[Objective] To investigate the effect of Tangshen Granules (a Qi-strengthening and blood-activating prescription mainly composed of Radix Astragali, Rhizoma Chuanxiong, Radix Notoginseng, Radix Puerariae,etc.) combined with irbesartan Tablets (an antagonist of angiotensin Ⅱ receptor) for the treatment of diabetic nephropathy (DN). [Methods] Eighty cases of DN were randomized to two groups: group A ( n = 40) was treated with Tangshen Granules and irbesartan Tablets and group B ( n = 40) with irbesartan Tablets alone as control. The therapeutic effect was observed after 8-week treatment. [Results] Serum creatine (SCr) and blood urea nitrogen (BUN) levels and urinary albumin excretion rate (UAER) were decreased after treatment (P

【Objective】To observe the therapeutic effect of Shen'ankang Granules(SG)for chronic renal failure(CRF)and to explore its therapeutic mechanism.【Methods】 Seventy-two CRF patients were equally randomized into groups A and B.The two groups were given oral use of Medicinal Charcoal Tablets and routine supportive and symptomatic treatment,and group A was given SG(mainly composed of Radix Astragali,Radix et Rhizoma Rhei,Herba Epimedii,Radix Notoginseng and Rhizoma Curcumae)additionally.The treatment lasted 8 weeks.The therapeutic effect in the two groups was compared after treatment.Meanwhile,the changes of blood urea nitrogen(BUN),serum creatine(SCr),endogenous creatine clearance rate(Ccr),urinary ?_2 microglobulin(?_2-M)and ?-N-acetyglucosamidase(NAG),as well as changes of serum fibrosis-associated proteins of type Ⅳ collagen(C-Ⅳ),type Ⅲ precollagen(PC-Ⅲ)and laminin(LN)levels were detected.【Results】The total therapeutic effect was 86.11% in group A,higher than 61.11% in group B(P0.05).The differences of serum C-Ⅳ,PC-Ⅲ and LN levels were significant between groups A and B(P

Objective To investigate the association between peripheral white blood cell count including its subtypes and cardiovascular disease (CVD) incidence and one-year all-cause mortality in maintenance hemodialysis (MHD) patients.Methods A total of 371 MHD patients at Zhongshan Hospital,Fudan University between March 2009 and February,2011 were enrolled.Demographic,hematological,nutritional and inflammatory markers were obtained.All patients were followed for one year to investigate the risks for CVD event and mortality.Spearman correlation and linear regression were used to assess the relationship between white blood cell count and other laboratory parameters.Difference in categorical factors between two groups were determined with Chi-square test,Difference in continuous values between two groups were assessed with t test.Kaplan-Meier analysis and Cox proportional hazards model were applied to assess one-year mortality predictors.Results Patients with CVD event had lower lymphocyte count level (1.17±0.38 vs 1.34±0.51,P＜ 0.05) and higher monocyte count level (0.44 ± 0.15 vs 0.37 ± 0.15,P＜0.01) than those without CVD event.Cox proportional hazard regression showed that an increased lymphocyte count was associated with reduced mortality risk,95％CI:0.136-0.719,P ＜ 0.01) and that an increased monocyte count was associated with increased mortality risk,95％ CI:2.657-74.396,P＜0.01) after adjustment for hsCRP.Conclusion Decreased lymphocyte level and increased monocyte level are significantly related to CVD event and are independent predictors of increased one-year all-cause mortality risk in MHD patients.

Objective To investigate the protection effects and possible mechanism of apoptotic effect of compound Xiancao granules on renal ischemia reperfusion injury ( IRI ) in rats. Methods Renal IRI rat model was established by clipping bilateral renal artery.The rats were divided into model control group (n=10), compound Xiancao granules group (n=10) and sham operation group (n=10).All Serum creatinine (Cr) and blood urea nitrogen (BUN) were determined to evaluate kidney function after IRI.Superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) activity in kidney were measured by colorimetric method. Expression of apoptotic regulatory genes Bcl-2 and Bax in renal tissue were detected by Western blotting.Renal tissue sections were stained by hematoxylin and eosin (HE) and examined under a light microscope. Results SOD and GSH-PX levels of the compound Xiancao granules group (278.1±16.2),(155.96±20.58) U?mg-1 were significantly higher than those of the model control group (196.3±12.1),(109.34±17.81) U?mg-1 (P<0.05). MDA, BUN and Cr (12.49±1.07) nmol?mL-1,(8.9±2.7) mmol?L-1,(149.7±8.5) μmol?L-1 were significantly reduced in the compound Xiancao granules group as compared with those of the model control group (17.32±1.26) nmol?mL-1,(14.6± 3.3) mmol?L-1,(206.1±11.2) μmol?L-1(P<0.05).Bax and Bcl-2 mRNA expression levels of sham operation group were significantly lower, and the Bax and Bcl-2 mRNA expression levels of model control group were significantly enhanced ( Bcl-2:P<0. 05, Bax: P<0. 01 ) . Bax mRNA expression level of compound Xiancao granules group was significantly decreased as compared with that of model control group ( P<0.05) , but Bcl-2 mRNA expression level of compound Xiancao granules group was significantly enhanced as compared with that of model control group (P<0.01). Conclusion These results suggested that compound Xiancao granules has protection effect on renal IRI in rats. The mechanisms may be related to its antioxidant activity and expression of the apoptotic genes such as Bcl-2 and Bax.

