Research on the mechanism of NLRP3 inflammasome in neurovascular unit impairment of diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)is a neurovascular disease caused by the neurovascular unit(NVU)impairment. Immune imbalance and inflammation are key factors that affect the normal function of NVU and lead to the progression of DR. Nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome is indicated as an important component of the inflammatory response, and it can identify endogenous danger signals, leading to the activation of caspase-1 and then activating a series of inflammatory cytokines and pyroptosis. Early activation of inflammasome maintains and promotes innate immunity against bacterial and viral infections, while excessive inflammasome activation results in excessive expression and ongoing action of inflammatory proteins, which in turn triggers off immune disorders and an inflammatory cascade that seriously harms the body. This review summarizes the recent research progress on the mechanism of NLRP3 inflammasome in NVU impairment of DR, including the related drugs targeting NLRP3 pathways.

Clinical Analysis of Acute Myeloid Leukemia Patients with Hemophagocytic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features of acute myeloid leukemia patients with hemophagocytic syndrome.@*METHODS@#The clinical data of 2 patients with acute myeloid leukemia complicated with hemophagocytic syndrome were collected, and the clinical characteristics and treatment outcomes were analyzed.@*RESULTS@#There were two patients with acute myeloid leukemia, including 1 male and 1 female，aged for 67 and 40 years old，respectively. Hemophagocytic syndrome occurred in one patient after induction therapy for acute myeloid leukemia and one patient after consolidation therapy. Both of the patients with hemophagocytic syndrome showed fever, hemocytopenia, high ferritin, high titer sCD25 levels and hemophagocytes in bone marrow. After achieved anti-infection, glucocorticoid, human immunoglobulin and etoposide regimens treatment, hemophagocytic syndrome was controlled in both of the two patients. One patient failed to induce acute myeloid leukemia and one patient achieved complete remission.@*CONCLUSION@#Acute myeloid leukemia complicated with hemophagocytic syndrome is rare. Early identification, early anti-infection combined with HLH94 regimen can control hemophagocytosis and improve prognosis.

Vascular endothelial growth factor induces inflammatory injury of pancreatic tissue by activating autophagy in hyperlipidemic acute pancreatitis rats / 生理学报

This study was to investigate the changes of autophagy in pancreatic tissue cells from hyperlipidemic acute pancreatitis (HLAP) rats and the molecular mechanism of autophagy to induce inflammatory injury in pancreatic tissue cells. Male Sprague Dawley (SD) rats were intraperitoneally injected with caerulein to establish acute pancreatitis (AP) model and then given a high fat diet to further prepare HLAP model. The HLAP rats were treated with autophagy inducer rapamycin or inhibitor 3-methyladenine. Pancreatic acinar (AR42J) cells were treated with caerulein to establish HLAP cell model. The HLAP cell model were treated with rapamycin or transfected with vascular endothelial growth factor (VEGF) siRNA. The inflammatory factors in serum and cell culture supernatant were detected by ELISA method. The histopathological changes of pancreatic tissue were observed by HE staining. The changes of ultrastructure and autophagy in pancreatic tissue were observed by electron microscopy. The expression levels of Beclin-1, microtubule- associated protein light chain 3-II (LC3-II), mammalian target of rapamycin complex 1 (mTORC1), and VEGF were measured by immunohistochemistry and Western blot. The results showed that, compared with control group, the autophagy levels and inflammatory injury of pancreatic tissue cells from HLAP model rats were obviously increased, and these changes were aggravated by rapamycin treatment, but alleviated by 3-methyladenine treatment. In HLAP cell model, rapamycin aggravated the autophagy levels and inflammatory injury, whereas VEGF siRNA transfection increased mTORC1 protein expression, thus alleviating the autophagy and inflammatory injury of HLAP cell model. These results suggest that VEGF-induced autophagy plays a key role in HLAP pancreatic tissue cell injury, and interference with VEGF-mTORC1 pathway can reduce the autophagy levels and alleviate the inflammatory injury. The present study provides a new target for prevention and treatment of HLAP.

