Hmgcs2 regulates M2 polarization of macrophages to repair myocardial injury induced by sepsis.

The respiratory and cardiovascular systems are often the most severely impacted by the rapid onset of sepsis, which can lead to multiple organ failure. The mortality has ranged from 10 to 40% when it has evolved into septic shock. This study sought to demonstrate the potential and role of Hmgcs2 in safeguarding against cardiovascular harm in septic mouse models. The cecal ligament and puncture (CLP) model was used to induce sepsis in C57BL/6 mice, with Hmgcs2 expression in the myocardium of the mice being heightened and inflammatory factors being augmented. Subsequently, we utilized ASOs to silence the hmgcs2 gene, and found that silencing accelerated septic myocardial injury and cardiac dysfunction in CLP mice models. In contrast, hmgcs2 attenuated inflammation and apoptosis and protected against septic cardiomyopathy in murine septicemia models. Src production, spurred on by Hmgcs2, triggered the PI3K/Akt pathway and augmented M2 macrophage polarization. Moreover, the inhibition of M2 polarization by an Src antagonist significantly contributed to apoptosis of cardiomyocytes. Our research revealed that Hmgcs2 inhibited the activation of pro-inflammatory macrophages and, through Src-dependent activation of PI3K/Akt pathway, promoted the anti-inflammatory phenotype, thus safeguarding myocardial damage from sepsis. This offers a novel theoretical basis for prevention and treatment of infectious complications.

A bispecific glycopeptide spatiotemporally regulates tumor microenvironment for inhibiting bladder cancer recurrence.

Up to 75% of bladder cancer patients suffer from recurrence due to postoperative tumor implantation. However, clinically used Bacillus Calmette-Guerin (BCG) treatment failed to inhibit the recurrence. Here, we report a bispecific glycopeptide (bsGP) that simultaneously targets CD206 on tumor-associated macrophages (TAMs) and CXCR4 on tumor cells. bsGP repolarizes protumoral M2-like TAMs to antitumor M1-like that mediated cytotoxicity and T cell recruitment. Meanwhile, bsGP is cleaved by the MMP-2 enzyme to form nanostructure for the long-term inhibition of CXCR4 downstream signaling, resulting in reduced tumor metastasis and promoted T cell infiltration. In orthotopic bladder tumor models, bsGP reduced the postoperative recurrence rate to 22%. In parallel, the recurrence rates of 89 and 78% were treated by doxycycline and BCG used in clinic, respectively. Mechanistic studies reveal that bsGP reduces the matrix microenvironment barrier, increasing the spatially redirected CD8+ T cells to tumor cells. We envision that bis-targeting CD206 and CXCR4 may pave the way to inhibit tumor metastasis and recurrence.

Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation.

Radiofrequency ablation (RFA) is an important strategy for treatment of advanced hepatocellular carcinoma (HCC). However, the prognostic indicators of RFA therapy are not known, and there are few strategies for RFA sensitization. The transcription factor sterol regulatory element binding protein 1 (SREBP)-1 regulates fatty-acid synthesis but also promotes the proliferation or metastasis of HCC cells. Here, the clinical importance of SREBP-1 and potential application of knockdown of SREBP-1 expression in RFA of advanced HCC was elucidated. In patients with advanced HCC receiving RFA, a high level of endogenous SREBP-1 expression correlated to poor survival. Inhibition of SREBP-1 activation using a novel small-molecule inhibitor, SI-1, not only inhibited the aerobic glycolysis of HCC cells, it also enhanced the antitumor effects of RFA on xenograft tumors. Overall, our results: (i) revealed the correlation between SREBP-1 and HCC severity; (ii) indicated that inhibition of SREBP-1 activation could be a promising approach for treatment of advanced HCC.

Novel inhibitor of OCT1 enhances the sensitivity of human esophageal squamous cell carcinoma cells to antitumor agents.

