Liver fibrosis is the inevitable course for the progression of chronic hepatitis B to liver cirrhosis and is also the most important risk factor for hepatocarcinogenesis, and therefore, blocking and reversing liver fibrosis is an important strategy to effectively reduce the development of chronic hepatitis B cirrhosis and liver cancer. There are currently no effective drugs and measures for the treatment of liver fibrosis in Western medicine, and traditional Chinese medicine (TCM) has unique advantages in the treatment of liver fibrosis; however, due to a lack of strict and standardized clinical research, there is still no high-quality evidence for support from the aspect of evidence-based medicine (EBM). With subsidies from National Science and Technology Major Project in the 12th and 13th five-year plans, the authors conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial on compound Biejia Ruangan tablets combined with entecavir in blocking and reversing chronic hepatitis B liver fibrosis. With liver biopsy as the gold standard, 1000 patients were enrolled to confirm the efficacy of compound Biejia Ruangan tablets combined with entecavir in blocking and reversing liver fibrosis and cirrhosis, and this study has become the first clinical trial investigating the anti-liver fibrosis effect of TCM supported by high-quality EBM evidence, bringing great hope to patients with chronic liver diseases and helping TCM move towards the world. This article introduces these research findings and reviews the current status and challenges of TCM in blocking and reversing liver fibrosis.

Objective:To provide clues for exploring the molecule mechanisms underlying ruptured intracranial aneurysms(IAs)by constructing a competitive endogenous RNA(ceRNA)network.Methods:Gene expression data sets of 21 ruptured IAs(RIAs)and 21 unruptured IAs samples were downloaded from the Gene Expression Omnibus(GEO)database.First, mRNAs and long non-coding RNAs(lncRNAs)related to ruptured IAs were identified by integrated analysis of weighted gene co-expression network analysis(WGCNA)and differential gene expression analysis with DESeq2, respectively.Then, mRNA-miRNA associations were obtained based on miRWalk 2.0; miRNA-lncRNA associations were predicted based on miRcode and data from the literature.Lastly, a ceRNA network including mRNAs, miRNAs, and lncRNAs was constructed via combining lncRNA-miRNA associations and lncRNA-miRNA associations.Results:A total of 470 mRNAs and 78 lncRNAs related to ruptured IAs were obtained through WGCNA and differential gene expression analysis.Based on the databases, 49 miRNAs were predicted to be able to bind to the above mRNAs and lncRNAs, and in combination with data from the literature, 13 miRNAs, 7 lncRNAs and 73 mRNAs were screened to construct a ceRNA network.Conclusions:A new ruptured IA-related ceRNA network including 13 miRNAs, 7 lncRNAs and 73 mRNAs has been constructed and may provide some clues for exploring the mechanisms underlying ruptured IAs.

OBJECTIVE:To study the effects of new Xianling gubao capsule on fracture healing in rats,and to provide reference for seeking new formula of"to reduce stockpiles and increase efficiency(to reduce stockpiles and constant efficiency)".METHODS:Rats were randomly divided into sham operation group(distilled water),model group(distilled water),Xianling gubao capsule group (350 mg/kg),new Xianling gubao capsule low-dose,medium-dose and high-dose groups (53,105,210 mg/kg),with 14 rats in each group. Except for sham operation group,right middle femur fracture model was established under the anesthetic state. Rats were given relevant medicine 10 mL/kg intragastrically after woken,once a day,for consecutive 4 weeks.After last administration,body weights of rats were determined;the formation of callus and histopathological changes in fracture were observed;biomechanics of fracture side(fracture stress and bone crushing force)was measured. The levels of inflammatory factors (TNF-α ,IL-1 β) in serum were detected by ELISA. RESULTS:Compared with sham operation group,body weight,fracture stress and bone crushing force of fracture side were decreased significantly(P<0.05 or P<0.01),while the serum levels of TNF-α and IL-1 β were increased significantly(P<0.01). In model group,the scab was visible around the fracture,and the trabecular bone was not mature and arranged in confusion. Compared with model group,body weights of rats were increased significantly in new Xianling gubao capsule high-dose group and Xianling gubao capsule group (P<0.05);fracture stress of fracture side were increased significantly in new Xianling gubao capsule medium-dose and high-dose groups and Xianling gubao capsule group(P<0.05 or P<0.01). The serum levels of TNF-α and IL-1β were decreased significantly(P<0.01). There was no statistical significance in above indexes among new Xianling gubao capsule groups and Xianling gubao capsule group(P>0.05).The area of the callus in each group was smaller;the fracture line became blurred;the fracture trace disappeared and the number of bone trabeculae increased. The cortical layer was thickened,and a large number of capillary implants were found in the bone marrow cavity. CONCLUSIONS:New Xianling gubao capsule has a significant role in promoting fracture healing,and can effectively improve the strength of bone biomechanics and inhibit the inflammatory reaction.

Objective: To study the expression of transmembrane protein CMTM2 in the testis and sperm of adult males and to approach the potential function of the protein in the male reproductive system.Methods: The expression of CMTM2 in human testis and sperm was confirmed by Western blot.Immunohistochemical staining was used for detecting CMTM2 localization in the testis tissue, TRITC-CMTM2 and FITC-Hoechst double immunofluorescence staining was performed to examine the subcellular localization of CMTM2 in the human sperm before and after acrosome reaction, that is, immunofluorescent staining was used for detecting CMTM2 localization in both the testis and sperm before and after the acrosome reaction.Results: CMTM2 was presented in both human testis and sperm.In the testis, CMTM2 immunoreactive particles were observed mainly in the membrane of the different stages of spermatogenic cells.In the human sperm, its immunoreactivity was restrictively localized to the posterior head where sperm-egg fusion occurred, and the CMTM2 localization was not affected by sperm acrosome reaction.CMTM2 was widely expressed in seminiferous tubules of the human testis, mainly in the cell membranes of spermatogenic cells, which was consistent with the previous reports.The immunofluorescence performed on frozen human testis slides showed similar findings with immunohistochemistry, which gave weight to the localization of CMTM2 in the cell membranes of spermatogenic cells at different stages.TRITC-CMTM2 and FITC-Hoechst double immunofluorescence staining was performed to examine the subcellular localization of CMTM2 in the human sperm before and after acrosome reaction.CMTM2 was localized at the posterior head of sperm before and after acrosome reaction.The localization and expression of CMTM2 were not affected by sperm acrosome reaction.Conclusion: Expression of CMTM2 in the male reproductive system of the adult human exhibits cell-and region-specific patterns, which suggests that they may play an important role in spermatogenesis and sperm-egg fusion.The expression of CMTM2 in the male reproductive system of the adult human exhibits cell-and region-specific patterns, which suggests that they may play an important role in spermatogenesis and sperm-egg fusion.However, it still remains to be further elucidated about the definite role of CMTM2 in male reproductive system and the process of spermatogenesis.And in vitro fertilization experiments are needed to confirm the role of CMTM2 in fertilization in future.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Humans ; Lymphoma, Follicular ; drug therapy ; Rituximab

OBJECTIVEA prospective, multicenter and non-interventional prospective study was conducted to evaluate the clinical features of rituximab combined with chemotherapy (R-Chemo) as first-line treatment on newly diagnosed Chinese patients with diffuse large B-cell lymphoma (DLBCL).

METHODSThis was a single arm, prospective, observational multicenter and phase IV clinical trial for 279 patients, who were newly diagnosed as CD20-positive DLBCL from 24 medical centers in China 2011 and 2012, no special exclusion criteria were used. All patients received rituximab based R-Chemo regimes, such as R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone) and other regimes as the first-line treatment. The treatment strategies were determined by physicians and patients without detailed description for treatment course, dose, interval time and examination. Clinical response and safety of all patients were investigated in 120 days after completion of last dose of rituximab.

RESULTSOf 279 patients, 258 with stage I-IV who received at least 1 cycle of rituximab treatment and completed at least one time of tumor assessment were enrolled into intention-to-treat analysis, including 148 male and 110 female. The median age of all patients was 57.2(12.8-88.4) years. ECOG performance statuses of 0 or 1 were observed in 91.1% of patients, international prognostic index levels in the low-risk and low-middle-risk groups in 76.4% of patients, the tumor diameters smaller than 7.5 cm in 69.0% of patients. All patients received 6 median cycles of R-Chemo treatment every 24.4 days. R-CHOP treatment was shown to improve the clinical response with overall response rates of 94.2%. Common adverse events included anemia, marrow failure, leukopenia, thrombocytopenia, digestive diseases, infection and liver toxicity. All adverse events are manageable.

CONCLUSIONNon-interventional clinical trial of R-Chemo remains the standard first-line treatment for newly diagnosed patients with DLBCL in real clinical practice, which is consistent with international treatment recommendations for DLBCL patients. R-Chemo can provide the clinical evidence and benefit as the first-line standard treatment for Chinese patients with DLBCL.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; Treatment Outcome

OBJECTIVE: To investigate the association of tyrosine hydroxylase (TH) C-824T polymorphism with essential hypertension (EH) susceptibility in Hunan Han population by a case-control study. METHODS: A case-control study was performed on 368 EH patients and 353 healthy controls of Han nationality recruited in Hunan province. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)was used to genotype the C-824T polymorphism. RESULTS: (1) Genotype frequencies for TH-824CC and -824CT+-824TT genotypes were 89.9% and 10.1%, respectively for EH patients and 88.7% and 11.3%, respectively for the controls. No significant difference in the genotype distribution of C-824T polymorphism between the patients and controls was observed (P=0.579). Allele frequencies of TH C-824T also showed no significant difference between the patients and controls (P=0.515). (2) When adjusted by EH risk factors, results of unconditional logistic regression analysis showed that there was no association between TH C-824T polymorphism and EH susceptibility (P=0.264). (3) When stratified by gender, no significant difference in the genotype distribution of TH C-824T polymorphism was observed between the patients and controls in either male or female subjects (P=0.841 and P=0.288). (4) Diastolic blood pressure (DBP) in individuals with -824 CT+TT genotype was significantly higher than that in individuals with -824 CC genotype in the controls (P=0.015). (5) When stratified by gender, significant difference in DBP between TH C-824T CT+TT genotype and CC genotype was observed in the male (P= 0.018) but not in the female (P=0.083) controls. CONCLUSION There is no association between TH gene C-824T polymorphism and EH susceptibility in Hunan Han population. The TH gene C-824T polymorphism is possibly associated with increased DBP in the males in Hunan Han population.
Adult ; Case-Control Studies ; China ; ethnology ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension ; enzymology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Sex Factors ; Tyrosine 3-Monooxygenase ; genetics

Objective To analyze the elonal gene rearrangement and complementarity determining region 3 (CDR3) Repertoire of TCR β-chain in fine needle aspiration biopsy (FNAB) specimens of peripheral T-cell lymphoma. Methods The TCR CDR3 region genes of 24 TCR Vβ subfamilies were amplified by utilizing RT-PCR technology, and the CDR3 size lengths of TCR β-chain were analyzed with genesean technology for 4 healthy individuals and 4 patients with peripheral T-cell lymphoma. The clonality of T cells presumed by spectratyping was further confirmed by CDR3 sequencing. Results TCR β-chain presented specific repertoire skewing in 4 cases with peripheral T-cell lymphoma, and only 1-4 TCR Vβ subfamily T cells were identified, respectively. Clonal expanded T cells, including mono, bioclonal and oligoclonal trend patterns, in one or more Vβ subfamilies were found in all cases. The mono expanded T cells have different CDR3 amino acid sequences. Conclusion Characteristic T cells cloning proliferation and selected usage of TCR Vβ subfamily T cells were found in 4 cases with peripheral T-cell lymphoma. The sequences of CDR3 in different TCR clone proliferation are different.

Objective To investigate the inhibitory effect of reiniosidc C (RC) on asymmetric dimethylarginine (ADMA)-induced soluble interacellular adhesion molecule-1 (slCAM-1) expression and its mechanisms. Methods Human umbical vein endothelial cells (HUVEC 12) were cultured.The level of slCAM-1 in the conditioned medium was determined by ELISA. Changes in intracellular reactive oxygen species (ROS) levels were determined by measuring the oxidative conversion of cell permeable 2', 7'-dichlorofluorescein diacetate (DCFH-DA) to fluorescent dichlorofluorescein (DCF) in fluorospectro- photometer, and the nuclear factor-κB (NF-κB) DNA-binding activity was determined by electrophoretic mobility shift assays (EMSA). Results sICAM 1 expressions [(138.02±16.40), (194.52±11.14), (274.28±13.11)ng/L]and the generation of ROS[(75.64±5.22),(100.18±11.15),(107.23±13.45)units] in HUVEC-12 were time dependently increased by ADMA (30 μmol/L). Furthermore, thc generation of ROS [(85.33±8.68), (70.69±7.65),(59.12±4.15)units], activation of NF-κB activity and expression of sICAM-1 [(336.58±23.32),(203.27±25.18) ,(174.13±14.53)ng/L] induced by ADMA were inhibited by reinioside C (1,3,10μmol/L) in a dose-dependent manner. This effect was found to be the same by L-arginine (0.5 mmol/L) as NOS substrate and by pyrrolidine dithiocarbamate (PDTC) (10 μmol/L)as inhibitor of NF-κB.Conclusions Reinioside C attenuates the increase of sICAM-1 induced by exogenous ADMA