Dietary zinc oxide (ZnO) at pharmacological level has been widely used to prevent and treat diarrhea in weaning piglets. Despite its importance for promoting animal health and performance, the influence of microbiome profiles in intestinal tracts by ZnO needs to be comprehensively investigated. In this study, we conducted a comparative microbial community analysis in the ileum and colon of piglets fed by either control diet, high ZnO (3,000 mg/kg) supplement or antibiotics (300 mg/kg chlortetracycline and 60 mg/kg colistin sulfate) supplement. Our results showed that both high dietary ZnO and in-feed antibiotics supplementations significantly increased 5 phyla of Spirochaetes, Tenericutes, Euryarchaeota, Verrucomicrobia, TM7, and reduced 1 phyla of Chlamydiae in ileal digesta. The relative abundance of opportunistic pathogens Campylobacterales were decreased while Enterobacteriales were increased in ZnO or antibiotics-supplemented group when compared to the control. In the colon, the phyla Euryarchaeota, the genus Methanobrevibacter, and the species Methanobrevibacter smithii were drastically increased by high dietary ZnO supplementation when compared with other groups. The microbial functional prediction analysis showed that high dietary ZnO and in-feed antibiotics had a higher abundance of transporter pathway enrichment in the ileum when compared with the control. While in the colon high dietary ZnO had a higher abundant enrichment of methane metabolism involving energy supply when compared with other groups. Both high dietary ZnO and antibiotics increased the microbiota diversity of ileal digesta while they decreased the microbiota diversity of the colonic digesta. Collectively, these results suggested that dietary ZnO and in-feed antibiotics supplementations presented similar effect on ileal microbiota, and mainly affected the non-predominant microbiota.

The current study was conducted to investigate the effects of dietary zinc oxide (ZnO) on the antioxidant capacity, small intestine development, and jejunal gene expression in weaned piglets. Ninety-six 21-day-old piglets were randomly assigned to three dietary treatments. Each treatment had eight replicates with four piglets per replicate. The piglets were fed either control diet (control) or control diet supplemented with in-feed antibiotics (300 mg/kg chlortetracycline and 60 mg/kg colistin sulfate) or pharmacological doses of ZnO (3000 mg/kg). The experiment lasted 4 weeks. Blood samples were collected at days 14 and 28, while intestinal samples were harvested at day 28 of the experiment. Dietary high doses of ZnO supplementation significantly increased the body weight (BW) at day 14 and average daily gain (ADG) of days 1 to 14 in weaned piglets, when compared to control group (P < 0.05). The incidence of diarrhea of piglets fed ZnO-supplemented diets, at either days 1 to 14, days 14 to 28, or the overall experimental period, was significantly decreased in comparison with those in other groups (P < 0.05). Supplementation with ZnO increased the villus height of the duodenum and ileum in weaned piglets and decreased the crypt depth of the duodenum, when compared to the other groups (P < 0.05). Dietary ZnO supplementation decreased the malondialdehyde (MDA) concentration at either day 14 or day 28, but increased total superoxide dismutase (T-SOD) at day 14, when compared to that in the control (P < 0.05). ZnO supplementation upregulated the messenger RNA (mRNA) expression of zonula occludens-1 (ZO-1) and occludin in the jejunum mucosa of weaned piglets, compared to those in the control (P < 0.05). The pro-inflammatory cytokine interleukin-lβ (IL-1β) mRNA expression in the jejunum mucosa was downregulated in the ZnO-supplemented group, compared with the control (P < 0.05). Both in-feed antibiotics and ZnO supplementation decreased the mRNA expression of interferon-γ (IFN-γ), but increased the mRNA expression of transforming growth factor-β (TGF-β), in the jejunum mucosa of piglets, when compared to those in the control (P < 0.05). In summary, supplemental ZnO was effective on the prevention of post-weaning diarrhea (PWD) in weaned piglets and showed comparative growth-promoting effect on in-feed antibiotics, probably by the mechanism of improvement of the antioxidant capacity, restoration of intestinal barrier function and development, and modulation of immune functions.

