OBJECTIVETo evaluate the reliability, validity, and responsiveness of traditional Chinese medicine (TCM) clinical outcomes rating scale for heart failure (HF) based on patients' report.

METHODSTCM clinical outcomes rating scale for HF (TCM-HF-PRO) were evaluated based on 340 HF patients' report from multiple centers. The completion of the investigation was recorded. Cronbach's α coefficient and split-half reliability were used for reliability analysis, and factor analysis was used to assess the construct validity of the rating scale. Pearson correlation analysis was then used for criterion validity analysis. Discriminant analysis was used to assess the responsiveness of the scale. All 340 HF patients having complete TCM-HF-PRO data were assigned to the treatment group and the control group by central randomization. The total TCM-HF-PRO scores of the two groups were compared using paired t-test to reflect the longitude responsiveness of the scale before treatment and at week 2 after treatment.

RESULTS(1) The recycling rate of the scale was 100.0%. One of them was not filled completely, which was rejected thereby. So the completion rate was 99.7%. The completion time for TCM-HF-PRO scale ranged 15 to 25 min. (2) The Cronbach's α coefficient of rating scale was 0.903, split-half reliability was 0.844 and 0.849. (3) Confirmatory factor analysis showed that 7 factors and items formed according to maximum load factor basically coincided with the construct of the rating scale, 7 factors accumulated contribution rate was 43.8%. TCM clinical outcomes rating scale for HF based on patients' report was relatively better correlated with the Minnesota living with HF questionnaire (r = 0.726, P < 0.01). (4) Discriminant analysis showed that the rating scale correctly classified more than 78.8% of case studies having confirmed initial differential diagnosis by experts. The total scale of the rating scale decreased more in the two group after treatment, with significant difference as compared with before treatment (P < 0.01.

CONCLUSIONTCM clinical outcomes rating scale for HF based on patients' report had good reliability, validity and responsiveness, hence it could be used to assess clinical efficacy for HF patients.

Diagnosis, Differential ; Discriminant Analysis ; Factor Analysis, Statistical ; Heart Failure ; diagnosis ; Humans ; Medicine, Chinese Traditional ; methods ; standards ; Reproducibility of Results ; Surveys and Questionnaires

The in vitro transcribed (IVT) mRNA technology has progressed rapidly and the application of mRNA vaccines in the COVID-19 pandemic made it become the most talked-about topic. Compared with protein drugs, IVT mRNA has a lower cost; it can be modular produced and its sequence can be modified easily, so it has a broad application prospect. However, due to its short history, mRNA drugs face the problem of lacking sufficient clinical data, and there is no quality control standard for mRNA drugs except mRNA vaccines. We overview the sequence design, delivery vectors, administration, application prospect and safety considerations of mRNA drugs. We also discussed the quality control of mRNA drugs briefly.

Cardiac Catheterization ; Heart Septal Defects, Ventricular ; therapy ; Humans ; Prosthesis Implantation ; instrumentation ; Septal Occluder Device

To explore the differences between the qualitative similarity and the quantitative similarity of chromatographic fingerprints of traditional Chinese medicines, the quantitative similarity calculated by vector shadow C%, apparent quantitative similarity R%, quantitative similarity P%, etc. were firstly proposed to disclose the quantitative information characteristics of traditional Chinese medicines fingerprints. The HPLC fingerprints of both the standard Fructus gardeniae and the ten batches of Fructus gardeniae produced in different places were evaluated by the new parameters to obtain good results. The contrasted fingerprint contained 35 peaks while geniposide was selected as the reference peak. The HPLC fingerprint had good precision and reproducibility with the RSD of the relative retention time less than 1.5% and the RSD of the relative peak area within 5%. The qualitative similarity and quantitative similarity between each crude drug and the contrasted fingerprint were quantitatively calculated, the values of C%, P%, etc., were applied in the quality control practice, which had less errors. What is more, this method could be used for the overall quality control of Fructus gardeniae and especially suits for qualitative and quantitative evaluations of the chromatographic fingerprints both in chemical constituent distribution and in contents. The quantitative parameters such as C% and P% can be used to objectively, authentically and thoroughly display the content information characteristics. When they combined with the qualitative similarity, it will be the good method to evaluate the chromatographic fingerprints of traditional Chinese medicines.
Chromatography, High Pressure Liquid ; methods ; Fruit ; chemistry ; Gardenia ; chemistry ; Medicine, Chinese Traditional ; methods ; standards ; Plants, Medicinal ; chemistry ; Quality Control ; Reproducibility of Results

AIMTo exploit the characteristic digital criterion for the potential information characteristics of traditional Chinese medicine chromatographic fingerprints, the 37 parameters such as F and I were firstly proposed to disclose the potential information characteristics of traditional Chinese medicine fingerprints.

