[A multi-center, randomized controlled study on the effect of Saccharomyces boulardii combined with triple therapy for the initial eradication of Helicobacter pylori infection].

Objective: To assess the efficacy and safety of Saccharomyces boulardii (S. boulardii) in combination with triple therapy as a first-line regimen for the eradication of Helicobacter pylori (H. pylori) in non-ulcer dyspepsia (NUD) patients. Methods: A total of 497 Helicobacter pylori-positive patients who underwent gastroscopy and diagnosed with NUD were enrolled from June 2018 to January 2020 in 9 medical centers across China. Participants were segmentedly randomly divided into 3 groups. Patients in group A received S. boulardii for 14 days and triple therapy for 10 days, while patients in group B received bismuth quadruple group for 10 days, and patients in group C received triple therapy for 10 days. The H. pylori status was determined by the 13C-urea breath test on the 44th day of the treatment. Symptom improvement and adverse reactions were assessed on the 14th and 44th day. Results: There were 229 males and 268 females in all 497 patients enrolled. They were aged 18-69 (46.1±11.8) years and 472 of them (158 cases in group A, 159 cases in group B, and 155 cases in group C) completed the trial. The intention-to-treat (ITT) eradication rates in patients in patients A, B and C were 77.8% (126/162), 80.1% (137/171) and 65.2% (107/164) respectively, and per protocol-based (PP) eradication rates were 79.7% (126/158), 86.2% (137/159) and 69.0% (107/155) respectively. The differences were statistically significant in ITT and PP analysis among 3 groups (ITT: χ²=11.14, P<0.01; PP: χ²=13.86, P<0.01). There was no significant difference between eradication rates of two quadruple therapys(all P>0.05), but both of them were significantly higher than that of standard triple therapy (both P<0.05). Statistics revealed that both quadruple therapys led to significantly higher symptom improvement of belching compared with that of standard triple therapy in day 14 (P<0.05). The relief of abdominal distension and belching symptom scores of group A were significantly higher than those of group C in day 44(all P<0.05). There was no serious adverse event reported. The incidence of diarrhea in group A was significantly lower than those in the other two groups (both P<0.05). Conclusions: The combination of S. boulardii and triple therapy can achieve a better eradication effect on H. pylori infection with NUD, and has advantages in symptom relief and safety.

The tumor necrosis factor-alpha-induced protein 8 family in immune homeostasis and inflammatory cancer diseases.

Within the immune system homeostasis is maintained by a myriad of mechanisms that include the regulation of immune cell activation and programmed cell death. The breakdown of immune homeostasis may lead to fatal inflammatory diseases. We set out to identify genes of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) family that has a functional role in the process of immune homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8), which functions as an oncogenic molecule, is also associated with enhanced cell survival and inhibition of apoptosis. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) governs immune homeostasis in both the innate and adaptive immune system and prevents hyper-responsiveness by negatively regulating signaling via T cell receptors and Toll-like receptors (TLRs). There also exist two highly homologous but uncharacterized proteins, TIPE1 and TIPE3. This review is an attempt to provide a summary of TNFAIP8 family associated with immune homeostasis and inflammatory cancer diseases.

COVID-19 prevention measures reduce dengue spread in Yunnan Province, China, but do not reduce established outbreak.

ABSTRACTThe COVID-19 pandemic and measures against it provided a unique opportunity to understand the transmission of other infectious diseases and to evaluate the efficacy of COVID-19 prevention measures on them. Here we show a dengue epidemic in Yunnan, China, during the pandemic of COVID-19 was dramatically reduced compared to non-pandemic years and, importantly, spread was confined to only one city, Ruili. Three key features characterized this dengue outbreak: (i) the urban-to-suburban spread was efficiently blocked; (ii) the scale of epidemic in urban region was less affected; (iii) co-circulation of multiple strains was attenuated. These results suggested that countermeasures taken during COVID-19 pandemic are efficient to prevent dengue transmission between cities and from urban to suburban, as well to reduce the co-circulation of multiple serotypes or genotypes. Nevertheless, as revealed by the spatial analysis, once the dengue outbreak was established, its distribution was very stable and resistant to measures against COVID-19, implying the possibility to develop a precise prediction method.

