Humans ; Fibrous Dysplasia, Polyostotic/complications* ; Hemangioma

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Objective:To analyze the clinicopathological features, survival and related prognostic factors of encapsulated papillary carcinoma (EPC) of breast.Methods:Data on EPC and invasive ductal carcinoma (IDC) of the breast from January 2010 to December 2015 were searched and screened using the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was used to adjust for baseline confounding between the EPC and IDC groups. The Kaplan-Meier method was used to calculate cumulative survival curves for overall survival (OS) and breast cancer-specific survival (BCSS). Prognostic value of these factors were assessed by univariate Log-rank test and multivariate Cox regression analysis.Results:In this study, 184 524 patients with IDC and 175 patients with EPC were included. Compared with patients with IDC, patients with EPC over 60 years old had a higher proportion, a lower rate of lymph node metastasis, and a higher proportion of estrogen receptor positive, progesterone receptor positive and human epidermal growth factor receptor 2 negative ( P<0.05). After PSM adjustment, OS of patients with EPC was worse than that of IDC, and BCSS was better than that of IDC ( P<0.05). Univariate and multivariate analysis showed that age, surgical approach and N stage were associated with poorer OS, while surgery approach, T stage, N stage and molecular typing were associated with worse BCSS ( P<0.05). Conclusions:Compared with IDC, EPC of breast has better BCSS and lower lymph node metastasis rate. There is a certain correlation between tumor stage and molecular type and prognosis of EPC.

Qingjin Huatan Decoction is a classic prescription with the effects of clearing heat, moistening lung, resolving phlegm, and relieving cough. In order to explore the critical quality attributes of Qingjin Huatan Decoction, we identified the blood components of Qingjin Huatan Decoction by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) under the following conditions, chromatographic column: Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm); mobile phase: 0.1% formic acid acetonitrile(A)-0.1% formic acid in water(B); gradient elution; flow rate: 0.2 mL·min~(-1); column temperature: 30 ℃; injection volume: 5 μL. The electrospray ionization(ESI) source was used to collect data in both positive and negative ion modes under the following conditions, capillary voltage: 3 kV for the positive ion mode and 2 kV for the negative ion mode; ion source temperature: 110 ℃; cone voltage: 30 V; cone gas flow rate: 50 L·h~(-1); nitrogen degassing temperature: 350 ℃; degassing volume flow rate: 800 L·h~(-1); scanning range: m/z 50-2 000. In this experiment, a total of 66 related components of Qingjin Huatan Decoction were identified, including 22 prototype components and 44 metabolites. The results of this study preliminarily revealed the pharmacodynamic material basis of Qingjin Huatan Decoction in vivo, which has provided an experimental basis for the determination of quality markers of Qingjin Huatan Decoction and the development of new drugs.
Chromatography, High Pressure Liquid/methods* ; Chromatography, Liquid ; Drugs, Chinese Herbal/chemistry* ; Tandem Mass Spectrometry/methods*

Hemophilia is an X-linked recessive inherited bleeding disorder. Despite the improved treatment in recent years with the advent of replacement therapies, the progression of atherosclerosis is not slowed down after the reduction of clotting factors in hemophilia. As life expectancy increases, more hemophilia patients will suffer from age-related cardiovascular diseases. Since cardiac surgery needs heparinization and cardiopulmonary bypass (CPB), it is extremely challenging to balance hemostasis and coagulation in patients with hemophilia. Here we report three cases of hemophilia patients who underwent cardiac surgery successfully.
Cardiac Surgical Procedures/adverse effects* ; Cardiopulmonary Bypass ; Hemophilia A/complications* ; Humans

