Addition of terlipressin to norepinephrine in septic shock and effect of renal perfusion: a pilot study

PurposeTerlipressin improves renal function in patients with septic shock. However, the mechanism remains unclear. Here, we aimed to evaluate the effects of terlipressin on renal perfusion in patients with septic shock.Materials and MethodsThis pilot study enrolled patients with septic shock in the intensive care unit of the tertiary hospital from September 2019 to May 2020. We randomly assigned patients to terlipressin and usual care groups using a 1:1 ratio. Terlipressin was intravenously pumped at a rate of 1.3 μg/kg/hour for 24 h. We monitored renal perfusion using renal contrast-enhanced ultrasound (CEUS). The primary outcome was peak sonographic signal intensity (a renal perfusion parameter monitored by CEUS) at 24 h after enrollment.Results22 patients were enrolled in this study with 10 in the terlipressin group and 12 in the usual care group. The baseline characteristics of patients between the two groups were comparable. The peak sonographic signal intensity at 24 h after enrollment in the terlipressin group (60.5 ± 8.6 dB) was significantly higher than that in the usual care group (52.4 ± 7.0 dB; mean difference, 7.1 dB; 95% CI, 0.4–13.9; adjusted p = .04). Patients in the terlipressin group had a lower time to peak, heart rates, norepinephrine dose, and a higher stroke volume at 24 h after enrollment. No significant difference in the urine output within 24 h and incidence of acute kidney injury within 28 days was found between the two groups.ConclusionsTerlipressin improves renal perfusion, increases stroke volume, and decreases norepinephrine dose and heart rates in patients with septic shock.     

Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit in vitro

Aim:

To examine the effects of anisomycin on glioma cells and the related mechanisms in vitro.

Methods:

The U251 and U87 human glioblastoma cell lines were tested. The growth of the cells was analyzed using a CCK-8 cell viability assay. Apoptosis was detected using a flow cytometry assay. The expression of proteins and phosphorylated kinases was detected using Western blotting.

Results:

Treatment of U251 and U87 cells with anisomycin (0.01–8 μmol/L) inhibited the cell growth in time- and concentration-dependent manners (the IC₅₀ values at 48 h were 0.233±0.021 and 0.192±0.018 μmol/L, respectively). Anisomycin (4 μmol/L) caused 21.5%±2.2% and 25.3%±3.1% of apoptosis proportion, respectively, in U251 and U87 cells. In the two cell lines, anisomycin (4 μmol/L) activated p38 MAPK and JNK, and inactivated ERK1/2. However, neither the p38 MAPK inhibitor SB203580 (10 μmol/L) nor the JNK inhibitor SP600125 (10 μmol/L) prevented anisomycin-induced cell death. On the other hand, anisomycin (4 μmol/L) reduced the level of PP2A/C subunit (catalytic subunit) in a time-dependent manner in the two cell lines. Treatment of the two cell lines with the PP2A inhibitor okadaic acid (100 nmol/L) caused marked cell death.

Conclusion:

Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit. The regulation of PP2A/C exression by anisomycin provides a clue to further study on its role in glioma therapy.     

丹参和透明质酸钠注射液对骨性关节炎治疗作用的实验研究

采取家兔膝关节制动方法建立骨性关节炎动物模型，用丹参注射液和透明质酸钠注射液关节腔内注射进行治疗，分别在制动后3、6、9周测量关节活动度，取关节软骨制成标本经光镜和透射电镜观察。结果显示，与单纯制动组比较，丹参治疗组和透明质酸钠治疗组的关节活动度明显改善，关节病变出现晚，程度轻，以早期最明显。表明丹参和透明质酸钠具有延缓和减轻关节退变的作用，对骨性关节炎早期有一定的治疗作用。     

Template-Mediated Synthesis of Hierarchically Porous Metal–Organic Frameworks for Efficient CO2/N2 Separation

Carbon dioxide (CO₂) is generally unavoidable during the production of fuel gases such as hydrogen (H₂) from steam reformation and syngas composed of carbon monoxide (CO) and hydrogen (H₂). Efficient separation of CO₂ from these gases is highly important to improve the energetic utilization efficiency and prevent poisoning during specific applications. Metal–organic frameworks (MOFs), featuring ordered porous frameworks, high surface areas and tunable pore structures, are emerging porous materials utilized as solid adsorbents for efficient CO₂ capture and separation. Furthermore, the construction of hierarchical MOFs with micropores and mesopores could further promote the dynamic separation processes, accelerating the diffusion of gas flow and exposing more adsorptive pore surface. Herein, we report a simple, efficient, one-pot template-mediated strategy to fabricate a hierarchically porous CuBTC (CuBTC-Water, BTC = 1,3,5-benzenetricarboxylate) for CO₂ separation, which demonstrates abundant mesopores and the superb dynamic separation ability of CO₂/N₂. Therefore, CuBTC-Water demonstrated a CO₂ uptake of 180.529 cm³ g⁻¹ at 273 K and 1 bar, and 94.147 cm³ g⁻¹ at 298 K and 1 bar, with selectivity for CO₂/N₂ mixtures as high as 56.547 at 273 K, much higher than microporous CuBTC. This work opens up a novel avenue to facilely fabricate hierarchically porous MOFs through one-pot synthesis for efficient dynamic CO₂ separation.     