Effect of PADI4 on the Expression of Inflammatory Cytokines During NB4 Cells Differentiation / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of peptidylarginine deiminase 4 (PADI4) during the process of differentiation into granulocyte of NB4 cells induced by all-trans-retinoic acid (ATRA) and whether PADI4 is involved in the inflammatory cytokines expression.@*METHODS@#Granulocyte differentiation model of NB4 cells induced by ATRA was established. The cell morphology changes were observed by Wright-Giemsa staining. The expression of cell differentiation marker CD11b was analyzed by flow cytometry. The mRNA and protein expression of PADI4 was detected by RT-PCR and Western blot, respectively. The expression of tumor necrosis factor (TNF) α and interleukin (IL) 1β was analyzed by ELISA, and also examined with the knockdown of PADI4 expression by siRNA.@*RESULTS@#After NB4 cells induced by ATRA, the cytoplasm increased and the ratio of nuclear to cytoplasmic was reduced. Nuclear dented, and rod-shaped nucleus, lobulated phenomenon increased (P<0.05). Flow cytometry analysis results showed that the cell surface molecule CD11b expression increased (P<0.01). RT-PCR and Western blot showed the expression of PADI4 increased at both transcriptional and translational levels during the process of the differentiation. ELISA showed TNF-α and IL-1β secretion increased in differentiated macrophages, while they could be inhibited by PADI4-specific siRNA.@*CONCLUSION@#During the differentiation into granulocyte of NB4 cells induced by ATRA, PADI4 expression increased. Furthermore, PADI4 appeared to play a critical role in inflammatory cytokines secretion.

Effect of Myofascial Trigger Points Electric Stimulation on Phantom Limb Pain after Lower Limb Amputation / 中国康复理论与实践

Objective:To explore the clinical efficacy of myofascial trigger point electric stimulation based on mirror therapy on phantom limb pain after lower limb amputation. Methods:From May to November, 2020, 50 patients with phantom limb pain after lower limb amputation were randomly divided into control group (n = 25) and experiment group (n = 25). Both groups accepted mirror therapy, while the experiment group received myofascial trigger point electric stimulation before mirror therapy, for four weeks. They were assessed with short-form of McGill Pain Questionnaire (SF-MPQ), Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), Timed 'Up & Go' Test (TUGT) and 6-minute walk test (6MWT) before and after treatment. Results:All the indexes improved in both groups after treatment (|t| > 8.210, P < 0.001), and improved more in the experiment group than in the control group (|t| > 5.103, P < 0.001), except the present pain intensity of SF-MPQ. Conclusion:Mirror therapy is effective on phantom limb pain after lower limb amputation in terms of pain, sleep, anxiety and walking, and the effect could be stronger after myofascial trigger point electric stimulation.

Ginsenoside Rg_1 induces leukemia stem cell senescence via SIRT1/TSC_2 signal axis / 中国中药杂志

The aim of this paper was to investigate the effect of SIRT1/TSC_2 signal axis on leukemia stem cell senescence induced by ginsenoside Rg_1. CD34~+CD38~- leukemia stem cells(CD34~+CD38~-LSCs) was isolated by magnetic cell sorting(MACS) and divided into two groups. The control group cells were routinely cultured, 40 μmol·L~(-1) ginsenoside Rg_1 was added to the control group for co-culture in Rg_1 group. The effect of Rg_l to induce CD34~+CD38~-LSCs senescence were evaluated by senescence-associated β-Galactosidase(SA-β-Gal) staining, cell cycle assay, CCK-8 and Colony-Assay. The expression of senescence associated SIRT1, TSC_2 mRNA and protein was examined by Real-time fluorescence quantitative PCR(FQ-PCR) and Western blot. The results showed that the CD34~+CD38~-LSCs could effectively be isolated by MACS, and the purity of CD34~+CD38~-LSCs is up to(95.86±3.04)%. Compared with the control group, the percentage of positive cells expressed SA-β-Gal in the Rg_1 group is increased, the senescence morphological changes were observed in the CD34~+CD38~-LSCs in the Rg_1 group. The proliferation inhibition rate and the number of cells entered G_0/G_1 phase in the Rg_1 group were increased, but the colony-formed ability was decreased, Rg_1 could significantly inhibit the proliferation and self-renewal ability of CD34~+CD38~-LSCs. The expression of SIRT1 and TSC_2 mRNA and protein were down regulated in the Rg_1 group compared with the control group. Our research implied that Rg_1 may induce the senescence of CD34~+CD38~-LSCs and SIRT1/TSC_2 signal axis plays a significant role in this process.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study / 中国结合医学杂志