OBJECTIVE: To investigate the effect of interference of CTPS gene on toosendanin-induced apoptosis of gastric cancer MKN-45 cells. METHODS: Bioinformatic analysis was used to analyze CTPS gene expression in human gastric cancer tissues and the overall survival of gastric cancer patients with high CTPS gene expression. Human gastric cancer MKN-45 cells were transfected with a short hairpin interfering RNA targeting CTPS gene, and 48 h later, qRT-PCR and Western blotting were used to detect cellular expression CTPS at both the mRNA and protein levels. MKN-45 cells with CTPS knockdown were treated with 80 nmol/L toosendanin for 48 h, and the cell viability was assessed with MTT assay; the cell morphology was observed using laser confocal microscope, and the expression of γH2AX was detected with immunofluorescence assay. RESULTS: Bioinformatic analysis suggested that CTPS was highly expressed in human gastric cancer tissues, and gastric cancer patients with high CTPS gene expression had a shorter overall survival. MKN-45 cells transfected with Sh-CTPS interference vector showed significantly lowered cell survival rate (P < 0.01) with obvious cell shrinkage, irregular morphology, typical apoptotic changes, and increased cell apoptosis rate (P < 0.05). Treatment of the transfected cells with 80 nmol/L toosendanin for 48 h resulted in further reduction of the cell survival rate (P < 0.001), and the cells showed an increased apoptotic rate (P < 0.05) with appearance of apoptotic bodies. CONCLUSION Interference of CTPS gene can promote TSN-induced apoptosis of gastric cancer MKN-45 cells.
Apoptosis ; Cell Line, Tumor ; Humans ; RNA, Small Interfering/metabolism* ; Silanes ; Stomach Neoplasms/metabolism* ; Triterpenes

Objective : To investigate the effect and mechanism of Src homology 2 domain - containing protein tyrosine phosphatase inhibitor PHPS1 on atherosclerotic plaque vulnerability in ApoE knockout mice , and to provide a new idea for the study of atherosclerosis. Methods : Sixteen 8 ⁃week⁃old ApoE - / - mice were randomly divided into control group and PHPS1 group. The aortic root was fixed with formalin and sectioned. The collagen and macrophage contents in the plaque were evaluated by Movat and Sirius red staining. The activity of ERK and the expression of MMP⁃9 in the descending aorta were detected by Western blot. Results : The plaque area (0. 52 ± 0. 05) , (0. 31 ± 0. 03 ) , collagen content (0. 062 ± 0. 013 ) , (0. 136 ± 0. 022) and macrophage cell ratio (0. 799 ± 0. 031) , (0. 621 ± 0. 043) were different between PHPS1 group and control group ( P < 0. 01) . The results of western blot showed that PHPS1 inhibited the activity of ERK and decreased the protein expression of MMP⁃9 (P <0. 01) . Conclusion PHPS 1 , an inhibitor of SHP⁃2 , can inhibit ERK activity and decrease the expression of MMP⁃9 , thus reducing the degradation of collagen in fibrous cap and stabilizing vulnerable atherosclerotic plaque.

Gut microbiome sequencing studies have great potential to translate microbial analysis outcomes into human health research. Sequencing strategies of 16S amplicon and whole-metagenome shotgun (WMS) are two main methods in microbiome research with respective advantages. However, how sample heterogeneity, sequencers and library preparation protocols affect the sequencing reproducibility of gut microbiome needs further investigation. This study aims to provide a reference for the selection of sequencing technologies by comparing differences in microbial composition from different sampling sites. The results of three widely adopted sequencers showed that the technical repetition correlation (r= 0. 94) was high in WMS method, while the biological repetition correlation (r = 0. 69) was low. Bray-Curtis distance identified that dissimilarity from biological replicates was larger than that of technical replicates (P<0. 001). In addition, dissimilarity and specific taxonomic profiles were observed between 16S and WMS datasets. Our results imply that homogenization is a necessary step before sample DNA extraction. The sequencers contributed less to taxonomic variation than the library preparation protocols. We developed an empirical Bayes approach that " borrowed information" in calculations and analyzed batch effect parameters using standardized data and prior distributions of (non-) parameters, which may improve population comparability between 16S and WMS and provide a basis for further application to fusion analysis of published 16S and microbial datasets.

Paeoniae Radix Alba is the dried root of Paeonia lactiflora, which was first recorded in the Shennong's Classic of Materia Medica and listed as the top grade. It is a common blood-tonifying herb, and its chemical components are mainly monoterpenes and their glycosides, triterpenes, flavonoids and so on. Modern research has demonstrated that Paeoniae Radix Alba has the activities of anti-inflammation, pain easing, liver protection, and anti-oxidation, and thus it is widely used in clinical practice and has broad development prospects. In this paper, the research progress on the chemical composition, pharmacological effects, and quality control of Paeoniae Radix Alba were summarized. On this basis, the Q-markers of Paeoniae Radix Alba were predicted from the aspects of mass transfer and traceability, chemical composition specificity, and availability and measurability of chemical components, which will provide a scientific basis for the quality evaluation of Paeoniae Radix Alba.
Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Monoterpenes ; Paeonia ; Plant Extracts