ObjectiveTo observe ovarian microvascular damage in rats with cold coagulation and blood stasis syndrome and to explore the mechanism by which Liangfang Wenjing decoction improves this condition in rats. MethodsFifty SPF female SD rats were randomly divided into a blank group， a model group， low-dose （8.1 g·kg^-1） and high-dose groups （16.2 g·kg^-1） of Liangfang Wenjing decoction， and a 4-phenylbutyric acid （0.1 g·kg^-1） group， with 10 rats in each group. The ice-water bath method was employed to establish the rat model of cold coagulation and blood stasis syndrome. Concurrent with modeling， Liangfang Wenjing decoction was administered continuously for 21 days， once daily. The rats' syndrome manifestations and estrous cycles were recorded. The enzyme-linked immunosorbent assay （ELISA） was used to detect serum reproductive hormone levels and levels of endothelin-1 （ET-1）， nitric oxide （NO）， thrombomodulin （TM）， and von Willebrand factor （vWF） in ovarian tissue. Prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， and fibrinogen （FIB） were measured. The ovarian microcirculatory blood perfusion was detected by laser speckle contrast imaging. Hematoxylin-eosin （HE） staining was performed to observe the ovarian histopathology， flow cytometry to detect ovarian apoptosis rate， and transmission electron microscopy to observe the ultrastructure of ovarian microvascular endothelial cells. Western blot was employed to detect the protein expression of endothelial nitric oxide synthase （eNOS）， phosphorylated eNOS （p-eNOS）， Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， inositol-requiring enzyme1α （IRE1α）， p-IRE1α， apoptosis signal-regulating kinase 1 （ASK1）， p-ASK1， c-Jun N-terminal kinase （JNK）， and p-JNK. Immunofluorescence was used to detect ovarian Bax and Bcl-2 expression in microvascular endothelial cells. ResultsCompared with the blank group， the model group showed signs of cold coagulation and blood stasis syndrome， prolonged estrus cycles， and reproductive hormone disorders. Histopathological results revealed a decrease in follicle counts at all stages and disorganized granulosa cell arrangement. Ovarian microcirculatory perfusion was significantly decreased （P<0.01）. PT， APTT， and TT were reduced （P<0.05， P<0.01）， while FIB levels were increased （P<0.05）. In ovarian tissue， NO content was decreased， while ET-1， vWF， and TM levels were increased significantly （P<0.01）. The apoptosis rate of ovarian cells was markedly increased （P<0.01）. Furthermore， p-eNOS/eNOS and Bcl-2 were decreased （P<0.05）， whereas Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK expression showed significant increases （P<0.05， P<0.01）. Compared with the model group， Liangfang Wenjing decoction intervention alleviated the symptoms of cold coagulation and blood stasis， gradually restored the estrus cycle， and improved ovarian histopathology and endothelial cell ultrastructure. Microcirculatory blood perfusion was significantly elevated （P<0.05）. NO content in ovarian tissue was elevated， while ET-1， vWF， and TM levels were significantly decreased （P<0.05， P<0.01）. The p-eNOS/eNOS ratio and Bcl-2 expression were significantly elevated （P<0.05）， while the expression of Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK was significantly decreased （P<0.05， P<0.01）. ConclusionLiangfang Wenjing decoction may regulate the IRE1α/ASK1/JNK signaling pathway to inhibit endoplasmic reticulum stress， attenuate apoptosis， and improve microvascular endothelial injury in ovaries of rats with cold coagulation and blood stasis syndrome.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective:To develop a recombinant protein vaccine based on KPC-2, a drug resistance target in Klebsiella pneumoniae, and evaluate its immunogenicity, protective efficacy and mechanism in a mouse model of pneumonia. Methods:KPC-2 was expressed in Escherichia coli and purified using GST affinity chromatography. A recombinant protein vaccine was prepared with KPC-2 and used to immunize New Zealand rabbits through subcutaneous injection. Serum samples were isolated from cardiac blood and Protein G chromatography was used to purify polyclonal antibodies against KPC-2. Opsonophagocytic killing assay was used to assess the bactericidal activity of the polyclonal antibodies in vitro. Female BALB/c mice were immunized three times with the recombinant protein vaccine, and the titers of specific IgG antibodies in serum were measured by indirect ELISA. One week after the last vaccination, the mice were infected with Klebsiella pneumoniae strain SRT through tracheal intubation, and received a single intravenous dose of meropenem (0.1 mg) 1 h later. The protective efficacy of the KPC-2 recombinant protein vaccine was evaluated by comparing the survival rates, bacterial colonization and histopathological changes between vaccine group and adjuvant group as well as the survival rates between meropenem group and normal saline group. Moreover, the protective efficacy of polyclonal antibodies against KPC-2 was evaluated through passive immunization. Results:The level of specific IgG antibodies in serum was significantly higher in the vaccine group than in the adjuvant group ( t=4.325, P<0.05). The survival rate in the vaccine group was also higher than that of the adjuvant group [70% (7/10) vs 10% (1/10), P<0.05]. Furthermore, lung inflammation was less severe and bacterial burden was reduced in the vaccine group as compared with those of the control group ( t=3.127, P<0.05). Both active and passive vaccination strategies demonstrated strong protective efficacy against Klebsiella pneumoniae infection, and had a synergistic effect when used in combination with antibiotic therapy. The polyclonal antibodies against KPC-2 had bactericidal activity in vitro ( t=5.427, P<0.05). Conclusions:The prepared KPC-2 vaccine has better immunogenicity and protective efficacy. It can induce strong humoral immune responses. This study suggest that drug resistance target may be used as a candidate antigen for future vaccine development.

