[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience].

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Exosome-based liquid biopsies in cancer: opportunities and challenges.

Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize liquid biopsies in cancer for early detection and treatment stratification, as well as residual disease and recurrence monitoring. Although most efforts have used circulating tumor cells and circulating tumor DNA for this purpose, exosomes and other extracellular vesicles have emerged as a platform with potentially broader and complementary applications. Exosomes/extracellular vesicles are small vesicles released by cells, including cancer cells, into the surrounding biofluids. These exosomes contain tumor-derived materials such as DNA, RNA, protein, lipid, sugar structures, and metabolites. In addition, exosomes carry molecules on their surface that provides clues regarding their origin, making it possible to sort vesicle types and enrich signatures from tissue-specific origins. Exosomes are part of the intercellular communication system and cancer cells frequently use them as biological messengers to benefit their growth. Since exosomes are part of the disease process, they have become of tremendous interest in biomarker research. Exosomes are remarkably stable in biofluids, such as plasma and urine, and can be isolated for clinical evaluation even in the early stages of the disease. Exosome-based biomarkers have quickly become adopted in the clinical arena and the first exosome RNA-based prostate cancer test has already helped >50 000 patients in their decision process and is now included in the National Comprehensive Cancer Network guidelines for early prostate cancer detection. This review will discuss the advantages and challenges of exosome-based liquid biopsies for tumor biomarkers and clinical implementation in the context of circulating tumor DNA and circulating tumor cells.

Significant relationship between parameters measured by transrectal color Doppler ultrasound and sexual dysfunction in patients with BPH 12 months after TURP.

BACKGROUND: A link between sexual dysfunction and lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) has been noticed. Transurethral resection of the prostate (TURP) remains the standard treatment for symptomatic BPH, whether TURP causes sexual dysfunction is still uncertain. In this retrospective study, we investigated the relationship between parameters measured by color Doppler ultrasound (CDU) and sexual dysfunction in patients with BPH 12 months after TURP. METHODS: The parameters include presumed circle area ratio (PCAR), maximal horizontal area of seminal vesicles (MHA), resistive index of the prostate (RIP), and peak systolic velocity in the flaccid penis (PSV). The international prostate symptom score was used to evaluate the lower urinary tract symptoms and the five-item version of the International Index of Erectile Function was used to evaluate sexual function before and after TURP. RESULTS: Of the 103 patients without sexual dysfunction before TURP, 11 (10.7%) had erectile dysfunction (ED) after TURP. These 11 patients had significantly lower PCAR, RIP, PSV and MHA than those without ED. The patients with retrograde ejaculation after TURP had significantly lower PCAR than those without retrograde ejaculation, and the patients with premature ejaculation after TURP had significantly lower MHA than those without premature ejaculation. Comparing the parameters between baseline and after TURP, PCAR, RIP, and MHA decreased significantly in the patients with sexual dysfunction, but no significant differences were noted in the patients without sexual dysfunction after TURP. CONCLUSIONS: More extended TURP can lead to a higher incidence of ED and retrograde ejaculation in BPH patients without sexual dysfunction before TURP. Patients with a lower volume of seminal vesicles after TURP may have a higher incidence of premature ejaculation.

[Research progress on effect of AP2/ERF transcription factors in regulating secondary metabolite biosynthesis].

AP2/ERF transcription factor is a kind of transcription factors widely existing in plants, and contains at least a conserved AP2/ERF domain composed of about 60-70 amino acids. AP2/ERF transcription factors are widely involved in a variety of physiological processes in plants, including plant development, fruit ripening, flower development and other plant development processes, as well as such stress response processes as damage, pathogen defense, high-salt condition and drought. In recent years, secondary metabolic engineering that takes transcription factors as genetic manipulation targets has developed rapidly in improving the content of active ingredients and the quality of medicinal plants. This paper reviews the recent progress in the regulation of secondary metabolites biosynthesis with AP2/ERF transcription factors, and provides theoretical basis for the exploration of efficient regulatory targets, the regulation of secondary metabolites in medicinal plants, the targeted improvement of the content of active ingredients in traditional Chinese medicine, and the sustainable supply of high-quality traditional Chinese medicines.