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies of the digestive system, and shows an especially high incidence in some regions of China. Octamer transcription factors are a family of transcription factors whose DNA-binding domain is a POU domain. OCT transcription factors (OCT-TFs) mediate maintenance of the pluripotency of embryonic stem cells. We measured expression of OCT-TFs in ESCC clinical specimens. Among the OCTs tested, OCT1 showed the highest expression in ESCC tissues. Using molecular docking, we discovered a small-molecule inhibitor, which we named "novel inhibitor of OCT1" (NIO-1), for OCT1. Treatment with NIO-1 inhibited recruitment of OCT1 to the promoter region of its downstream genes and, consequently, repressed OCT1 activation. Treatment with NIO-1 enhanced the susceptibility of ESCC cells to chemotherapeutic agents. Therefore, OCT1 may be a valuable target for ESCC treatment, and NIO-1 could be a promising therapeutic agent.

[One-step Preparation of Lanthanum-Magnesium Ferrite and Its Phosphate Adsorption Capacity in Aqueous Solutions].

Due to the shortage of phosphate and the eutrophication caused by phosphorus pollution, it is urgent to recover phosphate from wastewater. Given their high adsorption capacity and convenient separation from water to which a magnetic field is applied, ferrite composites have received increasing attention for phosphate recovery. In this study, Spinel La@MgFe2O4 was prepared using a one-step co-precipitation method. La3+ loading on grain boundary defects of MgFe2O4, and phosphorus absorption capacity were examined using X-ray diffraction (XRD), Fourier-transform infrared spectrometry (FTIR), X-ray photoelectron spectroscopy (XPS), and vibrating sample magnetometry (VSM). The structure of La@MgFe2O4 involved La3+ loading on grain boundary defects of MgFe2O4 in the form of La(OH)3. The addition of La changed the crystallinity and morphology of MgFe2O4, which greatly improved the capacity of MgFe2O4 for phosphorus adsorption. Saturation magnetization remained at 14 emu·g-1, which was easily separated from water using an external magnetic field. The maximum adsorption capacity was 143.156 mg·g-1 at pH 6 and 10℃, which was comparable to that achieved at 25℃. Kinetic observations showed that a low phosphorus concentration (10 mg·L-1) could result in extremely low phosphorus adsorption by La@MgFe2O4 after 30 min. The adsorption mechanism shows that phosphorus is removed through ligand exchange and the formation of inner spherical complexes. La@MgFe2O4 has highly selective adsorption with respect to phosphate, and the adsorbent can be reused many times after desorption. Based on addition of 1 g·L-1 of La@MgFe2O4 in the treatment of low temperature municipal wastewater in Northern China, phosphate concentrations could be reduced to less than 0.5 mg·L-1 an hour, offering a promising means of phosphate adsorption even in cold regions.

Effects of LncRNA HCP5/miR-214-3p/MAPK1 Molecular Network on Renal Cell Carcinoma Cells.

BACKGROUND: Recent researches have shown that long non-coding RNA (LncRNA) is often disordered and acts in many carcinomas. Clear cell renal cell carcinoma (ccRCC) is the main reason for carcinoma-related deaths, which are mainly caused by the metastasis. HCP5 is a newly discovered LcnRNA. Early studies have found that HCP5 acts in neoplasm metastasis, but the mechanism of HCP5 in ccRCC is still unclear. METHODS: The expression of HCP5 in human renal cell carcinoma (RCC) was detected by real-time quantitative PCR. The biological effect of LncRNAs in proliferation, migration, invasion and metastasis of RCC cells was explored by gain-of-function and loss-of-function tests. The molecular mechanism of LncRNAs was explored by RNA immunoprecipitation and Western blot. RESULTS: qRT-PCR revealed that HCP5 was enhanced in neoplasm tissues of ccRCC patients and correlated with the metastatic characteristics of RCC. Over-expression of HCP5 promoted the proliferation, migration and invasion of renal carcinoma cells. The deletion of HCP5 inhibited the proliferation, migration and invasion of RCC in vitro and the metastasis of RCC in vivo. Mechanically, HCP5 inhibited the growth and metastasis of ccRCC cells by regulating miR-214-3p/MAPK1 axis. CONCLUSION: HCP5, as a key LncRNA, can promote ccRCC metastasis by regulating miR-214-3p/MAPK1 axis and may be a biomarker and be helpful for judging the prognosis of ccRCC.

