OBJECTIVETo explore the effects and molecular mechanisms of rhein on reducing starvation-induced autophagic protein expression in renal tubular epithelial ( NRK-52E) cells.

METHODHank's balanced salt solution (HBSS) was used to induce NRK-52E cells to be in the state of starvation. After the intervention of HBSS for 0, 0.5,1, 2 and 6 hours, firstly, the protein expression of microtubule-associated protein 1 light chain 3(LC3 I/II), which is a key protein in autophagy, was detected. Secondly, the protein expressions of mammalian target of rapamycin (mTOR) and phosphorylated-mTOR Ser2448 (p-mTOR S2448) were examined. And then, after the co-treatment of rhein (5 mg x L(-1)) and HBSS (1 mL) without or with mTOR inhibitor, rapamycin (100 nmol x L(-1)), the protein expressions of LC3 I/II, mTOR and p-mTOR S2448 were tested, respectively.

RESULTHBSS could induce the up-regulation of LC3 II and the down-regulation of p-mTOR S2448 at protein expression level in NRK-52E cells. The co-treatment of rhein and HBSS could reversely regulate the protein expressions of LC3 II and p-mTOR S2448 in NRK-52E cells significantly. The co-treatment of rapamycin, rhein and HBSS could recover the level of LC3 II protein expression in HBSS-intervened NRK-52E cells.

CONCLUSIONHBSS induces autophagy in renal tubular epithelial cells by inhibiting mTOR signaling pathway activation. Rhein reduces the autophagic protein expression in renal tubular epithelial cells through regulating mTOR signaling pathway activation, which is the possible effects and molecular mechanisms.

Animals ; Anthraquinones ; pharmacology ; Autophagy ; drug effects ; Cells, Cultured ; Epithelial Cells ; drug effects ; metabolism ; Isotonic Solutions ; pharmacology ; Kidney Tubules ; drug effects ; metabolism ; Microtubule-Associated Proteins ; genetics ; Rats ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; genetics ; physiology

OBJECTIVETo study the clinical effects of Fuzheng Huayu Gantang comprehensive therapeutic program (FHGP) on post-hepatitis B liver cirrhosis associated with glyco-metabolic abnormality (LCGA).

METHODSThe patients with LCGA enrolled in the randomized controlled clinical trial were assigned to 2 groups, the treated group (68 cases) and the control group (74 cases), they were treated respectively by FHGP and conventional TCM and Western medicine therapeutic program for 3 months. Indexes including fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2 h PG), fasting insulin (FINS) were detected, homeostasis model assessment insulin resistance (HOMA-IR) was calculated, and the score of syndrome was recorded before and after treatment. Then the effects on syndrome and glyco-metabolic abnormality were evaluated through statistical analysis.

RESULTSLevel of 2 h PG after treatment was lowered in both groups (P < 0.01), but significant difference was found in the pre-treatment to post-treatment decrement of FPG and HOMA-IR between the two groups (P < 0.05). The syndrome improving rate and the total effective rate on glyco-metabolic abnormality in the treated group were significantly better than those in the control group respectively (85.3% vs 64.9% , P < 0.01; 80.9% vs 62.2%, P < 0.05).

CONCLUSIONFHGP has the capability to improve the syndrome and glyco-metabolic abnormality of patients with LCGA.

Adolescent ; Adult ; Aged ; Blood Glucose ; metabolism ; Combined Modality Therapy ; Drug Therapy ; methods ; Female ; Hepatitis B, Chronic ; complications ; Humans ; Insulin Resistance ; Liver Cirrhosis ; etiology ; metabolism ; therapy ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Phytotherapy ; methods ; Treatment Outcome

OBJECTIVETo explore the regulative effects and possible mechanisms of emodin on autophagy induced by starvation in rat's renal tubular epithelial cells (NRK-52E).

