Renal interstitial fibrosis （RIF） is a common pathological change process from the development of various chronic nephropathies to the end stage， and it is an important histological manifestation of renal function decline. At present， no effective anti-fibrosis drugs have been found in clinical practice. In recent years， with the continuous development of traditional Chinese medicine （TCM） pharmacology， molecular biology， system biology， and network pharmacology， the research on regulating RIF with TCM monomer， single TCM， TCM compound， Chinese patent medicine， and TCM injection is deepening. Among them， Jianpi Yishen recipe， Shendi Bushen capsules， Jianzhong Bushen Xiaozheng decoction， Liuwei Dihuangtang， and Lycium barbarum polysaccharides can regulate transforming growth factor-β/small mother against decapentaplegic （TGF-β₁/Smads）， Wnt/β-catenin， and neurogenic locus notch homolog protein （Notch） signaling pathways. Wulingsan， Zhenwutang， pachymic acid ZA， pachymic acid ZC， and pachymic acid ZD， which mainly induce diuresis， can regulate the Wnt/β-catenin signaling pathway. Hirudin， curcumin， and Fuzheng Huayu recipe， which mainly promote blood circulation， can inhibit inflammation-related pathways such as p-nuclear transcription factor-κB （NF-κB）， Toll-like receptor 4/p-nuclear transcription factor-κB （TLR4/NF-κB）， and Janus kinase 2/signal transducer and activator of transcription 3 （JAK/STAT）， so as to achieve anti-inflammatory and anti-oxidation effects and alleviate the progression of RIF. Shenshuai Xiezhuo decoction， Shenkang injection， and Shenshuai recipe， which are mainly used for invigorating Qi， removing blood stasis， and removing turbidity， can inhibit transdifferentiation of pericytes-myofibroblasts through vascular endothelial growth factor receptor （VEGFR） signaling pathway. At present， there are many studies on the regulation of the RIF signaling pathway by TCM， but there is a lack of a systematic summary. In this study， by combing the signaling pathway of TCM in the treatment of RIF， the effective target of TCM treatment is screened， and its possible mechanism is found， which provides new ideas for clinical treatment and new drug research and development.

OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.

Objective:To explore the locations of the lumbosacral nerve roots by use of the magnetic stimulation.Methods:Thirty healthy subjects were studied. The projections of the right L 2 to S 1 intervertebral foramina on their body surfaces were determined manually with ultrasound assistance. Magnetic stimulation was applied to different nerve root segments to induce compound muscle action potentials (CMAP) in the vastus medialis, tibialis anterior, and gastrocnemius muscles of the lower limbs. The changes in latency, amplitude, and motor threshold were observed. Results:Magnetic stimulation on the L 2-L 3 segment resulted in a significant direct excitation of the vastus medialis. That on the L 5-S 1 segment evoked a significant direct excitatory effect on the tibialis anterior and gastrocnemius, with a motor threshold below 40%, an amplitude exceeding 1mV, and many effective responses. However, during the magnetic stimulation on the L 4 segment, the amplitude of the vastus medialis was above 1mV, with no significant differences in the number of effective responses among the muscle groups. Moreover, there was a stepwise change in the latency of effective muscle responses to magnetic stimulation at different segments. The CMAP latencies of 12+ ms for the tibialis anterior and 13+ ms for the gastrocnemius indicated activation of the L 5 and L 4 nerve roots, respectively, while those of 6+ ms, 7+ ms, and 8+ ms for the vastus medialis suggested activation of the L 4, L 3, and L 2 nerve roots, respectively. Conclusions:Based on the responses (CMAP latency, amplitude and motor threshold) of the vastus medialis, tibialis anterior and gastrocnemius to magnetic stimulation at different L 2 to S 1 segments, the spinal nerve root segments responsible for innervation can be inferred.

