Interleukin-24 (IL-24) is a member of IL-10 family, which was cloned from human melanoma cells by the method of subtractive hybridization. IL-24 can inhibit the growth of tumor cells and angiogenesis and enhance radiation sensitivity and immune adjustment with non-toxic effects on normal cells.As a kind of cytokine with multiple anti-tumor functions, IL-24 will become a new weapon of gene therapy against cancer. The application and mechanism of IL-24 in the treatment of cancer will be discussed in this paper.

Objective To investigate the compliance with medical therapy in elderly patients with benign prostatic hyperplasia (BPH).Methods The BPH patients aged 66 to 93 treated with 5α-reductase inhibitor (finasteride) and/or α-blockers (tamsulosin,doxazosin or terazosin) were followed up for 6 months.The retrospective data,including international prostatic symptom score (IPSS),quality of life (QOL),maximum flow rate (Qmax),prostate volume (PV),the information of medical types,total number of days of medication supplied,discontinuation and switching of therapy,and adverse effects were collected and analyzed.Results In all 103 subjects,30 patients (29.1％) received α-blockers,25 patients (24.3％) received finasteride,and 48 patients (46.6％)received combination therapy.After a follow-up of 6 months,the medication possession ratio (MPR)was 0.89±0.23 with a good-compliance rate (MPR≥0.8),discontinuation rate and switching rate were 79.6％ (82 cases),5.8％ (6 cases) and 6.8％ (7 cases),respectively,while the efficacy rate,the adverse reaction rate,incidence of acute urinary retention (AUR) and incidence of BPH related operations were 73.8％ (76 cases),12.6％ (13 cases),15.5％ (16 cases) and 4.9％ (5 cases),separately.The MPR (0.90±0.24) and good-compliance rate (84.0％) in patients treated with finasteride were both greater than those with α-blockers (0.87 ± 0.25,76.7％) and combination therapy (0.89 ±0.22,79.2％),but with no significant difference.Compared with patients with badcompliance,the efficacy ratio of medical therapy was significant higher in patients with goodcompliance (81.7％ vs.42.9％),while the incidence of adverse effects and AUR were significant fewer (7.3％ vs.33.3％ and 9.8％ vs.38.1％).Conclusions Elderly patients received either monotherapy or combination therapy with finasteride and α-blockers have good-compliance,which might be associated with the good effect of medical therapy and fewer adverse effects.

Objective To explore the impact of intermittent androgen deprivation therapy on prostate volume and lower urinary tract symptoms (LUTS) in patients with prostate cancer combined with prostatic hyperplasia (BPH),and to evaluate the clinical effect of intermittent androgen deprivation therapy as compared with conventional drug in patients with BPH.Methods Patients with prostate cancer (n=57) and BPH (n=83) were respectively treated with intermittent androgen deprivation therapy and finasteride combined with alpha-receptor antagonist.Prostate volume,international prostate symptom score (IPSS),quality of life index (QOL) and maximum urinary flow rate (Qmax) in patients were observed before and 1,3,6 and 12 months after treatment.Results The improvements in prostate volume,IPSS,QOL and Qmax were higher in prostate cancer patients treated with intermittent androgen deprivation therapy than in BPH patients treated with finasteride combined with alpha-receptor antagonist (P ＜ 0.05).Conclusions Intermittent androgen deprivation therapy can significantly reduce prostate volume and improve LUTS in patients with prostate cancer,and has a better clinical effect than finasteride combined with alpha-receptor antagonist treatment.

Objective Establishing a fingerprint method to identify the characteristic chemicals in the roots of Gentiana macrophylla and evaluate their quality.Methods RP-HPLC was developed for fingerprint analysis and determination of four ingredients in G macrophylla roots from different sources.LC-ESI-TOF-MS was employed to identify the chromatographic peaks of the fingerprint.Results Five common peaks were identified by comparing their retention time with reference secoiridoid glucosides.Eight major peaks in chromatographic fingerprint were analyzed by on-line LC-ESI-TOF-MS.Four secoiridoid glucosides were identified based on their MS data.Conclusion The method is specific and could be served for the quality identification and comprehensive evaluation of G macrophylla.