[Update in immune regulatory dysfunction of dendritic cells in sepsis].

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Further development of sepsis usually leads to septic shock or even death. Many previous studies have focused on the abnormal reactions of monocytes/macrophages, neutrophils, complement system, or cytokine inflammation in sepsis. Many evidences in recent years suggest that dendritic cells, as the most powerful antigen-presenting cells in innate immune system of body, play important role during the process of immune disorders of sepsis. In this article, I review the main classification, immune function, monitoring method, regulatory pathways of dendritic cells and their clinical significance in immune disorders of sepsis, so as to find new strategies for immune regulation of sepsis.

Genomic signatures of 60 years of bidirectional selection for 8-week body weight in chickens.

Sixty years, constituting 60 generations, have passed since the founding of the Virginia body weight lines, an experimental population of White Plymouth Rock chickens. Using a stringent breeding scheme for divergent 8-week body weight, the lines, which originated from a common founder population, have responded to bidirectional selection with an approximate 15-fold difference in the selected trait. They provide a model system to study the genetics of complex traits in general and the influences of artificial selection on quantitative genetic architectures in particular. As we reflect on the 60th anniversary of the initiation of the Virginia body weight lines, there is opportunity to discuss the findings obtained using different analytical and experimental genetic and genomic strategies and integrate them with a recent pooled genome resequencing dataset. Hundreds of regions across the genome show differentiation between the 2 lines, reinforcing previous findings that response to selection relied on standing variation across many genes and giving insights into the haplotype complexity underlying regions associated with body weight.

The potential etiologic role of tumor necrosis factor in mediating multiple organ dysfunction in rats following intestinal ischemia-reperfusion injury.

Endogenous inflammatory cytokines may function as mediators in the development of remote organ damage in response to local ischemic insult. This study was designed to (a) explore the potential role of tumor necrosis factor (TNF) formation in the pathogenesis of systemic tissue injury, (b) determine the relationship between induction of TNF and gut-derived endotoxemia and/or bacterial translocation, and (c) evaluate the protective effect of anti-TNF monoclonal antibody (MoAb) for vital organs following intestinal ischemia-reperfusion in rats. Animals were subjected to superior mesenteric artery occlusion (SMAO) for 45 min. Systemic plasma TNF levels increased rapidly after the onset of reperfusion, reaching a peak value 2 h later (P < 0.01). TNF elevation was found to be associated with gut origin endotoxemia, where the maximal TNF levels occurred approximately 2 h after the initial appearance of endotoxin in portal vein. Prophylactic treatment with anti-TNF MoAb markedly blunted the elevation in plasma TNF levels and afforded protection from the development of hypotension, vital organs dysfunction, and metabolic acidosis. Significant improvement in 48-h survival rate was observed by administration of anti-TNF MoAb prior to inducing ischemia (P = 0.007). These findings suggest that intestinal ischemia-reperfusion could result in TNF production, which may play a key role in mediating subsequent septic response and systemic tissue injury. It seems likely that passage of endotoxin and bacteria from the gut can be responsible for the TNF formation

Plasma D (-)-lactate as a new marker for diagnosis of acute intestinal injury following ischemia-reperfusion.