Objective To investigate the acute toxicity,irritation,and other effects of Shexiang Anhe hemorrhoid ointment on hemorrhoid-phased model rats by examining the TLR4/p38 MAPK/NF-κB signaling pathway.Methods Sixteen New Zealand rabbits were randomly divided into an intact skin Shexiang Anhe hemorrhoid ointment group,intact skin control group,broken skin Shexiang Anhe hemorrhoid ointment group,and broken skin control group,with four rabbits in each group.In the experimental group,20 g of Shexiang Anhe hemorrhoid ointment(1 g/mL)was evenly applied to an area on the rabbits depleted of hair,and an equal volume of solvent(mixture of glycerol,lanolin,and water)was evenly applied to the area on the backs of the rabbits in the control group once a day for 14 days.Another 40 rats were taken and randomly divided into a normal group,model group,Maillard group,and hemorrhoid cream group,with 10 animals in each group.The cream was applied once a day for 14 days.The acute toxicity of the cream in the intact and broken skin of rabbits was observed by hematoxylin and eosin staining and other method after treatment.In situ photographs were taken of the perianal tissues of rats with hemorrhoids to observe the efficacy of Shexiang Anhe hemorrhoid ointment,and the length and width of the ulcers were measured with vernier calipers to calculate the area.Quantitative real time polymerase chain reaction was used to detect the expression of TLR4,p38 MAPK,and NF-κB mRNA in the perianal tissues of the rats.Results Compared with rabbits in the control groups with intact or broken skin,rabbits in the administered group showed no significant difference in body mass.The mean values for the irritation evaluation points for Shexiang Anhe hemorrhoid ointment on rabbits with broken skin for 1 h,24 h,48 h,and 72 h were 1.5,1,0.5,and 0.25,respectively,showing there was no obvious skin irritation.In the hemorrhoidal rats,Shexiang Anhe hemorrhoid ointment treatment significantly reduced hemorrhoid symptoms after 14 days administration;the ulcer area was significantly smaller(P＜0.05)and TLR4,p38 MAPK,and NF-κB mRNA levels were significantly lower compared with the findings in the model group(P＜0.05).Conclusions Shexiang Anhe hemorrhoid ointment is a safe topical treatment with minimal acute toxicity and irritation to the skin and achieved good efficacy in the treatment of hemorrhoidal rats.Its mechanism of action may be related to the inhibition of the TLR4/p38 MAPK/NF-κB signaling pathway.

OBJECTIVE To study the effects of Tibetan medi cine Shanhu qishiwei pill in lowering blood lipid of hyperlipidemia（HLP）model rats ，and to explore its mechanism primarily. METHODS According to their body weigh ，60 SD rats were randomly divide into normal group ，model group ，simvastatin group （positive control ，20 mg/kg）and Shanhu qishiwei pill low-dose，medium-dose and high-dose groups （50，100，200 mg/kg），with 10 rats in each group. Normal group was given conventional diet ，and other groups were given high-lipid diet to induce HLP model ，for consecutive 4 weeks. Administration groups were given relevant medicine intragastrically at the same time of modeling ；normal group and model group were given equal volume of normal saline intragastrically ，once a day ，for consecutive 4 weeks. After last administration ，the serum levels of TC ，TG， LDL-C and HDL-C were determined ；pathological changes of liver tissue were observed ；the protein expressions of AMPK ， p-AMPK，LKB1，and HMGCR in liver tissue were detected in each group. RESULTS Low-dose，medium-dose and high-dose of Shanhu qishiwei pill could significantly reduce the serum levels of TC ，TG and LDL-C and protein expression of HMGCR in liver tissue（P＜0.05），while significantly increased serum level of HDL-C ，phosphorylation level of AMPK ，protein expression of LKB 1 in liver tissue in HLP model rats （P＜0.05）；the pathological changes of liver tissue in HLP model rats were improved to different extents. CONCLUSIONS Shanhu qishiwei pill can reduce the blood lipid level of HLP model rats ，and its mechanism may be related to inhibiting the transmission of LKB 1/AMPK signal pathway and regulating lipid metabolism.

Objective To evaluate the effect of anticoagulant therapy by pulmonary ventilation/perfusion (V/Q) imaging in chronic thromboembolic pulmonary hypertension (CTEPH) patients.Methods Thirtysix CTEPH patients (16 males,20 females,average age:(53.8±13.8) years) diagnosed by pulmonary angiography from January 2013 to December 2015 were included in this retrospective study.All patients received anticoagulant therapy for more than 6 months.They underwent pulmonary V/Q imaging before and 6 months after anticoagulant therapy.The numbers of pulmonary segments with perfusion defect,percentage of perfusion defect score (PPDs) and pulmonary arterial systolic pressure (PASP) before and after anticoagulant therapy were measured by echocardiography.Pair t test was used for data analysis.Results Before anticoagulant therapy,there were 319 pulmonary segments with perfusion defect in 36 CTEPH patients,8.9± 3.4 on average,and reduced to 8.4+3.6 after anticoagulant therapy (t =3.101,P＜0.01).The PPDs before and after anticoagulant therapy were (43.3±19.7)％ and (40.8±+20.5)％ (t=2.364,P＜0.05).In the subgroup of 9 patients with improved pulmonary perfusion,the PASP significantly decreased from (68.7±27.3)to (56.1 +±34.8) mmHg (1 mm Hg =0.133 kPa;t =2.465,P＜ 0.05) after anticoagulant therapy.In contrast,in the subgroup of 27 patients with no improved pulmonary perfusion,the PASP before and after anticoagulant therapy were (71.3±26.9) and (76.7±35.0) mmHg respectively (t=-1.511,P＞0.05).Conclusion Pulmonary V/Q imaging is a reliable method for evaluating the changes of pulmonary perfusion before and after anticoagulant therapy,and it is valuable for assessing the effect of anticoagulant therapy in CTEPH patients.

