BACKGROUND:A large number of studies have shown that bone marrow mesenchymal stem cels (BMSCs) with differentiation ability can be used to treat kidney injury. Epimedium has good anti-inflammatory and immune restoration ability.
OBJECTIVE:To observe the effect of epimedium with BMSC transplantation on rat’s kidney disease caused by adriamycin nephrosis.
METHODS:Fifty rats were equivalently randomized to receive no treatment in control group, tail vein injection of normal saline plus intragastric injection of normal saline in model group, tail vein injection of BMSCs plus intragastric injection of epimedium decoction in combined group, tail vein injection of BMSCs in BMSCs group, and intragastric injection of epimedium decoction in epimedium group. Rat models of adriamycin nephrosis were made in the latter four groups through tail vein injection of doxorubicin hydrochloride, while rats in the control group were only given the same volume of normal saline. Twenty-four hours after modeling, rats in the latter four groups began to be given the corresponding treatments. Epimedium decoction was given in the combined and epimedium groups at a dose of 1 mL/d, for consecutive 1 week.
RESULTS AND CONCLUSION:Compared with the model group, mitigated kidney injury and reduced urinary protein level were found in rats undergoing BMSCs and/or epimedium decoction treatment; the levels of plasma albumin and catalase were significantly increased in the combined group and epimedium group, while the levels of serum cholesterol, triglycerides and malondialdehyde decreased; the mRNA expression of transforming growth factor β1 in the kidney tissues was dramaticaly declined in the combined group and BMSC group. To conclude, the combined use of epimedium and BMSCs is superior to their use alone in the treatment of kidney disease.

In order to overcome the effects of the anti-aliasing filter and the colored background noise, an adaptive algorithm is proposed to estimate the parameters of ion channel kinetics and the background noise, and whereafter the ion channel signal could be restored from the strong noisy patch-clamp recordings. The algorithm cross-couples the recursive expectation-maximization algorithm, which estimates optimally the parameters of hidden Markov model, and the recursive extended least square algorithm, which estimates optimally the characteristics of the background noise. Simulation suggests that this cross-coupling algorithm convergences consistently, and is very robust to the inexact conformation number.
Algorithms ; Ion Channels ; physiology ; Least-Squares Analysis ; Likelihood Functions ; Models, Theoretical ; Noise ; Patch-Clamp Techniques ; methods ; Signal Processing, Computer-Assisted

Objective To investigate the expression of the HER-2 in human breast carcinomas by comparing the concordance between IHC staining and FISH, and analyze the relationship between the gene expression of HER-2/neu and clinical characteristics of patients. Methods A prospective clinical trial was performed involving a large multicenter patients' samples. Totally 3 249 breast cancer samples were collected from October 2007 to September 2009 in 73 hospitals across mainland China. HER-2 status was assessed by both IHC and FISH using formalin-fixed paraffin sections of consecutive tumor samples. The relationship between the expression of HER-2/neu gene and clinical parameters was analyzed using statistical methods. Results HER-2/neu was detected by FISH in 42.6% (1342/3149) of cases, whereas IHC analysis found 46. 9% (1477/3149) of cases to be HER-2/neu positive (2 +/3 + ). A higher concordance was observed in 94. 1% (892/948) of the patients with scores of 3 + and 89. 9% (660/734) with scores of 0 + by IHC, but relatively low concordance was also observed in 71. 0% (514/725) of patients with scores of 1 + and 55. 9% (415/742) in scores of 2 + by IHC. HER-2/neu gene amplification was associated with negativity of estrogen receptor and progesterone receptor (r = 0. 45, P < 0.01) , high histological grade ( r = 0. 51,P<0.01), more than 4 positive lymph nodes (r =0. 35, P<0.01), advanced stage (r=0. 33, P< 0. 01) , large tumor size ( > 2 cm, r = 0. 38, P < 0. 01 ) , postmenopause (r = 0. 24, P < 0. 01). No statistically significant relationship was found between HER-2 gene status and the other variables including age(r=0.36, P = 0.068), CA125 (r=0.11, P=0.722) or CA153 (r = 0. 23, P=0.45) protein status, lymph node involvement (r=0. 15, P =0. 18), CEA (r = 0.22, P=0.074) , number stage of tumor (r = 0. 21, P = 0.056 ) and blood vessel invasion (r = 0. 12, P = 0. 133 ). Conclusions The comparison of IHC and FISH demonstrated an excellent correlation of HER-2/neu overexpression and gene amplification. The results availabledemonstrate that FISH-analysis as a gold standard should be performed to guide reasonable clinical treatment.

