miR-325-3p, a novel regulator of osteoclastogenesis in osteolysis of colorectal cancer through targeting S100A4.

BACKGROUND: To investigate effect of microRNA-325-3p (miR-325-3p) on bone metastasis of colorectal cancer (CRC) and the precise role on osteoclastogenesis. METHODS: CT-26 cells were injected into tibias to establish bone metastatic model of CRC in vivo. AgomiR-325-3p or antagomir-325-3p were injected in tail-veins of Balb/c mice to interfere the osteoclastogenesis and bone metastasis of CRC. Safranin O and Fast Green staining examined the changes of trabecular area and TRAP staining examined the osteoclast number in bone metastasis of CRC. Real-time PCR was conducted to test the RNA level of miR-325-3p and mRNA levels of TRAP and Cathepsin K in osteoclast precursors (OCPs). Dual-luciferase reporter system was utilized to identify the direct target of miR-325-3p. Conditioned medium from CT-26 cells was collected to stimulate the OCPs during osteoclastogenesis induced by RANKL and M-CSF in vitro. Western blot analysis was performed to examine the protein level of S100A4 in OCPs after interfered by agomiR-325-3p or antagomir-325-3p cultured in CM or not. RESULTS: miR-325-3p downregulated in OCPs in CRC microenvironment both in vivo and in vitro. By luciferase activity assay, S100A4 was the target gene of miR-325-3p and the protein level of S100A4 in OCPs upregulated in CRC microenvironment. Overexpression of miR-325-3p inhibited the osteoclastogenesis of OCPs and it can be reversed after transfection with plasmid containing S100A4. Treatment with miR-325-3p can preserve trabecular area in bone metastasis of CRC. CONCLUSION: miR-325-3p can prevent osteoclast formation through targeting S100A4 in OCPs. Overexpression of miR-325-3p efficiently decreased the osteoclast number and attenuated bone resorption in bone metastasis of CRC.

Interferon regulatory factor-1 as a positive regulator for high glucose-induced proliferation of vascular smooth muscle cells.

High glucose-induced proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of diabetic vascular diseases. However, molecular mediators responding for the proliferation of VSMCs remain to be determined. In this study, VSMCs were isolated from the rat thoracic aorta, and two cell models with Irf-1 knockdown and overexpression were established by transfecting cells with pGCsi-FU-Irf-1 and pGC-FU-Irf-1, respectively. Subsequently, high glucose was added to cells to induce proliferation. Proliferation assays were performed to see whether Irf-1 was involved in high glucose-induced proliferation of VSMCs. In addition, the expression of Irf-1 was detected in VSMCs stimulated with high glucose and the thoracic aorta of diabetic rats to confirm the relationship between Irf-1 expression and the proliferation of hyperglycemia-dependent VSMCs. The results showed that Irf-1 expression was significantly higher in the thoracic aorta of diabetic rats and VSMCs stimulated with high glucose than that in nondiabetic rats and untreated cells. Overexpression of Irf-1 accelerated the proliferation of VSMCs, and down-regulation of Irf-1 expression significantly depressed the proliferative ability of VSMCs under high-glucose conditions, indicating that Irf-1 was a positive regulator for high glucose-induced proliferation of VSMCs. It could be presumed that Irf-1 is associated with the accelerated proliferation of VSMCs in diabetic vascular diseases and may prove to be a potential target gene for disease treatment.

An Inducible Nitric Oxide Synthase Dimerization Inhibitor Prevents the Progression of Osteoarthritis.