Objective To establish PKD2 gene recombinant lentivirus and to investigate its restorative effects on polycystin-2 and Wnt/β-catenin signaling pathways in Pkd2-null cell lines.Methods From August 2016 to February 2017,PKD2 gene was cleaved from the pcDNA3.1-TM-PKD2 plasmid and was inserted into the pLV-sfGFP 2A Puro by restriction enzymes Xba Ⅰ and Xho Ⅰ.The recombinant pLV-sfGFP-PKD2 plasmid was sequenced to verify a correct construction.Then we obtained recombinant lentiviruses by co-transfecting 293T cells with recombinant plasmid and packaging plasmids.B3/D3 (Pkd2 +/-) and B2/E8 (Pkd2-/-) cell lines were used to evaluate the effectiveness of lentivirus,they were divided into experimental group,control group,blank group and treated with pLV-sfGFP-PKD2 virus,pLV-sfGFP virus or culture media,respectively.The expression of PC2 was detected by Western blotting and immunofluorescence staining.Finally the cell proliferation was evaluated by detecting of proliferating cell nuclear antigen.The changes of Wnt/β-catenin signaling pathway were evaluated by real-time quantitative PCR.Results Enzyme digestion analysis and DNA sequencing showed that the recombinant plasmid pLV-sfGFP-PKD2 was constructed successfully.After infected with pLV-sfGFP-PKD2 virus,the expression of PC2 in the experimental group B2 and E8 cells(0.668 ±0.013,0.763 ±0.021) was restored to the normal level,compared with control group B3 and D3 cells,respectively (0.687 ± 0.015,P =0.164;0.776 ± 0.008,P =0.409).The proliferative activity in experimental group B2 cells(0.573 ±0.010) was significantly lower than that in control group B2 cells (0.848 ±0.031,P ＜0.01),and was returned to the level of blank group B3 cells (0.585 ±0.017,P =0.369).Reexpression of PKD2 in experimental group B2 cells also reduced the expression of Wnt7a,β-catenin,back to blank group B3 cells' level(0.037 ±0.005 vs.0.037 ±0.004,P=0.969;0.554 ±0.008 vs.0.571 ±0.013,P =0.64).Conclusions The recombinant pLV-sfGFP-PKD2 lentivirus has been constructed successfully.The lentivirus could rectify the absence of PC2 in PKD2-null cell lines,by which the hyperactivated Wnt/β-catenin signaling pathway and the abnormal cell proliferation caused by PC2 deficiency could be also restored to normal levels.

Objective: To explore the dialectical relationship between immunosuppressed cell expression and TCM inpatients with liver cancer. Methods: The clinical data of 237 HBV-related primary liver cancer patients were collectedand the differences of MDSC expression and clinical BCLC stage and intrahepatic metastasis were analyzed. Peripheralvenous blood was taken for the detection of MDSC (CD33/CDl4/HLA-DR-/low/CDllb) expression in mononuclear cells, helper T cells (Th1, Th2) and interleukin (IL-12, IL-4) ) detection. Results: There was a significant difference betweenliver stagnation and spleen deficiency syndrome (24.21％) and qi stagnation and blood stasis syndrome (5.54％) (Χ2=11.544, P ＜ 0.05) . The expression of MDSC (21.03％) was higher than that of liver-kidney yin deficiency (5.10％) in advanced hepatocellular carcinoma (＞ 5 cm) (Χ2= 8.223, P ＜ 0.005); the expression of Th2 in liver stagnation and spleendeficiency was higher than that of qi stagnation. There was a significant difference between groups in blood stasis group (t = 10.341, P ＜ 0.05) . The expression of Th2 in wet sputum was higher than that in liver and kidney yin deficiency group.There was significant difference between groups (t = 16.307, P ＜ 0.01) . The IL-4 in liver stagnation and spleendeficiency group (76.57 ± 5.01) was higher than that in qi stagnation and blood stasis group (121.70 ± 6.22); There was asignificant difference between groups (t = 21.414, P ＜ 0.05) . There was a significant difference in IL-4 (375.12 ± 5.31) inthe liver-kidney yin deficiency group compared with the group with wet phlegm (115.46 ± 4.15) (t = 12.455, P ＜ 0.05) .Conclusion: MDSC participates in tumor proliferation, invasion and metastasis by regulating Th2 and IL-4, which isclosely related to the dialectical classification of TCM.

