Abstract:Monoclonal gammopathy of renal significance (MGRS) is a pathological state which presents with a spectrum of renal lesions. MGRS is characterized by pathogenic monoclonal immunoglobulins or light chains produced by a premalignant plasma cell or B cell clone. In view of inadequate understanding in the past, the low detection rate of MGRS often results in poor outcomes and reduces quality of life of patients. Thus, MGRS stands for a group of clinical refractory renal diseases. To date, no standard treatment strategy for MGRS is available. Current consensus suggests a clone-directed approach that aims to eradicate the offending clone, but its long-term prognosis is not clear. In this article, we discuss the diagnostic methods, highlight treatment advances, and introduce integrated Chinese and Western medicine in the management of MGRS.
Keywords:monoclonal gammopathy of renal significance;Chinese medicine;integrative medicine
Abstract:Objective:To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy.Methods:A multi-centre, randomized, singleblind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted.Results:In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period.Conclusion:HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883)
Keywords:mixed haemorrhoids;high suspension and low incision surgery;randomized controlled trial;Milligan-Morgan haemorrhoidectomy
Abstract:Objective:To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities.Methods:The data set was collected from the Chinese medicine (CM) electronic medical records of 33, 458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis.Results:The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup.Conclusion:The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups.
Abstract:Objective:To preliminarily explore the potential effect of β-glucan on Chinese medicine (CM) concept protective qi deficiency (PQD), and the methodology for future definitive studies.Methods:To have a standardized assessment of PQD, a list of 13 potentially PQD-relevant parameters were firstly created, each with defined quantitative or categorial scales. Using the data from 37 participants with (21 cases) or without (16 cases) PQD, multivariate logistic modeling was conducted to create a preliminary diagnostic PQD risk score. Subsequently, 21 participants diagnosed with PQD were treated with β-glucan in a dose of 200 mg/day for 8 weeks. Data were collected for trial acceptability measures (rate of recruitment, withdrawal, and compliance), and the participants were assessed for PQD status at baseline and every 2 weeks thereafter.Results:The preliminary logistic model consisted of 3 parameters (low voice and apathy, aversion to wind and cold, and Cun pulse). The resulting risk score demonstrated a degree of PQD-predicting accuracy that, as evaluated by statistical (discrimination and classification) methods, was higher than those obtained from any of the individual candidate parameters. The 21 PQD participants treated with β-glucan demonstrated good receptibility and a time-dependent improvement in PQD status as evidenced by the decrease of PQD participant to 9.5% at the end of study.Conclusions:This study demonstrated the effect of proof-of-concept of β-glucan on improving PQD and the proof-of-concept of a multivariate-model-derived diagnostic PQD risk score. It also indicated feasibility for future definitive studies. Studies like this embody an innovative approach that uses therapies derived from the mainstream biomedicine to enrich therapeutics guided by CM principle. (Trial registration No. NCT03829228)
Abstract:Background:Colorectal cancer (CRC) is the second most common cause of cancer-related deaths and has the third highest incidence in the world. Almost half of the patients with CRC have metastases at the time of diagnosis. However, the treatment for patients with metastatic CRC that progresses after approved conventional chemotherapy is still controversial. Chinese medicine (CM) has unique characteristics and advantages in treating metastatic CRC.Objective:To assess the effectiveness and safety of CM in patients with metastatic CRC after failure of conventional chemotherapy.Methods:The study is a multicenter prospective cohort study. A total of 384 patients with documented metastatic CRC after failure of conventional chemotherapy will be included from 9 hospitals at Beijing, Shanghai, Nanjing, and Guizhou, and assigned to three groups according to paitents' wishes: (1) integrated Chinese and Western medicine (ICM) group receiving CM herbal treatment combined with Western medicine (WM) anti-tumor therapy, (2) Chinese medicine (CM) group receiving only CM herbal treatment, and (3) WM group receiving only WM anti-tumor therapy. The primary endpoint is the overall survival (OS). Secondary endpoints include the progression free survival (PFS), quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire, tumor control, and CM symptom score.Discussion:This prospective study will assess the effectiveness and safety of CM in treating metastatic CRC after conventional chemotherapy failure. Patients in the ICM group will be compared with those in the WM group and CM group. If certified to be effective, national provision of CM treatment in metastatic CRC will probably be advised. (Registration No. NCT02923622)