OBJECTIVE@#To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction.@*METHODS@#Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period.@*RESULTS@#After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min•1.73 m, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min•1.73 m, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min•1.73 m per year.@*CONCLUSION@#Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Short-term clinical efficacy observation of adjunctive Er,Cr:YSGG laser application following subgingival scaling in patients with severe periodontitis / 上海交通大学学报（医学版）

Objective • To observe the short-term clinical efficacy of adjunctive Er,Cr:YSGG laser application following subgingival scaling in patients with severe periodontitis. Methods • In this parallel control design clinical trial, 46 patients with severe periodontitis were selected. Baseline examination was performed 2 weeks after supragingival scaling. Then the patients were randomly divided into the test group and the control group, with 23 cases in each group. After ultrasonic subgingival scaling, sites with probing depth (PD) ≥ 5 mm of patients in two groups received subgingival debridement with Er,Cr:YSGG laser and hand curettes, receptively. The changes in plaque index (PLI), PD, clinical attachment level (CAL), the percentage of bleeding on probing (BOP) positive sites, and the degree of subjective pain during treatment with visual analogue scale(VAS)were compared between two groups at baseline, 6 weeks after treatment, and 3 months after treatment. Results • For sites with PD ≥ 5 mm, PLI, PD, CAL, and the percentage of BOP positive sites significantly reduced for both groups at 6 weeks and 3 months after treatment compared with baseline (all P=0.000). For sites with 5 mm ≤ PD ≤ 6 mm, the CAL of the test group was significantly lower compared with the control group at 6 weeks after treatment (P=0.036). For sites with PD ≥ 7 mm, the PDs of the test group were significantly lower compared with the control group at 6 weeks and 3 months after treatment (P=0.002, P=0.039). The PD reduction between baseline and 6 weeks after treatment was greater in the test group compared with the control group (P=0.015). The CAL of the test group was lower compared with the control group at 6 weeks after treatment (P=0.011). The VAS of the test group was significantly lower than that of the control group (P=0.005). Conclusion • Adjunctive Er,Cr:YSGG laser application following subgingival scaling can achieve similar short-term clinical efficacy compared with traditional hand curettes. Er,Cr:YSGG laser may be beneficial particularly on the reduction of PD and regain of CAL in deep pockets on a short-term basis, which can make the patients more comfortable. Subgingival scaling with adjunctive Er,Cr:YSGG laser application can be an effective way for the non-surgical periodontal therapy.

Short-term clinical efficacy observation of adjunctive Er, Cr:YSGG laser application following subgingival scaling in patients with severe periodontitis / 上海交通大学学报（医学版）

Objective · To observe the short-term clinical efficacy of adjunctive Er, Cr:YSGG laser application following subgingival scaling in patients with severe periodontitis. Methods · In this parallel control design clinical trial, 46 patients with severe periodontitis were selected. Baseline examination was performed 2 weeks after supragingival scaling. Then the patients were randomly divided into the test group and the control group, with 23 cases in each group. After ultrasonic subgingival scaling, sites with probing depth (PD) ≥5 mm of patients in two groups received subgingival debridement with Er, Cr:YSGG laser and hand curettes, receptively. The changes in plaque index (PLI), PD, clinical attachment level (CAL), the percentage of bleeding on probing (BOP) positive sites, and the degree of subjective pain during treatment with visual analogue scale (VAS) were compared between two groups at baseline, 6 weeks after treatment, and 3 months after treatment. Results · For sites with PD≥5 mm, PLI, PD, CAL, and the percentage of BOP positive sites significantly reduced for both groups at 6 weeks and 3 months after treatment compared with baseline (all P=0.000). For sites with 5 mm ≤ PD ≤ 6 mm, the CAL of the test group was significantly lower compared with the control group at 6 weeks after treatment (P=0.036). For sites with PD ≥ 7 mm, the PDs of the test group were significantly lower compared with the control group at 6 weeks and 3 months after treatment (P=0.002, P=0.039). The PD reduction between baseline and 6 weeks after treatment was greater in the test group compared with the control group (P=0.015). The CAL of the test group was lower compared with the control group at 6 weeks after treatment (P=0.011). The VAS of the test group was significantly lower than that of the control group (P=0.005). Conclusion · Adjunctive Er, Cr:YSGG laser application following subgingival scaling can achieve similar short-term clinical efficacy compared with traditional hand curettes. Er, Cr:YSGG laser may be beneficial particularly on the reduction of PD and regain of CAL in deep pockets on a short-term basis, which can make the patients more comfortable. Subgingival scaling with adjunctive Er, Cr:YSGG laser application can be an effective way for the non-surgical periodontal therapy.