Objective: Osteoarthritis (OA) is a degenerative joint disease. Excessive nitric oxide (NO) mediates the chondrocyte inflammatory response, apoptosis, and extracellular matrix (ECM) degradation during the occurrence and development of OA. NO in chondrocytes is mainly produced by inducible nitric oxide synthase (iNOS). The aim of this study was to design and synthesize an iNOS dimerization inhibitor and evaluate its effects on chondrocyte inflammation and articular cartilage injury in OA via in vitro and in vivo experiments. Design: The title compound 22o was designed, synthesized, and screened based on a previous study. The effects of different concentrations (5, 10, and 20 µM) of compound 22o on chondrocyte inflammatory response and ECM anabolism or catabolism were evaluated by Western blot and real-time quantitative reverse transcription-polymerase chain reaction using the rat chondrocyte model of IL-1ß-induced OA. Furthermore, different doses (40 and 80 mg/kg) of compound 22o were administered by gavage to a rat OA model induced by anterior cruciate ligament transection (ACLT), and their protective effects on the articular cartilage were evaluated by histopathology and immunohistochemistry. Results: Compound 22o showed effective iNOS inhibitory activity by inhibiting the dimerization of iNOS. It inhibited the IL-1ß-induced expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase 3 (MMP3) in the chondrocytes, decreased NO production, and significantly increased the expression levels of the ECM anabolic markers, aggrecan (ACAN), and collagen type II (COL2A1). Gavage with compound 22o was found to be effective in the rat OA model induced by ACLT, wherein it regulated the anabolism and catabolism and exerted a protective effect on the articular cartilage. Conclusions: Compound 22o inhibited the inflammatory response and catabolism of the chondrocytes and reduced articular cartilage injury in the rat OA model, indicating its potential as a disease-modifying OA drug.

Glycemic Measures and Risk of Mortality in Older Chinese: The Guangzhou Biobank Cohort Study.

CONTEXT: China has the largest number of people with type 2 diabetes mellitus (T2DM) in the world. Data from previous studies have suggested that up to one-fifth of individuals with diabetes would be missed without an oral glucose tolerance test (OGTT). To date, there is little information on the mortality risk of these individuals. OBJECTIVE: We estimated the association of different indicators of hyperglycemia with mortality in the general Chinese population. DESIGN: Prospective cohort study. SETTING: China. PARTICIPANTS: A total of 17 939 participants aged 50+ years. EXPOSURES: Previously diagnosed diabetes and newly detected diabetes defined by fasting glucose (≥7.0 mmol/L), 2-hour postload glucose (≥11.1 mmol/L), or hemoglobin A1c (HbA1c, ≥6.5%). MAIN OUTCOMES MEASURES: Deaths from all-cause, cardiovascular disease, and cancer were identified by record linkage with death registration. RESULTS: During 7.8 (SD, 1.5) years' follow-up, 1439 deaths were recorded. Of 3706 participants with T2DM, 2126 (57%) had known T2DM, 118 (3%) were identified by isolated elevated fasting glucose, 1022 (28%) had isolated elevated postload glucose, and 440 (12%) had both elevated fasting and postload glucose. Compared with normoglycemia, the hazard ratio (95% confidence interval) of all-cause mortality was 1.71 (1.46-2.00), 0.96 (0.47-1.93), 1.43 (1.15-1.78), and 1.82 (1.35-2.45) for the 4 groups, respectively. T2DM defined by elevated HbA1c was not significantly associated with all-cause mortality (hazard ratio, 1.17; 95% confidence interval, 0.81-1.69). CONCLUSION: Individuals with isolated higher 2-h postload glucose had a higher risk of mortality by 43% than those with normoglycemia. Underuse of OGTT leads to substantial underdetection of individuals with a higher mortality risk and lost opportunities for early intervention.

Coumarin glycosides from Hydrangea paniculata slow down the progression of diabetic nephropathy by targeting Nrf2 anti-oxidation and smad2/3-mediated profibrosis.

