Abstract:Graft-versus-host disease (GVHD) is the most common complication after allogeneic hematopoietic stem cell transplantation, and also an important factor affecting the survival and quality of life in patients after transplantation. Currently, immunosuppressive therapy is commonly used for GVHD, but the curative effect is not ideal. How to effectively prevent and treat GVHD is one of the difficulties to be solved urgently in the field of transplantation. In this paper, we summarize the latest progress in pathogenesis, prevention and treatment of GVHD with Chinese medicine (CM). We hope it will provide ideas and methods for exploring the mechanism and establishing a new comprehensive therapy for GVHD with CM.
Abstract:Objective:To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue (调肝健脾和血) and Tiaogan Jiedu Huashi (调肝解毒化湿) fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients.Methods:A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented.Results:The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between two groups on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns.Conclusion:Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Abstract:Objective:To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (青黄散, QHP) or low-intensity chemotherapy (LIC).Methods:Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed.Results:Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, P>0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all P>0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age > 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (P>0.05).Conclusion:QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.
Keywords:acute myeloid leukemia;Qinghuang Powder;Realgar;arsenic;elderly patient;Chinese medicine
Abstract:Objective:To investigate the inhibitory effect of Linggui Zhugan Decoction (LZD, 苓桂术甘汤) on the ventricular remodeling (VR) after acute myocardial infarction (AMI) and related mRNA and proteins expression in transforming growth factor-beta 1 (TGF-β1)/Smad signaling pathway, and explain its putative mechanism.Methods:A VR model was generated by ligation of coronary artery in rats. Two weeks after surgery, 60 rats were randomly divided into the model group, the sham-operation group (distilled water), the positive control group (2.4 mg/kg simvastatin), and the low-, medium- and high-dose LZD groups (2.1, 4.2, 8.4 g crude drug/kg, respectively) by a random number table, 10 rats in each group. Rats in each group was treated for 4 weeks. Changes of hemodynamics indices and cardiac weight index were detected by the PowerLab data acquisition and analysis recording instrument. Morphology changes of myocardial tissue were observed by hematoxylin-eosin and Masson staining. The expressions of TGF-β1, Smad2, Smad3, p-Smad2 and p-Smad3 in myocardial tissue were detected by Western blotting. The mRNA expressions of TGF-β1, Smad2 and Smad3 were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expressions of matrix metalloprotein 2 (MMP2), MMP9, collagen Ⅰ and collagen Ⅲ were observed by immunohistochemical methods.Results:VR rats showed significant dysfunction in hemodynamic indices and cardiac structure and function. Compared with the shamoperation group, myocardial tissue damage, interstitial fibrosis occurred in the model rats, left ventricular systolic pressure (LVSP), left ventricular pressure maximum contraction rate (+dp/dtmax) and left ventricular pressure maximum relaxation rate (-dp/dtmax) decreased significantly (all P<0.01), while left ventricular end-diastolic pressure (LVEDP), cardiac weight index and left ventricular weight index elevated significantly, meanwhile TGF-β1, p-Smad2, p-Smad3, Smad2, Smad3, MMP2, MMP9, collagen Ⅰ, collagen Ⅲ protein expressions in myocardial tissue and TGF-β1, Smad2 and Smad3 mRNA expressions increased significantly (all P<0.01). Compared with the model group, LZD could significantly improve the pathological changes of myocardial tissue, increase LVSP, +dp/dtmax and -dp/dtmax, lower LVEDP, reduce the whole heart weight index and left ventricular weight index and inhibit the over-expressions of TGF-β1, p-Smad2, p-Smad3, Smad2, Smad3, MMP2, MMP9, collagen Ⅰ and collagen Ⅲ proteins in myocardial tissue and mRNA expressions of TGF-β1, Smad2 and Smad3 (P<0.05 or P<0.01).Conclusion:LZD can significantly suppress VR induced by AMI, and its underlying mechanism may be associated with its inhibitory effect on the TGF-β1/Smad signaling pathway.
Abstract:Objective:To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbitsMethods:Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL) method, and apoptosis index (AI) was calculated.Results:Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01).Conclusion:CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.
Keywords:ophiopogon polysaccharide;notoginseng total saponins;Rhizoma Coptidis alkaloids;advanced glycation end products;p-C-N-Jun terminal kinase;diabetic atherosclerosis;myocardial apoptosis
Abstract:Objective:To investigate the effect of hydrogen-rich Korean Red Ginseng (KRG) water (HRGW) mixture on the spermatogenesis and sperm motility of mice of different ages.Methods:Eighty young (3 month-old) and aged (12 month-old) male mice were randomly assigned to 4 groups (n=10 per group) including control group, hydrogen-rich water (HRW) group (10 mL/kg daily), KRG group (50 mg/kg daily) and HRGW group (10 mL/kg HRW and 50 mg/kg KRG daily) by an oral zoned needle for 4 weeks. Sperm count and motility were measured using sperm suspension released from cauda epididymis. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and reactive oxygen species (ROS) in serum have also been estimated. Tubular changes were examined through histological hematoxylin and eosin staining. Expression of antioxidation (PPx3, PPx4, GSTm5 and GPx4), spermatogenesis (inhibin-α, neptin-2 and CREM), antiaging (SIRT1 and SIRT2), and angiogenesis [visfatin and vascular endothelial growth factor (VEGF)] related genes were examined through realtime polymerase chain reaction.Results:HRW and KRG treatment stimulated spermatogenesis followed by increasing sperm production and sperm motility (P<0.05). These effects were strengthened synergistically by a HRGW mixture (P<0.05 or P<0.01). HRGW greatly increased the expressions of antioxidation, antiaging, spermatogenesis related genes and VEGF especially in aged mice (P<0.05). Serum testosterone and FSH levels also increased, while serum ROS level decreased (all P<0.05).Conclusion:HRGW increases sperm production and motility by enhancing antioxidation and stimulating spermatogenesis and sex hormone production, particularly in aged mice.