Adsorption Property of Avilamycin on Silica Gel-based Absorbent / 中国药学杂志

OBJECTIVE: To investigate the kinetic and thermodynamic characteristics of adsorption of avilamycin on silica gel. METHODS: By measuring the adsorption of avilamycin on silica gel at different temperatures, the adsorption kinetics curves and adsorption isotherm were drawn, and the kinetics and thermodynamic parameters were studied. RESULTS: The adsorption of avilamycin on silica gel could be described well by Pseudo-second-order model. The adsorption process had feature of shrinking nonreactive core model, and the internal diffusion was the main rate-limiting step. The equilibrium adsorption data of avilamycin on silica gel fit the Langmuir isotherms well. The thermodynamic parameters were as follows:change in entropy (ΔS) was 108.115 2 J·mol-1·K-1, change in enthalpy (ΔH) was 24.654 6 J·mol-1, and changes in free energy (ΔG) were -8.752 9, -8.104 3, and -7.455 6 J·mol-1 at 309, 303 and 297 K, respectively. CONCLUSION: The RESULTS: of this study provide a theoretical basis for further study on the isolation and purification of high purity avilamycin by silica gel.

Treating glioma with umbilical cord mesenchymal stem cells: mechanism of action, safety and future application / 中国组织工程研究

BACKGROUND: Umbilical cord mesenchymal stem cells (UC-MSCs) are a group of cells that have self-renewal, highly proliferative and multidrug differentiation potential. The properties of UC-MSCs and their tumor tropism make them an ideal tool for glioma cell therapy. These cells can act by paracrine or as a delivery system for genes and drugs. It has been demonstrated that UC-MSCs can inhibit the growth of glioma and improve the survival after transplantation into the brain. OBJECTIVE: To summarize the molecular mechanisms and safety of UC-MSCs in the treatment of glioma and to provide a useful reference for further research. METHODS: We searched the PubMed and CNKI databases from 2000 to 2017 with the English terms of "glioma; umbilical cord mesenchymal stem cells" and the Chinese terms of "glioma; umbilical cord mesenchymal stem cells; safety; molecular mechanism". Based on the inclusion and exclusion criteria, 55 articles were finally reserved for review. RESULTS AND CONCLUSION: UC-MSCs have obvious effect on treating glioma. These cells can treat glioma through homing mechanism and paracrine mechanism as gene carrier and co-culture. Moreover, UC-MSCs have certain safety in the treatment of glioma.

Role of mature liver cells and oval cells in liver regeneration after liver injury / 中国组织工程研究

BACKGROUND: Retrorsine (RS) is a chemical agent for the long-term inhibition of mature liver cell division and proliferation. OBJECTIVE: To establish a rat model of liver injury by combined use of RS and 1/3 partial hepatectomy, to observe the proliferation of liver cells and oval cells in rats after liver injury, and to discuss the relationship between liver regeneration and mature liver cells and oval cells after liver injury. METHODS: Thirty male Sprague-Dawely rats were randomized into two groups (n=15 per group): RS group and control group. Rats in the RS group were subjected to intraperitoneal injection of RS, 30 mg/kg, twice in total, with 2 weeks in between; and rats in the control group were injected physiological saline instead of RS. Four weeks after the last injection, the 1/3 partial hepatectomy was performed in two groups of rats. Liver pathological and morphological changes as well as cell proliferation were observed, and CK19 and C-kit immunohistochemical detections of the rat liver in the two groups were conducted at different time points after operation. RESULTS AND CONCLUSION: At 20 days after operation, the body mass of the RS group rats was still lower than the baseline, and the liver increase was obviously less than that in the control group; there was cell body swelling shown by hematoxylin-eosin staining, loose cytoplasm, extensive vacuoles degeneration of liver cells, and clustered or scattered oval cells around the portal area of small bile duct and in the hepatic lobule. However, in the control group, the body mass was close to the baseline, liver damage was lighter than that in the RS group, a large number of mature liver cells proliferated under BrdU Immunofluorescence at 20 days after operation; liver oval cells proliferated and distributed in the liver cell line at 14 days after operation, with morphology and immunohistochemical markers consistent with oval cells in the RS group. These findings indicate that the rat model of acute liver injury is successfully established by combining retrorsine with 1/3 partial hepatectomy, liver poisoning and the proliferation of liver stem cells and mature liver cells after poisoning can be seen in the experiment, which firmly confirm that liver cell renewal and regeneration after injury is accredited to the combined action of liver stem cells in liver basin and mature liver cells.