BACKGROUND: Water extract of Hydrangea paniculata (HP) stem, rich in coumarin glycosides, has been demonstrated to have renal protective effect in several experimental kidney injury animal models. Currently, it is under pre-clinical development as a class 5 herbal drug against membranous nephropathy. However, whether it also benefits diabetic nephropathy (DN) is not clear. PURPOSE: This study was performed to investigate the protective effect of HP on streptozotocin-induced experimental DN, and further understand its molecular mechanisms. METHODS: In the present study, type 1 diabetes rat model was established by the intraperitoneal injection of streptozotocin. HP was orally administered every day for three months. Biochemical analysis and histopathological staining were conducted to evaluate the renal functions. In vivo pharmacokinetic study was conducted to analyse the metabolites of HP with high blood drug concentration. In vitro assay using these metabolites was performed to analyse their ability to reduce reactive oxygen species (ROS) production induced under high glucose (HG) condition by flow cytometry. Reverse transcription-polymerase chain reaction was conducted to analyse the mRNA level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and IL6 and western blot was performed to analyse the phosphorylation status of smad 2/3 in HK2 cells under TGFß1 stimulation. RESULTS: The treatment with HP significantly reduced the blood urea nitrogen and serum creatinine content, and urine albumin excretion in diabetic rats, and increased the creatinine clearance rate. Periodic acid-schiff and methenamine staining and immunohistochemistry revealed that HP also ameliorated glomerulosclerosis and tubular vacuolar degeneration, as well as the deposition of fibronectin and collagen IV in the glomeruli. Pharmacokinetic study results revealed that the major coumarin compounds from HP were metabolised into umbelliferone and esculetin. By in vitro assay, umbelliferone and esculetin were found to significantly decrease ROS production induced by HG content, as well as increase the mRNA level of Nrf2. HP and its metabolites also can down-regulate fibronectin secretion in HK2 cells stimulated by TGFß1 and inhibit smad2/3 phosphorylation. CONCLUSION: HP has beneficial effect on DN by increasing Nrf2 expression and inhibiting TGF-smad signal activation. Further, it can be a novel herbal drug against DN.

Nicousamide attenuates renal dysfunction and glomerular injury in remnant kidneys by inhibiting TGF-ß1 internalisation and renin activity.

Nicousamide has been shown to exert renal protective effects against diabetic nephropathy and has moved to a phase II clinical trial in China for diabetic nephropathy indication. To expand its clinical indications, 5/6-nephrectomised rats were used to mimic glomerular and vascular sclerosis and tubulointerstitial scarring, with subsequent progression towards end-stage renal disease. Adult Wistar rats underwent 5/6 nephrectomy to induce the development of chronic kidney disease, with a sham operation performed as a control. The nephrectomised animals were treated orally with either saline, nicousamide (7.5,15, or 45 mg/kg), benazepril (4 mg/kg), or losartan (10 mg/kg) daily for 20 weeks. At 8, 16, and 20 weeks of treatment, blood pressure was measured in each animal, and blood and urine samples were collected for biochemical analysis, while kidney remnants were collected for histological examination. Levels of fibronectin and transforming growth factor beta 1 (TGF-ß1) were measured in kidneys by immunohistochemistry. Renin activity in the plasma was measured by an enzyme-linked immunosorbent assay. The results showed that nicousamide treatment significantly reduced systemic hypertension, proteinuria, and blood urea nitrogen (P < 0.05), effectively alleviated glomerular sclerosis scores and tubulointerstitial injuries in a dose-dependent manner (P < 0.01), and markedly decreased fibronectin and TGF-ß1 levels in kidney tissues of the 5/6-nephrectomised animals. In vitro studies suggested that nicousamide could moderately inhibit the renin activity and strongly block the TGF-ß1 internalisation into fibroblast cells. In summary, nicousamide may protect from renal failure through dual targeting, which involves a TGF-ß1-dependent mechanism and inhibition of renin activity.

