The present study investigated the relationship between connexin 43 (Cx43) expression in alveolar type II epithelial cells (ATII) and alveolar air-blood barrier permeability, and the effect of microRNA-206 (miR-206) on the expression of Cx43 in sepsis-induced acute lung injury. For the in vivo study, rats were divided into the sham, caecum ligation and perforation (CLP), CLP+Cx43 inhibitors (Cx43-In) and CLP+miR-206 analogs (miR-206-Mi) groups. CLP method was used to prepare an acute lung injury model of sepsis. Following successful modeling, lung tissue was collected for hematoxylin and eosin (HE) staining, and the wet to dry weight ratio (W/D) and protein content in bronchoalveolar lavage fluid (BALF) were detected. Cx43 expression in lung tissue was determined by immunohistochemistry and western blot analysis. Additionally, miR-206 and Cx43 expression levels in lung tissue were detected by reverse transcription-quantitative polymerase chain reaction. Rat ATII cells were cultured in Transwells plates to form monolayers, then treated with Cx43 mRNA inhibitors or miR-206 analogs. The cell monolayers were then stimulated with lipopolysaccharide and their permeability was evaluated by detecting fluorescein-labeled dextran at the lower chamber of the Transwells. The dual luciferase reporter gene assay was used to investigate whether miR-206 targeted the 3′ untranslated region of Cx43 mRNA to regulate Cx43 expression, thereby regulating the permeability of the alveolar air-blood barrier. Results demonstrated that the CLP method induced damage to the alveolar structure, thickened the alveolar wall, caused hyperemia and hemorrhage in the pulmonary interstitium and caused infiltration of inflammatory cells. Edema in the pulmonary interstitium and alveolar space, exudation of neutrophilic granulocyte and pink edema fluid in alveolar cavities were also observed. W/D ratio, the BALF protein content, and expression of Cx43mRNA and Cx43 were increased significantly, whilst miR-206 expression decreased compared with the control group. The lung tissue inflammatory response was attenuated, and the W/D ratio and BALF protein content decreased in the Cx43-In and miR-206-Mi groups compared with the CLP group. Moreover, Cx43 mRNA and protein expression were decreased significantly in the Cx43-In and miR-206-Mi groups. In addition, the dual luciferase reporter gene assay determined that the untranslated region of Cx43 mRNA had a complementary sequence to miR-206. Of note, Cx43 mRNA expression in the miR-206-Mi group was not significantly decreased in vitro . In conclusion, the increase in ATII cell Cx43 expression during sepsis-induced acute lung injury resulted in an increase in the permeability of the alveolar air-blood barrier. miR-206 targeted the Cx43 mRNA 3′untranslated region to downregulate Cx43 expression, which further improved the permeability of the alveolar air-blood barrier.

Sepsis may directly lead to multiple organ failure, which is among the leading causes of mortality in critically ill patients. According to data released by the Global Sepsis Alliance, the number of mortalities due to sepsis exceeded the combined number for prostate cancer, breast cancer and AIDS in 2012. To date, studies have reported that resveratrol has marked positive effects including anti-inflammatory, anti-oxidative and pro-microcirculatory functions in sepsis-induced organ injury, significantly improving the survival time and mortality of sepsis animals. The present systematic review sought to further clarify the efficacy and safety of resveratrol in the treatment of sepsis. Studies on resveratrol application in the treatment of sepsis-induced organ injury in animal models were reviewed by searching various Chinese and other language databases (PubMed, Embase, CNKI, WanFang and WeiPu) and by manually searching the references of related articles. The selection and evaluation of the studies was performed by two independent reviewers. A total of 260 related studies were initially identified. Following application of the exclusion factors and inclusion criteria, 11 studies were included. Meta-analysis revealed that resveratrol exerted significant protective effect in sepsis-induced animal models of organ injury, through anti-inflammatory, anti-oxidant and pro-microcirculatory functions compared with in the placebo group. While nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (NRF-2) are the two major signaling pathways to have been associated with the anti-inflammatory and anti-oxidative effects of resveratrol, these factors were not quantified for mean values, therefore not suitable for systematic evaluation. For related factors, the results of meta-analysis were as follows: For tumor necrosis factor-α (TNF-α), the standardized mean difference (SMD) was-13.50 [95% confidence interval (CI):-22.08,-4.91; P=0.002]; for malondialdehyde (MDA), the SMD was-3.10 (95% CI:-5.27,-0.93; P=0.005); for mean arterial pressure the SMD was 1.34 (95% CI: 0.07, 2.62; P=0.04); for interleukin (IL)-6 the SMD was-9.57 (95% CI:-20.90, 1.75; P=0.10); and for IL-10 the SMD was 0.80 (95% CI:-0.73, 2.34; P=0.31). It was concluded that resveratrol exerted significant anti-inflammatory and anti-oxidative effects through NF-κB and NRF-2 signaling pathways in animal models of sepsis-induced multiple organ injury, manifesting as significant downregulation of TNF-α and MDA expression and improved microcirculation, therefore ameliorating septic damage to the body, which may ultimately improve survival ratios.