Objective:To explore the relationship between metabolic acidosis and cardiac valve calcification in maintenance hemodialysis (MHD) patients in the Pearl River Delta Region.Methods:Patients on MHD greater than 3 months who were treated in 10 blood purification centers in the Pearl River Delta Region from July 1 to September 30, 2019 were selected for this multicenter cross-sectional study. Based on a Doppler ultrasound, MHD patients were further divided into non-valve calcification group and valve calcification group. The demographics data, frequency of dialysis, blood pressure, single pool Kt/V(spKt/V), dialysis medications and laboratory data were collected and compared. Spearman correlation analysis was used to analyze the correlation between serum carbon dioxide combining power (CO 2CP) and cardiac valve calcification. Multivariate logistic regression model was used to analyze the influencing factors of cardiac valve calcification. Results:A total of 664 MHD patients were included in this study, with age of (57.0±14.2) years old and dialysis age of 43.0 (22.3, 71.7) months, including 395 males (59.5%) and 269 females (40.5%). Among them, there were 119 patients (17.9%) with diabetes and 186 patients (28.0%) with dialysis 2 times per week. There were 329 patients (49.5%) in the valve calcification group, and 335 patients (50.5%) in the non-valve calcification group. Compared to those in non-valve calcification group, valve calcification group had longer duration of dialysis, higher proportion of patients with dialysis 2 times per week, higher levels of diastolic blood pressure, fasting blood glucose, intact parathyroid hormone and ferritin, higher proportion of patients with blood CO 2CP<19 mmol/L (median CO 2CP), higher proportion of patients on usage of calcium channel blocker, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, α-receptor blocker, β-receptor blocker, calcitriol and lanthanum carbonate (all P<0.05), while the levels of spKt/V, hemoglobin, serum CO 2CP, corrected calcium, blood phosphorus, blood alkaline phosphatase, albumin, total cholesterol, triacylglycerol, low-density lipoprotein, high-density lipoprotein, transferrin saturation, and the proportion of patients on usage of sevelamer and cinacalcet were lower (all P<0.05). Spearman analysis showed significant negative correlation between serum CO 2CP and valve calcification ( rs=-0.697, P<0.001). Multivariate logistic regression analysis showed that dialysis performed twice a week ( OR=2.789, 95% CI 1.232-6.305, P=0.014), blood total cholesterol ( OR=1.449, 95% CI 1.014-2.071, P=0.042), CO 2CP<19 mmol/L ( OR=22.412, 95% CI 10.640-47.210, P<0.001) were the influencing factor of valve calcification in MHD patients. Conclusions:MHD patients with cardiac valve calcification have significant acid loading. Metabolic acidosis is an independent influencing factor for cardiac valve calcification in MHD patients.

OBJECTIVEThis study investigated the role and mechanism of calcineurin (CaN)-nuclear factor of activated T cells (NFAT) pathway in the myoblast apoptosis induced by cyclic tensile strain.

METHODSMyoblasts were cultured using an in vitro-mechanical stimulation model and imposed with tension for different hours with a multi-channel cell stress loading system. Cyclosporine (CsA) was used as CaN inhibitor to clarify the role of CaN in the apoptosis induced by cyclic stress. Hochest 33258 staining and flow cytometry detection were performed to detect the apoptotic cells. Real-time polymerase chain reaction was conducted to detect the mRNA expression of CaN and NFAT. Protein levels of NFAT3 were evaluated by Western blot.

RESULTSThe apoptosis rate increased with the extension of loading time. The mRNA expression of the CaN subunits, CnA and CnB, and the protein levels of NFAT3 also increased. When the myoblasts were incubated with CsA, the apoptosis rate decreased, the mRNA expression of CnA and NFAT3 significantly decreased, and the NFAT3 protein expression levels became significantly lower than those of the groups without CsA.

CONCLUSIONContinuous cyclic tensile stress can induce myoblast apoptosis. The CaN-NFAT signaling pathway may be involved in the cyclic stretch-induced apoptosis of myoblasts.