Abstract:Objective:To examine the role of carvacrol in modulating PI3K/AKT signaling involved in human breast cancer pathogenesis using in vitro experimental model MCF-7 cells.Methods:MTT and lactate dehydrogenase assays were performed with cells treated with different doses of carvacrol (0–250 μmol/L) at different time points (24 and 48 h). The nuclear morphology was assessed in MCF-7 cells with propidium iodide (PI) and acridine orange/ethidium bromide (AO/EB) staining and analyzed by fluorescence microscopy. Events like cell cycle arrest and apoptosis were observed by flow cytometric analysis and expressions of p-Rb, cyclin D1, cyclin-dependent kinase 4 (CDK4), CDK6, Bax, Bcl-2, PI3K/p-AKT were analyzed by immunoblot.Results:Carvacrol significantly reduced cell viability with the half maximal inhibitory concentration value of 200 μmol/L at 24 and 48 h (P<0.05). importantly, there was a significant increase in the accumulation of the G0/G1 phase upon treatment with carvacrol in MCF-7 cells (P<0.05 or P<0.01). A remarkable decrease in protein expressions of p-Rb, cyclin D1, CDK4 and CDK6 denoted cell cycle arrest (P<0.05 or P<0.01). In addition, carvacrol treatment significantly inhibited PI3K/p-AKT protein expressions leading to induction of apoptosis mediated by decreased Bcl2 and increased Bax protein expressions. Further, Annexin V/PI staining by FACS analysis, dual staining by AO/EB and PI staining studies suggested induction of apoptosis by carvacrol through PI3K/Akt signaling pathway in MCF-7 cells.Conclusion:Carvacrol significantly inhibited the breast cancer MCF-7 cell proliferation and induced apoptosis via suppressing PI3/AKT signaling pathway.
Abstract:Objective:To study the mechanism of the anti-tumor effect of Morinda citrifolia (noni).Methods:The influences of noni juice on cell proliferation, apoptosis, invasion, migration and the activity of AKT/nuclear factor-κB (NF-κB) signaling pathway in A549 human lung cancer cells were detected by MTT, cell counting kit-8, colony formation, Annexin V/PI double labeling, transwell, scratch test and immunoblotting assay, respectively. A549 cells were inoculated into the right axilla of nude mice, followed by noni juice treatment. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell proliferation and expression of apoptosis-related proteins were measured by immunohistochemistry, and the activity of NF-κB signaling pathway was measured by immunoblotting.Results:The in vitro studies showed that noni juice inhibited the A549 cells proliferation, migration and invasion. Noni juice also promoted cells apoptosis in A549 cells. Immunoblotting assay showed that the phosphorylation level of AKT, p50, and STAT3 proteins was inhibited to different extents after noni juice treatment. The in vivo studies showed that noni juice effectively suppressed tumor formation of A549 cells in nude mice. Noni juice treatment inhibited the expression of Ki67, PCNA, and Bcl-2 protein in the tumor; while promoted the expression of caspase-3 protein. Additionally, we also found that noni juice treatment could restrain the activity of AKT/NF-κB signaling pathway in the tumor tissue.Conclusion:Noni juice inhibited the proliferation of A549 lung cancer cells, induced apoptosis, and inhibited cell invasion and migration via regulating AKT/NF-κB signaling pathway.
Keywords:Morinda citrifolia;noni juice;Chinese medicine;lung cancer cell;AKT/NF-κB signaling pathway
Abstract:Objectives:To reveal the mechanisms behind the dual effects of Crataegus aronia (C. aronia) aqueous extract on platelet aggregation by focusing on function, regulation, expression, and signaling of platelets P2Y12 receptors.Methods:Adult male Wistar rats (120±10 g) were classified as control received the vehicle, C. aronia (200 mg/kg), and C. aronia (2, 000 mg/kg)-treated rats. After treatments for consecutive 7 days, hematological and molecular experiments were conducted to detect alterations in platelet aggregation, thromboxane B2 (THXB2) and intracellular reactive oxygen species (ROS) content; protein levels of P2Y12, p-Akt, cyclic adenosine monophosphate (cAMP), phosphorylated vasodilator-stimulated-phosphoprotein (p-VASP), nuclear factor κB (NF-κB), P-selectin, etc. in platelets were determined by Western blot; mRNA expressions of P2Y12 and some inflammatory markers were determined by real-time polymerase chain reaction.Results:At a concentration of 200 mg/kg, C. aronia inhibited platelet aggregation through multiple interconnected mechanisms including downregulation P2Y12 synthesis and expression, stimulating intracellular cAMP levels and protein levels of p-VASP, inhibiting platelets THXB2 release and protein levels of P-selectin. Also, it inhibited platelets level of ROS and of NF-κB, a major signaling pathway that stimulates the expression of P2Y12 and THXA2 synthesis. Opposite findings were seen in platelets of rats received C. aronia at a concentration of 2, 000 mg/kg. Interestingly, co-administration of N-acetylcysteine prevented all hematological and molecular alterations exerted by the high dose of the extract and inhibited platelet aggregation.Conclusion:Oral administration of C. aronia at low dose inhibits platelet aggregation by reducing THXB2 release, expression of P-selectin and activating cAMP and Akt signaling through two major mechanisms including downregulation of P2Y12 and inhibition of ROS-induced activation of NF-κB, an effect that is observed to be in the opposite direction with its high dose.