[Molecular mechanism of Puerariae Lobatae Radix in treatment of hepatocellular carcinoma based on network pharmacology].

To investigate the potential mechanism of Puerariae Lobatae Radix in the treatment of hepatocellular carcinoma by network pharmacology and in vitro cell experiment. The main active components of Puerariae Lobatae Radix and their predicted targets were obtained from TCMSP, and the disease targets were obtained from GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets. The "compound-target-disease" network diagram was constructed in Cytoscape 3.7.1, and the common targets were input into the STRING database to build the PPI network of proteins interaction. GO function and KEGG pathway enrichment analysis on effective targets were performed by using R software. Autodock vina 1.1.2 was used for molecular docking. Finally, the core targets and pathways were preliminarily verified by in vitro experiments. The proliferation of human hepatocellular carcinoma cells was detected by CCK-8 and EDU enzyme staining, and the expressions of PTEN, PDK1, Akt and GSK3 were detected by Western blot. In this study, 10 components of Puerariae Lobatae Radix(9 components involved in hepatocellular carcinoma-related targets and signaling pathways), and 149 hepatocellular carcinoma-related targets and 156 signaling pathways were screened out. The results of network analysis indicated that Puerariae Lobatae Radix may play an anti-hepatocellular carcinoma effect on key targets, such as Akt, IL6, MAPK3, EGFR, and key pathways, such as PI3 K-Akt. The results of molecular docking indicated that puerarin, genistein and daidzein had a good binding ability with the key targets such as AKT1, MAPK3, MAPK1 and CASP3, and puerarin had the lowest Vina score with AKT1 and MAPK3 and also similar to them. In vitro cell experiments confirmed that puerarin has a significantly inhibitory effect on the proliferation of human hepatocellular carcinoma cells. Western blot results showed that puerarin could increase the phosphorylation of PTEN in human hepatocellular carcinoma cells through the PTEN/Akt/GSK3ß signaling pathway, and the phosphorylation level of its downstream Akt decreased. This series of studies confirm that puerarin can treat hepatocellular carcinoma by blocking PTEN/Akt/GSK3ß cellular signaling pathway, so as to provide ideas for subsequent studies for the molecular mechanism of puerarin in the treatment of liver cancer.

[Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in treatment of rheumatoid arthritis].

Tripterygium wilfordii Hook.f.(TwHF) is one of the most effective traditional Chinese herbal medicines against rheumatoid arthritis. As the representative agents of TwHF, Tripterygium Glycoside Tablets(TGT) and Tripterygium wilfordii Tablets(TWT) were included as Class A drugs in the 2019 edition of Medicine Catalogue for National Basic Medical Insurance, Injury Insurance and Maternity Insurance, and TGT was also included in 2018 edition of National Essential Drug List and 2015 edition of Chinese Pharmacopoeia. However, it is difficult to grasp the specific clinical applications of TGT and TWT. Side effects occur from time to time. The curative effect is uneven in patients. And the package inserts of TGT and TWT are not described in details. In order to standardize the clinical application of Tripterygium wilfordii preparations, 38 authoritative units and 48 well-known experts in rheumatoid immunology clinical department, drug supervision and management, pharmacy and evidence-based medicine research fields jointly developed Tripterygium Glycoside Tablets and Tripterygium wilfordii Tablets Medication Guide for reference in clinical application, teaching and scientific research. The guideline followed the "evidence-based, consensus-assisted and experience-based" principles to form "recommendations" for the evidence supported ones, and form "consensus suggestions" for those without evidence support by using nominal group method. In this way, the medication recommendations on function, usage and dosage, drug combinations, precautions, efficacy, safety and other aspects of TGT and TWT can be provided. The application of this Guide will help to avoid or reduce the adverse reactions of T. wilfordii preparations, enhance the efficacy and reduce the cost of medicine, with certain demonstration and promotion values to improve the rational use level of traditional Chinese medicine.