Objective To investigate softening-hardness dissipating-binds effects of Fuzheng Huayu (reinforcing-healthy qi resolving-stasis)Tablet combined with anti-virus therapy on liver fibrosis, and relationship between these effects and regulation of pathway of miR-122-interleukin-10-reactive oxygen species(miR-122/IL-10/ROS).Methods The patients with chronic hepatitis and liver fibrosis(n=85)were chosen from Aug.2015 to Aug.2016,and then divided randomly into test group(n=45)and control group(n=40).The control group was treated with entecavir(0.5 mg/d)and monoammonium glycyrrhizinate(0.1 g/d),and test group, additionally with Fuzheng Huayu Tablet(4.5 g/d)for 48 weeks.After treatment,ISHAK fibrosis score was reviewed through routine pathology, and activities of serum superoxide dismutase(SOD)and ROS were detected by using ELISA.The expressions of miR-122 mRNA and IL-10 mRNA were detected by using RT-PCR, and content of serum inflammatory factors of liver fibrosis, including procollagen III N-terminal peptide(PCIIINP), type IV collagen(IV-C), hyaluronidase(HA)and laminin(LN),were detected by using immunoturbidimetry.Results ISHAK fibrosis score had no significant difference between 2 groups before treatment,and decreased in 2 groups after treatment,which was superior in test group to that in control group(P<0.05).The content of serum inflammatory factors of liver fibrosis all decreased in 2 groups after treatment,and the decreases of PCIIINP and HA were more significant in test group compared with control group(P <0.05).The activities of ROS and SOD had no difference in 2 groups before treatment,and ROS decreased in 2 groups after treatment.The inhibitory effect on ROS was better in test group than that in control group after treatment(P<0.05), and SOD increase was effectively relieved in test group after treatment(P <0.05).The expressions of miR-122 mRNA and IL-10 mRNA all decreased in 2 groups after treatment, which was more significant in test group compared with control group(P<0.05).Conclusion Fuzheng Huayu Tablet reduces directly the levels of collagen and HA, degrades abnormal deposition of extracellular matrix,and regulates dynamic balance of collagen,and it antagonizes effectively the genetic expressions of IL-10 and miR-122,relieves inflammatory disorders and controls progress of histology.

Objective To prospectively compare cadmium-zinc-telluride (CZT) SPECT gated myocardial perfusion imaging (GMPI),conventional SPECT MPI and cardiac MRI for the assessment of left ventricular volume and ejection fraction in patients with heart failure.Methods From July 2016 to October 2016,a total of 35 patients (27 males,8 females,average age:(52.7±14.9) years) with heart failure were consecutively included.All patients underwent CZT SPECT GMPI,conventional SPECT GMPI and cardiac MRI within 7 d.LVEDV,LVESV and LVEF of three imaging modalities were calculated.One-way analysis of variance,Pearson correlation analysis and Bland-Altman analysis were used.Results CZT SPECT showed excellent correlation with conventional SPECT for LVEDV,LVESV and LVEF (r values:0.983,0.986 and 0.910,respectively;all P＜0.001).Bland-Altman analysis revealed good agreement between CZT SPECT and conventional SPECT for LVEDV,LVESV and LVEF.The correlation between CZT SPECT and cardiac MRI for LVEDV,LVESV and LVEF were all significant (r values:0.864,0.896 and 0.836,respectively;all P＜0.001).Compared with cardiac MRI,CZT SPECT showed systemic underestimation of LVEDV and LVESV and good agreement of LVEF by Bland-Altman analysis.Conclusions CZT SPECT has high clinical value for patients with heart failure.Despite underestimating LVEDV and LVESV,it correlated well with cardiac MRI.It also has a good agreement with conventional SPECT on left ventricular volume and LVEF.