EGF-PE4O重组毒素对喉鳞癌细胞株Hep-2的毒性作用

观察EGF－PE40重组毒素对喉鳞癌细胞的毒性作用,为寻找新型的治疗头颈鳞癌的生物制剂奠定基础。应用MTT比色法测定EGF－PE40重组毒素的生物学活性。并在光镜下观察Hep－2细胞形态变化。确定MTT比色法中Hep－2细胞浓度为2×104／well。选择10％SDS－0．01mol／LHCI作为MTT结晶的溶解液,当EGF－PE40重组毒素为0．53ng／ml时,50％的Hep－2细胞死亡,在一定范围内,随重组毒素增加,细胞损伤加重。     

腹腔镜下十二指肠吻合术治疗新生儿十二指肠梗阻

Objective To evaluate the feasibility and indication of laparoscopie duodenoduoden-ostorny for neonates with congenital duodenal obstruction- Methods From May 2004 to Feburary 2008,6 newborns with duodenal obstruction underwent exploratory laparoscopy. With a lower-pressure pneumoperitoneum of 5～8 mmHg and a suspending suture for right liver elevator, the procedure was performed using 3 cannulas of 3.3 mm to 5.5 mm diameter. Under the laparoscopic vision, the cause of duodenal obstruction was diagnosed and a sutured anastomosis was performed after the duodenum mo-bilized. Results Findings at laparoscopy included duodenal diaphragm in 3 cases,annular pancreas in 2 cases, and preduodenal portal vein in 1 case. Three cases with duodenal diaphragmatic stenosis were en-countered a partial excision of the diaphragm after vertical incision of the anterior part of duodenum followed laparoscopically by a transverse suture. A diamond-shaped side-to-side duodenoduodenal anas-tomosis was successfully carried out in 2 cases of annular pancreas through a laparoseopic approach, but a duodenojejunostomy was converted to mini-laparotomy during the laparoscopic course of a predu-odenal portal vein. The average operative time was 102 16.5 min (85～135 min). Visualization was ex-cellent, and there were no intraoperative complications. Feedings were started on postoperative day 3 to 5. All cases were on full feedings after 8 to 10 days. Follow-up upper gastrointestinal tests showed no evidence of stricture or obstruction. Conclusions The duodenoduodenostomy with laparoseopy can be performed in neonates securely and appropriated for a full-term newborn with tolerance CO2 pneumo-peritoneum. It provides an excellent and micro-invasive way to evaluate and treat congenital duodenal obstruction.     

Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell carcinoma

Objective: The mainstay treatment of esophageal squamous cell carcinoma(ESCC) involves chemotherapy and immunotherapy. However, alternative therapies are required for patients who are refractory or intolerant to existing therapies.Methods: In this single-arm, multicenter, open-label phase Ib study, 30 patients received an intravenous infusion of SCT200, an antiepidermal growth factor receptor(EGFR) monoclonal antibody, 6.0 mg/kg once a week for 6 weeks, followed by 8.0 mg/kg once every 2 weeks u...     

Giganteaside D induces ROS-mediated apoptosis in human hepatocellular carcinoma cells through the MAPK pathway

Purpose

Every year, almost one million individuals are diagnosed with hepatocellular carcinoma (HCC) worldwide and more than 690,000 patients die of it. At present, most therapeutic anti-HCC agents are not effective, which is due to the appearance of chemo-resistance and/or toxic side effects. Therefore, it is imperative to find novel more effective anti-HCC agents. Here, we evaluated the effect of giganteaside D (GD), an oleanolic acid saponin from P. scabiosaefolia, on the growth and apoptosis of HCC cells.

Methods and results

Using MTT and clonogenic assays, we found that GD exhibited a significant growth inhibitory effect on the HCC-derived cell lines HepG2 and Bel-7402. In addition, we found that GD induced mitochondria-mediated apoptosis in these HCC-derived cells, as indicated by a decreased mitochondrial potential, activation of Caspase-9 and Caspase-3, cleavage of PARP and release of Cytochrome C from the mitochondria. Besides, we found that GD stimulated the generation of reactive oxygen species (ROS) and that blockage of ROS attenuated the GD-induced mitochondria-mediated apoptosis. Additionally, we found that GD treatment led to a decrease in phosphorylated Erk (p-Erk) and triggered the generation of p-JNK, both components of the mitogen-activated protein kinase (MAPK) signaling pathway. Inhibition of Erk or JNK by specific inhibitors or siRNAs augmented or attenuated the cytotoxic and apoptotic effects of GD.

Conclusions

From our results we conclude that GD can induce ROS-mediated apoptosis in HCC-derived cells through the MAPK pathway. This observation may open up avenues to explore the future use of GD as a HCC chemotherapeutic agent.