Objective. At present, the most appropriate management of Henoch–Schonlein purpura nephritis (HSPN) with nephrotic-range proteinuria still remains controversial; thus, the purpose of this study is to evaluate safety and efficacy of traditional Chinese medicine (TCM), Qingre-Lishi-Yishen Formula (QLYF), integrated with regular oral glucocorticoid and cyclophosphamide intravenous pulse therapeutic regimen in children suffered from moderately severe HSPN with nephrotic proteinuria. Methods. From 1 January 2012, to 1 January 2016, totally 150 hospitalized children suffered from HSPN with nephrotic proteinuria were included. All were treated with glucocorticoid and cyclophosphamide, and 100 of them were treated with integrative traditional Chinese decoction QLYF. Patients were followed up for 2 years. Rate of adverse event occurrence, short-term clinical effects, long-term clinical effects, and TCM therapeutic evaluation were all compared. Results. Total adverse event rate was lower in the QLYF group (χ2 = 5.357, p=0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p<0.05), and no cases of hepatic and renal toxicities related to the herbal medicine were observed in the QLYF group. For short-term clinical efficacy evaluation, lower levels of 24 hour proteinuria (p<0.05) and urine blood cell count (p<0.05) were found in the QLYF group. For long-term efficacy evaluation, better clinical control rate effective rate, lower recurrence rate (p<0.05), and fewer TCM syndrome score (p<0.05) were found in the QLYF group. Conclusion. Compared with merely using regular oral glucocorticoid plus cyclophosphamide pulse therapeutic regimen, the therapeutic regimen that integrates QLYF with the abovementioned western medicine might be a safe means to decrease the occurrence rate of adverse events and improve short-term and long-term clinical effects in children who suffered from moderately severe HSPN with nephrotic proteinuria.

Objective We investigate the correlation between the patterns of traditional Chinese medicine (TCM) syndromes and the damage of renal function, immunologic function index, and blood coagulation index in patients with Henoch-Schönlein purpura nephritis (HSPN) and thus provide the therapeutic effects of Chinese herbs decoction on HSPN. Methods We studied 262 hospitalized patients diagnosed with HSPN between 1 February 2016 and 1 January 2017. Indexes like renal function, immunologic function, and blood coagulation were measured. The patients were classified into four different patterns of TCM symptoms. Results In a total of 262 patients with HSPN, dampness-heat accumulation accounted for 59.5%, which is the highest proportion of TCM symptom patterns, liver-kidney yin deficiency accounted for 17.6%, qi and yin deficiency ratio reached 12.6%, and blood-heat bleeding accounted for 9.9%. 24-hour proteinuria was heavier in the dampness-heat accumulation patients who had immune disorders and were in hypercoagulative state and hyperfibrinolysis conditions. Conclusion We analyzed and summarized the clinical characteristics of patients with HSPN and found that dampness-heat accumulation was dominant in patients and was always accompanied by immune disorders and coagulation disorders. These results provided the largest therapeutic effects of Chinese herbs decoction for clinical treatment.