Strategy to delay the progression of chronic kidney disease by targeting gut microbiota and uremic toxins metabolism pathway / 药学学报

Chronic kidney disease (CKD) is a serious chronic disease with high incidence, poor prognosis, and a variety of complications. Indoxyl-sulfate (IS) and p-cresol sulfate (PCS) are two typical gut-derived uremic toxins, which are produced by the co-metabolism of intestinal microbes and the host. With the progression of CKD, gut-derived uremic toxins such as IS and PCS accumulate in patients with CKD and thereafter accelerate the progression of CKD. Gut microbiota is closely related with CKD, and targeting gut microbiota to regulate gut-derived uremic toxins synthesis and metabolic pathways may be a promising strategy to delay the progression of CKD. In this paper, the relationship between gut microbiota, gut-derived uremic toxins, and CKD was analyzed, and the strategy to delay the progression of CKD by targeting gut microbiota and uremic toxins metabolism pathway was proposed.

Compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos regulate insulin signaling pathway and alleviate insulin resistance in mice / 药学学报

Insulin resistance refers to the impaired ability of insulin to regulate glucose metabolism in peripheral organs, which is considered to be the etiology of type 2 diabetes. This study aims to explore the mechanism of improving insulin resistance by compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos (DH). Insulin resistance was conducted on C56BL/6J mice by treatment of high fat diet. The energy intake and body weight, plasma levels of triglycerides, total cholesterol, insulin and glucose, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT), as well as gene transcription and protein expression levels of insulin signaling pathway in liver, heart, kidney, and skeletal muscle of insulin resistance mice were evaluated. Animal experiments and welfare were performed in compliance with the guidelines of Animal Ethics Committee of Nanjing University of Chinese Medicine. The results showed that DH treatment significantly alleviated the excessive food intake and weight gain, and significantly decreased the levels of plasma triglycerides and total cholesterol, and constantly mitigated the hyperinsulinemia in insulin resistance mice. The results of OGTT and ITT suggested that DH treatment dramatically improved the response of insulin resistance mice to insulin stimulated glucose metabolism. Furthermore, the imbalance of metabolic arm and mitogenic arm of insulin signaling pathway in insulin resistance mice was normalized after DH treatment. DH treatment regulated insulin signaling pathway and improved the ability of glucose metabolism of insulin resistance mice.

Clinical effects of warmed humidified carbon dioxide insufflation in infants undergoing major laparoscopic surgery.

PURPOSE: Some studies have reported that warmed humidified carbon dioxide (CO2) insufflation in adult laparoscopic surgery could reduce pain and improve the core body temperature (CBT). However, similar studies are lacking in infants. Thus, this study aimed to investigate the clinical effects of warmed, humidified CO2 insufflation in pediatric patients undergoing major laparoscopic surgeries. METHODS: From January 2015 to December 2017, infants who underwent major laparoscopic surgeries in Ningbo Women and Children's Hospital were randomized to Group A (standard CO2 insufflation) or Group B (warmed humidified CO2 insufflation, 35°C, 95% relative humidity). Change in CBT at the end of surgery was the primary outcome. Secondary outcomes included surgery time, intraoperative blood loss, oxygen saturation (SO2), and Face, Legs, Activity, Cry and Consolability (FLACC) scale. These variables were compared between the 2 groups. RESULTS: Sixty-three infants (38 females, 25 males) were included; 30 patients were in Group A and 33 in Group B. The diseases treated with the laparoscopic approach included congenital megacolon, congenital diaphragmatic hernia, and intestinal malrotation. No deaths were noted. CBT was significantly higher in Group B at the end of surgery (P = .021). The occurrence of postoperative shivering (P = .02), hypothermia (P = .032), bowel movement (P = .044), and hospital stay (P = .038) was significantly different between the 2 groups; Group B had less shivering and hypothermia occurrence after surgery. Moreover, Group B demonstrated a more rapid postoperative recovery of bowel movement and shortened hospital stay than Group A. There was no statistical difference in operative time (P = .162), intraoperative blood loss (P = .541), SO2 (P = .59), and FLACC scale (P = .65) between the 2 groups. CONCLUSION: The use of warmed humidified CO2 insufflation in infants undergoing major laparoscopic surgery was helpful for maintaining normothermia and was associated with several positive postoperative outcomes, including less shivering and hypothermia, faster recovery of bowel movement, and shortened hospital stay.

