematopoietic cells, while BM-derived c-kit(+) cells produced the lowest number of hematopoietic cells. Compared with E10.5 AGM-derived c-kit(+) cells, E14.5 FL- and BM- derived c-kit(+) cells inclined to differentiate after 7 to 10 days of culture in vitro. E10.5 AGM and E14.5 FL-derived c-kit(+) cells exhibited a higher migration activity than BM-derived c-kit(+) cells. Moreover, E10.5 AGM-derived c-kit(+) cells showed a higher ability to form mixed colony-forming unit (CFU-Mix) colony. In conclusion, compared with FL- and BM-derived c-kit(+) cells, E10.5 AGM-derived c-kit(+) hematopoietic progenitor cells exhibit better proliferation, migration potential, and have a higher ability to maintain the undifferentiation state in vitro, providing an insight into their clinical manipulation.

[Study on Wnt and Notch signalling involves in regulation of hematopoietic microenvironment.].

OBJECTIVE: To explore the mechanism of Wnt and Notch pathway involved modulating time and spatial restricted hematopoiesis. METHODS: Murine hematopoietic stem and progenitor cells (HSPCs) were isolated from bone marrow (BM) by using c-kit microbeads. E10.5 aorta-gonad-mesonephros (AGM), E12.5, E14.5, E16.5 fetal liver (FL) and adult BM derived stromal cells (StroCs) were isolated and co-cultured with c-kit(+)HSPCs. The floating cells in co-culture system were sorted and counted by FACS. Gene expressions of Wnt and Notch pathway were detected by quantitative PCR and protein expressions by immunostaining. RESULTS: Co-culturing HSPCs with AGM and FL-derived StroCs resulted in an expansion of c-kit(+)population from 0.4 x 10(5)/well to (19.2 +/- 3.2) x 10(5)/well and (26.8 +/- 5.4) x 10(5)/well, respectively, being greater than that with BM-derived StroCs (P < 0.05). The percentage of c-kit(+)cells detected in AGM- and BM- derived StroCs culture system was (75.2 +/- 7.1)%, (74.1 +/- 6.2)% respectively, being higher than FL- derived StroCs culture system (63.4 +/- 5.3)% (P < 0.05). Wnt and Notch pathway genes expression varied at different phases of hematopoiesis. Wnt was highly expressed in AGM and FL derived StroCs, and, Notch did in AGM and BM derived StroCs. CONCLUSION: Wnt and Notch pathway are important modulators in regulating time and spatial restricted hematopoiesis.

[Study on the antibacterial mechanisms of copper-bearing montmorillonite].

Vibrio parahaemolyticus ATCC 27519 was chosen as indicator of aquacultural pathogenic bacteria to determine the antibacterial activity and mechanism of copper-bearing montmorillonite (Cu-MMT) in vitro. The results indicated that montmorillonite (MMT) had no antibacterial activity. The minimum inhibitory concentration (MIC) and bactericidal concentration (MBC) of Cu-MMT on Vibrio parahaemolyticus were 75 and 300 mg/L, respectively. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) of bacteria were examined and the results showed treatment with Cu-MMT could lead to significant release of intracellular enzymes from the tested bacteria suggesting that the permeability of the cell membrane increased and bacteria suffered injury. Three typical inhibitors (malonic acid, iodine acetic acid and phosphate sodium) were used to further study the inhibitory pathways of respiratory metabolism. Cu-MMT effectively inhibited respiratory metabolism of Vibrio parahaemolyticus, with the respiratory inhibition percent (I(R)) of 31.8%. The respiratory superposing inhibition percent after addition of phosphate sodium, iodine acetic acid and malonic acid was 48.6%, 27.8% and 17.5%, respectively. These results indicated that the effect of malonic acid on superposing inhibition percent of Cu-MMT for bacteria is the lowest; thus, the synergic action between Cu-MMT and malonic acid is the weakest, indicating that they inhibited the same pathway of respiratory metabolism, i.e. the TCA pathway, which is the most important pathway of carbohydrate metabolism. The atomic force microscope image of Vibrio parahaemolyticus exposed to Cu-MMT showed that Cu-MMT could rupture the bacterial cell membrane.

Effects of fructooligosaccharide on conversion of L-tryptophan to skatole and indole by mixed populations of pig fecal bacteria.

An in vitro study was conducted to examine the effects of fructooligosaccharide (FOS) at levels of 0.5, 1.0, and 1.5% on conversion of L-tryptophan to skatole and indole by a mixed bacterial population from the large intestines of pigs. Microbial suspensions were anaerobically incubated at 38 degrees C for 24 h. Samples were periodically removed for determination of pH and indole compounds. After 24 h incubation, microbial populations in each culture media were analyzed. Addition of 0.5, 1.0, and 1.5% FOS to the slurries with L-tryptophan significantly decreased the skatole concentration, the peak value of indole-3-acetic acid and the medium pH. The viable counts of Bifidobacterium were significantly higher as compared with the control. Addition of 1.0 and 1.5% FOS significantly decreased the rate of tryptophan degradation and the relative rate of skatole production. The relative rate of indole production was significantly increased. The viable counts of Clostridium and Escherichia coli were significantly reduced. The total viable counts of anaerobes were significantly increased. These results suggest that the reduced concentration of skatole observed in the presence of FOS may be caused by the decreased tryptophan degradation due to the increased need for amino acids in the synthesis of bacterial cellular protein, and by shifting microbial metabolism of tryptophan toward indole production at the expense of skatole, which might result from the changed microbial ecosystem and pH. Our observations open the possibility of inhibiting microbial production of skatole and decreasing the skatole concentration in backfat by feeding pigs diets containing FOS, but it remains to be demonstrated in vivo.