Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective: To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on the pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) based on the available clinical evidence. METHODS: We searched PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, VIP, CBM and Wanfang Database up to February 2021 for published randomized controlled trials (RCT) relevant to TEAS for the improvement of the pregnancy outcomes of IVF-ET. We performed literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria, followed by a meta-analysis with the RevMan 5.3 software. RESULTS: A total of 2 206 cases of IVF-ET from 9 RCTs were included, 1 018 in the TEAS group and 1 188 in the control. The clinical pregnancy rate was significantly higher in the TEAS than in the mock TEAS and non-TEAS control groups (RR = 1.85, 95% CI: 1.42－2.42, P < 0.001; RR = 1.23, 95% CI: 1.10－1.39, P = 0.0004), and so was it before and after oocyte retrieval (RR = 1.50, 95% CI: 1.03－2.17, P = 0.03; RR = 1.47, 95% CI: 1.12－1.92, P = 0.005). The TEAS group also showed dramatically improved embryo implantation rate (RR = 1.49, 95% CI: 1.24－1.79, P < 0.0001) and live birth rate (RR = 1.44, 95% CI: 1.04－1.98, P = 0.03) compared with the control. CONCLUSIONS As a safe and non-invasive treatment, TEAS can significantly improve the pregnancy outcomes of IVF-ET, with definite effectiveness. /.
Acupuncture Points ; Embryo Transfer ; Female ; Fertilization in Vitro ; Humans ; Pregnancy ; Pregnancy Outcome ; Randomized Controlled Trials as Topic

Objective To explore the association of cardiac disease associated genetic variants and the high incidence of Yunnan sudden unexplained death （YNSUD） in Yi nationality. Methods The genomic DNA was extracted from peripheral blood samples collected from 205 Yi villagers from YNSUD aggregative villages （inpatient group） and 197 healthy Yi villagers from neighboring villages （control group）. Fifty-two single nucleotide variants （SNVs） of 25 cardiac disease associated genes were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS）. The SPSS 17.0 was used to analyze data. The pathogenicities of variants with differences between the two groups that have statistical significance were predicted by protein function prediction software PolyPhen-2 and SIFT. All villagers from inpatient group were given electrocardiogram （ECG） examination using a 12-lead electrocardiograph. Results The allele frequency and the genotype frequency of missense mutation DSG2 （rs2278792, c.2318G>A, p.R773K） of pathogenic genes of arrhythmogenic right ventricular cardiomyopathy （ARVC） in inpatient group was higher than that in control group （P<0.05）. Abnormal ECG changes were detected in 71 individuals （34.6%） in the inpatient group, among which 54 individuals carried R773K mutation, including clockwise （counterclockwise） rotation, left （right） axis deviation, ST segment and T wave alteration and heart-blocking. Conclusion Definite pathogenic mutations have not been found in the 52 cardiac disease genes associated SNVs detected in Yi nationality in regions with high incidence of YNSUD. The cause of high incidence of YNSUD in Yi nationality needs further study.
Arrhythmogenic Right Ventricular Dysplasia ; China/epidemiology* ; Death, Sudden/etiology* ; Death, Sudden, Cardiac/etiology* ; Ethnicity/genetics* ; Humans ; Incidence ; Mutation

A rapid analysis method based on ultraviolet-visual(UV-Vis) spectroscopy, near infrared(NIR) spectroscopy and multivariable data analysis was established for quality evaluation of Shengxuebao Mixture. The contents of eight active ingredients of Shengxuebao Mixture including albiflorin, paeoniflorin, 2, 3, 5, 4'-tetra-hydroxy-stilbene-2-O-β-D-glucopyranoside, specnuezhenide,ecliptasaponin D, emodin, calycosin-7-glucoside and astragaloside Ⅳ were simultaneously detected by using this method. HPLC-UV-MS was used as a reference method for determining the contents of these ingredients. Partial least squares(PLS) analysis was implemented as a linear method for multivariate models calibrated between UV spectrum/NIR spectrum and contents of 8 ingredients. Finally, the performance of the model was evaluated by 24 batches of test samples. The results showed that both UV-Vis and NIR models gave a good calibration ability with an R~2 value above 0.9, and the prediction ability was also satisfactory, with an R~2 value higher than 0.83 for UV-Vis model and higher than 0.79 for NIR model. The overall results demonstrate that the established method is accurate, robust and fast, therefore, it can be used for rapid quality evaluation of Shengxuebao Mixture.
Calibration ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Least-Squares Analysis ; Mass Spectrometry ; Spectroscopy, Near-Infrared

