Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

OBJECTIVE: To evaluate the short-term outcome of regenerative surgery for peri-implantitis therapy. METHODS: From March 2018 to January 2019, 9 patients with 10 implants who suffered from peri-implantitis were included in the present research. Vertical bone defect at least 3mm in depth with 2 or more residual bone walls was confirmed around each implant by radiographic examination. Restorations were replaced by healing abutments on 3 implants with the consent of the patients. Guided bone regeneration surgery was performed after a hygienic phase. During surgery, full thickness flaps were elevated on both buccal and lingual aspects. Titanium curette was used for inflammatory granulation tissue removal and implant surface cleaning. The implant surface was decontaminated by chemical rinsing with 3% hydrogen peroxide solution. After being thoroughly rinsed with saline, the bone substitutes were placed in bone defects which were covered by collagen membranes. 6 months after non-submerged healing, the clinical parameters including peri-implant probing depth (PD, distance between pocket bottom and peri-implant soft tissue margin) and radiographic bone level (BL, distance form implant shoulder to the first bone-to-implant contact) were used to evaluate the regenerative outcome. PD was measured at six sites (mesial, middle and distal sites at both buccal and lingual aspects) around each implant, and BL was measured at the mesial and distal surfaces of each implant on a periapical radiograph. RESULTS: The deepest PD and largest BL of each implant ranged from 6-10 mm and 3.2-8.3 mm respectively. All the implants healed uneventfully after surgery. The mean peri-implant PD at baseline and 6 months after surgery were (6.2±1.4) mm and (3.1±0.6) mm respectively, and a mean (3.0±1.5) mm radiographic bone gain was observed, P<0.01. Treatment success was defined as: no sites with residual PD≥6 mm, no bleeding on probing, and BL elevation of at least 1 mm. Nine implants from 8 patients fulfilled the success criteria. Residual pockets with 6 mm in depth and bleeding on probing could be detected in only one implant. CONCLUSION Within the limitation of the present research, guided bone regeneration surgery can be used for the treatment of bone defect that resulted from peri-implantitis. Significant PD reduction and radiographic bone gain can be obtained after 6 months observation.
Alveolar Bone Loss ; Bone Substitutes ; Collagen ; Dental Implants ; Humans ; Peri-Implantitis ; Surgical Flaps ; Treatment Outcome

BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine (CM) theory. However, it was not well accounted in most of randomized controlled trials (RCTs). OBJECTIVES: To determine whether CM syndrome differentiation affects the treatment results, functional constipation (FC) was selected as a target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for constipation with excessive heat syndrome, was selected for study. METHODS: It is an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in, 8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients diagnosed as excessive heat syndrome will be recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang Affiliated Hospital of Tianjin University of Traditional Chinese Medicine. Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group, modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no more than two herbal granules can be added according to the syndrome differentiation for individual participants. The primary end point is the mean of complete spontaneous bowel movements (CSBMs) per week during the treatment period. Secondary end points include mean of CSBMs per week during follow-up, stool form, global symptom improvement, constipation and constipation-related symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION This trial is designed to evaluate the effectiveness of these three interventions for FC patients with the CM syndrome of excessive heat, and to determine the change of CM syndrome and the progress of disease during the treatment course. The results are important to explore whether syndrome differentiation is important for the therapeutic effect of a formula on a disease. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742); protocol version: MZRW/NSFC-81173363 (2015.05.04)].
Constipation ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Outcome Assessment (Health Care) ; Prospective Studies ; Randomized Controlled Trials as Topic

Stomach pain in Chinese medicine (CM) is a very common disorder in clinical practice and it has been listed as one of the pilot three conditions in Hong Kong to develop evidence-based CM clinical practice guidelines (CM CPGs). The aim of this stomach Pain CPG is to summarize the treatment methods of stomach pain with CM and evaluate reasonably, then to guide local licensed CM practitioners and provide beneficial reference for social medical decision makers and patients. In this manuscript, we defined stomach pain in CM and the category of chronic gastritis in Western medicine. The clinical manifestation, CM pattern classification, and CM intervention including herbal medicine treatment based on pattern differentiation, symptomatic treatment, acupuncture treatment, regulation and nursing were illustrated.

OBJECTIVETo investigate the potential involvement of DMT1 (IRE) protein in the brain vascular system in vivo during Pb exposure.

METHODSThree groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the mRNA.

RESULTSPb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1 (IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1 (IRE) mRNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1 (IRE).

CONCLUSIONThese results suggest that Pb is transported into the brain through DMT1 (IRE), and the ERK MAPK pathway is involved in DMT1 (IRE)-mediated transport regulation in brain vascular system in vivo.

Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Cation Transport Proteins ; drug effects ; genetics ; physiology ; Cerebral Cortex ; drug effects ; metabolism ; Dietary Supplements ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Gene Expression Regulation ; drug effects ; Iron ; administration & dosage ; metabolism ; Lead ; administration & dosage ; pharmacokinetics ; MAP Kinase Signaling System ; physiology ; Male ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley

This study was aimed to establish a stable animal model of left ventricular hypertrophy (LVH) to provide theoretical and experimental basis for understanding the development of LVH. The abdominal aorta of male Wistar rats (80-100 g) was constricted to a diameter of 0.55 mm between the branches of the celiac and anterior mesenteric arteries. Echocardiography using a linear phased array probe was performed as well as pathological examination and plasma B-type natriuretic peptide (BNP) measurement at 3, 4 and 6 weeks after abdominal aortic constriction (AAC). The results showed that the acute mortality rate (within 24 h) of this modified rat model was 8%. Animals who underwent AAC demonstrated significantly increased interventricular septal (IVS), LV posterior wall (LVPWd), LV mass index (LVMI), cross-sectional area (CSA) of myocytes, and perivascular fibrosis; the ejection fraction (EF), fractional shortening (FS), and cardiac output (CO) were consistently lower at each time point after AAC. Notably, differences in these parameters between AAC group and sham group were significant by 3 weeks and reached peaks at 4th week. Following AAC, the plasma BNP was gradually elevated compared with the sham group at 3rd and 6th week. It was concluded that this modified AAC model can develop LVH, both stably and safely, by week four post-surgery; echocardiography is able to assess changes in chamber dimensions and systolic properties accurately in rats with LVH.
Animals ; Aorta, Abdominal ; pathology ; Constriction, Pathologic ; complications ; Disease Models, Animal ; Echocardiography ; methods ; Enzyme-Linked Immunosorbent Assay ; Heart ; physiopathology ; Hypertrophy, Left Ventricular ; blood ; etiology ; pathology ; Male ; Myocardium ; pathology ; Natriuretic Peptide, Brain ; blood ; Rats, Wistar ; Time Factors

This study was aimed to establish a stable animal model of left ventricular hypertrophy (LVH) to provide theoretical and experimental basis for understanding the development of LVH. The abdominal aorta of male Wistar rats (80-100 g) was constricted to a diameter of 0.55 mm between the branches of the celiac and anterior mesenteric arteries. Echocardiography using a linear phased array probe was performed as well as pathological examination and plasma B-type natriuretic peptide (BNP) measurement at 3, 4 and 6 weeks after abdominal aortic constriction (AAC). The results showed that the acute mortality rate (within 24 h) of this modified rat model was 8%. Animals who underwent AAC demonstrated significantly increased interventricular septal (IVS), LV posterior wall (LVPWd), LV mass index (LVMI), cross-sectional area (CSA) of myocytes, and perivascular fibrosis; the ejection fraction (EF), fractional shortening (FS), and cardiac output (CO) were consistently lower at each time point after AAC. Notably, differences in these parameters between AAC group and sham group were significant by 3 weeks and reached peaks at 4th week. Following AAC, the plasma BNP was gradually elevated compared with the sham group at 3rd and 6th week. It was concluded that this modified AAC model can develop LVH, both stably and safely, by week four post-surgery; echocardiography is able to assess changes in chamber dimensions and systolic properties accurately in rats with LVH.

OBJECTIVEDuring the process of tissue remodeling in human tumor transplantation models, the roles of the inoculated tumor cells and host tissue in tumor progression is still largely unknown. The aim of this study was to investigate the relationships and interactions between these two sides using GFP-RFP double fluorescence tracing technique.

METHODSRed fluorescence protein (RFP) gene was stably transfected into glioma stem cell line SU3, then SU3-RFP cells were transplanted into the brain of athymic nude mice with green fluorescence protein (GFP) expression. After the intracerebral tumors were formed, the relationship and interaction between GFP cells and RFP cells were analyzed. Highly proliferative GFP cells were screened out, and monocloned with micro-pipetting. DNA content assay, chromosome banding and carcinogenicity test of the GFP cells were performed to observe the GFP cells' cancerous phenotype in nude mice.

RESULTSIn the transplantable tumor tissue, besides a great quantity of RFP cells, there were still a proportion of GFP cells and GFP/RFP fusion cells. The proportion of RFP cells, GFP cells and GFP/RFP cells were (88.99 ± 1.46)%, (5.59 ± 1.00)%, and (4.11 ± 1.020)%, respectively. Two monoclonal host GFP cells (H1 and H9) were cloned, which demonstrated the properties of immortality, loss of contact inhibition, and ultra-tetraploid when cultured in vitro. Both H1 and H9 cells expressed CNP, a specific marker of oligodendrocytes. The GFP cells also demonstrated 100% tumorigenic rate and high invasive properties in vivo.

CONCLUSIONSIn this glioma transplantation model, the transplanted tumor tissues contained not only transplanted glioma stem cells but also cancerous host GFP cells. Our findings offer important clues to further research on the relationships among different members in the tumor microenvironment.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase ; metabolism ; Animals ; Brain ; cytology ; metabolism ; Cell Communication ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Glioma ; metabolism ; pathology ; Green Fluorescent Proteins ; metabolism ; Humans ; Intermediate Filament Proteins ; metabolism ; Luminescent Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Nude ; Neoplasm Transplantation ; Neoplastic Stem Cells ; cytology ; metabolism ; Nerve Tissue Proteins ; metabolism ; Nestin ; Neuroglia ; cytology ; metabolism ; Transfection ; Tumor Microenvironment

Objective To explore the safety and efficacy of cochlear implantation among elderly patients with severe to profound hearing loss. Methods Eight pre-elderly and elderly patients with an medium age of 58 years who suffered from bilateral severe to profound sensorineural hearing loss received cochlear implantation between November 2008 and November 2009. The patients' tolerance to implant surgery and the occurrence of complications were observed. Three months after switch-on, aided threshold and speech performance were measured. Results The surgery was uneventful in all cases with normal intraoperative neural response telemetry elicited. Three months after switch-on, average aided threshold across speech frequencies was 35 -50 dB HL measured in sound field with warble tone. The results of speech audiometry showed large variation between individuals. Some patients achieved good performance in monosyllable recognition test, disyllables threshold test and sentences recognition test under both bubble noise and quiet conditons. Conclusions Pre-elderly and elderly patients can endure a state of general anesthesia for cochlear surgery without complications. Cochlear implant can provide reconstruction of speech recognition capabilities for elderly patients suffering from severe to profound hearing loss. Cochlear implantation can improve the quality of life of elderly patients with hearing loss.