Expression of leptin and its receptor correlates with hypoxia-inducible factor-1α in infants with cyanotic congenital heart disease / 基础医学与临床

Objective To investigate the correlation between serum leptin level and body mass index(BMI)in in-fants with cyanosis congenital heart disease,and the relationship between leptin and Ob gene receptor(Ob-R)and hypoxia-inducible factor 1α(HIF-1α)in myocardium.Methods A total of 52 children under 6 months of age with congenital heart disease who underwent surgical treatment in the Department of Congenital Heart Surgery,Fuwai Hospital from January 2019 to October 2020 were included in this study.According to the arterial partial pressure of oxygen(PaO2)of 90 mmHg,they were divided into cyanotic group(n=30)and acyanotic group(n=22).Their height and weight were collected to calculate BMI.The serum leptin level was measured by ELISA.The ex-pressions of HIF-1α and Ob-R in myocardial tissue were detected by RT-PCR and Western blot.In animal mod-el,SD rats were divided into normoxia group and hypoxia intervention group,which were subjected to continuous hypoxia(10％ O2)for 4 weeks.The hypoxia intervention group received intraperitoneal injection of HIF-1α in-hibitor digoxin(2 mg/kg)daily from the 14 th to 21st day of hypoxia,respectively.The body weight of rats was recorded,and the expressions of HIF-1α and Ob-R were detected by RT-qPCR and Western blot.Results Com-pared with the acyanosis group,the cyanosis group had a significantly lower BMI(P<0.05)and a lower leptin/BMI ratio(leptin/BMI)(P<0.05).Spearman correlation analysis confirmed that serum leptin in the circulatory system was positively correlated with BMI(P<0.05).In the cyanosis group,the expression of Ob-R increased with the upregulation of HIF-1α,showing a positive correlation.In animal model,with the down-regulation of HIF-1α expression in digoxin injection,the Ob-R level was significantly lower than that in the control group(P<0.05),the trend of weight loss was significantly inhibited(P<0.05).The right ventricular hypertrophy in-dex was significantly lower than that in the control group(P<0.05).Conclusions HIF-1α regulates the expres-sion of Ob-R in myocardial tissue,and the mechanism of its association with leptin and Ob-R may help to find new therapeutic target for improving the prognosis of infants with congenital heart disease.

Research progress of IDO1-mediated tryptophan metabolism in sepsis / 药学学报

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

Molecular typing and precise treatment strategies for colorectal cancer: from experience to precision / 中华消化外科杂志

Represented by colorectal cancer, gastrointestinal malignancies have unique clinical characteristics and biological behaviors, ranking high in the incidence and mortality rates in China. In recent years, with technological innovations and continuous optimization of disease management models, the concept of "precision surgery" has been driving the transformation of colorectal cancer surgery from traditional empirical surgical paradigms to modern precision surgical paradigms. Rapid advancements have been made in colorectal surgical treatment, including surgical techniques, instrument platforms, various novel targeted therapies, and immune combination therapies, which have demonstrated significant efficacy in colorectal cancer treatment. Meanwhile, with 30 years of development in laparoscopic colorectal surgery in China, the surgical approach for colorectal cancer has shifted from traditional open-bellied surgery to minimally invasive surgery. The diagnostic and therapeutic models for colorectal cancer patients have gradually transitioned from experience-driven to precision-based and individualized care. Guided by the concept of "precision surgery", this article combines the current status and trends in colorectal cancer surgery to discuss relevant molecular subtyping and precision treatment strategies, aiming to promote precise surgery and comprehensive treatment for colorectal cancer.

The application progress on diagnostic scales of laryngopharyngeal reflux disease / 临床耳鼻咽喉头颈外科杂志

At present, objective methods for diagnosing laryngopharyngeal reflux disease(LPRD) are not minimally invasive, effective, and economical. Diagnostic scales are widely used worldwide due to the advantages of inexpensive, noninvasive, and easy to operate. The reflux symptom index(RSI) and the reflux finding score(RFS) are preferred to use in clinical diagnosis. However, many controversies have appeared in the application of RSI and RFS in recent years, causing many troubles to clinical diagnosis. Therefore, this review briefly discusses the problems of RSI and RFS in clinical applications to provide reference for diagnosing LPRD accurately.