Cisplatin is the major chemotherapeutic drug in gastric cancer, particularly in treating advanced gastric cancer. Tumour cells often develop resistance to chemotherapeutic drugs, which seriously affects the efficacy of chemotherapy. GPR30 is a novel oestrogen receptor that is involved in the invasion, metastasis and drug resistance of many tumours. Targeting GPR30 has been shown to increase the drug sensitivity of breast cancer cells. However, few studies have investigated the role of GPR30 in gastric cancer. Epithelial‐mesenchymal transition (EMT) has been shown to be associated with the development of chemotherapeutic drug resistance. In this study, we demonstrated that GPR30 is involved in cisplatin resistance by promoting EMT in gastric cancer. GPR30 knockdown resulted in increased sensitivity of different gastric cancer (GC) cells to cisplatin and alterations in the epithelial/mesenchymal markers. Furthermore, G15 significantly enhanced the cisplatin sensitivity of GC cells while G1 inhibited this phenomenon. In addition, EMT occurred when AGS and BGC‐823 were treated with cisplatin. Down‐regulation of GPR30 with G15 inhibited this transformation, while G1 promoted it. Taken together, these results revealed the role of GPR30 in the formation of cisplatin resistance, suggesting that targeting GPR30 signalling may be a potential strategy for improving the efficacy of chemotherapy in gastric cancer.

Background and aim: Paclitaxel (PTX) plus 5-fluorouracil (5-Fu) has become the standard chemotherapy for advanced gastric cancer (GC). Apatinib, a small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, improves outcomes in GC patients as a third-line treatment. However, its impact on the chemosensitivity of GC remains to be determined. Hence, we aimed to assess the efficacy and safety of apatinib combined with chemotherapy in vivo and in vitro. Methods: The MGC803 cell viability was determined by Cell Counting Kit-8 assay, and the interactions between apatinib and conventional cytotoxic agents revealed by combination index values were calculated using Calcusyn 2.0 software. We also used a zebrafish embryo xenograft model to validate the synergistic interactions. Furthermore, 4 patients with late-stage GC were enrolled to explore the efficacy and safety of PTX/Tegafur Gimeracil Oteracil Potassium (S1) (PS) chemotherapy plus apatinib in conversion surgery. Results: Apatinib showed synergistic interactions with both PTX and 5-Fu in vivo. The zebrafish embryo xenograft model also demonstrated that apatinib significantly enhanced the antitumor activity of PTX and 5-Fu. Apatinib plus PS chemotherapy was well tolerated before surgery. Objective response to preoperative SPA treatment was achieved in all 4 patients. No postoperative bleeding events or wound-healing complications were observed. No postperative morbidity occurred and no morbidity was encountered. Pathological examination showed that all patients had grade Ib pathological response. Conclusion: The experimental data suggested that apatinib improves the efficacy of PTX and 5-Fu both in vitro and in vivo. Clinical evidence showed that a combination of PS chemotherapy with apatinib may be an efficient and acceptable safety treatment for late-stage GC, especially in conversion surgery.

Dual-specificity phosphatase-1 (DUSP1) is an oncogene that is associated with cancer progression following drug resistance. In order to investigate the potential relationship between DUSP1 and apatinib resistance in gastric cancer cells, we preformed many assays to study this problem. DUSP1 gene was detected by RT-qPCR assay, proteins in MAPK pathway were quantified by western blot assay, and CCK-8 assay, flow cytometry and Hoechest 33342 stain were performed to detect the resistance of cells, cell cycles and apoptosis, respectively. Immunohistochemical staining was used to discover the expression of DUSP1 protein in patients' tumor or paratumor tissues. It was found that apatinib (Apa)-resistant gastric cancer (GC) cells showed increased expression of DUSP1, whereas the knockdown of DUSP1 in resistant cells resensitized these cells to Apa. The restored sensitivity to Apa was the result of inactivation of mitogen-activated protein kinase (MAPK) signaling and the induction of apoptosis. The in vitro use of Apa in combination with a DUSP1 inhibitor, triptolide, exerted significant effects on inhibiting the expression of DUSP1, growth inhibition, and apoptosis via the inactivation of MAPK signaling. In patients who did not undergo chemotherapy or targeted therapy, the expression of DUSP1 in adjacent tissues was higher when compared with that observed in tumor tissues. In addition, the expression of DUSP1 was higher in the early stages of GC than in the advanced stages. The expression of DUSP1 in tumor tissues was not associated with the survival rate of the patients. Therefore, increased expression of DUSP1 may be responsible for Apa resistance, and DUSP1 may serve as a biomarker for Apa efficacy. In conclusion, inducing the downregulation of DUSP1 may be a promising strategy to overcome Apa resistance.

Objectives: Spontaneous rupture of the urinary bladder (SRUB) is extremely rare and might be misdiagnosed, leading to a high mortality rate. The current study aimed to identify the cause, clinical features, and diagnosis strategy of SRUB.Methodology: We presented a case report for two women (79 and 63 years old) misdiagnosed with acute abdomen and acute kidney injury, respectively, who were finally confirmed to have SRUB by a series of investigations and exploratory surgery. Meanwhile, literature from multiple databases was reviewed. PubMed, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Biological Medical Literature Database (CBM), WANFANG DATA, and the Chongqing VIP database for Chinese Technical Periodicals (VIP) were searched with the keywords “spontaneous bladder rupture” or “spontaneous rupture of bladder” or “spontaneous rupture of urinary bladder.” All statistical analyses were conducted using SPSS 20.0 software.Results: A total of 137 Chinese and 182 English literature papers were included in this article review. A total of 713 SRUB patients were analyzed, including the two patients reported by us. The most common cause of SRUB was alcohol intoxication, lower urinary tract obstruction, bladder tumor or inflammation, pregnancy-related causes, bladder dysfunction, pelvic radiotherapy, and history of bladder surgery or bladder diverticulum. Most cases were diagnosed by exploratory laparotomy and CT cystography. Patients with extraperitoneal rupture could present with abdominal pain, abdominal distention, dysuria, oliguria or anuria, and fever. While the main symptoms of intraperitoneal rupture patients could be various and non-specific. The common misdiagnoses include acute abdomen, inflammatory digestive disease, bladder tumor or inflammation, and renal failure. Most of the patients (84.57%) were treated by open surgical repair, and most of them were intraperitoneal rupture patients. Overall, 1.12% of patients were treated by laparoscopic surgery, and all of them were intraperitoneal rupture patients. Besides, 17 intraperitoneal rupture patients and 6 extraperitoneal rupture patients were treated by indwelling catheterization and antibiotic therapy. Nine patients died of delayed diagnosis and treatment.Conclusions: SRUB often presents with various and non-specific symptoms, which results in misdiagnosis or delayed treatment. Medical staff noticing abdominal pain suggestive of peritonitis with urinary symptoms should be suspicious of bladder rupture, especially in patients with a history of bladder disease. CT cystography can be the best preoperative non-invasive examination tool for both diagnosis and evaluation. Conservative management in the form of urine drainage and antibiotic therapy can be used in patients without severe infection, bleeding, or major injury. Otherwise, surgical treatment is recommended. Early diagnosis and management of SRUB are crucial for an uneventful recovery.

BackgroundMany studies have evaluated the relationship between alkaline phosphatase (ALP) and the prognosis for prostate cancer (PCa). But they have not reached a widespread consensus yet. Therefore, we completed a meta-analysis to ascertain the significance of ALP and the prognosis for PCa.MethodsA literature search was performed in the PubMed, Embase, and Web of Science databases. HRs concerning overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) were extracted to evaluate the impacts of ALP on the prognosis for PCa. Subgroup analyses were conducted on different study types, regions, sample sizes, and cutoff values. Sensitivity analysis was performed by removing one study in sequence.ResultsA total of 63 studies from 54 articles with 16,135 patients were included in this meta-analysis. The pooled results indicated that high baseline ALP was associated with obviously poor OS (HR=1.74, 95% CI: 1.47–2.06) and PFS (HR=1.60, 95% CI: 1.13–2.26) in patients with PCa. The pooled HR for bone-specific ALP and OS was 1.76 (95% CI: 1.45–2.15). However, no association between ALP and CSS (HR=1.002, 95% CI: 0.998–1.005) was found for PCa. The results of subgroup analyses were all in accordance with the main findings. Sensitivity analysis suggested that no single study could affect the stability of the results.ConclusionHigh serum ALP is significantly associated with poor OS and PFS except for CSS in PCa. ALP is an efficient and convenient biomarker for PCa prognosis.

Trametes robiniophila Murr. (Huaier) is a widely used anti-cancer agent in China. Strong evidence for the anti-proliferative activity of Huaier has been reported; however, its anti-metastatic potential against gastric cancer (GC) as well as its underlying mechanism of action are unknown. Here, we show that treatment with an aqueous Huaier extract over a range of concentrations significantly suppressed both the invasiveness and migratory ability of GC cells. Huaier could also partly reverse the epithelial-mesenchymal transition (EMT), as characterized by increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal markers N-cadherin and vimentin. In addition, Huaier-treated cells expressed lower levels of Twist compared to untreated controls, and overexpression of Twist via transfection could partially abolish the anti-metastatic activity of Huaier. Furthermore, elevated Twist expression was correlated with an advanced TNM stage, a high rate of lymph node metastasis, and reduced disease-free survival in GC patients. These findings reveal a novel anti-metastatic mechanism for Huaier, which inhibits the EMT by targeting Twist, suggesting its potential application against a GC relapse.