A Multi-center, Randomized, Controlled and Open Clinical Trial of Heyan Kuntai Capsule () and Hormone Therapy in Perimenopausal Women / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Heyan Kuntai Capsule (, HYKT) and hormone therapy (HT) on perimenopausal syndromes (PMSs).</p><p><b>METHODS</b>From 2005 to 2008, 390 women with PMSs were recruited from 4 clinic centers. The inclusion criteria included ages 40 to 60 years, estradiol (E2) below 30 ng/L, and follicle stimulating hormone (FSH) above 40 IU/L, etc. The patients were randomly assigned to HYKT group or HT group by random number table method, administrated HYKT or conjugated estrogen with/without medroxyprogesterone acetate tablets for 12 months. During treatment, the patients were interviewed quarterly, Kupperman Menopausal Index (KMI) scores, hot flush scores, insomnia scores, Menopause-Specific Quality of Life (MENQOL) scores and adverse effects were used for evaluating drug efficacy and safety respectively. The last interview was made at the end of 12-month treatment RESULTS: After treatment, KMI scores of HYKT group and HT group were both significantly decreased compared with baseline (P <0.01) and there was no significant difference between groups (P >0.05), except that KMI of HYKT group was higher after 3-month treatment (P <0.05). After treatment, hot flush and insomnia scores were both improved significantly in two groups (P <0.01); and HT had a better performance than HYKT in improving hot flush (P <0.05). MENQOL were significantly improved in both groups after treatment (P <0.01); but there was no significant difference between two groups (P >0.05). The incidence of adverse event in the HYKT group was much lower than that in the HT group (P <0.01).</p><p><b>CONCLUSIONS</b>HYKT could effectively relieve PMSs and improve patients quality of life without severe adverse reactions. Although HYKT exerted curative effects more slowly than hormone, it possessed better safety profile than hormone.</p>

Preparation and Quality Evaluation of Avilamycin Self-emulsifying Microemulsion / 中国药学杂志

OBJECTIVE: To optimize the formulation of avilamycin self-microemulsifying drug delivery system (SMEDDS) using central composite design-response surface method and evaluate its quality. METHODS: The compositions of avilamycin SMEDDS were screened by solubility experiment and self-emulsifying grading test. The formulation was optimized using Design Expert Software, taking particle size and Zeta potential as dependent variables and the usage amounts of oil, surfactant and cosurfactant as independent variables. RESULTS: The optimized formulation was quickly and conveniently obtained as follows: 36.67% propylene glycollaurate, 42.83% cremophor RH40 and 20.50% diethylene glycol monoethyl ether.The average diameter of the preparation was (28.34±0.06)nm, the Zeta potential was (-1.98±0.24)mV and PDI was (0.15±0.005). CONCLUSION: The central composite design and response surface method is useful for the formula optimization of avilamycin self-microemulsifying drug delivery system.The prediction accuracy of the established mode1 is good.