Synthesis of matrine derivative ZS10 and its mechanism of apoptosis induced by PI3K/AKT signaling pathway in human hepatocellular carcinoma cell line BEL-7402 / 中国药理学通报

Aim To explore the signaling pathway of matrine derivative ZS10 in inhibiting proliferation and inducing apoptosis of BEL-7402 cells. Methods ZS10 was synthesized by organic synthesis. The inhibitory effect of ZS10 on the proliferation of BEL-7402 cells was analyzed by MTT method at the time of 24 h, 48 h and 72 h, respectively, and IC50 was calculated. DAPI staining was used to observe the state of BEL-7402 cells. Clone formation method was used to observe the colony formation of BEL-7402 cells, flow cytometry was used to observe the cell cycle arrest and apoptosis of BEL7402 cells, and Western blot was used to detect the expression level of PI3K/AKT pathway and related proteins. Results MTT results showed that the IC50 was(6.62±1.11)μmol·L-1; DAPI staining showed that the cell state changed significantly with the increase of drug concentration, and the results of colony formation showed that ZS10 significantly inhibited the colony formation of BEL-7402 cells. The results of flow cytometry showed that ZS10 induced S phase arrest and cycle apoptosis of BEL-7402 cells. Western blot showed that ZS10 at the concentration of 08 μ mol·L-1 could regulate the PI3K/AKT pathway and its related proteins in a dose-dependent manner. Compared with the control group, the expression of PI3K, AKT, P-AKT and anti-apoptotic protein Bcl-2 significantly decreased, the expression of pro-apoptotic protein Bax significantly increased, the expression of Cyclin D1 and CDK2 significantly decreased, and the expression of EGFR and N-cadherin, Vimentin significantly decreased in the treatment group. The expression of E-cadherin increased. Conclusions Matrine derivative ZS10 can inhibit the growth and proliferation of hepatocellular carcinoma cell line BEL-7402.

Study on the relationship between the age at natural menopause and postmenopausal metabolic syndrome / 中华预防医学杂志

To explore the relationship between the early or delayed age at natural menopause and metabolic syndrome (MS) in women. A total of 4 734 natural menopausal women who completed the baseline survey from November 2017 to January 2020 in the Guangzhou Middle-aged and Elderly Chronic Disease Prospective Cohort Study were selected in this cross-sectional study. Data on general demographic characteristics, disease history and female physiological health indicators were collected. Logistic regression model and restricted cubic spline curve were used to analyze the relationship between the age at natural menopause and MS. The results showed that the mean age of the subjects was (60±6) years old. The median (Q1,Q3) age at natural menopause was 50 (49, 52) years old, and the prevalence of MS was 14.8%(699/4 734). After adjusting for confounders, the age at natural menopause was closely related to MS in an approximate"U"shape. Compared with the group of normal age at natural menopause, the early age at menopause (OR=1.52, 95%CI: 1.12-2.06) and delayed age at menopause (OR=1.77, 95%CI: 1.36-2.30) had a higher risk of MS. In the group with time since menopause ≤6 years and 7-9 years, the risk of MS in the group with delayed age at menopause was 2.40 times (95%CI: 1.54-3.75) and 2.19 times (95%CI: 1.11-4.31) higher than that in the group with normal menopausal age, respectively. In conclusion, the early and delayed age at natural menopause increased the risk of MS. The increased risk of MS in delayed age at natural menopause mainly occurred within 10 years since menopause.

Progress in the relationship between head and neck squamous cell carcinom and the microbial community / 临床耳鼻咽喉头颈外科杂志

Microorganisms are one of the important factors which maintain the homeostasis of human health. Despite recent advances, the relationship between microorganisms and head and neck squamous cell carcinoma （HNSCC） is still unclear, and the impact of microorganisms on the incidence and prognosis of HNSCC cannot be neglected. Therefore, this article provides a systematic and comprehensive review summarizing the epidemiological evidence of microbial dysbiosis related to HNSCC and discusses the associations between them.