Abstract:Objective:To evaluate the inhibitory effect of bear bile powder (BBP) on hepatocellular carcinoma (HCC) growth in vivo and investigate the underlying mechanisms.Methods:A HCC xenograft mouse model was developed by producing with huh7 cells. After 5 days following xenograft implantation, ten HCC xenograft mice were given intra-gastric administration with 10 mg/(kg•d) dose of BBP or saline for 3 weeks. Tumor growth in HCC xenograft mice was evaluated by measuring the tumor weight and volume. Cell apoptosis, proliferation or tumor angiogenesis were examined via immunohistochemical (IHC) staining for transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), proliferating cell nuclear antigen (PCNA) or cluster of differentiation 31 (CD31), respectively. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) were determined by Western blot. The mRNA and protein expressions of Bcl-2, Bax, Cyclin D1 and Cyclin-dependent kinase 4 (CDK4) in HCC tumor tissues were respectively determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The protein expression of vascular endothelial growth factor A (VEGF-A) in tumor tissues was examined by IHC staining.Results:BBP treatment led to a significant decrease on tumor volume and tumor weight in HCC mice (P<0.05) and had no effect on the change of body weight. In addition, BBP profoundly promoted cell apoptosis, inhibited cell proliferation and intratumoral microvessel density in HCC tumor tissues (P<0.05). Moreover, BBP treatment remarkably suppressed the STAT3 phosphorylation and modulated the expression of critical target genes including Bcl-2, Bax, Cyclin D1, CDK4 and VEGF-A in HCC mice.Conclusion:BBP exerts its anti-cancer activities via suppressing STAT3 signaling pathway and affecting multiple intracellular targets.
Keywords:bear bile powder;Chinese medicine;hepatocellular carcinoma;signal transducer and activator of transcription 3 pathway
Abstract:Background:Neck pain caused by cervical spondylosis (CS) is a chronic pain condition, with an increasingly high incidence in the general population. Electroacupuncture is a common analgesic modality that has been widely applied in neck pain treatment. However, current electroacupuncture instruments used in the clinic have low intelligence levels and obscure parameter standards. We here designed this study for assessing the effect and safety of a new, intelligent electroacupuncture instrument, the CX-DZ-Ⅱ, in treating neck pain.Methods:The present study is a prospective, two-center, randomized, controlled, open-label, non-inferiority trial for CX-DZ-Ⅱ on treating neck pain caused by CS. Totally 160 eligible patients will be included in this trial and randomly assigned to an experimental group and a control group in a 1:1 ratio. A semi-standard acupoint selection strategy will be employed. In the experimental group, selected acupoints will be stimulated by CX-DZ-Ⅱ. Electroacupuncture treatment will be accomplished by a pre-existing electroacupuncture instrument in the control group. The duration of treatment will be 2 weeks. The primary outcome is the change of Visual Analog Scale (VAS) score after one course of treatment. The secondary outcomes include the VAS scores after each treatment, the responder rate, drug-usage rate of non-steroidal antipyretic analgesics, the rate of adverse events occurrence, and the performance of instrument.Discussion:This study will evaluate the effect and safety of the CX-DZ-Ⅱ intelligent electroacupuncture therapeutic instrument in comparison with a pre-existing non-intelligent instrument in the treatment of neck pain caused by CS. The results will hopefully demonstrate a more optimal electroacupuncture instrument for the treatment of neck pain. (Trial registration No. gov NCT03005301).
Abstract:Objective:To evaluate the efficacy and safety of topical delivery of modified Da-Cheng-Qi Decoction (加味大承气汤, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design.Methods:Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcomes were the remission of intestinal obstruction, improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators.Results:Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, were as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal functions or blood coagulation were observed.Conclusion:Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.
Abstract:The development of Chinese medicine and Western medicine andrology is based on different social background and academic systems, either Chinese medicine or Western medicine andrology has their limitations, therefore, integration of Chinese and Western medicine (ICWM) andrology is in a great need. After more than 30 years of development, andrology has made great achievements in the construction of specialized academic association, holding academic conferences and publication of academic monographs, and the research progress on this field is mainly in the combination of disease and syndrome, microdifferentiation of symptoms and signs and basic research development. However, the comprehensive theoretic system of ICWM andrology has not yet established, and the related studies are still on the primary stage. In the future studies, great efforts still need to be made to expand the methods for the investigation of ICWM, and make innovations in the field of andrology.
Abstract:With the increasing number of cardiovascular patients, more and more people are living with diseases. Cardiac rehabilitation (CR) is an effective treatment and prevention measure for cardiovascular disease (CVD), which aims to relieve both psychological and physiological stress of CVD, reduce risk of death from CVD, improve cardiovascular function and patients' quality of life. Tai Chi is popular in China and mainly used as a daily leisure activity for the elderly to strengthen their bodies. This review discusses whether Tai Chi could be taken as a positive intervention in CR and what is the exact role and its mechanisms as exercise therapy for CVD. The authors detail the role of Tai Chi on CR from the aspects of exercise capacity, risk factors of CVD and psychological factors, etc., as well as highlight the limitation of Tai Chi research at present.