Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Melasma， as a kind of melanosis， often occurs over the face of young and middle-aged women， which seriously affects the physical and mental health of patients. At present， it is believed that the occurrence of melasma is related to various factors such as ultraviolet radiation and changes in sex hormone levels in the body. However， the exact pathogenesis of melasma is still unclear and its clinical efficacy is not ideal. Therefore， it is of great clinical significance and social value to carry out basic researches on melasma diseases. Among them， the animal model of melasma acts as an important tool for studying melasma， and it is particularly important to clarify the pathophysiological mechanism of the occurrence and development of melasma. The common modeling methods include ultraviolet modeling， progesterone modeling and ultraviolet combined with progesterone modeling. However， there are still some problems in the practical application of animal models of melasma due to many influencing factors in the preparation of such animal models， and there is still a lack of a more complete and recognized model preparation scheme to this day， which reduces the success rate of model preparation and limits its application and popularization to some extent. In view of the key problems in the establishment and application of animal models of melasma， we comprehensively summarized the research status of the models from such aspects as experimental animals， modeling methods and model evaluation， and discussed the effects of different modeling methods and animal species， animal age and other factors on animal model of melasma by referring to and sorting out the recent literatures at home and abroad in recent years. This is to provide references for the preparation of more scientific， reasonable， economic and convenient animal models of melasma， lay a foundation for in-depth researches on the pathogenesis， prevention and treatment of melasma， and also provide reference for other animal model research.

Objective:Define traditional Chinese medicine (TCM) therapeutic principles and methods and common prescriptions of benign prostatic hyperplasia (BPH) based on clinical experience of famous doctors. Method:China National Knowledge Infrastructure, China Biology Medicine disc, China Science and Technology Journal Database, Wanfang database were systematically retrieved for literatures of famous doctors in diagnosis and treatment of BPH from January 1, 1997 to December 31, 2018.A literature analysis database was established for integration and analysis of relevant content of TCM therapeutic principles and methods and prescriptions. SPSS 20.0 software was used for statistics to obtain TCM therapeutic principles and methods, common prescriptions and drug distribution regularity of BPH. Result:A total of 109 qualified literatures were included in this study, involving 66 famous doctors and experts, and 9 kinds of BPH therapeutic principles were obtained, including "treatment of both symptoms and root cause of disease", "tonification and purgation in combination", "coordination of Yin and Yang". There are 55 kinds of therapies, including "promoting blood circulation for removing blood stasis", "clearing heat and promoting dampness", "warming and recuperating kidney Yang", "softening and resolving hard mass" and " invigorating kidney Qi". And BPH was mostly diagnosed and treated based on kidney, spleen and lung. Through collection and summarization, totally 38 formulas commonly used in treating BPH obtained. The most commonly used ones were "Guizhi Fuling Wan", "Zishen Tongguan Wan", "Buzhong Yiqi Tang", " Bazheng Tang" and "Jisheng Shenqi Wan". There were 217 commonly used herbs, mainly including " Astragali Radix", "Rehmanniae Radix Praeparata", "Atractylodis Macrocephalae Rhizoma", "Glycyrrhizae Radix et Rhizoma", "Angelicae Sinensis Radix", "Radix Achyranthis Bidentatae", "Peach Kernel", "Pangolin Scales", "Vaccariae Semen", "Salviae Miltiorrhizae Radix et Rhizoma", "Poria", "Rhizoma Alismatis" and "Plantain Seed". Conclusion:The treatment of BPH is based on the principles of "treatment of both symptoms and root cause of disease, and tonification and purgation in combination". The commonly used therapies include prescription for "promoting blood circulation for removing blood stasis", "clearing heat and promoting dampness" and "warming and recuperating kidney Yang". The corresponding prescriptions shall be based on symptoms.