AIM: To observe the kinetics of D (-)-lactate alteration in both portal and systemic circulation systems, and its relationship with intestinal injury in rats subjected to acute intestinal ischemia-reperfusion. METHODS: Anesthetized rats underwent a 75-min superior mesenteric artery occlusion followed by a 6-h reperfusion. Plasma D (-)-lactate levels were measured by an enzymatic spectrophotometric assay. RESULTS: Intestinal ischemia for 75 min resulted in a significant elevation of D (-)-lactate levels in the portal vein, as compared with the baseline values (P < 0.05). Plasma D (-)-lactate levels had a tendency to further increase after reperfusion, up to 6 h. Similar alterations in D (-)-lactate were also found in systemic circulation, and there were no significant differences between the portal and systemic circulations at any time point. Moreover, the macropathological evaluation scores were significantly correlated to the portal D (-)-lactate levels in animals at various time points (r = 0.415, P < 0.01). In addition, there was a remarkable rise of endotoxin concentration within the portal vein at the end of the 75-min ischemic period (P < 0.05), reaching a peak at 2 h post-reperfusion. CONCLUSION: Acute intestinal ischemia is associated with failure of the mucosal barrier resulting in increased plasma D (-)-lactate levels in both portal and systemic blood. The subsequent reperfusion might further increase D (-)-lactate levels, which are correlated to the macropathological alterations. Plasma D (-)-lactate may be a useful marker of intestinal injury following both ischemia and reperfusion insults.

Relationship between plasma D(-)-lactate and intestinal damage after severe injuries in rats.

AIM: To explore the kinetic changes in plasma D(-)-lactate and lipopolysaccharide (LPS) levels, and investigate whether D(-)-lactate could be used as a marker of intestinal injury in rats following gut ischemia/reperfusion, burn, and acute necrotizing pancreatitis (ANP). METHODS: Three models were developed in rats: (1)gut ischemia/reperfusion obtained by one hour of superior mesenteric artery occlusion followed by reperfusion; (2)severe burn injury created by 30% of total body surface area (TBSA) full-thickness scald burn; and (3)ANP induced by continuous inverse infusion of sodium taurocholate and trypsin into main pancreatic duct. Plasma levels of D(-)-lactate in systemic circulation and LPS in portal circulation were measured by enzymatic-spectrophotometric method and limulus amebocyte lysate (LAL) test kit, respectively. Tissue samples of intestine were taken for histological analysis. RESULTS: One hour gut ischemia followed by reperfusion injuries resulted in a significant elevation in plasma D(-)-lactate and LPS levels, and there was a significant correlation between the plasma D(-)-lactate and LPS (r = 0.719, P<0.05). The plasma concentrations of D(-)-lactate and LPS increased significantly at 6h postburn, and there was also a remarkable correlation between them (r=0.877 P<0.01). D(-)-lactate and LPS levels elevated significantly at 2h after ANP, with a similar significant correlation between the two levels (r = 0.798, P < 0.01). The desquamation of intestine villi and infiltration of inflammatory cells in the lamina propria were observed in all groups. CONCLUSION: The changes of plasma D(-)-lactate levels in systemic blood paralleled with LPS levels in the portal vein blood. The measurement of plasma D(-)-lactate level may be a useful marker to assess the intestinal injury and to monitor an increase of intestinal permeability and endotoxemia following severe injuries in early stage.

Pulmonary oedema in isolated lung lobe after inhalation injury.

Pulmonary oedema was produced in isolated lung lobes with steam and provided direct continuous measurements of transudation as it occurred. Transvascular flux (Qf) and weight gain (Gw) of the lobe increased immediately and the transudation reached its peak within half an hour after inhalation injury. Studies of protein content, colloid osmotic pressure of bronchial exudate and water content of lung, reconfirmed the increase in pulmonary capillary permeability. Marked haemoconcentration was revealed. Plasma leaked 113 g (25 per cent), plasma protein leaked 1.96 g (9.7 per cent) during the experiment. Based on the measured arterial pressure (Pa), vein pressure (Pv), arterial occlusion (Pao), venous occlusion (Pvo), double occlusion (Pdo) and blood flow through the lobe (Qt), the total vascular (Rt), arterial (Ra), middle compartment (Rmid) and venous (Rv) resistances were calculated. All the resistances were increased and the Qt showed a decrease after inhalation injury.

The association of circulating endotoxaemia with the development of multiple organ failure in burned patients.