METHODSThe HPLC fingerprints of the Ginkgo biloba extract (GBE) , Ginkgo leaf extract and diphyridamole injection (GLEDI), Ixeris sonchifolia Hance (ISH) and Ixeris sonchifolia Hance injection (ISHI) were compared each other.

RESULTSAs far as the peak signal intensity, the uniform of peak signal, resolution and the fingerprint information were concerned. The GBE fingerprint was better than the GLEDI's, and the ISH fingerprint was also better than the ISHI's, then GBE fingerprint was close to the ISHI' s.

CONCLUSIONThe 37 parameters such as F and I can be used to objectively, authentically and thoroughly display the potential information characteristics of the traditional Chinese medicine chromatographic fingerprints.

Asteraceae ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Ginkgo biloba ; chemistry ; Medicine, Chinese Traditional ; Plant Leaves ; chemistry

To study the effect of micro (mi)RNA on cellular proliferation induced by hepatitis B x protein, HBx, in human liver cells and to investigate the underlying molecular mechanism of this cancer-related effect. The human L02 hepatocyte cell line was stably transfected with HBx (L02/HBx) or an HBx mutant (L02/HBx-d382) that induces higher levels of cellular proliferation. The differential miRNA expression profiles were determined by microarray analysis and confirmed by real-time PCR. Two miRNAs, miR-338-3p and miR-551b, that were found to be significantly down-regulated in the L02/HBx-d382 cells were selected for further study and transfected individually into cells using the lipofectamine procedure. The cell survival rate was analyzed by MTT assay, and cell cycles were assessed by flow cytometry. Expressions of cyclinD1, cyclinG1, and E2F1 were assessed by real-time PCR and Western blotting. Compared with the microarray miRNA profile of L02/pcDNA3.0 cells, six miRNAs were up-regulated and five miRNAs were down-regulated in the L02/HBx-d382 cells, while four miRNAs were up-regulated and 12 were down-regulated in the L02/HBx cells. The microarray results were consistent with real-time PCR results. Transfection of miR-338-3p and miR-551b significantly inhibited the cell survival rates (P less than 0.001) and induced G0/G1 phase cycle arrest. According to MTT results: for L02/HBx-d382 cells, compared with lipofectamine or non-transfected (NC) controls, the t value of miR-338-3p was 10.402, 9.133 and the t value of miR-551b was 8.763, 7.403; for L02/HBx cells, compared with lipofectamine or NC controls, the t value of miR-338-3p was 9.105, 8.074 and the t value of miR-551b was 7.673, 7.52. According to flow cytometry results: for L02/HBx-d382 cells, compared with lipofectamine or NC controls, the t value of miR-338-3p was 12.173, 11.107 and the t value of miR-551b was 15.364, 13.377; for L02/HBx cells, compared with lipofectamine or NC controls, the t value of miR-338-3p was 15.416, 13.378, and the t value of miR-551b was 13.276, 13.109. The protein levels of cyclinD1, cyclinG1, and E2F1 were significantly reduced by both miR-338-3p and miR-551b ( P less than 0.001). For L02/HBx-d382 cells, compared with lipofectamine or NC controls: E2F1 had t = 11.132, 10.031 and 12.017, 10.973, respectively; cyclinD1 had t = 15.654, 15.013 and 15.447, 14.733, respectively; cyclinG1 had t = 8.017, 7.661 and 7.402, 7.417, respectively. For L02/HBx cells, compared with lipofectamine or NC controls: E2F1 had t = 14.244, 13.331 and 15.022, 14.468, respectively; cyclinD1 had t = 8.695, 8.137 and 7.877, 7.503, respectively; cyclinG1 had t = 7.73, 7.471 and 7.596, 7.41, respectively. In contrast, the mRNA levels for E2F1, cyclinD1, and cylcinG1 showed no significant differences between the miRNA transfected cells and controls. Wild-type HBx and the high proliferation-inducing mutant HBx can influence the miRNA expression profile of L02 cells. HBx down-regulates miR-338-3p and miR-551b in L02 cells, and the high proliferation-inducing mutant has a more robust effect. The mechanism of miR-338-3p- or miR-551b-mediated cell growth inhibition appears to be related to the direct modulation of cyclinD1, cyclinG1, and E2F1.
Blotting, Western ; Carcinoma, Hepatocellular ; genetics ; metabolism ; pathology ; Cell Cycle ; Cell Line ; Cell Proliferation ; Cyclins ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Genes, Viral ; Hepatitis B virus ; genetics ; metabolism ; Hepatocytes ; metabolism ; pathology ; Humans ; Liver Neoplasms ; genetics ; metabolism ; pathology ; MicroRNAs ; genetics ; metabolism ; Mutation ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger ; genetics ; Real-Time Polymerase Chain Reaction ; Trans-Activators ; genetics ; metabolism ; Transfection