An oligopeptide improves solubility of paclitaxel by non-covalent interaction / 药学学报

Based on the principle of non-covalent interactions between oligopeptides and paclitaxel for improving the solubility of paclitaxel, an oligopeptide, N terminal-W(L)-FFGREKD-C terminal (W8), was designed and the solubilization effect of W8 on paclitaxel was detected through experiments. The binding efficiency and the possible optimal conformation were optimized by molecular docking program. The solubilization effect of W8 on paclitaxel was determined by RP-HPLC. And the solubilization mechanism of oligopeptide to paclitaxel was proposed at molecular level. It was indicated from the docking result that there existed pi-pi interactions and several hydrogen-bond interactions between the oligopeptide and paclitaxel. After being solubilized by the oligopeptide, the aqueous solubility of paclitaxel was increased to 28 times. This study provided basis for further research of the solubilization of paclitaxel by oligopeptide and confirmed a novel approach for the design of safe oligopeptide solubilizing excipient.

Homodimerization of human mu-opioid receptor overexpressed in Sf9 insect cells.

In this study, we demonstrate that human mu-opioid receptors do form SDS-resistant homodimers and examine the ability of human mu-opioid receptors to dimerize and the role of agonists in the dimerization. Increasing concentrations and longer exposure of agonists reduce the levels of dimmer with a corresponding increase in the levels of monomer. This effect is achieved with both peptide and alkaloid opioid agonists and it is antagonist reversible. These results suggest that human mu-opioid receptors are present as receptor oligomers and interconversion between dimeric and monomeric forms may be important for biological activity.

Transfecting and killing effect of herpes simplex virus thymidine kinase (HSV-TK) gene on human gastric carcinoma in vitro / 第二军医大学学报

Objective: To study retrovirus (RV)-mediated transduction of gastric carcinoma cells with the herpes simplex virus thymidine kinase (HSV-tk) gene and the subsequent treatment with ganciclovir(GCV). Methods: The TK gene was transfected into human gastric carcinoma cell line MKN28 using HSV-TK that packed with PA317 cell, the sensitivity of MKN28TK cells to GCV was examined in vitro. Results: The retroviral-mediated HSV-TK gene can be transfected to MKN28 cells. The growth rate of MKN28 cells transfected with HSV-TK gene did not change. MKN28TK cells became significantly sensitive to GCV and had bystander effect. Conclusion: Transfection of gastric carcinoma with HSV-TK has higher transfection efficiency. MKN28TK cells are significantly sensitive to GCV.

Transfecting and killing effect of herpes simplex virus thymidine kinase (HSV-TK) gene on human gastric carcinoma in vitro / 第二军医大学学报

Objective: To study retrovirus (RV)-mediated transduction of gastric carcinoma cells with the herpes simplex virus thymidine kinase (HSV-tk) gene and the subsequent treatment with ganciclovir(GCV). Methods: The TK gene was transfected into human gastric carcinoma cell line MKN28 using HSV-TK that packed with PA317 cell, the sensitivity of MKN28TK cells to GCV was examined in vitro. Results: The retroviral-mediated HSV-TK gene can be transfected to MKN28 cells. The growth rate of MKN28 cells transfected with HSV-TK gene did not change. MKN28TK cells became significantly sensitive to GCV and had bystander effect. Conclusion: Transfection of gastric carcinoma with HSV-TK has higher transfection efficiency. MKN28TK cells are significantly sensitive to GCV.

Post-thyroidectomy Hypocalcemia in High- Risk Patients Following Total Thyroidectomy

PURPOSE: Parathyroid injury is the major cause of post-thyroidectomy hypocalcemia. This prospective study aimed to define the relation between the preservation status of the parathyroid glands and post-thyroidectomy hypocalcemia as well as to determine whether the number of preserved parathyroid glands could be a guideline for the management of post-thyroidectomy hypocalcemia. METHODS: We analyzed a total of 76 cases of total thyroidectomy due to malignancy were analysed. Parathyroid gland status at the end of thyroidectomy was classified as preserved intact, discolored (color change or equivocal viability), or autotransplanted. Patients were grouped according to the number of intact preserved parathyroid glands into group 1 (more than two), group 2 (one), or group 3 (zero). The total and ionized serum calcium levels of each group were monitored for three days after surgery. RESULTS: The number of intact preserved parathyroid glands was not found to be closely related to serum calcium level, although ionized serum calcium level was significantly lower in group 1 than group 2 (P<0.001). Hypocalcemia was not found in group 1. Hypocalcemia was found in 31% (10/32) of group 2. Among the 32 patients of group 2, all 4 parathyroid gland were identified in 9 patients and 4 patients were shown to be hypocalcemic. Therefore, the incidence of hypocalcemia for patients in whom only one intact parathyroid was preserved and all 4 parathyroid were indentified was 44% (4/9). Hypocalcemia was transient in all patients. CONCLUSION: The parathyroid glands should be preserved as much as possible to minimize post-thyroidectomy hypocalcemia. The number of intact preserved parathyroid glands can be a good guideline for predicting post-thyroidectomy hypocalcemia and proper care management.