Objective:To comprehensively collect the clinical research evidence of Wuqinxi, and provide reference for the future clinical research.Methods:China National Knowledge Infrastructure (CNKI), WanFang Database, VIP, China Biology Medicine disc (CBM), PubMed, Embase, Cochrane Library, and Web of Science were searched. The retrieval time limit was from the establishment of each database to March 31, 2021. After screening and extracting, SPSS 22.0 was used to analyze the basic characteristics, sample size, control and intervention measures, outcomes.Results:Totally 230 studies were included, of which 58.26% (134/230) were randomized controlled trial. The top 6 diseases were chronic obstructive pulmonary disease, osteoporosis, cervical pain, low back pain, diabetes and knee osteoarthritis. Common outcome included four items of blood lipid tests, blood glucose, immunological indicators and the evaluation of disease-related symptoms, such as pain, sleep and range of motion. The median frequency of Wuqinxi was once a day, 45 minutes each time, 5 days a week and lasted for 3 months. 94.78% (218/230) of the studies reported positive results. The safety and compliance of Wuqinxi intervention were good.Conclusions:The number of clinical studies on Wuqinxi is significantly less than Baduanjin and Taijiquan. It is necessary to formulate the report specification of intervention measures for Wuqinxi, so as to report the intervention plan of Wuqinxi more clearly and transparently.

Objective:To conduct a bibliometric analysis of the implementation research of the normalization process theory in the nursing field, so as to provide a reference for future in-depth research.Methods:We searched the China National Knowledge Infrastructure, WanFang, VIP, Biomedical Literature Database, PubMed, Web of Science, Embase, Proquest, Cochrane Central Register of Controlled Trials and CINAHL. The search period was from the establishment of the database to June 18, 2021, to collect all researches related to the normalization process theory in the nursing field. The year of publication, country or region and research institution of the article, fund project, research type and subject of the article were extracted and analyzed statistically.Results:A total of 154 articles were included, with the publication period from 2010 to 2021, of which 61.69% (95/154) were from the UK. The research scholars were mainly from colleges and universities, and 62.34% (96/154) of the research was qualitative research. The clinical disease spectrum included 18 diseases, which were distributed in 9 disease systems, and there were 3 diseases with an article frequency of more than 10 times, which were mental and behavioral disorders, endocrine, nutritional and metabolic diseases, and circulatory system diseases. The key research topics included 11 categories, mainly in chronic disease management, psychological care, mobile medicine, telemedicine and other aspects.Conclusions:The normalization process theory helps clinicians and nurses understand and assess the factors that facilitate or hinder the inclusion of health care interventions in routine practice. Based on the characteristics of this theory, nursing scholars in China can conduct qualitative research and hybrid research based on research problems, and try to localize the normalization process theory.

Objective:To systematically summarizes the application topics, evaluation dimensions, data sources and evaluation results of the RE-AIM framework in the nursing field implementation research and provides a reference for the outcome evaluation of the nursing field implementation research in the future.Methods:The scoping review framework of Levac was adopted to systematically search PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database and other databases, and the retrieval time was from establishment of databases to July 3, 2021. The literatures that were evaluated using the RE-AIM framework in the implementation science in the field of nursing were included, and the data were independently extracted and analyzed by 2 members of the research group.Results:A total of 9 literatures were included, with different research topics. The literature adopted three dimensions of effectiveness, adoption rate and implementation. Both quantitative and qualitative data were collected. The accessibility was 23.8%-100.0% and the adoption was 35.7%-100.0%. The sustainability dimension lacked long-term evaluation.Conclusions:When adopting the RE-AIM framework, nursing researchers should select important and appropriate dimensions and evaluation contents, collect quantitative and qualitative data, and report results truthfully, in detail and comprehensively.