Apoptosis ; Calcineurin ; genetics ; Cyclosporine ; Flow Cytometry ; Myoblasts ; physiology ; NFATC Transcription Factors ; metabolism ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; T-Lymphocytes

BACKGROUND:Endoplasmic reticulum stress participates in the occurrence and development of many diseases, such as atherosclerosis, diabetes, and Alzheimer’s disease. GRP78 is a marker of endoplasmic reticulum stress. The expression of GRP78 reflects the degree of endoplasmic reticulum stress.
OBJECTIVE:To investigate the effect of cyclic stretch on GRP78 expression of L6 rat myoblasts, and to identify the relationship between cyclic stretch and endoplasmic reticulum stress.
METHODS:In vitro culture-tensile stimulation models of myoblasts of L6 rats were established successful y. The expression of GRP78 of myoblasts exposed to cyclic stretch was determined by reverse transcription-PCR and western blot assay. Stretch groups were subjected to 15%surface elongation at a frequency of 10 cycles per minute, over a period of 1, 6, 12 and 24 hours. cells were simultaneously seeded on a plate in the control and experimental groups with no stimulation.
RESULTS AND CONCLUSION:The expression of GRP78 mRNA was continuously elevated over time after stretched treatment, and significant differences were detected as compared with the control group (P<0.05). GRP78 protein expression began to increase at 1 hour after stretched treatment, was significantly increased at 6 hours, peaked at 24 hours, and significant differences were visible as compared with the control group (P<0.05). In conclusion, cyclic stretch induced the occurrence of endoplasmic reticulum stress, which was enhanced with prolonged time. However, prolonged stretch caused severe endoplasmic reticulum stress and leaded to apoptosis of myoblasts.

Permeability is one of the determinants of intestinal absorption and oral bioavailability. The non-cell-based permeation model is a kind of in vitro permeability measurement tool, which has the advantages of high efficiency, low cost, stable property, easy to use and customizable. According to the barrier type, non-cell-based permeation model can be divided into biomimetic barriers containing (phosphate) lipids and non-biomimetic barriers without lipids. Biomimetic permeation models include parallel artificial membrane permeability assay, vesicle-based permeation assay and PermeaPad®. Non biomimetic permeation models include Hollow fiber membrane models based on polyether sulfone materials. In foreign countries, the application of these four barriers for different purposes is gradually becoming a hot spot in drug absorption research. However, in China, there are only more applied studies on PMAPM and few published applied studies on the other three barriers. In order to meet the development needs of insoluble drug formulations, the author summarized the permeability devices and permeability calculation methods, searched the application of non-cell-based permeation model in the permeability of BSCⅡ drugs in recent years, and summarized the characteristic applications of three Biomimetic permeation models and hollow fiber membranes.

ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine （SCOP） and explore the treatment mechanism. MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups： control （0.9% NaCl， n=10）， model （SCOP 1 mg·kg^-1·d^-1， n=10）， low-， medium-， and high-dose Dihuang Yinzi （SCOP 1 mg·kg^-1·d^-1 + Dihuang Yinzi 5.5， 11.0， and 22.0 g·kg^-1·d^-1， n=10）， and donepezil （SCOP 1 mg·kg^-1·d^-1 + donepezil 0.84 mg·kg^-1·d^-1， n=10）. Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week， and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week， 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 （SIRT2）， α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid （AMPA） receptor 1 （GluA1）， protein kinase A （PKA）， cAMP response element-binding protein （CREB）， phosphorylated-CREB （p-CREB）， postsynaptic density protein 95 （PSD95）， growth-associated protein-43 （GAP-43）， and synaptophysin （SYN） in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin （DCX） in the hippocampal dentate gyrus （DG） region. ResultsCompared with the control group， the model group showed impaired learning and memory （P<0.01）， obvious neuronal damage in the hippocampal CA1 region， a reduction in neuron survival （P<0.01）， a decrease in DCX expression in the hippocampal DG region （P<0.01）， down-regulated proteins levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 in the hippocampal tissue （P<0.05， P<0.01）， and an up-regulated protein level of SIRT2 （P<0.01）. Compared with the model group， the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory （P<0.05， P<0.01）， while the low-， medium-， and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival （P<0.05， P<0.01）. The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression （P<0.05， P<0.01）. The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1， PKA， p-CREB/CREB， PSD95， SYN， and GAP-43 （P<0.05， P<0.01） and down-regulation in the protein level of SIRT2 （P<0.01）. ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2， activating the PKA/CREB signaling pathway， improving synaptic plasticity， and reducing hippocampal neuronal damage.