Shaoyao Gancaotang, first seen in Treatise on Febrile and Miscellaneous Diseases, is composed of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle in equal proportion.It has the functions of preserving Yin to nourish blood, harmonizing liver and spleen, relieving spasm and pain.This formula is applied in leg and foot spasm and abdominal pain caused by blood deficiency, body fluid consuming and the unmoistened muscles and veins.It has been highly praised and used by medical experts throughout the ages and has extended its application scope.Modern pharmacological studies have shown that Shaoyao Gancaotang has significant effects in antispasmodic, analgesic, antitussive and other areas, and is used to treat spastic diseases, painful diseases, inflammatory diseases and so on.This paper will systematically elaborate the historical evolution, compatibility analysis, pharmacological and pharmacodynamic studies, modern clinical application of Shaoyao Gancaotang, in order to provide theoretical basis and reference for the development of this famous classical formula.

OBJECTIVE: To compare the registration accuracy of three-dimensional (3D) facial scans for the design of full-arch implant supported restoration by five methods and to explore the suitable registration method. METHODS: According to the criteria, ten patients with maxillary edentulous jaw or end-stage dentition requiring implant supported restorations were enrolled in this study. A special rim with individual feature marks reflected appropriate occlusal relationship and esthetic characteristics was made for each patient. Both 3D facial scan data of natural laughter and with opener traction to expose the teeth or occlusal rim of each patient were acquired by facial scan and input to the digital analysis software Geomagic Qualify 2012. The dataset was superimposed by five different methods: seven facial anatomical landmark points alignment, facial immobile area alignment (forehead and nasal area), facial anatomical landmark points and immobile area combining alignment, facial feature points alignment, facial and intraoral feature points alignment with the same local coordinate system. The three-dimensional deviation of the same selected area was calculated, the smaller the deviation, the higher the registration accuracy. The 3D deviation was compared among the three registration methods of facial anatomical landmark points, facial immobile area alignment and the combination of the above two methods. Friedman test was performed to analyze the difference among the three methods (α=0.05). The effect of the aid of the facial and intraoral feature points were evaluated. Paired t test were performed to analyze the difference (P<0.05). RESULTS: The average three-dimensional deviation of the selected area after alignment with the facial anatomical landmarks was (1.501 2±0.406 1) mm, significantly larger than that of the facial immobile area best-fit alignment [(0.629 1±0.150 6) mm] and the combination of the two methods[(0.629 1±0.150 6) mm] (P < 0.001). The aid of the facial feature points could significantly reduce the deviation (t=1.001 3, P < 0.001). There was no significant statistical difference in the remaining groups. CONCLUSION The forehead area of the 3D facial scan can be exposed as much as possible. The establishment of facial characteristic landmark points and the use of the invariant area alignment can improve the accuracy of registration. It should be clinically feasible to apply three-dimensional facial scan to the design of full-arch implant supported restoration with the registration of the immobile area on the face especially the forehead area.
Computer-Aided Design ; Humans ; Imaging, Three-Dimensional ; Jaw, Edentulous/diagnostic imaging* ; Maxilla/diagnostic imaging* ; Radionuclide Imaging