Objective:To investigate the protective effect and possible mechanism of Tangshenbao on renal damage in diabetic nephropathy (DN) rats.Methods:Totally 36 SPF male SD rats were randomly divided into normal group ( n=6) and model group ( n=30). The DN rat model was prepared by single high-dose intraperitoneal injection of STZ. According to the random number table method, the rats were divided into model group, irbesartan group and Tangshenbao low-, medium- and high-dosage groups, with 6 rats in each group. Drug intervention lasted for 8 weeks. The general condition and body weight of rats in each group were recorded. The blood glucose, kidney index, 24 h urine protein (24 h UTP), SCr and BUN levels were detected. The pathological morphology of renal tissue was observed by PAS staining and transmission electron microscopy. The mRNA and protein expressions of Ets-1, TGF-β1, Smad2 and Smad3 in renal tissue were detected by real-time fluorescence quantitative PCR and Western blot. Results:Compared with model group, the body weight of Tangshenbao low, medium and high dose groups and irbesartan group significantly increased ( P<0.01). The kidney index decreased ( P<0.05 or P<0.01). The contents of 24 hUTP, BUN and SCr significantly decreased ( P<0.05 or P<0.01). Glomerular volume was significantly reduced ( P<0.05 or P<0.01), the mRNA expressions of Ets-1 (1.59 ± 0.06, 1.47 ± 0.04, 1.31 ± 0.03, 1.39 ± 0.03 vs. 1.64 ± 0.04), TGF-β1 (1.65 ± 0.05, 1.59 ± 0.03, 1.38 ± 0.05, 1.49 ± 0.04 vs. 1.77 ± 0.08), Smad2 (1.48 ± 0.05,1.39 ± 0.05, 1.22 ± 0.03, 1.31 ± 0.04 vs. 1.54 ± 0.05), Smad3 (1.57 ± 0.04, 1.48 ± 0.03, 1.28 ± 0.03, 1.39 ± 0.02 vs. 1.64 ± 0.05) in renal tissue of rats significantly decreased ( P<0.05 or P<0.01), the protein expressions of Ets-1 (1.33 ± 0.32, 1.16 ± 0.38, 0.77 ± 0.06, 0.84 ± 0.06 vs. 1.97 ± 0.43), TGF-β1 ( 1.35 ± 0.14, 1.24 ± 0.22, 0.94 ± 0.13, 1.07 ± 0.06 vs. 1.63 ± 0.20), Smad2 (1.24 ± 0.26, 1.14 ± 0.31, 0.77 ± 0.28, 0.85 ± 0.19 vs. 1.72 ± 0.34) and Smad3 (1.29 ± 0.14, 1.19 ± 0.21, 0.85 ± 0.39, 0.90 ± 0.37 vs. 1.76 ± 0.21) decreased ( P<0.05 or P<0.01). Conclusion:Tangshenbao can improve renal damage in DN rats, and its mechanism may be related to the inhibition of Ets-1 expression and TGF-β1/Smads signaling pathway.

Since the outbreak of COVID-19, several prevention and control measures have been successively promulgated in Wuhan. To name a few, setup of designated hospitals for severe COVID-19 patients is key to enforcing the policy of pooling patients, experts, resources and standardizing treatment. These efforts contribute decisively to improving the cure rate and reducing the mortality of COVID-19. As one of the designated hospitals composed of multiple medical teams, Wuhan Union Hospital put in place a joint working mode for treating severe COVID-19 patients, and found solutions to the main problems and difficulties in management. Its experiences provide references for the operation of joint medical institutions in emergency.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*