OBJECTIVETo investigate the effect of microRNA-140 (miR-140) on the migration and invasion of colorectal cancer (CRC) cells and the possible mechanism.

METHODSmiR-140 mimics, miR-140 specific inhibitor or small interfering RNA (siRNA) against Smad3 were transfected into human CRC cell line RKO cells respectively, using Oligofectamine or Lipofectamine2000. Quantitative real-time PCR (real-time PCR) was used to measure the expression levels of miR-140 and Smad3 mRNA. Smad3 protein was analyzed by Western blot. The in vitro cell migrating and invasive abilities were determined by wound-healing and Transwell chamber assay after up-regulating or down-regulating miR-140 or knocking down Smad3.

RESULTSThe Western blot assays showed that the Smad3 protein level was significantly reduced after up-regulating miR-140 (0.04 ± 0.01), compared with that of (0.47 ± 0.02, P < 0.05) in the control group and that of (0.52 ± 0.06) in the negative control group (P < 0.05 for both). The results of real-time PCR indicated that no significant difference was found in the levels of Smad3 mRNA between miR-140 transfection and NC groups (1.11 ± 0.13 vs. 1.00 ± 0.06, P > 0.05). The wound-healing assay showed that the migrating ability was dramatically attenuated by miR-140 compared with that in the control and NC groups, whereas no significance was found when compared with that of the Smad3 siRNA transfected cells. The number of cells migrating through Transwell chamber without matrigel in the miR-140 group was (76.2 ± 4.4), remarkably lowered than that in the control (267.1 ± 4.9) and NC (336.1 ± 5.7) groups (P < 0.05 for both), but no significant difference between the miR-140 (76.2 ± 4.4) and Smad3 siRNA (83.5 ± 7.3) groups. Transwell chamber with matrigel assay showed that number of cells penetrating through the membrane was (109.5 ± 7.4) in the miR-140 group, significantly lower than that in the control (403.1 ± 5.1) and NC (392.6 ± 8.4) groups (P < 0.05 for both), while Smad3 siRNA transfection had a similar effect (138.8 ± 3.6)(P > 0.05). Down-regulation of miR-140 increased the level of smad3 protein expression, and partially reversed the inhibition of the cell migration and invasion mediated by miR-140. Co-transfection of miR-140 inhibitor and Smad3 siRNA had no significant effect on the Smad3 protein expression and the abilities of cell migration and invasion.

CONCLUSIONSmiR-140 regulates the Smad3 expression at the post-transcriptional level. miR-140 suppresses the migrating and invasive abilities of CRC cells, possibly through down-regulation of Smad3. The findings of this study suggest that miR-140 may have a unique potential as a possible biomarker candidate for diagnosis and therapy of tumor metastasis.

Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Colorectal Neoplasms ; metabolism ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; MicroRNAs ; Neoplasm Invasiveness ; RNA, Messenger ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Smad3 Protein ; genetics ; metabolism ; Transfection ; Up-Regulation