In this study, we examined the relationship of plasma endotoxin levels to the development of multiple organ failure (MOF), and the outcome in patients with thermal injury. A prospective cohort study of 17 patients admitted with burns covering more than 70 per cent of body surface area was undertaken. Circulating endotoxin concentrations were measured by modified limulus amoebocyte lysate assay in serial samples of plasma. Seven out of 17 burned patients developed MOF according to multiple criteria. The plasma endotoxin concentrations of patients with MOF were 0.512-1.127 EU/ml, which were significantly higher than that of 10 patients without MOF (0.216-0.553 EU/ml), on 3, 14, 21 and 28 days postburn (p < 0.05-0.01). A significantly higher incidence of positive endotoxin tests (> or = 0.120 EU/ml) was found in patients who developed MOF as compared to those patients who did not develop MOF during the observation period (p < 0.05). As the mean endotoxin levels increased, the incidence of MOF and death rate also increased, and persistent endotoxemia carried a poor prognosis. The present investigation provides further evidence that endotoxemia in severely burned patients commonly occurs. Circulating endotoxin has also been found to be strongly associated with the development of MOF and mortality following major burn injury.

Role of gut-derived endotoxaemia and bacterial translocation in rats after thermal injury: effects of selective decontamination of the digestive tract.

This study was performed to investigate: (1) the role of gut-derived endotoxin/bacterial translocation in the pathogenesis of sepsis, and (2) the possible effects of selective decontamination of the digestive tract (SDD) on mortality in rats following 40 per cent full-thickness scald injury. In the SDD-treated group, Enterobacteriaceae and yeasts were eradicated from the caecal mucosa, while the mucosal flora consisting of mainly anaerobes was well preserved, within 3 days. The incidence of bacterial translocation to the mesenteric lymph nodes (MLN) and viscerae was significantly lowered on postburn days 1, 3 and 5 (P < 0.05-0.01). Meanwhile, pretreatment with SDD resulted in reductions of the faecal endotoxin levels in different segments of intestinal tract to less than 0.5 per cent (0.04-0.45 per cent) of the untreated control; there was also a significant attenuation of the elevation of endotoxin concentrations in both portal and systemic blood. Intestinal diamine oxidase (DAO) activity returned to baseline on day 5 in rats receiving SDD but not in controls. The 5-day survival rate in the SDD-treated group was elevated by 26.7 per cent as compared with controls (P < 0.05). These data suggested that endotoxin/bacterial translocation took place early and commonly, which in turn contributed to postburn sepsis and mortality. SDD was effective in preventing gut origin endotoxaemia and bacterial translocation, and improving the survival rate in rats following severe thermal injuries.

The use of blood in burn shock. Clinical and experimental study.

We have given whole blood as one of the main constituents of burn shock resuscitation for the past 28 years. To appraise the value of using whole blood, we have summarized the clinical experience of 2630 burn patients. Overall mortality was 4.18%. The lethal area of the burn were 50% of the population is expected to die was 82.8% total body surface area and 57.4% third-degree burns. The incidence of renal failure, pulmonary edema, and gastrointestinal bleeding was 0.9%, 0.4%, and 0.6% respectively. To confirm the advantage of transfusion of whole blood, we have carried out a series of experimental studies. Two groups of 25 dogs with 25% total body surface area full-thickness burns were treated with two resuscitation regimens. Group I was treated with whole blood, and group II with no blood, during the shock phase. After 48 hours, the infusions were stopped. Measurements were made before the burn and 2, 24, 48, 72, and 144 hours after the burn injury. The animals were then killed for histologic studies. From our data, we concluded that whole blood used in burn shock did not increase hemoconcentration or viscosity; it improved anemia, oncotic pressure, hypoproteinemia, acid-base balance, oxygenation, hemodynamics, and myocardial contractility, promoted cardionatrin secretion, reduced edema of tissue, and protected viscera from degenerative changes and bacterial colonization.