[Experiment on Recovery of Phosphorus from Aqueous Solution by Calcium Doped Fe3O4].

Adsorption is an economical and effective method for recovering phosphate from wastewater. In order to improve the adsorption capacity of Fe3O4 for phosphate and for easy separation from water under the action of an external magnetic field, CaO2 was used in this study as an oxidant to partially oxidize Fe2+. A phosphorus recovery adsorbent, Ca doped Fe3O4 (CMIO), was prepared and was characterized by X-ray diffraction (XRD), X-ray fluorescence (XRF) and vibrating sample magnetometer (VSM) techniques. The results showed that CMIO had a Ca2+ doped Fe3O4 crystal structure with a saturation magnetization of 38.82 emu·g-1, which was easily separated from water by using an external magnetic field. The phosphorus adsorption capacity of the CMIO decreased with an increase of pH value. When pH=2 and T=25℃, the maximum adsorption capacity was 24.10 mg·g-1, which is almost five times the adsorption capacity of pure Fe3O4. The phosphorus adsorption of CMIO was in accord with the Langmuir isotherm adsorption model, and the adsorption process followed the pseudo-second order kinetic model. The complexation of phosphate occurred on the inner surface of the CMIO to form a ≡Fe-Ca-P ternary complex, which can adsorb phosphorus. Compared with other anions in the aqueous solution, CMIO had good adsorption selectivity to PO43-, and the adsorbed PO43- could be desorbed by NaOH solution.The quality loss of the CMIO was less than 4% once, and multiple recycling was possible.

Extracorporeal Shock Wave Lithotripsy for Chinese Patients With Pancreatic Stones: A Prospective Study of 214 Cases.

OBJECTIVES: This study aims to evaluate prospectively the safety and efficacy of extracorporeal shock wave lithotripsy (ESWL) in Chinese patients. METHODS: A total of 214 patients with painful chronic pancreatitis and pancreatic stones who underwent ESWL followed by endoscopic retrograde cholangiopancreatography from March 2011 to February 2012 in Changhai Hospital were enrolled. The main pancreatic duct clearance rate and complications were recorded prospectively. Symptoms, weight, quality of life, and pancreatic function were assessed before and after ESWL and endotherapy. RESULTS: A total of 473 ESWL procedures were performed in 214 patients. Stones were fragmented in all cases. Complete clearance of main pancreatic duct stones and successful endoscopic decompression were achieved in 155 (72.4%) and 188 (90.8%) of 214 patients, respectively. Complications were observed after 20 sessions (20 of 473, 4.23%). Follow-up (n = 195) after 18.5 ± 3.3 months showed that complete and partial pain relief were achieved in 71.3% and 24.0% of the patients, respectively. The scores for the quality of life (5.8 ± 1.7 vs 8.1 ± 1.2, P < 0.05) and mental health from the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (62.2 ± 21.5 vs 68.5 ± 16.4, P < 0.05) improved after ESWL. CONCLUSIONS: Thus, ESWL is a safe and effective method to treat Chinese patients with pancreatic stones. This procedure can significantly improve the success rate of endotherapy.

Extracorporeal shock wave lithotripsy is a safe and effective treatment for pancreatic stones coexisting with pancreatic pseudocysts.