Objective:To investigate characteristics and changes of skin microbiota in atopic dermatitis-like mouse models induced by different concentrations of 2,4-dinitrochlorobenzene (DNCB) .Methods:Totally, 30 male specific-pathogen-free BALB/c mice were randomly divided into 3 groups by using a random number table: negative control group topically treated with 200 μl of mixture of acetone and olive oil at a volume ratio of 3∶1 on the back twice a week for 6 consecutive weeks; high-and low-concentration DNCB groups both topically treated with 200 μl of 1% DNCB on the first and third day at the first week, followed by topical application of 200 μl of 0.5% and 0.1% DNCB, respectively, twice a week for 5 weeks from the second week. Twenty-four hours after the last treatment, the severity of skin lesions was evaluated, and the transepidermal water loss and stratum corneum hydration were measured. After the experiment, the mice were sacrificed, and skin tissues were resected from the back of the mice for histopathological examination. Full-thickness skin tissue samples were obtained from the back of 3 mice in each group. Illumina Miseq PE300 high-throughput sequencing was performed to sequence the V3-V4 variable region of 16S rRNA gene of skin microbiota on the back of the mice, and the composition and structure of the skin microbiota and changes in the relative abundance of different genera were analyzed. One-way analysis of variance was used to analyze differences in indices among the 3 groups, and the Games-Howell method was used for multiple comparisons.Results:The severity scores of skin lesions were significantly higher in the high-and low-concentration DNCB groups (9.83 ± 2.45 points, 2.71 ± 0.56 points, respectively) than in the negative control group (0.51 ± 0.12 points, t=-7.19,-2.85, respectively, both P < 0.05) . Compared with the negative control group, the high-and low-concentration DNCB groups showed significantly increased transepidermal water loss ( t=-7.72,-2.68, respectively, both P < 0.05) , but significantly decreased stratum corneum hydration ( t=6.77, 5.99, respectively, both P < 0.05) ; the transepidermal water loss was significantly higher in the high-concentration DNCB group than in the low-concentration DNCB group ( t=2.76, P < 0.05) , while no significant difference in the stratum corneum hydration was observed between the high-and low-concentration DNCB groups ( P > 0.05) . There was a significant difference in the relative abundance of Corynebacterium among the 3 groups ( F=249.85, P < 0.001) , which was highest in the high-concentration DNCB group. No significant differences in the observed species and Chao1 index of the skin samples were observed among the 3 groups (both P > 0.05) , and the Shannon index was significantly lower in the high-concentration DNCB group than in the low-concentration DNCB group and negative control group ( t=6.96,-6.37, respectively, both P < 0.05) . Conclusion:DNCB could induce atopic dermatitis-like dermatitis in mice, and the severity of skin lesions and degree of barrier function impairment were related to the concentration of DNCB; the species diversity of skin microbiota markedly decreased in the high-concentration DNCB group, indicating that high-concentration DNCB modeling has more advantages in studying microbiological changes associated with atopic dermatitis.

Objective To observe the effects of Huoxue Digui Decoction on iron accumulation and ferroptosis in renal podocytes of diabetic nephropathy(DN)mice.Methods Totally 50 C57BL/6J mice were randomly divided into normal group(6 mice)and modeling group(44 mice).The DN model was established by streptozotocin injection.Mice conforming to DN model were randomly divided into model group(8 mice),and sulforaphane group,Huoxue Digui Decoction low-,medium-and high-dosage groups(6 mice for each group).The sulforaphane group was injected with sulforaphane intraperitoneally,while Huoxue Digui Decoction low-,medium-and high-dosage groups were orally administered with corresponding solution for 12 consecutive weeks.The fasting blood glucose,blood urea nitrogen,serum creatinine,24 h urinary albumin were detected,HE staining was used to observe the morphology of renal tissue,PAS staining was used to observe glycogen deposition in renal tissue,Masson staining was used to observe fibrosis in renal tissue;transmission electron microscopy was used to observe the ultrastructure of renal tissue,immunohistochemistry was used to detect the expressions of Podocin and Nephrin in renal tissue,Western blot was used to detect the protein expressions of glutathione peroxidase 4(GPX4),ACSL4,nuclear factor E2 related factor 2(Nrf2)and ferroportin 1(FPN1)in renal tissue,Prussian blue staining was used to observe the deposition of ferric ion in renal tissue.Results Compared with the normal group,the fasting blood glucose,blood urea nitrogen,serum creatinine and 24 h urinary albumin in model group significantly increased(P<0.01),with renal tissue capillary atrophy,increased glycogen deposition,and worsening fibrosis,the expressions of Podocin and Nephrin in renal tissue were down-regulated,while the expressions of GPX4,Nrf2 and FPN1 protein were significantly decreased(P<0.01),the expression of ACSL4 protein significantly increased(P<0.01),and the deposition of ferric ion in renal tissue increased.Compared with the model group,the fasting blood glucose,blood urea nitrogen,serum creatinine and 24 h urinary albumin in sulforaphane group and Huoxue Digui Decoction groups were reduced to different degrees(P<0.05,P<0.01),renal tissue pathological damage was reduced to varying degrees,glycogen deposition was reduced,and fibrosis was alleviated,the expressions of Podocin and Nephrin in renal tissue were up-regulated,while the expressions of GPX4,Nrf2 and FPN1 protein significantly increased(P<0.01),the expression of ACSL4 protein significantly decreased(P<0.05,P<0.01),and the deposition of ferric ion in renal tissue was reduced.Conclusion Huoxue Digui Decoction can alleviate renal pathological injury,reduce blood glucose and delay the progression of DN mice.The mechanism may be related to regulating the expressions of Nrf2 and FPN1,inhibiting iron accumulation and ferroptosis in renal podocytes of DN mice.