Abstract:Objective:To investigate the potential mechanisms of electroacupuncture (EA) to prevent ischemic stroke.Methods:The method of middle cerebral artery occlusion (MCAO) was employed to establish a rat model of ischemic stroke. Seventy-eight Sprague-Dawley rats were divided into the sham group, MCAO + EA control (EC) group, and MCAO + EA (EA) group according to a random number table (n=26 per group). EA was applied to the acupoints of Baihui (DU 20) and Shenting (DU 24) 5 min and 6 h, respectively after the onset of MCAO for 30 min. Rats in the sham and EC groups received only light isoflurane anesthesia for 30 min after MCAO. The neuroprotective effects of EA were evaluated by rota-rod test, neurological deficit scores and infarct volumes. Additionally, Nissl staining and immunostaining were performed to examine brain damage, rod formation, cellular apoptosis, and neuronal loss induced by ischemia. The activities of caspase-3, and expression levels of cofilin and p-cofilin in mitochondria and cytoplasm after ischemic injury were determined by Western blot.Results:Compared with the EC group, EA significantly improved neuromotor function and cognitive ability after ischemic stroke (P<0.05 or P<0.01). Therapeutic use of EA also resulted in a significant decrease of cofilin rod formation and microtubule-associated protein-2 (MAP2) degradation in the cortical penumbra area compared with the EC rats (P<0.01). Furthermore, Western blot analysis showed that EA stimulation significantly inhibited mitochondrial translocation of cofilin and caspase-3 cleavage (P<0.05 or P<0.01). Additionally, brain damage (infarct volume and neuropathy), cellular apoptosis and neuronal loss induced by ischemia were remarkably suppressed by EA in the cortical penumbra of rats (P<0.05 or P<0.01).Conclusion:EA treatment after ischemic stroke may attenuate ischemic brain injury and cellular apoptosis through the regulation of mitochondrial translocation of cofilin, a novel mechanism of EA therapy.
Keywords:electroacupuncture;cofilin;apoptosis;ischemic stroke;mitochondrial translocation;Chinese medicine
Abstract:Objective:To assess the effect of oral Chinese medicine (OCM) combined with Western medicine (WM) on cancer pain.Methods:PubMed, Embase, Cochrane Library, Clinical Trials Registry Platform, Chinese National Knowledge Infrastructure (CNKI), Wanfang and VIP databases were searched from their inception to September 2019. Randomized controlled trials (RCTs) treating cancer pain by Chinese medicine (CM) combined with WM were included. The primary outcome were total pain relief rate and the quality of life (QOL), and the other outcomes were the average daily dosage of analgesics, the primary time of pain, the analgesic duration time, and adverse events. The methodological quality of RCTs was assessed in accordance with Cochrane 5.1.0 handbook of systematic reviews of interventions. Evidence level was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.Results:There were 1, 087 patients in the 14 studies, with 544 in the experiment group and 543 in the control group. These studies were all conducted in China, and published between 2006 and 2019. Compared with the WM, OCM combined with WM could significantly relieve the cancer pain [risk ratio (RR)=1.43, 95% confidence interval (CI): 1.32, 1.56), improve QOL (RR=8.57, 95% CI: 4.25, 12.89), decrease the primary time of pain (RR=–0.20, 95% CI: –0.24, –0.16], prolong the analgesic duration time (RR=3.47, 95% CI: 2.09, 4.85), reduce the dosage of analgesics (RR=–19.52, 95% CI: –36.32, –2.72), and reduce side events (RR=0.49, 95% CI: 0.37, 0.65). Evidence levels for total pain relief rate, primary time of pain and side events were low, evidence level for QOL, analgesic duration time and average daily dosage of analgesics were very low.Conclusions:Compared with the WM, OCM combined with WM could significantly relieve the cancer pain, improve the QOL, decrease the primary time of pain, prolong the analgesic duration time, reduce the dosage of analgesics and side events. The evidence levels were low or very low.
Keywords:oral Chinese medicine;cancer pain;clinical trial;meta-analysis