Background/Aims: The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. Methods: The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosisrelated proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. Results: CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells.miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. Conclusions CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.

OBJECTIVE: To evaluate the effects of auricular acupoint bloodletting (AB) and auricular acupressure (AA) on sleep quality and the levels of melatonin (MT), glutamic acid (Glu), and γ -aminobutyric acid (GABA) in college students with primary insomnia, and to explore the possible mechanism. METHODS: Totally 74 college students at Hebei University of Chinese Medicine with primary insomnia were selected from October 2019 to October 2020. All patients were assigned to AB+AA group (37 cases, received combination of AB and AA) and AA group (37 cases, received only AA on the same acupoints) by a random number table. Each group was treated twice a week for 4 weeks. The Pittsburgh Sleep Quality Index (PSQI) score, Chinese medicine (CM) syndrome score, total effective rate, serum concentrations of MT, Glu, and GABA, and Glu/GABA ratio were compared between the two groups after treatment and at follow-up. The safety of therapy was also evaluated. RESULTS: After 4-week treatment, the total scores of PSQI, each PSQI component score, and the CM syndrome scores in both groups all decreased (P<0.05); the serum MT concentrations in both groups all increased (P<0.05). The concentrations of Glu and GABA in the AB+AA group were significantly higher than those in the AA group after treatment (P<0.05). However, there was no significant difference in the ratio of Glu/GABA in both groups before and after treatment (P>0.05). At follow-up, the CM syndrome score in the AB+AA group was significantly lower than that in the AA group (P<0.05). There was no significant difference between the two groups in total effective rates and adverse events (P>0.05). CONCLUSIONS Both AB+AA and AA can relieve insomnia symptoms, but a stronger long-term effect were observed for AB+AA. AB+AA can promote the secretion of MT, increase the levels of Glu and GABA more effective than AA, and regulate their imbalance, and thus it may be benificial for treating insomnia.
Humans ; Acupressure ; Acupuncture Points ; Bloodletting ; Sleep Initiation and Maintenance Disorders/therapy* ; Sleep Quality ; Syndrome ; Students ; gamma-Aminobutyric Acid

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*

As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

In recent years, layer-by-layer self-assembly (LbL) has developed rapidly. It has been widely used in various industries such as medicine and metallurgy because of its simplicity, flexibility and controllability. In the study of drug delivery system, hollow microcapsules constructed by LbL method as drug carrier have great advantages in drug release, circulation in vivo and bioavailability, providing a technical platform for targeted drug release. In this paper, we summarize the types of film-forming materials and the driving force used in LbL technology, the way of loading drug into hollow micro capsule, and the variety of loaded drugs. We focus on the release mechanism, its evaluation and safety evaluation of self-assembled film as drug carrier in vivo and in vitro. The review shows the great application prospect of LbL technology in the field of drug delivery.

The aim of this study is to prepare acetaminophen sustained-release tablets by hot melt extrusion 3D printing technology based on the concept of "Quality by Design" (QbD). Firstly, the failure mode and effect analysis (FMEA) was used to determine the critical process parameters (CPPs), then full-factor experimental design was used to analyze the critical quality attributes (CQAs) and to establish the design space. The results showed that the content of plasticizer, the path spacing and the shell numbers are independent variable for the experimental design. The design space was concluded to be plasticizer content: 9%, and the shell number: 3-5, the path spacing: 1.05-1.2 mm. In this study, 3D printing technology was used to prepare acetaminophen sustained-release tablets in accordance with the concept of QbD, which improved the durability of the process and ensured the uniform and controllable quality of the preparation and also provided experimental basis for personalised medicine.

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.

This study was aimed to develop a sandwich ELISA kit for the diagnosis of bovine tuberculosis.And it was applied and evaluated in the quarantine of bovine tuberculosis.We established a bovine IFN-γ release method in vitro and developing three batches of kits.The sensitivity,repeatability and retention period of the kit were all evaluated.Totally 961 serum samples were tested using the developed sandwich ELISA kit tuberculin skin test and a commercial ELISA kit.Our results showed that the detection limit of this ELISA was 8.21 mg/mL.The repeatability tests showed good reproducibility in the intraassay and inter-assay.At the same time,the retention period of the kit was more than 12 months.Compared with the tuberculin skin test,the positive coincidence rate was 70.59％ and the negative coincidence rate was 99.20％,while the total coincidence rate was 98.44％.And compared with the BOVIGAMTM kit,the positive coincidence rate was 91.30％ and the negative coincidence rate was 99.78％,while the total coincidence rate reached 99.58％.At the same time,the sensitivity and specificity of the sandwich kit were 85.00％ and 100％,respectively.We established a bovine IFN-γ release method in vitro and developing corresponding kits successfully have a good application prospect.

OBJECTIVETo systematically review the clinical practice guidelines (CPGs) for ischemic stroke in Chinese medicine (CM) with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument.

METHODSCM CPGs for ischemic stroke were searched in 5 online databases and hand-searches in CPGrelated handbooks published from January 1990 to December 2012. The CPGs were categorized into evidence based (EB) guideline, consensus based with no explicit consideration of evidence based (CB-EB) guideline and consensus based (CB) guideline according to the development method. Three reviewers independently appraised the CPGs based on AGREE II instrument, and compared the CPGs' recommendations on CM pattern classification and treatment.

RESULTSFive CM CPGs for ischemic stroke were identified and included. Among them, one CPG was EB guideline, two were CB guidelines and two were CB-EB guidelines. The quality score of the EB guideline was higher than those of the CB-EB and CB guidelines. Five CM patterns in the CPGs were recommended in the EB CPG. The comprehensive protocol of integrative Chinese and Western medicine recommended in the EB CPG was mostly recommended for ischemic stroke in the CPGs. The recommendations varied based on the CM patterns.

CONCLUSIONThe quality of EB CPG was higher than those of CB and CB-EB CPGs in CM for ischemic stroke and integrative approaches were included in CPGs as major interventions.

Biomedical Research ; Brain Ischemia ; complications ; therapy ; Health Planning Guidelines ; Humans ; Medicine, Chinese Traditional ; Practice Guidelines as Topic ; Stroke ; complications ; therapy