[Editorial explanation for Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in treatment of rheumatoid arthritis].

Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the treatment of rheumatoid arthritis(T/CACM 1337-2020) was approved on June, 2020 by the Standardization Office of Chinese Association of Chinese Medicine. Our group developed this guideline for the clinical application of Tripterygium Glycosides/Tripterygium wilfordii Tablets according to the manual for the clinical experts consensus of Chinese patent medicine from January, 2018, when this project was approved by Chinese Association of Chinese Medicine. In this article, the detailed information on our compilation process was provided, in order to facilitate the understanding and the application of the guideline, as well as provide reference for the development of clinical practice guideline for other Chinese patent medicine.

[A clinical analysis of 14 cases of prostatic stromal tumor of uncertain malignant potential].

OBJECTIVE: To investigate the clinical and pathologic characteristics, diagnosis, treatment, prognosis and survival of prostatic stromal tumor of uncertain malignant potential. METHODS: Overall 14 patients with prostatic stromal tumor of uncertain malignant potential were treated from October 2008 to April 2020, the patient age ranged from 27 to 78 years (mean 54 years). The disease duration was 1 to 180 months (mean duration of 46 months). The clinical manifestations mainly included urinary obstructive symptoms and urethral irritating symptoms. The tumors were located in the peripheral zone or the transition zone. Digital rectum examination indicated prostatic tumor. Serum prostatic specific antigen level was always normal or elevated. Transrectal ultrasonography and magnetic resonance imaging indicated prostatic tumor. Magnetic resonance imaging in showed large, round, well-defined masses, which were diffusely heterogeneous signal on T2 weighted imaging. Following the administration of intravenous contrast medium, the lesion had diffuse and heterogeneous enhancement. RESULTS: In the study, 3 cases underwent prostate biopsy, 2 cases underwent transurethral resection of the prostate, 9 cases underwent radical excision or transurethral resection of the prostate with definite diagnosis of pathologic features. Under the light microscope, the interstitial cells of stromal tumor of uncertain malignant potential were overgrowth and fusiform cells showed some degree of pleomorphism, nuclei with few mitotic figures, and necrosis was not often seen. Immunohistochemical staining showed that prostate specific antigen was negative, while vimentin was positive in the tumor tissue, CD34, progesterone receptor and smooth muscle actin were positive in the majority, and Ki67 positive index was 1%-20% (mean 6%). Twelve cases were followed-up, and the time of survival varied from 10 to 96 months (mean 65 months), two cases were lost to the follow-up, one case died of disease at the end of 10 months, nine cases were free of disease recurrence after surgery, two cases underwent more transurethral resection of the prostate due to local recurrence. CONCLUSION: STUMP is a very rare tumor of the specialized prostatic stroma with an unpredictable clinical behavior. The clinical manifestations, transrectal ultrasonography and magnetic resonance imaging are valuable for the diagnosis of prostatic stromal tumor of uncertain malignant potential. Its definite diagnosis depends on pathological examination. Up to now, early surgery and combined therapy are effective treatments for prostatic stromal tumor of uncertain malignant potential.

Efficacy of supplemented Er-xian decoction combined with acupoint application for poor ovarian response.

This study aims to observe the efficacy of supplemented Er-xian decoction combined with acupoint application in treating poor ovarian response (POR). This study was a randomized controlled trial. A total of 80 patients, who were treated in the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from January 2016 to December 2017, were divided into two groups by tables of random numbers: experimental group (n = 40), and control group (n = 40). In the experimental group, patients orally received supplemented Er-xian decoction with acupoint application. In the control group, a Kuntai capsule was administered according to the course of treatment. The therapeutic effects in the two groups were observed and compared. In the experimental group, the total effective rate was 90%, the cure rate was 15% (six patients), the markedly effective rate was 35% (14 patients), the effective rate was 40% (16 patients), and the ineffective rate was 10% (four patients). In the control group, the total effective rate was 50%, the cure rate was 5% (two patients), the markedly effective rate was 15% (six patients), the effective rate was 30% (12 patients), and the ineffective rate was 50% (20 patients). The differences were statistically significant (P > 0.05). Definite efficacy was observed when a poor ovarian response was treated by supplemented Er-xian decoction combined with acupoint application. Improvements in perimenopausal symptoms, menstruation conditions, hormone levels, inhibin B (INHB), and antral follicle count (AFC) were markedly better in the experimental group than in the control group. In addition, the treatment was safe and had few side effects.