Diabetic kidney disease （DKD）， one of the leading causes of end-stage renal disease， shows increasing prevalence and mortality， seriously affecting the physical and mental health of patients. As a crucial link in the occurrence and development of DKD， pyroptosis can lead to kidney cell injury and inflammation through the abnormal activation of reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor protein 3 （NLRP3）， Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）/NLRP3， nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， mitogen-activated protein kinase （MAPK）/NLRP3， and hypoxia-inducible factor-1α （HIF-1α）/NLRP3 signaling pathways， which accelerate the progression of DKD. In recent years， traditional Chinese medicine （TCM） has demonstrated definite efficacy in the treatment of DKD via multiple targets and pathways. Studies have shown that various TCM active components， including glycosides， flavonoids， polyphenols， terpenoids， and alkaloids， as well as TCM compound prescriptions for clearing heat and detoxifying， tonifying deficiency and consolidating root， and eliminating stasis and descending turbidity， can target relevant signaling pathways to inhibit pyroptosis and intervene in the development of DKD， providing new possibilities for precision treatment of DKD. This article systematically reviews the relevant pathways of pyroptosis and summarizes the research achievements and mechanisms of TCM active components and compound prescriptions in the treatment of DKD via pyroptosis in recent years. This review aims to provide new directions and ideas for the treatment and research of DKD with TCM and promote the modernization and development of TCM.

OBJECTIVE To observe the effects of Xuesaitong soft capsule on the complement-inflammatory receptor system in patients with type 2 diabetic nephropathy. METHODS A total of 92 patients with type 2 diabetic nephropathy were divided into control group and observation group by random number table method ，with 46 cases in each group. Patients in the control group were given basic treatment programs （including low-salt and low-protein diet ，quitting smoking and alcohol ，appropriate exercise ， lowering blood pressure ，blood sugar and lipid ，etc.）. The patients in the observation group took Xuesaitong soft capsules orally on the basis of the treatment of the control group ，0.55 g each time ，3 times a day. The treatment course of both groups was 4 weeks. Compare the renal function of the two groups of patients [24 h urine protein quantification ，serum creatinine （Scr），blood urea nitrogen，glomerular filtration rate （GFR）]，fasting blood glucose ，glycosylated hemoglobin ，complement factors [C3，C5， complement factor H （CFH），C5b-9]，inflammatory factors [interleukin 1（IL-1），tumor necrosis factor α（TNF-α），IL-6，monocyte chemoattractant protein- 1（MCP-1）]，renal tubular injury markers [β2-microglobulin（β2-MG），retinol binding protein 4（RBP4）， neutrophil gelatinase associated lipocalin] levels；correlation between renal tubular damage and complement-inflammatory receptor system was analyzed in the observation group before and after treatment. RESULTS Compared with before treatment ，24 h urine protein quantity ，Scr，C3，IL-1，TNF-α，MCP-1，β2-MG and RBP 4 of 2 groups were reduced significantly after treatment ，while GFR and CFH were significantly increased ；except for C 3，the observation group was significantly better than the control group （P＜ 0.05）. C 5 of the observation group was significantly decreased after treatment and was significantly lower than the control group （P＜0.05）. There were no statistically significant 60979837。E-mail：shanght126@126.com differences in other indicators of the two groups before and after treatment and between groups （P＞0.05）. C 3，MCP-1 and TNF-α were significantly correlated with renal tubular com damage （P＜0.05），and esp ecially C 3. CONCLUSIONS Xuesaitong soft capsule can reduce renal tubular damage in patients with type 2 diabetic nephropathy and improve renal function by acting on the complement system and reducing inflammation.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.