The concept and diagnosis of multiple systems organ failure.

There are still controversies concerning the concept and diagnosis of multiple systems organ failure (MSOF), since the term does not precisely define its true nature, and its differential diagnosis with other irrelevant clinical conditions, such as senile dysfunction of organs, agonal state, etc, remains unclarified. Our studies on both human burn patients and rat model by means of electron spin resonance (ESR) showed that there was an excessive generation of free oxygen radicals resulting in lipid peroxidation of cell membrane of various tissues. The intestine seemed to be particularly sensitive to hypoperfusion-reperfusion injury, as diamine oxidase activity of the ileum was lowered and translocation of bacteria occurred, indicating failure of intestinal mucosal barrier function. Concomitant determinations of plasma endotoxin (LPS) and tumor necrosis factor alpha (TNFa) levels showed significant elevation, especially in patients who finally developed MSOF. The data suggested that intestinally derived bacteria and/or LPS exacerbate the systemic responses initiated by ischemia reperfusion injury and the presence of large amounts of devitalized tissue. Early diagnosis is important in order to improve the prognosis. However, current criteria of diagnosis for MSOF do not conduce to an early diagnosis, as they only describe the end stage manifestations, while our therapeutic strategy should be directed against different levels of initiators, systemic mediators, and effectors of injury. Therefore, it is important to emphasize the role of septic responses in the development of the syndrome. We propose that the name of the syndrome be changed to "sepsis with organ dysfunction" or "mediator injury of organs".

Bacterial translocation and multiple system organ failure in bowel ischemia and reperfusion.

Portal circulation was reduced to 50-60% for one hour by partial occlusion of the superior mesenteric artery for the purpose of studying the relationship between reperfusion injury, bacterial translocation and multiple system organ failure. Forty dogs were divided randomly into four groups, and 1 x 10(10)/kg E. coli O111B4 were fed to each animal 12 hours before operation. Group I constituted the controls, in which sham operations were performed. The experimental procedure was completed in all the animals of the other three groups. Rubia yunnanensis, an anti-oxidant, was given to group III. Amikacin was given to group IV. The results showed that group II was characterized by bacteremia, hypoxemia, and hypotension as compared with group I. The levels of superoxide dismutase (SOD) in the whole blood were markedly lowered and malondialdehyde (MDA) values significantly elevated in group II after reperfusion compared with group I. Plasma levels of anaphylatoxin C5a and B2 (TXB2) were significantly raised in group II beginning with the reperfusion when compared with groups I, III and IV. Pathological changes in the intestine, liver and lung were remarkable only in group II, including acute necrosis of the intestinal mucosa, granulocyte infiltration, hemorrhage and edema of the lung, degenerative changes of myocardial and hepatic cells, and bacterial invasion of the blood, liver and lung. These results suggested that bowel ischemia and reperfusion may promote gut barrier failure and bacterial translocation, then contribute to the development to multiple system organ failure (MSOF) by allowing bacteria or endotoxin normally contained within the gut to reach the portal and systemic circulations where it fuels the septic process. Oxygen free radicals, anaphylatoxin and thromboxane may be potential factors in the development of gut barrier failure and MSOF.

Special spectacles facilitating debridement. Report of use in 300 cases.

According to the difference of light reflection of tissue with different degree of viability, spectacles were made from glass permitting light of certain wavelength to pass to help distinguish viable from nonviable tissue. They were used in debridement of wounds in 300 patients. The results showed that the quality of debridement was improved as evidenced by better healing and shorter healing time. These spectacles were helpful, especially for young and unexperienced operators to distinguish viable from nonviable tissue. They were also used to predict flap viability in plastic surgery.

Protective effect of Re-LPS antiserum on experimental multiple system organ failure.