OBJECTIVES: To analyze the differentially expressed genes (DEGs) with radiation-induced rat lung injury, and to reveal the protective mechanism for mild hypothermia in the radiation-induced lung injury in rats at the transcriptome level. METHODS: A total of 10 male SD rats aged 6-8 weeks were randomly divided into 2 groups to establish a rat model of radiation-induced lung injury, and one group was treated with mild hypothermia. RNA was extracted from left lung tissue of each group, and sequenced by BGISEQ-500 platform. Significance analysis of DEGs was carried out by edgeR software. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to analyze the gene function. Then 5 key DEGs were verified by real-time reverse transcription PCR (real-time RT-PCR). RESULTS: There were 2 790 DEGs (false discovery rate<0.001, |log CONCLUSIONS The DEGs and pathways related to mild hypothermia protection against radiation-induced lung injury in rats are obtained, which provides an experimental basis for the protection of mild hypothermia against radiation-induced lung injury.
Animals ; Gene Expression Profiling ; Hypothermia ; Lung Injury ; Male ; RNA-Seq ; Rats ; Rats, Sprague-Dawley ; Transcriptome

Objective:To investigate the improved performance of hepatic elastography combined with the serum biomarkers for the diagnosis of biliary atresia.Methods:A total of 193 patients with suspected biliary atresia in Beijing Children′s Hospital from March 2019 to November 2020 were consecutively collected. All patients were randomly divided into the training cohort and validation cohort at a ratio of 7∶3. LASSO regression analysis was used for the selection of the model index based on the data set from the training cohort including the serum biomarkers, demographic features (age and sex) and hepatic elastic measurement, and a diagnostic model for biliary atresia was subsequently developed by weighting on the basis of the dominance ration. The performance of the model was respectively evaluated with respect to the discrimination and calibration in each cohort.Results:Alanine aminotransferase (ALT), glutamyl transferase (GGT) and hepatic elastic measurement were selected to build the model. The area under the ROC curve of the final diagnostic model was 0.943 with a sensitivity of 90.9% and a specificity of 85.7% in the training cohort, and 0.955 in the validation cohort. Hosmer-Lemeshow test ( P=0.292, P=0.951) and calibration curves further validated its satisfactory calibration in both cohorts. As demonstrated by Delong et al.test, employing the model in the training cohort achieved the best diagnostic performance compared with using single model index ( P<0.001, P=0.016, P<0.001). In the validation cohort, the decision curve analysis showed the model had a higher overall net benefit over using hepatic elastography alone in every predicted probability. Conclusions:The diagnostic model for biliary atresia, which incorporates ALT, GGT and hepatic elastic measurement, can improve the performance of hepatic elastography with a higher clinical value.

Objective:To comparative investigate the HPV16 virus-specific immune characteristics of HPV vaccinees, cervical precancerous lesions patients and cervical cancer patients.Methods:Six female HPV vaccinees, five patients with cervical precancerous lesions or cervical cancer and 8 healthy female volunteers from Beijing were recruited as subjects. Peripheral anticoagulated blood specimens were collected from these subjects and the peripheral blood mononuclear cells (PBMCs) and plasma were isolated. After culturing in vitro with the stimulation of L1 protein peptide pool derived from HPV16 for 9-10 days, the percentage of CD4 + and CD8 + -T lymphocytes secreting cytokines IFN-γ, IL-2 and TNF-α in the PBMCs were detected by flow cytometry. The level of HPV16 IgG antibody in plasma was determined by ELISA. Results:The IgG levels of vaccinees were significantly higher than those of healthy donors as well as patients with cervical precancerous lesions or cervical cancer. Moreover, the specific CD4 + T cell immune level of vaccinees against HPV16 was significantly higher than that of healthy controls. Furthermore, there was a positive correlation between the level of specific T cell immunity and the level of antibody against HPV16 in all the donors (Pearson, r>0.4, p<0.05). Conclusions:The virus-specific immune responses, i. e. humoral responses as well as cellular immune responses are presenting diversely among different HPV-related subjects. HPV vaccinees possess robust humoral immunity and CD4 + T cell responses.

This article combs the current situation of traditional Chinese medicine (TCM) characteristic nursing education in TCM hospitals, and puts forward corresponding thoughts on the existing problems. Moreover, this article points out that TCM hospitals should innovate the training model, build a team of teachers with a reasonable structure and complementary schools, set up a reasonable content of TCM characteristic nursing education system, and provide comprehensive economic and policy support.