Echinostoma hortense (Digenea: Echinostomatidae) is one of the intestinal flukes with medical importance in humans. However, the mitochondrial (mt) genome of this fluke has not been known yet. The present study has determined the complete mt genome sequences of E. hortense and assessed the phylogenetic relationships with other digenean species for which the complete mt genome sequences are available in GenBank using concatenated amino acid sequences inferred from 12 protein-coding genes. The mt genome of E. hortense contained 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non-coding region. The length of the mt genome of E. hortense was 14,994 bp, which was somewhat smaller than those of other trematode species. Phylogenetic analyses based on concatenated nucleotide sequence datasets for all 12 protein-coding genes using maximum parsimony (MP) method showed that E. hortense and Hypoderaeum conoideum gathered together, and they were closer to each other than to Fasciolidae and other echinostomatid trematodes. The availability of the complete mt genome sequences of E. hortense provides important genetic markers for diagnostics, population genetics, and evolutionary studies of digeneans.
Amino Acid Sequence ; Base Sequence ; Databases, Nucleic Acid ; Dataset ; Echinostoma* ; Echinostomatidae ; Fasciolidae ; Genes, rRNA ; Genetic Markers ; Genetics, Population ; Genome ; Genome, Mitochondrial* ; Humans ; RNA, Transfer ; Trematoda

OBJECTIVETo investigate the relationship between the resistance index (RI) of the renal artery and serum creatinine (Cr) level in patients early (within one month) after renal transplantation.

METHODSA total of 123 patients receiving renal transplantation underwent examinations by color Doppler ultrasound for measurement of the RI of the renal artery within one month after the operation. According to the results of RI measurement, the patients were divided into RI≥0.75 and RI<0.75 groups for analyzing the correlation between RI and serum Cr level measured at the same time points.

RESULTSThe RI and Cr levels in patients with RI≥0.75 showed a significant positive correlation (P<0.05), whereas they showed an inverse correlation in patients with RI<0.75 (P<0.05). The patients with RI≥0.75 had significantly lower RI of the renal artery and Cr level than those with RI≥0.75.

CONCLUSIONRI is significantly correlated to Cr, and may serve as an indicator for predicting renal graft function after transplantation.

Adolescent ; Adult ; Aged ; Creatinine ; blood ; Female ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Postoperative Period ; Renal Artery ; diagnostic imaging ; physiopathology ; Ultrasonography, Doppler ; Vascular Resistance ; Young Adult

OBJECTIVETo observe the suppressive effect on the expression of pro-inflammatory cytokines in liver from brain dead (BD) rats through inhibition of p38 mitogen-activated protein kinase (MAPK) signaling pathway by SB203580.

METHODSA total of 30 male Wistar rats weighing from 180 to 200 g were randomly divided into 3 experimental groups: (1) BD group (n = 10): brain death was induced in rats; (2) BD+SB203580 group (n = 10): brain death was successfully induced and SB203580 (10 mg/kg) was given through dorsal vein of penis. After brain death artificial ventilation was maintained for 6 hours and only those with mean arterial blood pressure more than 80 mm Hg (1 mm Hg = 0.133 kPa) were accepted as BD donors. (3) Control group (n = 10): living healthy rats. The expressions of TNFalpha and IL-1beta mRNA in liver tissues were analyzed by RT-PCR and the protein expressions of TNFalpha, IL-1beta and phosphorylated p38MAPK were detected by Western blot.

RESULTSThe phosphorylated p38MAPK detected in the liver in BD group was significantly increased compared with the control group (q = 172.53, P < 0.01), and the expressions of TNFalpha and IL-1beta mRNA and proteins in liver were also significantly increased in BD group compared with the control group (q = 123.99, 135.35, 243.09 and 192.23, respectively, P < 0.01). The phosphorylated p38MAPK was decreased in BD+SB203580 group and significantly decreased compared with the BD group (q = 63.90, P is less than 0.05), but higher than that in control group (q = 108.63, P < 0.01). The expressions of TNFalpha and IL-1beta mRNA and proteins in liver were significantly decreased in BD+SB203580 group compared with the BD group (q = 55.11, 98.13, 61.03 and 50.85, respectively, P < 0.01), but higher than that in control group (q = 68.89, 37.22, 182.06 and 141.38, respectively, P < 0.01). SB203580 can suppress the expression of pro-inflammatory cytokines in the liver of brain dead rats through the inhibition of p38MAPK signaling pathway which may reduce the immunogenicity of donor livers.

Animals ; Brain Death ; metabolism ; Imidazoles ; pharmacology ; Inflammation ; Interleukin-1beta ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Male ; Pyridines ; pharmacology ; Rats ; Rats, Wistar ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism