Infusion of Human Mesenchymal Stem Cells Improves Regenerative Niche in Thioacetamide-Injured Mouse Liver

BACKGROUND@#This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. @*METHODS@#Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. @*RESULTS@#WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-b1-stimulation in Smad2 phosphorylation and RhoA upregulation. @*CONCLUSION@#These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

Infusion of Human Mesenchymal Stem Cells Improves Regenerative Niche in Thioacetamide-Injured Mouse Liver

BACKGROUND@#This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. @*METHODS@#Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. @*RESULTS@#WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-b1-stimulation in Smad2 phosphorylation and RhoA upregulation. @*CONCLUSION@#These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.

Babaodan Capsules for viral hepatitis: systematic review of clinical efficacy and safety and Meta-analysis of randomized clinical trials / 中国中药杂志

To systemically analyze the efficacy and safety of Babaodan Capsules in treatment of viral hepatitis. Databases such as CNKI,Wan Fang Date,VIP,Sino Med,PubMed,and Cochrane Library were electronically searched for relevant randomized controlled trials about Babaodan Capsules in the treatment of viral hepatitis,from database establishment to November 11,2018. Two researchers independently screened the literature and extracted data according to the inclusion criteria. GRADE system was used to evaluate evidence quality,and we used the Cochrane Rev Man 5. 3 software for Meta-analysis. Six randomized controlled trials including 520 subjects were included. Babaodan Capsules combined with conventional treatment were used as intervention measures,and the conventional treatment was used as the control measures. The results showed Babaodan Capsules combined with conventional treatment had better efficacy on reducing the total bilirubin( MD =-16. 25,95% CI[-19. 86,-12. 63]),alanine aminotransferase( MD =-26. 62,95% CI[-41. 18,-12. 06]),total bile acid( MD=-46. 02,95%CI[-49. 18,-42. 85]) and improving clinical efficiency( RR = 1. 34,95%CI[1. 13,1. 59]) than conventional treatment alone. In addition,Babaodan Capsules combined with conventional treatment can delay the progression of liver fibrosis to some extent. Qualitative analysis showed that the combined treatment regimen was more effective in relieving clinical symptoms. There was no significant difference between the two regimens in increasing albumin and prothrombin activity. Babaodan Capsules combined with conventional treatment showed no adverse reactions. In summary,for patients with viral hepatitis,the combination of Babaodan Capsules and conventional treatment has more advantages in reducing total bilirubin,alanine aminotransferase and total bile acid and is more effective in improving clinical symptoms as compared with conventional Western medicine,with no serious adverse reactions. Its clinical application with syndrome differentiation method can be considered. However,due to the limited number and quality of the original researches,more multi-center,high-quality randomized controlled trials are needed for further verification.

Efficacy and safety of huperzine A in treating patients with mild cognitive impairment: a systematic review and Meta-analysis / 中国中药杂志

To evaluate the efficacy and safety of huperzine in treating patients with mild cognitive impairment. The randomized controlled trials(RCT) were retrieved from EMbase, Cochrane Library, PubMed, CNKI, Wanfang and VIP. The methodology quality of the included studies was evaluated, and a Meta-analysis was performed using RevMan 5.3 software. A total of nine RCTs were included. The Meta-analysis results showed that compared with placebo, Huperzine significantly increased the scores of memory quotient(MQ) and mini-mental state examination(MMSE). However, there was no statistical difference between oral tablet and capsule. Compared with placebo, huperzine A was superior in the scores of MQ and MMSE. Huperzine is safe with mild side effects. Due to the low quality of original studies, more high-quality studies are needed to verify its efficacy.