This study examines the possible beneficial effect of Re-LPS (F515) antiserum on experimental multiple system organ failure (MSOF) in rabbits. The results showed that the plasma LPS level was significantly decreased, and it took a shorter period to clear up LPS in experimental than in control rabbits after receiving Re-LPS antiserum. Pretreatment with antiserum can markedly improve the function of the liver, lungs, kidneys, blood and gastrointestinal tract. The MSOF incidence in the group of rabbits receiving immune sera was only 11.2% and the survival rate was raised by about 40.0%. The results suggest that early passive immunotherapy may neutralize gut-derived endotoxin, inhibit endotoxin-induced mediators release and prevent development of severe complications due to sepsis. It is therefore postulated that LPS core antiserum may provide a prophylactic effect on the development of experimental MSOF.

[Influential factors of water evaporation from burn wound].

To determine various influential factors of water evaporation from burn wound, we scalded 120 rats and divided them randomly into 12 groups. The rate of evaporation was studied under different temperatures and moistures. The experimental results showed that high temperature and low moisture were beneficial to the treatment of burn wound. Escharectomy, skin grafting and film forming agents could reduce evaporation. Azone could change the permeability of the skin and accelerate water evaporation.

[Delayed fluid resuscitation induced bacterial translocation after lethal thermal injury: role of oxygen free radical injury of intestinal mucosa].

The Present investigation was undertaken to examine the effect of delayed fluid resuscitation (DFR), after lethal thermal injury on oxygen free radical (OFR) injury of intestinal mucosa and its relationship to bacterial translocation. Four groups of gnotobiotic rats with 5 strains of bacteria were studied: sham injury group (control) (n = 6): early fluid resuscitation (EFR) group (n = 24) receiving resuscitation (Parkland) immediately after scald (40% TBSA, third degree); DFR group (n = 24) receiving resuscitation 6 hours after scald; treatment group (n = 12), rats with DFR receiving VitE and VitC treatment before resuscitation 12, 24, 48 and 72 hours after injury, animals (n = 6, at each point) were sacrificed. Plasma endotoxin level, mucosal SOD, GSHPx, MDA and diamine oxidase (DAO) of ileum were determined, and cultures of the mesenteric lymph nodes (MLN), liver, spleen, heart, lung, kidney and blood were done. The level of mucosal MDA and plasma endotoxin and the incidence of bacteria translocation (IBT) to tissues were significantly higher and mucosal SOD, GSHPx, DAO activity significantly lower in DFR group as compared with that in EFR group at most of the time points. In DFR group, mucosal MDA content was negatively correlated with mucosal DAO activity, which correlated positively with plasma endotoxin level and IBT. After treatment with VitE and VitC, mucosal MDA content was decreased, plasma endotoxin level and IBT were significantly decreased, and mucosal DAO activity was significantly increased. Our data indicated that DFR in cases of burn shock can result in OFR injury of intestinal mucosa, disrupting mucosal barrier and promoting translocation of intestinal bacteria and endotoxin.

The safety and efficacy of early-stage bi-weekly alendronate to improve bone mineral density and bone turnover in chinese post-menopausal women at risk of osteoporosis.

The efficacy and safety of early, low frequency antiresorptive drug intervention for osteopaenia on bone mineral density (BMD) and bone turnover in Chinese post-menopausal women at risk of developing osteoporosis were investigated. A total of 180 women aged 40 - 70 years were enrolled and equally randomized to receive either 70 mg alendronate once every 2 weeks plus 0.5 µg alfacalcidol daily (treatment group) or alfacalcidol 0.5 µg daily alone (control group) for 12 months. In the treatment group, lumbar spine and total hip BMD at 12 months had increased significantly from baseline and compared with the control group. There were also significant reductions in serum levels of the bone turnover biomarkers, bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen, compared with the control. No serious adverse events were observed in either group and safety profiles were similar. It was concluded that early intervention with 70 mg alendronate once every 2 weeks was safe, well tolerated and more effective than alfacalcidol alone (control) in increasing BMD and reducing bone turnover, and might prevent serious outcomes, such as fragility fractures, reduce rates of adverse effects and improve patient compliance.