Research progress in drugs targeting tumor associated macrophage / 药学学报

Tumor brings great threat to human public health. In recent years, incidence rate and mortality of tumor were rapidly increased in the world. Anti-tumor therapies have undergone the development of cytotoxic therapy, targeted therapy, and immunotherapy. Among them, tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years, although it also brings some related side effects. Tumor microenvironment (TME) is composed of immune cells, vascular vessels, fibroblasts, the extracellular matrix, etc. TME significantly affects the efficacy of immunotherapy. Macrophages in the TME are named as tumor associated macrophages (TAMs). Recently, increasing studies have shown that TAMs play an important role in the regulation of tumor immunity, especially in tumor immune surveillance and immune escape. Currently, more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage. Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy, we first reviewed the subtypes and functions of TAMs, as well as the roles of TAMs in tumors. Furthermore, we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs. The current review will provide new ideas and novel insights for tumor immunotherapy.

High-value utilization technology and approach of Chinese medicinal residues under background of "Dual Carbon" / 中国中药杂志

In recent years, the traditional Chinese medicine(TCM)industry has experienced rapid development, resulting in a significant amount of Chinese medicinal residues generated during the industrial manufacturing process. Currently, the main methods of handling Chinese medicinal residues include stacking, landfilling, and incineration, which lead to substantial resource waste and potential environmental pollution. With "carbon peak" and "carbon neutrality"( "Dual Carbon")becoming national strategic goals, the TCM industry is ushering in a new wave of "low-carbon" trends, and the high-value utilization of Chinese medicinal residues has become a breakthrough for implementing a low-carbon economy in the TCM sector. From the perspective of a low-carbon economy, this article reviewed literature in China and abroad to summarize the microbial transformation technology, enzymatic conversion technology, biomass pyrolysis, gasification, hydrothermal liquefaction, and other high-value utilization technologies for Chinese medicinal residues. It also overviewed the applications of Chinese medicinal residue in feed additives, organic fertilizers, edible mushroom cultivation substrates, preparation of activated carbon for wastewater treatment, and new energy batteries. Considering the current status of resource utilization of Chinese medicinal residues, feasible strategies and suggestions for resource development and utilization were proposed to improve the quality and efficiency of the Chinese medicinal resource industry chain and promote green development, thereby providing research ideas and theoretical basis for achieving carbon peak and carbon neutrality goals.

Progress on targets and therapeutic drugs for pancreatic cancer / 药学学报

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

Embolic stroke of undetermined source: potential etiology and secondary prevention / 国际脑血管病杂志

The secondary prevention of embolic stroke of undetermined source (ESUS) is still mainly antiplatelet therapy, but the recurrence rate of stroke in this patient population is still very high. This article reviews the potential etiology of ESUS, its potential embolic mechanisms, and secondary prevention of ESUS.

Total Coumarins from Hydrangea paniculata Protect against Cisplatin-Induced Acute Kidney Damage in Mice by Suppressing Renal Inflammation and Apoptosis.

Aim. Hydrangea paniculata (HP) Sieb. is a medical herb which is widely distributed in southern China, and current study is to evaluate renal protective effect of aqueous extract of HP by cisplatin-induced acute kidney injury (AKI) in animal model and its underlying mechanisms. Materials and Methods. HP extract was prepared and the major ingredients were coumarin glycosides. AKI mouse models were established by single i.p. injection of 20 mg/kg cisplatin, and HP was orally administrated for total five times. The renal biochemical functions, pathological staining, kidney oxidative stress, and inflammatory status were measured. Apoptosis of tubular cells and infiltration of macrophages and neutrophils were also tested. Results. HP administration could improve the renal function by decreasing concentration of blood urea nitrogen (BUN) and creatinine and attenuates renal oxidative stress and tubular pathological injury and apoptosis; further research demonstrated that HP could inhibit the overproduction of proinflammatory cytokines and regulate caspase and BCL-2 family proteins. HP also reduced renal infiltration of macrophages and neutrophils, and its effect might be by downregulating phosphorylation of ERK1/2 and stat3 signaling pathway. Conclusions. This present study suggests that HP could ameliorate cisplatin induced kidney damage by antioxidation and suppressing renal inflammation and tubular cell apoptosis.