Efficacy and safety of Gantaishu Capsules for viral B hepatitis:a systematic review and Meta-analysis / 中国中药杂志

To evaluate the efficacy and safety of Gantaishu Capsules in the treatment of viral B hepatitis. The randomized controlled trials( RCT) retrieved from Cochrane Library,PubMed,Sino Med,CNKI,Wan Fang and VIP were enrolled. The methodology quality of the included studies was evaluated,and a Meta-analysis was performed using Rev Man 5. 3 software. A total of six randomized controlled trials were included. Meta-analysis results showed that the similarities in the negative conversion rate of HBe Ag( RR = 2. 09,95%CI[0. 90,4. 85],P = 0. 09,I2= 0%),the HBV-DNA negative rate( RR = 1. 49,95% CI[0. 56,3. 95],P = 0. 43,I2= 0%) and the changes in ALT levels before and after treatment( RR =-6. 28,95%CI[-72. 83,60. 27],P = 0. 85,I2= 99%),with no statistical difference. In terms of quality of life,Gantaishu Capsules can significantly alleviate the symptoms of hepatitis B patients,with less adverse reactions. Gantaishu Capsules and Dongbao Gantai Tablets were similar in antiviral effect. In this term,Gantaishu Capsules was superior to Dangfei Liganning Capsules. It can significantly alleviate the symptoms of chronic hepatitis B patients,with a good clinical safety.Therefore,it can be applied in the case of syndrome differentiation and treatment. In view of the low quality of the included studies,more high-quality clinical trials were required to confirm its efficacy.

Nerve growth factor upregulates sirtuin 1 expression in cholestasis: a potential therapeutic target

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.

Clinical application evaluation and revision suggestions of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis / 中国中药杂志

To investigate the clinical application of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis, in order to promote the follow-up revision and further promotion of the Guidelines. Copies of 500 application evaluation questionnaire and 500 copies of applicability evaluation questionnaire were given to the clinicians who had used this Guideline in China, both in a form of registered questionnaire, and a database was established by Excel 2016 for descriptive statistical analysis. Copies of 211 application evaluation questionnaire and 211 copies of applicability evaluation questionnaire were collected. We can conclude from the survey that we should adjust the whole content and structure on the basis of better evaluation of the present recommendation scheme, update the prescription selection and clinical evidence of the recommendation scheme, and put forward the improvement measures for the hindrance factors in the application of the Guideline. Furthermore, in order to promote the Guideline more clearly, we should strengthen the doctor-patient education, improve guidance quality and increase the publicity, providing basis for the implementation and promotion strategies of the Guideline.

Interpretation and prospect of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis / 中国中药杂志

Clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis is strictly in accordance with the latest diagnostic criteria for sepsis (sepsis-3) for the treatment of septic patients at different stages through syndrome differentiation. At present, the abuse of antibiotics and the prevalence of drug-resistant bacteria are very serious, without effective solutions. Thus, this is the first time to focus on traditional Chinese medicine combined with antibiotics to treat sepsis, in order to minimize the incidence of drug-resistant bacteria. This Guideline tends to systematically analyze the sepsis period, septic shock period as well as different clinical symptoms and traditional Chinese medicine measures for organ dysfunction in the sepsis process. By analyzing and interpreting the Guideline systematically, the clinicians could understand its purpose, significance and core ideas more thoroughly, and grasp the recommended specific interventions as well as their advantages and disadvantages, hoping to better implement the Guideline, provide guidance to clinicians and standardize the treatment of sepsis by traditional Chinese medicine.

The study of natural head posture in edentulous patients before and after oral rehabilitation / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To study the natural head posture (NHP) of edentulous patients compared with dentate people and to understand NHP shift immediately inserting complete dentures and three months after denture wearing.</p><p><b>METHODS</b>The NHPs of twenty edentulous patients and twenty-two dentate subjects were recorded with cephalometric technique. The NTPs of edentulous patients were exposed three times, before inserting, right after inserting and three months after inserting dentures. The NHPs of dentate subjects were recorded once as a controlled group. Six angles measured from the radiographs were evaluated for the NHP and three angles and two linear measures for the mandibular position.</p><p><b>RESULTS</b>Compared with dentate subjects, the craniomandibular angles of the edentulous patients increased and the camber of the cervical columns decreased, but changes of the NHP were not significant. The mandible showed a significant upward moving (P < 0.05) and an insignificant forward moving. At the time of denture insertion, the camber of the cervical columns significantly increased (P < 0.05). Three months after using the dentures, the craniomandibular angles of the patients obviously decreased. (P < 0.05).</p><p><b>CONCLUSION</b>The shift of NHP after denture inserting does exist. The shifted NHP of the patients with dentures is a new balanced posture and closer to the normal position than the NHP of them without dentures.</p>