5-FU-Injured Bone Marrow Stromal Cells Initiate Stress-induced Premature Senescence of Hematopoietic Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the damage effect of 5-fluorouracil(5-FU) with tumor inhibition concentration on human bone marrow mesenchymal stem cells (hBMSC) and influence of its effect on the hematopoietic cells.</p><p><b>METHODS</b>The Cell Counting Kit-8 was used for determining the sensitivity of breast cancer cell line MCF-7, colon cancer cell line HCT-116 and HS-5 derived from human bone marrow stronal cell line to the different doses of 5-fluorouracil in vitro. After HS-5 was treated with 5-fluorouracil, crystal violet staining assay was used to count the number of colony forming unit-fibroblast, the distribution of cell cycle was analyzed by flow cytometry (FCM), apoptosis was assessed by Annexin V/PI double-stained method and Hoechest staining; DCFH-DA staining was used to analyse the level of reactive oxygen species (ROS), ELISA and immuofluorescence were used to detect cytokines KL, GM-CSF, RANTS and SDF. The hUCB-MNC was counted by trypan blue staining after co-culture with HS-5, FCM was used to detect the cell cycle distribution, ROS level and the ratio of CD34cells. The levels of glutathione peroxidase (GSH-Px) and total superoxide dismutase(T-SOD) were measured by enzymatic assay. The senescence associated-β-galactosidase (SA-β-Gal) staining was used to detect the senescent hUCB-MNC.</p><p><b>RESULTS</b>5-Fluorouracil of 12.5 µg/ml-100 µg/ml inhibited the proliferation of MCF-7, HCT-116 and HS-5 cells in dose-dependent and time-dependent manner, among them HS-5 was more sensitive to 5- fluorouracil. After treatment with 5-fluorouracil, the HS-5 cell cycle was blocked. The apoptosis rate and the intracellular ROS level of HS-5 significantly increased. Also HS-5-secreted hematopoietic growth factors decreased and inflammatory chemokines increased. After co-cultured with 5-fluorouracil-treated HS-5, the number of hUCB-MNC and the ratio of CD34cells were decreased. hUCB-MNC cell cycle blocked in Gphase. The antioxidant capacity also decreased and the intracellular ROS level increased significantly. The senescent hUCB-MNC increased.</p><p><b>CONCLUSION</b>5-Fluorouracil can result in oxidative damage of bone marrow stromal cells and change of function secreting bioactivators, thus induce oxidative stress in hematopoietic cells to initiate stress-induced premature senescence (SIPS).</p>

Effects of acute hypoxia on telomere length of rat gastric mucosa tissue and underlying mechanism / 生理学报

The present study was aimed to investigate the effect of acute hypoxia on telomere length of rat gastric mucosa tissue and possible mechanism. Forty male Wistar rats were randomly divided into control group (resided in Lanzhou, 1 500 m) and experimental group (hypoxia chamber, 5 000 m). The experimental group was further divided into 3 subgroups and exposed to hypoxia for 1, 3, 7 d (n = 10), respectively. The morphological changes of the gastric mucosa tissue were observed by HE staining. By means of real-time PCR, ELISA and chemical immunofluorescence methods, the telomere length, the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor 1α (HIF-1α) and HIF-2α, and reactive oxygen species (ROS) level in gastric mucosa tissue were measured, respectively. The results showed that, with the extension of hypoxia-exposure time, the injury in gastric mucosa cells progressively became worse, and telomere length was increased gradually, along with intracellular ROS generation. The changes of TERT and HIF-1α expressions induced by acute hypoxia were in the same trend as that of telomere length. There were positive correlations between TERT mRNA expression and telomere length and between TERT and HIF-1α expressions, but not between TERT and HIF-2α mRNA expressions. These results suggest that under acute severe hypoxia environment, ROS could damage the gastric mucosa tissue cells, meanwhile the expressions of TERT and telomerase activity may be up-regulated by HIF-1α, which can elongate the telomere length and protect gastric mucosa tissue against fatal injury.

Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.</p><p><b>METHODS</b>It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.</p><p><b>RESULTS</b>The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.</p><p><b>CONCLUSIONS</b>Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.</p><p><b>TRIAL REGISTRATION</b>chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.</p>

Ultrasonographic observation of the breast in early postmenopausal women during therapy with Cimicifuga foetida extract and sequential therapy with estrogen and progestin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women.</p><p><b>METHODS</b>This was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment.</p><p><b>RESULTS</b>In comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P < 0.05) after treatment, the same as Group C (11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05). In comparing breast duct width before and after 1 and 2 years of treatment, no significant difference was seen in Group A (1.07 ± 0.19 mm vs. 1.02 ± 0.18 mm and 0.98 ± 0.21 mm, P > 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check.</p><p><b>CONCLUSIONS</b>In early postmenopausal patients, C. foetida extract therapy and estrogen and progesterone therapy at low doses did not increase the incidence of malignant breast tumors.</p>