BACKGROUND AND AIMS: We aimed to investigate outcomes of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) for the removal of large pancreatic stones coexisting with pancreatic pseudocysts (PPCs) in chronic pancreatitis (CP). METHODS: This is a prospective study performed in CP patients with at least 1 stone (≥5 mm). Patients were divided into the PPC group (stones coexisting with PPCs) or the control group (stones alone). Patients were initially subjected to successive P-ESWL treatments, followed by ERCP. Primary outcomes were P-ESWL adverse events, and secondary outcomes were stone clearance, long-term pain relief, improved quality-of-life scores, and PPC regression. RESULTS: A total of 849 patients (59 in the PPC group and 790 in the control group) was subjected to P-ESWL between March 2011 and October 2013. Occurrences of P-ESWL adverse events were similar between the PPC group and the control group (11.86% vs 12.41%, P = .940). After the treatment of initial P-ESWL combined with ERCP, the complete, partial, and nonclearance of stones occurred in 67.24%, 20.69%, and 12.07%, respectively, of patients in PPC group, with no significant difference from the control group (complete, partial, and nonclearance: 83.17%, 10.40%, and 11.39%, respectively; P = .106). Fifty-five of 59 patients (93.22%) with PPCs were followed for a median period of 21.9 months (range, 12.0-45.1). PPCs disappeared in 56.36% (31/55) and 76.36% (42/55) of patients after 3 months and 1 year of follow-up visits, respectively. Moreover, complete and partial pain relief were achieved in 63.64% (35/55) and 25.45% (14/55) of patients, respectively. The scores for quality of life (P < .001), physical health (P < .001), and weight loss (P < .001) improved. CONCLUSIONS: In our multispecialty tertiary center, initial P-ESWL followed by ERCP was safe in patients with coexisting pancreatic stones and PPCs and effective for stone clearance, main pancreatic duct drainage, and pain relief.

Identification of potential biomarkers for clear cell renal cell carcinoma based on microRNA-mRNA pathway relationships.

BACKGROUND: MicroRNAs (miRNAs) play important roles in tumor genesis. miRNA dysregulation has been widely studied and demonstrated in clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We applied a newly proposed method for selecting miRNAs that discriminate between healthy controls and cancers. We initially extracted different miRNAs and mRNAs and then selected miRNA-mRNA dysregulation pairs. The pathways that involved mRNAs were acquired according to the functional enrichment. We integrated the miRNAs, mRNAs, and pathways and constructed the miRNA-mRNA pathway relationships based on the derived significant miRNAs. RESULTS: We acquired 566 antiregulated miRNA-mRNA pairs including 56 miRNAs and 485 mRNAs. Three significant pathways related to ccRCC, namely, arginine and proline metabolism, aldosterone-regulated sodium reabsorption, and oxidative phosphorylation, were observed. Based on the miRNA-mRNA pathway relationships, five significant miRNAs were identified as potential biomarkers: hsa-miR-425, hsa-miR-136, hsa-miR-335, hsa-miR-340, and hsa-miR-320d. CONCLUSION: This integrative network approach revealed important miRNAs in the ccRCC that can identify specific disease biomarkers, which can be used as targets for cancer treatment.

Risk factors for complications of pancreatic extracorporeal shock wave lithotripsy.

BACKGROUND AND STUDY AIMS: Extracorporeal shock wave lithotripsy is recommended as treatment for stones in chronic pancreatitis. The aim of this study was to investigate the risk factors for complications of pancreatic extracorporeal shock wave lithotripsy (P-ESWL). PATIENTS AND METHODS: Patients with painful chronic pancreatitis and pancreatic stones (> 5 mm diameter) who were treated with P-ESWL between March 2011 and June 2013 were prospectively included. Adverse events after P-ESWL were classified as complications and transient adverse events, depending on severity. The major complications of P-ESWL included post-ESWL pancreatitis, bleeding, infection, steinstrasse, and perforation. Multivariate analyses based on univariate analysis were performed to detect risk factors of overall and moderate-to-severe complications. RESULTS: A total of 634 patients underwent 1470 P-ESWL procedures. The overall complication rate was 6.7 % of all procedures. Complications occurred in 62 patients (9.8 %) after the first ESWL procedure. The risk factors for complications were pancreas divisum (odds ratio [OR] 1.28) and the interval between diagnosis of chronic pancreatitis and P-ESWL (OR 1.28). Protective factors were male sex (OR 0.50), diabetes (OR 0.45), and steatorrhea (OR 0.43). Male sex, the only identified predictor for moderate-to-severe complications, was a protective factor (OR 0.19). For the second P-ESWL procedure, complications occurred in 22/409 patients (5.4 %). Complication and asymptomatic hyperamylasemia after the first ESWL session were significantly associated with higher risk for complications after the second ESWL session (P < 0.05). CONCLUSIONS: Patient-related factors were important in determining a high risk of P-ESWL complications when no procedure-related factors were identified. Patients suffering from complications after the first ESWL session were also likely to experience complications in subsequent P-ESWL sessions.