Is a 'healthy diet' and a 'calcium-rich diet' the same thing? Qualitative study examining perceptions of a calcium-rich diet in individuals who have received bone health education.

BACKGROUND: In the present study, we aimed to (i) examine perceptions of achieving calcium and vitamin D recommended dietary allowance (RDA) and (ii) determine how participants talked about food in relation to RDA recommendations. METHODS: Participants aged ≥50 years who were prescribed osteoporosis medication and received two modes of bone health education were eligible. Relying on a qualitative description design, we interviewed participants 1 month after they had attended an education session and received a self-management booklet. Calcium and vitamin D intakes were estimated by in-depth questions about diet and supplements and compared with perceptions of achieved RDA levels. Interview transcripts were analysed based on an analytic hierarchical process. RESULTS: Forty-five participants (29 reporting previous fragility fractures) were included. Calcium and vitamin D RDA appeared to be potentially achieved by 64% and 93% of participants, respectively, primarily because of reliance on supplements. Few participants talked about vitamin D in relation to food intake and 49% of participants were unclear about the calcium content of food. Most considered that a healthy diet was equivalent to a calcium-rich diet. We noted no differences in our findings in the subset of individuals with fragility fractures. CONCLUSIONS: Despite reporting a prescription for osteoporosis medication and receiving bone health education, a substantial number of individuals appeared to have sub-optimal calcium levels. This may be attributed to the challenge of achieving RDA with diet alone and the misconception of a healthy diet as a calcium-rich diet.

Field study on the uptake, accumulation and risk assessment of perchlorate in a soil-chard/spinach system: Impact of agronomic practices and fertilization.

The application of excessive fertilizer represents a primary source of entry for perchlorate into crop systems and thus has raised widespread concern regarding food safety. Several studies have reported the occurrence of perchlorate in vegetables. However, limited information is available on the fate of perchlorate in the soil-plant system. In this study, we performed field experiments to evaluate the effects of the application rate of Chilean nitrate fertilizer and the type of fertilization (manual or fertigation) on the uptake of perchlorate by plants grown in open fields. Interestingly, in the control, chard and spinach accumulated 21.3 and 25.9 µg kg-1, respectively. For both agronomic practices, the content of perchlorate in chard and spinach increased as the fertilizer application rate increased, with fertigation promoting more significant accumulations. Spinach accumulated almost two times more perchlorate than chard for all treatments; however, the concentrations generally remained below regulatory values. The intake of spinach and chard presented a low risk to human health for all age groups. These findings enhance our understanding of the environmental impact of the use of fertilizers in agriculture and food safety.

[Influencing factors for reproductive health of female workers in petrochemical industry].

Objective: To investigate the reproductive health status of female workers in petrochemical industry, and to provide a reference for improving reproductive health status and developing preventive and control measures for female workers in petrochemical industry. Methods: A face-to-face questionnaire survey was performed from January to October, 2016. The Questionnaire on Women's Reproductive Health was used to investigate the reproductive health of female workers in petrochemical industry. The multivariate logistic regression model was used to identify the influencing factors for reproductive health of female workers in petrochemical industry. Results: Among the 7485 female workers, 1 268 (40.9%) had abnormal menstrual period, 1 437 (46.4%) had abnormal menstrual volume, 177 (28.5%) had hyperplasia of mammary glands, and 1 807 (24.6%) had gynecological inflammation. The reproductive system diseases in female workers in petrochemical industry were associated with the factors including age, marital status, education level, unhealthy living habits, abortion, overtime work, work shift, workload, video operation, occupational exposure, positive events, and negative events, and among these factors, negative events (odds ratio[OR]= 1.856) , unhealthy living habits (OR=1.542) , and positive events (OR=1.516) had greater impact on reproductive system diseases. Conclusion: Many chemical substances in the occupational environment of petrochemical industry can cause damage to the reproductive system, which not only affects the health of the female workers, but also poses potential threats to the health of their offspring. Occupational exposure, unhealthy living habits, overtime work, and work shift have great influence on reproductive system diseases in female workers.

[Prevalence and risk factors of diabetic retinopathy in hospital patients].

Objective: To analyze the prevalence and risk factors of diabetic retinopathy (DR) in ophthalmic patients. Methods: A cross-sectional study was performed. Diabetic patients who were admitted to Department of Ophthalmology, Traditional Chinese Medicine Hospital of Muping between October 2012 and June 2013 were included. General information and medical history were obtained from each subject by questionaires. Laboratory and detailed ophthalmic examinations were performed during the study. DR was diagnosed and graded by mydriatic fundus photography. Prevalence of DR was calculated and logistic regression was used to analyze the relationship between DR and various factors. Results: A total of 676 diabetic patients were included, and 455 of them presented with DR at a morbidity rate of 67.31%. Among DR patients, the number of mild, moderate, severe non-proliferative diabetic retinopathy (NPDR) patients and proliferative diabetic retinopathy (PDR) patients were 211 (46.37%), 167 (36.70%), 57 (12.53%) and 20 (4.40%), respectively. There was no significant difference in the prevalence of DR among different age groups (χ(2)=6.527, P=0.089). However, there was a significant difference between different disease duration groups (χ(2)=39.401, P<0.001), as well as between insulin therapy group and non-insulin therapy group (χ(2)=7.378, P=0.007). The multivariate logistic regression analysis demonstrated the independent risk factors for DR occurrence were hemoglobin A1c (HbA1c) (OR=1.131, 95%CI: 1.022-1.252, P=0.011) and duration of diabetes (OR=1.077, 95%CI: 1.046-1.108, P<0.001). Conclusions: The prevalence of DR in ophthalmic patients was associated with duration of diabetes, HbA1c, obesity, smoke, nephropaty and insulin therapy. Increased HbA1c level and longer duration of diabetes were independent risk factors for DR in diabetic patients.

Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China.

BACKGROUND: The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence. METHODS: A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count. RESULTS: A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05). CONCLUSION: Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.

Danshen (Salvia miltiorrhiza) protects ovariectomized rats fed with high-saturated fat-sucrose diet from bone loss.

Dietary patterns may interfere with the efficacy of herbal intervention. Our results demonstrated the protective effects of Salvia miltiorrhiza aqueous extract (SMA) on bone metabolism were influenced by levels of dietary fat and sucrose in ovariectomized (OVX) rats through its actions on attenuating lipid deposition and oxidative stress in rats. INTRODUCTION: Salvia miltiorrhiza (SM), also known as Danshen, has been tested as an osteoporosis treatment in a series of small, short human trials that generally report improvements in bone property. However, dietary patterns may interfere with the effects of herbal intervention. We hypothesized that dietary fat and sucrose levels could influence the effects of SM supplementation on bone in estrogen-deficient animals. METHODS: Six-month-old Sprague-Dawley sham or OVX rats were fed either a low-saturated fat-sucrose (LFS, a diet that was similar in composition to normal rat chow) or a high-fat-sucrose (HFS) diet and OVX rats were treated (8 rats/group) with SM aqueous extract (SMA, 600 mg/kg/day), 17ß-estradiol (1 mg/kg/day), or vehicle for 12 weeks. RESULTS: SMA significantly improved bone properties as revealed by the increase in trabecular bone mineral density and decrease in trabecular separation at proximal metaphysis of the tibia (PT) in HFS-fed OVX rats, but not in LFS-fed OVX rats. SMA greatly reduced lipid deposition and malondialdehyde levels, improved the activities of superoxide dismutase, catalase, and glutathione peroxidase in the livers of HFS-fed OVX rats. SMA could directly improve the proliferation and differentiation in vitro in an H2O2-induced preosteoblast cell model by attenuating cellular reactive oxygen species levels. CONCLUSIONS: The protective effects of SMA on bone metabolism were influenced by dietary fat and sucrose levels in OVX rats. The ability of SMA to reduce bone loss in HFS-fed OVX rats was associated with the attenuation of lipid deposition and oxidative stress levels.