Protective effect of Angelica sinensis polysaccharides on subacute renal damages induced by D-galactose in mice and its mechanism / 中国中药杂志

To explore the protective effect of Angelica sinensis polysaccharides(ASP) on subacute renal damages induced by D-galactose in mice and its mechanism. Male C57BL/6J mice were randomly divided into 3 groups, with 10 mice in each group. The D-galactose model group was subcutaneously injected with D-galactose (120 mg x kg(-1)), qd x 42; the ASP + D-galactose model group was intraperitoneally injected with ASP since the 8th day of the replication of the D-galactose model, qd x 35; and the normal control group was subcutaneously injected with saline at the same dose and time. On the 2nd day of after the injection, the peripheral blood was collected to measure the content of BUN, Crea, UA, Cys-C; paraffin sections were made to observe the renal histomorphology by HE staining; senescence-associated β-g-alactosidase (SA-β-Gal) stain was used to observe the relative optical density (ROD) in renal tissues; transmission electron microscopy was assayed to observe the renal ultrastructure; the renal tissue homogenate was prepared to measure the content of SOD, GSH-PX, MDA; the content of AGEs and 8-OH-dG were measured by ELISA. According to the result, compared with the D-galactose model group, the ASP + D-galactose model group showed obviously decreases in the content of BUN, Crea, UA, Cysc, AGES, 8-OH-dG, the number of hardening renal corpuscle, renal capsular space and renal tubular lumen, ROD of SA-β-Gal staining positive kidney cells, mesangial cells, basement membrane thickness, podocyte secondary processes fusion and MDA and increases in the number of normal renal corpuscle, ribosome and rough endoplasmic reticulum in podocytes, the activity of SOD and GSH-PX. In Conclusion, A. sinensis polysaccharides can antagonize kidney subacute damages induced by D-galactose in mice. Its protective mechanism may be correlated with the inhibition of the oxidative stress injury.

Biological mechanisms of human-derived leukemia stem cells senescence regulated by Angelica sinensis polysaccharide / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the biological mechanisms underlying Angelica sindsis polysaccharide (ASP) -induced aging of human-derived leukemia stem cells (LSCs) in vitro.</p><p><b>METHOD</b>Acute myelogenous leukemia stem cells were isolated by magnetic activated cell sorting (MACS). The ability of LSC proliferation treated by various concentration of ASP(20-80 mg · L(-1)) in vitro for 48 hours were tested using cell counting Kit-8 ( CCK8) , colony forming were evaluated by methylcellulose CFU assay. The ultra structure changes of AML CD34+ CD38- cells were analyzed by transmission electron microscopy. The aging cells were detected with senescence-β-galactosidase Kit staining. Expression of aging-related p53, p21, p16, Rb mRNA and P16, Rb, CDK4 and Cyclin E protein were detected by quantitative reverse transcription polymerase chain reaction( qRT-PCR) and Western blotting, respectively.</p><p><b>RESULT</b>The purity of the CD34 + CD38 - cells is (91.15 ± 2.41)% after sorted and showed good morphology. The proliferation of LSC was exhibited significantly concentration-dependent inhibited after exposure to various concentration of ASP. Treated by 40 mg · L(-1) ASP for 48 hours, the percentage of positive cells stained by SA-β-Gal was dramatically increased (P < 0.01) and the colony-formed ability has been weakened (P < 0.01). The observation of ultrastructure showed that cell heterochromatin condensation and fragmentation, mitochondrial swelling, lysosomes increased in number. Aging-related p53, p21, p16, Rb and P16, Rb were up-regulated, protein regulatory cell-cycle CDK4 and Cyclin E were down-regulated. ASP may induce the senescence of LSCs effectively in vitro, P16-Rb cell signaling pathway play a significant role in this process.</p><p><b>CONCLUSION</b>ASP can induce human leukemia stem cell senescence in vitro, the mechanism involved may be related to ASP regulation P16-Rb signaling pathways.</p>