Cost-utility analysis of pertuzumab combined with trastuzumab and docetaxel in first-line treatment of HER 2- positive metastatic breast cancer / 中国药房

OBJECTIVE To study the metabolites of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats and to investigate its metabolic regularity. METHODS In vitro incubation system of liver microsomes of rats was built. The jolkinolide A，jolkinolide B ，17-hydroxyl jolkinolide A and 17-hydroxyl jolkinolide B were added into incubation system of liver microsomes in rats activated by reduced nicotinamide adenine dinucleotide phosphate ，incubated at 37 ℃ for 30 min，and then terminated the reaction with acetonitrile. Taking the negative group （adding acetonitrile firstly and then starting incubation for 30 min）as the reference，the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used ；Anaylyst®TF 1.7.1、PeakView® 2.2，MetabolitePilot 1.5 and MasterView 1.2 software were used to speculate and identify the fragmentation law of mass spectrometry and metabolites. RESULTS Four diterpenoids were easy to lose neutral fragments such as H 2O and CO in secondary mass spectrometry. Jolkinolide A and 17-hydroxyl jolkinolide A showed similar metabolism pathway ，including dihydroxylation，dehydrogenation，and monohydroxylation ；six and five metabolites were identified respectively. Jolkinolide B and 17-hydroxyl jolkinolide B showed similar metabolism pathway ，including monohydroxylation ，hydration and isomerization. Five metabolites were identified. CONCLUSIONS Both jolkinolide A and 17-hydroxyl jolkinolide A produce the metabolites of hydroxylation and dehydrogenation in liver microsomes of rats ；both jolkinolide B and 17-hydroxyl jolkinolide B produce the metabolites of hydroxylation ，hydration and isomerization in liver microsomes of rats. The metabolites of four diterpenoids are phase Ⅰ metabolites.

Mid- and long-term results of different techniques for subaortic stenosis / 中国胸心血管外科临床杂志

@#Objective    To evaluate the mid- and long-term outcomes of different surgical techniques for subaortic stenosis. Methods    The clinical data of 75 patients with subaortic stenosis who underwent surgery in our hospital from January 2008 to January 2018 were retrospectively analyzed, including 48 males and 27 females, with a median age of 72 (48, 132) months and mean weight of 21.35±15.82 kg. There were 40 (53.3%) patients combined with aortic regurgitation; 38 (50.7%) patients were the first time and 37 patients were the second time to receive the operation. According to the surgical techniques, 75 patients were divided into two groups: a group A (40 patients with simple subaortic membrane resection) and a group B (35 patients with subaortic membrane and muscle resection or modified Konno procedure). Results    Two (2.67%) patients died in hospital. There was one late death in the group B. The average preoperative and postoperative pressure gradient of all patients was 69.96±42.02 mm Hg and 7.44±12.45 mm Hg, respectively. All patients were followed up for 51 (12, 120) months. Pressure gradient at follow-up in the group A and the group B was 8.83±14.52 mm Hg and 5.86±9.53 mm Hg, respectively with no statistical difference (P=0.294). Four patients in the group A and 2 patients in the group B needed reintervention. However, there was no statistical difference in the long-term reintervention rate between the two groups (P=0.480). Conclusion    For the different degree of lesions in the left ventricular outflow tract, our management strategy is feasible. Although there is no statistical difference between two the groups in the long-term reintervention rate after simple valvular membrane resection, prolonged follow-up is necessary to examine the long-term outcomes of different surgical techniques.