Improvement in erectile function in a rat model of high cholesterol diet-induced atherosclerosis by atorvastatin in a manner that is independent of its lipid-lowering property.

The purpose of the present study is to explore the effects of a lipid-lowering drug atorvastatin, a three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in the treatment of erectile dysfunction (ED) in a rat model of atherosclerosis (AS) and the possible mechanisms underneath. A high-cholesterol diet was administrated to Sprague-Dawley rats in an attempt to induce an ASED model, which was later confirmed by abdominal aorta histopathology and erectile function evaluation. ASED rats were further assigned to non-treatment group, atorvastatin low-dose treatment group (5 mg kg-1  day-1 ), high-dose group (10 mg kg-1  day-1 ) and sildenafil (1.5 mg kg-1  day-1 ) treatment group. Lipid profile, erectile function, oxidative stress biochemical markers, endothelial nitric oxide synthase (eNOS) and extracellular superoxide dismutase (SODEX ) mRNA expression were evaluated after 8-week treatment duration. Erectile function was impaired in AS rat model, which was preserved in atorvastatin and sildenafil intervention groups. The oxidative stress biochemical markers were attenuated, while eNOS and SODEX mRNA expression were restored in atorvastatin and sildenafil groups, which were found to be involved in ED pathogenesis. However, the lipid profile remained unaltered in the treatment group, and it was elevated in ASED rats. This kind of lipid-lowering agent, or atorvastatin, has the utilisation potential in ASED treatment, even before lipid profiles altered. This effect on erectile function preservation of atorvastatin was attributed to its preservation of endothelial function, possibly through amelioration of oxidative stress and improvement in eNOS expression.

Supplementation with nutrients modulating insulin-like growth factor-1 negatively correlated with changes in the levels of pro-inflammatory cytokines in community-dwelling elderly people at risk of undernutrition.

BACKGROUND: Suboptimal nutrition accompanied by chronic low-grade increases in circulating cytokine levels is more common in elderly people. We explored the improvement in nutritional status, especially in the level of insulin-like growth factor-1 (IGF-1) and its relationship with changes in circulating cytokine levels, after providing extra protein and energy content to community-dwelling older adults at risk of undernutrition. METHODS: Sixty nondiabetic subjects, aged ≥65 years and living independently in a community for elderly people, with a serum pre-albumin level ≤30 mg dL-1 and a body mass index <25 kg m-2 , were recruited. The subjects were followed for a 2-week pre-intervention period, during which they maintained routine dietary habits. This was followed by an intervention period, during which they received oral nutritional supplementation for 2 weeks. RESULTS: Following 2 weeks of intervention, there were significant increases in total lymphocyte count (TLC) and insulin-like growth factor (IGF)-1, pre-albumin and transferrin compared to baseline. Body weight and mid-arm circumference significantly increased without alteration of tricep skinfold thickness at the end of the intervention. There was a significant reduction in interleukin (IL)-6 levels and a trend toward a decrease in the tumor necrosis factor (TNF)-α levels. At baseline, age was negatively correlated with IGF-1 levels and positively correlated with IL-6 and TNF-α levels. The change (▵, from baseline) in IGF-1 level was positively correlated with age and negatively correlated with ▵IL-6 and ▵TNF-α. CONCLUSIONS: A 2-week intervention with oral nutritional supplementation improved nutritional status and decreased circulating cytokine levels. Specifically, ▵IGF-1 was negatively correlated with changes in pro-inflammatory cytokine levels in community-dwelling elderly people at risk of undernutrition. (Clinicaltrials.gov: NCT02656186).