OBJECTIVETo establish an animal model of titanium implant and to investigate the effects of low intensity pulsed ultrasound (LIPUS) on the implant osseointegration.

METHODSTwenty-four female Sprague Dawley (SD) rats were used. Titanium implants were inserted into tibia metaphysis bilaterally in each SD rat. Since the second day following implant surgery, LIPUS stimulation were carried out around the implant on the right side for 20 minutes per day, and implants on the left side remain untouched as self-control. Eight rats were sacrificed and tibiae specimens were harvested on the end of the 4th, 8th, and 12th week respectively. X-ray picture, micro-CT analysis and histological sections were performed to evaluate the effects of LIPUS on the implant osseointegration.

RESULTSOsseointegration at the interface between the implant and bone tissue was observed bilaterally. In the micro-CT histomorphometry analysis, the percentage of osseointegration (%OI) of experiment side were (45.708 ± 3.316)%, (46.231 ± 1.954)%, and (46.807 ± 1.451)% on the end of the 4th, 8th, and 12th week. Meanwhile, the %OI of control side were (43.021 ± 3.558)%, (44.272 ± 3.023)%, and (44.894 ± 4.215)% respectively. The %OI on the 4th weekend, bone volume ratio (BV/TV) on the 4th and 8th weekend, trabecular thickness (Tb. Th) and degree of anisotropy (DA) on the 8th and 12th weekend of the experiment side tibia were significantly greater than those on the control side (P < 0.05). The histological examination showed that the thickness of new bone around the implant and the bone-implant contact area was obviously greater in the LIPUS treated side compared to the control side.

CONCLUSIONSThe LIPUS therapy may accelerate the bone healing and osseointegration at the interface between titanium implant and bone, and promote remodeling of bone trabecula on the early stage.

Animals ; Biomechanical Phenomena ; Bone Density ; Female ; Implants, Experimental ; Osseointegration ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tibia ; surgery ; Titanium ; chemistry ; Ultrasonic Therapy ; methods ; X-Ray Microtomography ; methods

OBJECTIVETo carry out expert survey for traditional Chinese medicine (TCM) syndrome characteristics of different clinical types of coronary artery disease (CAD).

METHODSBy using Delphi method, we carried out two rounds of nationwide expert surveys for modern TCM characteristics of syndrome elements and syndrome types of CAD.

RESULTSBased on expert consensus, qi deficiency, blood stasis, phlegm turbidity, qi deficiency blood stasis, and intermingled phlegm and blood stasis are common TCM syndromes for different clinical types of CAD. Of them, qi stagnation, blood stasis, phlegm turbidity, heat accumulation, cold coagulation, yang deficiency, deficiency of both qi and yang were more often seen in patients with unstable angina than in those with stable angina. Qi deficiency, yin deficiency, and deficiency of both qi and yin were less seen. We could see more excess syndrome and less deficiency syndrome (such as qi deficiency, yin deficiency, etc.) in acute ST-segment elevation myocardial infarction (STEMI) than acute non-ST-segment elevation myocardial infarction (NSTEMI). Qi deficiency, blood stasis, water retention, yang deficiency, phlegm turbidity, yin deficiency, Xin-qi deficiency, and qi deficiency blood stasis induced water retention are the most common TCM syndrome types of CAD heart failure (HF). Blood deficiency, yin deficiency, heat accumulation, deficiency of both Xin and Pi, deficiency of both qi and blood, deficiency of both qi and yin, yin deficiency and fire hyperactivity were more often seen in CAD arrhythmias.

CONCLUSIONSTCM syndrome distributions of different clinical types of CAD have common laws and individual characteristics. Results based on the expert consensus supplied evidence and support for clinical diagnosis and treatment of CAD.

Angina Pectoris ; Angina, Unstable ; China ; Coronary Artery Disease ; diagnosis ; therapy ; Coronary Disease ; diagnosis ; Data Collection ; Heart Failure ; diagnosis ; Humans ; Medicine, Chinese Traditional ; methods ; Qi ; Syndrome ; Yang Deficiency ; diagnosis ; Yin Deficiency ; diagnosis

BACKGROUND: It is quite difficult to produce a decellularized lung scaffold, in which cells are removed and the extracellular matrix components (ECM) are preserved effectively. Perfusion of detergent-enzymes is an effective method with wide applications for decellularized lung scaffolds. OBJECTIVE: To investigate the effects of two detergents (sodium deoxycholate, SDC and sodium dodecyl sulfate, SDS) on the preparation of decellularized lung scaffolds. METHODS: Twenty-four male Sprague-Dawley rats were randomized into three groups: control group with no intervention, SDC group and SDS group. Decellularized lung scaffolds were prepared by perfusion of SDC or SDS combined with enzymes. The rat lung tissues in the three groups were taken for histological staining, immunofluorescent staining and DNA quantification. A549 cells were cultured and seeded onto the decellularized lung scaffolds for 7 days followed by hematoxylin-eosin staining. The decellularized lung scaffolds prepared by perfusion of SDC or SDS were subcutaneously implanted into the rat back, and the implants were retrieved and assessed by Masson staining after 2 weeks. RESULTS AND CONCLUSION: In the control group, there were abundant cells in the lung tissues. In the other two groups, the decellularized lung scaffolds were nearly transparent, and the morphology of the SDC scaffold was more close to the native lung. There were no residual cells and nuclei on the two scaffolds, and the DNA content in the SDS and SDC groups was significantly lower than that in the control group (P＜ 0.01). At 7 days of culture, A549 cells cultured on the SDS and SDC scaffolds migrated from the edge to the center of the scaffold. Comparatively speaking, the migration ability of A549 cells on the SDC scaffolds was stronger, and there was obvious cell invasion and growth in the middle part of the lung. After 2 weeks of scaffold transplantation, the SDC implants poorly fused with the surrounding tissues, with a clear boundary, a large number of infiltrating cells distributed evenly, and intravascular blood cells were clearly visible; the number of new blood vessels with larger diameter in the SDC scaffold was significantly higher than that in the SDS scaffold. These findings indicate that the SDC scaffold has better biocompatibility than the SDS scaffold, which can fuse with the surrounding tissues faster and produce more infiltrating cells and new blood vessels.

AIM:To investigate the expression and localization of autophagy related protein microtublule associated protein 1 light chain 3 (LC3) at various stages of follicular development and atresia in the mice.METHODS:On 0,1,2,3,4 and 5 day after intraperitoneal injection of pregnant mare serum gonadotropin (PMSG),expression and positioning situation of autophagy related protein LC3 and apoptosis related protein cleaved caspase-3 were examined by the method of immunohistochemical staining.The protein levels of cleaved caspase-3 and LC3 were determined by Western blot in cultured mouse granulosa cells after incubation under serum-free conditions in the absence or presence of FSH.LC3 subcellular localization in granulosa cells were studied by the method of immunofluorescence.RESULTS:The LC3 protein expressed in granulosa cells during all developmental stages mainly.Granulosa cells of atretic follicles that showed intense staining of cleaved caspase-3 and LC3.The protein levels of cleaved caspase-3 and LC3-Ⅱ in the granulosa cells significantly decreased at 1 d and 2 d after intraperitoneal injection of PMSG (P ＜ 0.05).The protein levels of cleaved caspase3 and LC3-Ⅱ in the granulosa cells increased in turn on 3,4 and 5 day after intraperitoneal injection of PMSG.The positive correlation between LC3-Ⅱ and cleaved caspase-3 protein levels was observed (r2 =0.8299,P ＜ 0.05).The LC3-Ⅱ protein expressed with punctuate structures in granulosa cell cytoplasm cultured under serum-free conditions in the presence of FSH.CONCLUSION:LC3 is expressed in the follicular granulosa cells with cell specificity and regional specificity.Autophagy is induced mainly in granulosa cells during folliculogenesis and shows positive correlation with apoptosis.Ovarian granulosa cell autophagy and apoptosis are gonadotropic hormone dependent.