Tele-ICU: the way forward in geriatric care?

Aging population is set to increase in the near future, and will need specialized care when admitted to ICUs. The elderly are beset with chronic conditions, such as cardiovascular, COPD, diabetes, renal complications and depression. Specialist opinions can now be made available through telemedicine facilities. Tele-ICU is a specialized hub consisting of highly skilled staff trained in critical care able to deliver timely, quality care service to patients admitted to ICUs in remote areas using highly advanced information technology services. These specialists in the tele-ICU hub are able to analyze and gather data arriving at timely interventional management decisions and provide this vital feedback to the nursing staff and doctors manning remote ICU locations where specialized intensivist may not be available. Known clinical benefits of such a system include better patient outcomes, reduced medical errors, mortality and reduced hospital length of stay. The main disadvantage in implementation could be the upfront high cost involved, for which low-cost models are being explored. In the face of delivering such remote care, it is up to the local health policy to make legislative changes to include associated legal and ethical issues. Considering the burgeoning aging population, tele-ICU could become the way forward in delivering geriatric critical care.

Scientific publications in obstetrics and gynecology journals from China, 2000-2009.

OBJECTIVE: To analyze the output of scientific publications in obstetrics and gynecology journals from 3 principal regions of China: mainland China, Taiwan, and Hong Kong. METHODS: Information on article numbers, impact factors, citation reports, and publication in high-impact obstetrics and gynecology journals by Chinese authors between January 1, 2000, and December 31, 2009, was extracted from PubMed and WoS databases. Comparisons of quantity and quality were done by Kruskal-Wallis and rank-sum tests. RESULTS: There were 3044 articles from mainland China (n=1042), Taiwan (n=1304), and Hong Kong (n=698). The cumulative impact factors and citations of articles from Taiwan were highest among the 3 regions. In terms of average impact factor and number of citations per article, Hong Kong exceeded mainland China and Taiwan. Fertility and Sterility, Human Reproduction and Gynecologic Oncology were among the most popular obstetrics and gynecology journals used by authors in the 3 regions. CONCLUSION: The annual number of articles published in obstetrics and gynecology journals from the 3 regions of China increased during the past decade, especially for mainland China. However, the quality of articles from mainland China arouses attention because the average citation of articles from Hong Kong and Taiwan was higher than that of articles from the mainland.

[A study on pathological changes of brain after high +Gx exposure in rhesus monkey].

OBJECTIVE: To study the pathological morphological changes of cerebral cortex and hippocampi in rhesus monkey caused by +Gx exposure, and to explore the relation between +Gx level and pathological changes. METHOD: Healthy rhesus monkeys were randomly divided into one control group and three experimental groups (+15 Gx, +18 Gx, +21 Gx). Monkeys in each group were exposed to the corresponding level of +Gx, after that, the required tissue was qualitatively studied on the basis of pathological morphology. RESULT: 1) Different morphology changes were observed in pyramidal neurons and astrocytes in the cerebral cortex and hippocampi by light microscopy. The higher the +Gx level, the more the changes were observed. In addition, the trauma was more serious in the hippocampi. 2) Chromatin marginating, karyotheca fold, apoptosis body and swollen mitochondria with blurred cristae were observed in pyramidal cell under electron microscope after +Gx exposure, and degenerative changes were also observed in some cases after higher +Gx. CONCLUSION: High level of +Gx causes acute pathological trauma of brain tissues in rhesus monkey, and consanguineous relationship exists between pathological changes and level of +Gx.

The study on automorphism group of ESESOC.

It is necessary to generate the automorphism group of a chemical graph in computer-aided structure elucidation. In this paper, an algorithm was developed by the all-paths topological symmetry algorithm to build the automorphism group of a chemical graph. A comparison of several topological symmetry algorithms reveals that the all-paths algorithm (APA) could yield the correct class of a chemical graph. It lays a foundation for the ESESOC system in computer-aided structure elucidation.