[Diagnosis and treatment of T1a-T1b prostate cancer].

OBJECTIVE: To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of incidental (stage T1a-T1b) prostate cancer. METHODS: Seven hundred and seventy-one patients who underwent TURP from May 2004 to September 2013 were analyzed retrospectively. In our institution, TURP specimens should be totally submitted in an extensive sampling method. The tumor area was outlined by estimation of an experienced genitourinary pathologist and calculated by the image analysis system software (Image J 1.47 h). The tumor area was then multiplied by the thickness of tissue. The total sum of all tumor volume was the estimated tumor volume. The clinical and pathological factors, follow-up results were obtained and we aimed to collect information about the period of watchful waiting (WW), PSA progression status, intervention status during the follow-up, the reason for intervention on WW and the type of intervention. RESULTS: The average age of 771 patients was (71.3±5.9) years old, and the average BMI was (23.9±3.1) kg/m2, preoperative average tPSA was (4.4±2.8) µg/L. Eighty-six (11.2%) cases of incidental prostate cancer were detected. The patients in T1a group (77 cases, 89.5%) had tumor volumes of (12.3±12.6) mm3, and the patients in T1b group had tumor volumes of (105.1±41.8) mm3.The range of tumor volume was 0.4-180.2 mm3. The volume of all the 86 cases was less than 500 mm3 as the threshold of insignificant cancer. All the patients were managed by WW. The mean follow-up time was 88.9 (27.9-150.1) months.The Gleason score was <7 in 79 patients, and ≥7 in 7 patients. There was no significant difference in age, preoperative tPSA, preoperative PSAD, postoperative tPSA, prostate volume and TURP resection between T1a group and T1b group (P>0.05). Among 84 patients without follow-up losts, PSA progression occurred in 5 patients. One T1a patient underwent radical prostatectomy (RP) as an intervention, and 3 patients underwent hormone therapy. One patient in T1b group underwent radiotherapy for PSA progression and one was treated because of patient preference without evidence of disease progression. There were no patients who died due to prostate cancer. CONCLUSION: Eighty-six (11.2%) cases of incidental prostate cancer were detected. The tumor volume of all the cases was insignificant cancer.The clinical outcomes of IPCa were satisfactory with the initial treatment of WW in the Chinese population.

Effect of a p38 MAPK inhibitor on FFA-induced hepatic insulin resistance in vivo.

The mechanisms whereby prolonged plasma free fatty acids elevation, as found in obesity, causes hepatic insulin resistance are not fully clarified. We herein investigated whether inhibition of p38 mitogen-activated protein kinase (MAPK) prevented hepatic insulin resistance following prolonged lipid infusion. Chronically cannulated rats were subdivided into one of four intravenous (i.v.) treatments that lasted 48 h: Saline (5.5 µl min(-1)), Intralipid plus heparin (IH, 20% Intralipid+20 U ml(-1) heparin; 5.5 µl min(-1)), IH+p38 MAPK inhibitor (SB239063) and SB239063 alone. During the last 2 h of treatment, a hyperinsulinemic (5 mU kg(-1) min(-1)) euglycemic clamp together with [3-(3)H] glucose methodology was carried out to distinguish hepatic from peripheral insulin sensitivity. We found that SB239063 prevented IH-induced hepatic insulin resistance, but not peripheral insulin resistance. SB239063 also prevented IH-induced phosphorylation of activating transcription factor 2 (ATF2), a marker of p38 MAPK activity, in the liver. Moreover, in another lipid infusion model in mice, SB239063 prevented hepatic but not peripheral insulin resistance caused by 48 h combined ethyloleate plus ethylpalmitate infusion. Our results suggest that inhibition of p38 MAPK may be a useful strategy in alleviating hepatic insulin resistance in obesity-associated disorders.