Purpose To investigate the value of application of D2-40/CD34-CK cocktail antibodies by double immunohistochemical staining for assessment of lymphovascular invasion (LVI) and to determine its prognostic significance in colorectal cancer with insufficient lymph node harvest. Methods Specimens from 133 cases of colorectal cancer with less than 12 lymph nodes were selected. HE staining and double immunohistochemical staining of the cocktail antibodies were performed to compare the difference of the two methods in screening for LVI. The The relationship between LVI confirmed by cocktail antibody immunohistochemical staining and clinicopathological characteristics and overall survival (OS) of patients was analyzed. Results (1) The detection rates of cocktail antibody double immunohistochemical staining and HE staining for LVI were 42.9％ (57/133) and 21.8％ (29/133) with statistically significant difference (P < 0.001). (2) The presence of LVI confirmed by double staining was significantly associated with Dukes staging, depth of invasion, clinical stages, lymph node metastasis and tumor budding (P < 0.05). (3) The presence of LVI, the location and extent of LVI, and the number of tumor cells in thrombus ≥5.5 for cases with LVI ≤2 clusters, were significantly associated with OS (P < 0.05). Conclusion D2-40/CD34-CK cocktail antibodies double staining is superior to routine HE staining in assessing LVI. LVI is intimately associated with tumor stage, lymph nodes metastasis and tumor budding, and it is an independent prognostic factor for CRC patients. It should be a supplementary examination for these patients with insufficient lymph node harvest.

Objective: To screen the frosting qualitymarkers (Q-marker) of Mori Foliumand identify Mori Folium after frost. Method: The HPLC-DAD-MSⁿ fingerprints of Mori Folium before and after frost were established,the common peaks were markedand the characteristic components were selected by orthogonal partial least squares discrimination analysis (OPLS-DA). The components with a large content change were used as marker components,and the relatively stable component was used as an internal reference component. The ratio of the marker components to the peak area of the internal reference component was used as component characteristic to identify the frost of Mori Folium,andqualitative study of frosting markerswere performed by MSⁿ and authentic standards. Result: The fingerprints were established and 33 common peaks were marked. Through OPLS-DA,peaks 1,23,14 were determined as marker components,peak 12 was determined as internal reference component. The frosting quality markers of Mori Folium were characterized as citric acid derivatives,saponin F,tryptophan and neochlorogenic acid by MSⁿ and standards. The ratios of the peak areas of citric acid derivatives,saponin F,tryptophan and neochlorogenic acid before and after frost were 0.15±0.054,1.0±0.48; 0.14±0.073,0.98±0.48,0.13±0.088,0.89±0.49,respectively. Conclusion: In the fingerprints established in this study,the peak area ratios of citric acid derivatives,saponin F,tryptophan to new chlorogenic acid had specificity,which can be used as frosting quality markers for identification of Mori Folium. This study expanded the connotation of the Q-marker specificity of traditional Chinese medicine. The results can provide experimental data for the quality evaluation and drug-forming properties of Mori Folium,and provide reference for similar research.

Objective To explore how to apply the teaching mode combined flipped class with PBL teaching method to improve college students' ability of English reading and writing and the effectiveness of classroom. Methods In the class of college English reading and writing, students at grade 2015 were randomly divided into two groups. The experimental group (43 students) was adopted the class teaching with " flipped class and PBL teaching method"and the control group (43 students) was adopted traditional class teaching mode taught by the same teacher. The teaching effects of two groups were studied in a comparative way. The students' final grade, related data in the learning process, students'view of the two teaching modes are studied by analysis of basic data and questionnaire. Results At the end of the semester, the results of the experimental group are better than those of the control group. In the survey of the two class teaching modes, the students in the experimental group spent more time in the learning process than that of the control group.Students think that the teaching mode combined flipped class and PBL teaching method not only improves their autonomic learning ability, classroom participation, the English reading and writing ability, but also helps them perform better in the average scores in the final exam compared to the traditional classroom. Students are more satisfied with the new classroom teaching mode than with traditional one. Conclusion The teaching mode combined flipped class with PBL teaching method can promote the students'autonomous learning, contribute to absorb and internalize knowledge, improve the students'learning interest and learning efficiency, and improve teachers teaching ability.