METHODFirstly, Hank's balanced salt solution (HBSS) was used to induce starvation and the protein expression of microtubule-associated protein 1 light chain 3 (LC3) I/II, an autophagic marker of mammalian congener, was detected by Western blot with or without the treatment of emodin. Secondly, the changes of red fluorescent protein-microtubule associated protein light chain3 (RFP-LC3) fluorescent particles, treated by HBSS (1 mL) and bafilomycin A1 (10 nmol x L(-1)) with or without emodin, were observed through fluorescence microscopy in NRK-52E cells transient transfected by RFP-LC3 plasmid. With the intervention of mammalian target of rapamycin mTOR inhibitor rapamycin (100 nmol x L(-1)) , the effect of blocking mTOR signaling pathway on autophagic inhibition of emodin was observed. Finally, the effect of mTOR signaling pathway on autophagic inhibition of emodin was further evaluated through the over-expression of endogenous mTOR inhibitory protein DEP domain-containing mTOR-interacting protein-(DEPTOR).

RESULTHBSS hunger could induce high protein expression of LC3 II in NRK-52E cells, and the intervention of emodin could reverse the unregulated protein expression of LC3 II induced by HBSS. The number of RFP-LC3 fluorescent particles was increased after the co-treatment of HBSS and bafilomycin A1, and this increase was inhibited by emodin. After the co-treatment of rapamycin, emodin and HBSS, the LC3 II protein expression restored in NRK-52E cells, compared with the treatment of HBSS. Over-expression of DEPTOR could also block the inhibitive effect of emodin on LC3 II protein expression.

CONCLUSIONEmodin could inhibit HBSS-induced LC3 II protein expression and the activation of autophagy in NRK-52E cells, and the effect of blocking autophagy may be mediated through mTOR signaling pathway.

Animals ; Autophagy ; drug effects ; Cell Line ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Emodin ; pharmacology ; Isotonic Solutions ; adverse effects ; Kidney Tubules ; cytology ; drug effects ; metabolism ; Microtubule-Associated Proteins ; genetics ; metabolism ; Rats ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; genetics ; metabolism

OBJECTIVETo assess the performance of FibroScan in evaluating the curative effects of traditional Chinese medicine (TCM) on liver fibrosis, and to analyze factors influencing the diagnostic accuracy.

METHODSData of FibroScan values, types of disease, use of drug, liver function indexes, prothrombin time (PT) and international normalized ratio (INR) were collected at both pre- (1 month prior) and post-FibroScan for 102 patients who underwent at least two FibroScan procedures. Patients were subgrouped according to presence of fibrosis, presence of cirrhosis, and TCM formulation and statistically analyzed.

RESULTSThe pre- and post-FibroScan mean liver stiffness measurements (LSMs) were significantly different when the variation of LSM was more than or equal to2 kPa for the non-fibrotic group (vs. the fibrotic group), or when the variation wasmore than or equal to4 kPa for the cirrhotic group (vs. the non-cirrhotic group). In addition, the three TCM formulation groups showed significant differences, with the most robust difference exhibited between the FuZheng HuaYu formulation group and the other treatment groups (P = 0.010). No significant differences were observed for the liver function indexes, PT, or INR. However, the post-FibroScan levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) was significantly reduced in patients with reduced LSM.

CONCLUSIONFibroScan may be a useful non-invasive clinical tool for evaluating the comprehensive curative effect of treatments for chronic liver diseases, and its performance is not obviously impacted by ALT, AST, GGT, PT, and INR. The criteria for efficacy established by FibroScan are 2 kPa for the patients without liver fibrosis and 4 kPa for patients with liver cirrhosis.

OBJECTIVETo study the role of changes of matrix metalloproteinase-2, 9 (MMP-2, 9) activity in the development of dimethylnitrosamine (DMN)-induced liver fibrosis in rats.

METHODSThe rat liver fibrosis model was established by peritoneal injection of DMN (at a dose of 10 mg/kg, 3 times a week, for 4 weeks). The dynamic changes of liver fibrosis were observed at different time points (1d, 2d, 3d, 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks). The MMP-2, 9 activity was measured by zymogram method. Liver ultrastructure was observed by electron microscope. The expressions of type IV collagen (CIV), laminin (LN), type I collagen (CI) and alpha-smooth muscle actin (alpha-SMA) were examined by immunohistochemistry. The tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) content was measured by Western blot method.

RESULTSThe MMP-2, 9 activity (gray value) significantly increased in the 2d and 3d DMN model rats (2d: normal/model group, MMP-2: 54.72+/-4.56/70.76+/-7.63; F = 16.27, P < 0.05; MMP-9: 25.72+/-4.29/51.76+/-15.33, F=13.38, P < 0.05). The positive staining area percentage of CIV in the sinusoidal walls decreased in the 2d, 3d and 1 weeks model rats (2d: normal/model group, 6.06+/-1.35/2.86+/-0.63, F=69.12, P < 0.05), but significantly increased in the 4w model rats (normal/model group, 6.06+/-1.35/8.04+/-1.50, F=14.42, P < 0.05). There was a remarkable negative correlation between the MMP-9 activity and expression of CIV in the sinusoidal walls (r = -0.729, P < 0.05). Positive expressions of LN and CI increased, and the strongest positive staining of them displayed in the 4w model rats. The formation of basement membrane was also observed in the 4 weeks model rats. Expression of TIMP-2 significantly increased in the late stage of fibrosis.

CONCLUSIONSThe increase of MMPs activity, especially MMP-9 which degrades the CIV normally distributed under the sinusoidal endothelium is the important factor in the formation of sinusoidal capillarization. The deposition and reconstitution of LN and new synthetic CIV, adding the deposition of CI constitute the high density basement membrane. The increase of TIMP-2 expression in the late stage of the fibrosis may be one of reasons why natural resolution of DMN-induced liver fibrosis is difficult.

Animals ; Collagen Type IV ; analysis ; Laminin ; analysis ; Liver ; chemistry ; ultrastructure ; Liver Cirrhosis, Experimental ; enzymology ; pathology ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-2 ; analysis

OBJECTIVETo investigate the clinical characteristics, international prognostic index and treatment of primary non-Hodgkin's lymphoma (NHL) of the nasopharynx.

METHODSFrom January 1983 to December 1997, 136 patients with previously untreated NHL of the nasopharynx were retrospectively reviewed. All patients were confirmed pathologically and classified by Working Formulation system. There were 18 patients with high-grade, 77 intermediate, 2 low-grade and 39 unclassifiable lymphoma. According to Ann Arbor classification, 25 patients had stage I, 91 stage II, 12 stage III and 8 stage IV lesions. Primary therapy was radiotherapy alone in 13 patients and radiotherapy combined with chemotherapy in 12 patients with stage I disease. In 88 patients with stage II, radiotherapy alone was given to 31 patients, and a combination of radiotherapy and chemotherapy to 57 patients. Chemotherapy was primary treatment for advanced stage III/IV diseases.

RESULTSThe overall survival rate (OS), cancer specific survival rate (CSS) and disease-free survival rate (DFS) at 5 and 10 years for all patients were 56.2%, 61.2%, 51.1% and 48.3%, 58.0%, 46.5%, respectively. As for international prognostic index (IPI), the 5-year CSS was 70.9% for 0 risk factor, 44.9% for 1 risk factor, 30.0% for 2 or 3 risk factors, respectively (P = 0.004). For stage I patients, the 5-year CSS was 83.1% for RT alone and 82.2% for combined modality therapy, respectively (P = 0.779). For patients with stage II, the 5-year CSS was 46.0% for radiotherapy alone and 70.9% for combined modality therapy. There was significant difference between them (P = 0.04). Multivariate analysis by Cox regression showed that Ann Arbor stage, B symptom and IPI were independent prognostic factors.

CONCLUSIONInternational prognostic index is an important prognostic factor for Non-Hodgkin's lymphoma of the nasopharynx and the combined modality therapy may be optimal for the stage II patients.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Bleomycin ; administration & dosage ; Child ; Combined Modality Therapy ; Cyclophosphamide ; administration & dosage ; Disease-Free Survival ; Doxorubicin ; administration & dosage ; Female ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; radiotherapy ; therapy ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; radiotherapy ; therapy ; Neoplasm Staging ; Prednisone ; administration & dosage ; Prognosis ; Retrospective Studies ; Survival Rate ; Vincristine ; administration & dosage

OBJECTIVETo investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms.

METHODSRats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers.

RESULTSHQH ameliorated the rat's general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis.

CONCLUSIONHQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.

Animals ; Apoptosis ; drug effects ; Body Weight ; drug effects ; Caspase 3 ; metabolism ; Chromatography, High Pressure Liquid ; Cytochromes c ; metabolism ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Kidney ; drug effects ; pathology ; Kidney Diseases ; blood ; chemically induced ; complications ; drug therapy ; Kidney Glomerulus ; drug effects ; pathology ; ultrastructure ; Kidney Tubules ; drug effects ; pathology ; ultrastructure ; Male ; Membrane Proteins ; metabolism ; NF-KappaB Inhibitor alpha ; metabolism ; NF-kappa B ; metabolism ; Organ Size ; drug effects ; Proteinuria ; blood ; complications ; drug therapy ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo explore the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative analgesia of ureteroscopic holmium laser lithotripsy.

METHODSOne hundred and twenty adult patients, American Association of Anesthesiologists (ASA) Class Ⅰ or Ⅱ, scheduled to ureteroscopic holmium laser lithotripsy, were randomly assigned into an observation group and a control group, 60 cases in each one. The patients in the observation group were treated with TEAS for postoperative analgesia. TEAS was implemented at bilateral Shenshu (BL 23) and Yinlingquan (SP 9) at the time of back ward and postoperative 4 h, 8 h, 12 h. TEAS at 7:00, 11:00 and 15:00 at the above acupoints were used on the second and third days; while placebo (twice a day, 100 mg a time) was used. Tramadol hydrochloride tablets for postoperative analgesia were applied in the contnol group, twice a day, 100 mg a time, and electrode sheets without stimulation were put on Shenshu (BL 23) and Yinlingquan (SP 9). When analgesia was insufficient with the score of visual analogue scale (VAS)≥3, the patients were treated with tramadol tablets for remedy analgesia. The VAS score, the concentrations of serotonin (5-HT) and substance P (SP) in 3 mL venous blood at the time of back ward (T), postoperative 4 h (T), 12 h (T), 24 h (T), and 48 h (T) were detected respectively. The total amount of medication for remedy analgesia and the incidence of adverse reactions, such as nausea and vomiting within postoperative 48 h were compared between the two groups.

RESULTSThe VAS scores at T through T were lower than those at T in the two groups (all <0.05). Compared with the control group, the VAS scores at T through T in the observation group were lower (all <0.05). The total dose of remedy analgesic medicine within 48 h after operation in the observation group was lower than that in the control group (<0.05). Compared with the control group, the concentrations of 5-HT at T, T, T and SP at T through T were lower (all <0.05). The numbers of constipation, nausea and vomiting in the observation group were less than those in the control group (both <0.05).

CONCLUSIONTEAS can relieve the pain and reduce the total amount of analgesic medicine, the levels of substance causing pain and the incidence of adverse reactions after ureteroscopic holmium laser lithotripsy.

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation ( RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid ( CONCLUSIONS For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.
Birth Weight ; Cesarean Section ; China ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Pregnancy ; Retrospective Studies

Ten batches of Angelica sinensis from three producing areas( Tuoxiang,Minxian and Weiyuan of Gansu province) were selected as the research objects,and processed into raw A. sinensis,A. sinensis with alcohol,and A. sinensis with soil respectively through the standard processing methods. Ultra-high performance liquid chromatography( UPLC) was used to establish fingerprint for three processed products of A. sinensis,and determine the contents of 9 phenolic acids and phthalide compounds. The similarity was analyzed with Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine,which showed that the chromatographic peaks of the same processed samples of A. sinensis were basically similar,with all similarities greater than 0. 950. The difference between different processed products and their control spectra was not obvious,with all similarities also higher than 0. 950.On the basis of using principal component analysis( PCA) and OPLS-DA to seek the difference components between groups,the improved distance coefficient method can be used to effectively distinguish the three processed products of A. sinensis by fingerprint similarity. At the same time,the determination method of nine phenolic acids and phthalide in A. sinensis was established by UPLC,and the comparison between different processed products was carried out. The results showed that the content of various components was changed as compared with the raw A. sinensis. The contents of coniferyl ferulate and ligustilide in the A. sinensis with alcohol were increased significantly,and the content of coniferyl ferulate was obviously increased in A. sinensis with soil. The method established in this paper can effectively distinguish different processed products of A. sinensis and determine the content of the main components in them.
4-Butyrolactone ; analogs & derivatives ; analysis ; Angelica sinensis ; chemistry ; Benzofurans ; analysis ; Chromatography, High Pressure Liquid ; Coumaric Acids ; analysis ; Drugs, Chinese Herbal ; analysis ; Hydroxybenzoates ; analysis ; Medicine, Chinese Traditional ; Principal Component Analysis