Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/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 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 establish a meth od for the simultaneous determination of 7 active components in Mori Australis Cortex and Mori Cortex from different sources in Chongqing area ，so as to provide reference for improving the quality control standards of Mori Australis Cortex and Mori Cortex and comparing the equivalence of their quality. METHODS ：HPLC method was used to determine the contents of neochlorogenic acid ，mulberroside A ，chlorogenic acid ，astragalin，kaempferol，morusin and isoquercetin in 58 batches of Mori Australis Cortex and Mori Cortex. The chromatographic column was Diamonsil C 18 with mobile phase consisted of 0.1％ formic acid solution-acetonitrile （gradient elution ） at the flow rate of 1.0 mL/min. The detection wavelength was 280 nm，column temperature was 30 ℃，and the injection volume was 10 μL. Using SPSS 22.0 software， independent sample t-test，principal component analysis and cluster analysis were used to analyze the content difference of the above-mentioned 7 active components in Mori Australis Cortex and Mori Cortex. RESULTS ：There was a good linear relationship between the peak area and the concentration of the above 7 active components （r≥0.999 0）. The RSDs of precision ，stability（24 h），repeatability，durability and recovery were less than 3％. The average contents of neochlorogenic acid ，mulberroside A ， chlorogenic acid ， astragalin， kaempferol， morusin and 023-58576130。E-mail：1025473978@qq.com isoquercetin in Mori Australis Cortex were 0.304，22.462， 1.730，1.308，1.593，2.842 and 0.657 mg/g，respectively. Those of Mori Cortex were 0.305，22.995，2.486，2.438， 2.916，4.158 and 1.264 mg/g，respectively. The results of independent sample t-test showed that only the content of kaempferol in the above 7 active components of Mori Australis Cortex and Mori Cortex had significant difference （P＜0.05）. The results of principal component analysis and cluster analysis showed that there was no significant difference in the contents of above 7 active components between Mori Australis Cortex and Mori Cortex. CONCLUSIONS：The established HPLC method is simple ，sensitive and accurate ，which can provide a reference for improving the quality control standard of Mori Australis Cortex and Mori Cortex. Mori Australis Cortex and Mori Cortex have certain quality equivalence in main active components ，and the Mori Australis Cortex from M. australis and M. cathayana can be used as a substitute for the Mori Cortex.

BACKGROUND: The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm. METHODS: The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models. RESULTS: Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients. CONCLUSIONS The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.
Acute-On-Chronic Liver Failure ; Humans ; Prognosis ; Proportional Hazards Models ; ROC Curve ; Retrospective Studies

BACKGROUND: There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China. METHODS: From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups. RESULTS: Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300). CONCLUSIONS Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.
China ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, T-Cell, Peripheral/therapy* ; Neoplasm Recurrence, Local ; Retrospective Studies ; Transplantation, Autologous ; Transplantation, Homologous ; Treatment Outcome

Objective:To study the effects of different arbuscular mycorrhizal（AM） fungi combinations on the growth and quality of Paris polyphylla var. yunnanensis seedlings，in order to provide reference for the cultivation of high quality P. polyphylla var. yunnanensis. Method:Through the room temperature pot inoculation test method，nine groups of different AM fungi combinations were inoculated into sterilized soil，and the control group was not inoculated. The effects of different AM fungi combinations on root infection rate，photosynthetic parameters，physiological indexes and chemical components of P. polyphylla var. yunnanensis seedlings were observed. Result:The spore density in rhizosphere soil，the infection rate and intensity of AM fungi in roots，and the activities of succinate dehydrogenase and alkaline phosphatase in roots of P. polyphylla var. yunnanensis were significantly increased by inoculating the combination of exogenous AM fungi. Compared with the control group，the contents of chlorophyll，malondialdehyde，soluble sugar，soluble protein content and the activities of antioxidant enzymes in leaves of P. polyphylla var. yunnanensis were increased in different AM fungi treatment groups. The content of total saponin increased from T1 to T2，decreased rapidly from T2 to T4，and increased at T5. Conclusion:Different mixed AM fungus can form a good symbiotic relationship with the roots of P. polyphylla var. yunnanensis，improve the mycorrhizal vitality，enhance the resistance of P. polyphylla var. yunnanensis to adverse environment，promote the growth and development of P. polyphylla var. yunnanensis and improve the quality of rhizome. According to the comprehensive inoculation effect，the combination of S5，S8 and S9 AM fungus has the best effect，which provides reference value for the application of mycorrhizal biotechnology of P. polyphylla var. yunnanensis.

Objective:To study the effects of different arbuscular mycorrhizal （AM） fungi combinations on rhizosphere soil physicochemical properties and microbial quantity in the seedlings of Paris polyphylla var. yunnanensis at different inoculation periods，so as to lay a foundation for cultivating high-quality P. polyphylla var. yunnanensis. Method:The spore density，infection rate，nutrient and enzyme activity in the soil around the roots of P. polyphylla var. yunnanensis seedlings under different AM fungi combinations and different inoculation periods were analyzed by the greenhouse pot inoculation trials and soil agrochemical analysis methods. Result:The infection rate of different AM fungi treatment groups was more than 80% in different inoculation periods，and the spore density was higher than control （CK） group in some periods. It reflected that the relationship between AM fungi and roots of Paris polyphylla seedlings was favorable. The content of nitrogen in the soil decreased，but the content of available P，available K and soil pH increased. The soil nutrients in the cultivar one-year seedlings and wild seedlings were higher. The total number of soil microorganisms showed that bacteria>actinomycetes>fungi. The cultivar two-year seedlings with AM fungi combinations of S3，S5 and S8 had better soil structure and higher biomass carbon content. The growth rates of phosphatase and protease activity were higher in the soil，but catalase activity was lowest. In the treatment groups S2，S3，S4，S5 and S6，the soil enzyme activities of the wild seedlings and one-year-old seedlings were best. Conclusion:Different AM fungal treatment groups and different inoculation periods had certain effects on rhizosphere soil physicochemical properties and microbial quantity in the seedlings of P. polyphylla var. yunnanensis， which provided a technical basis for the cultivation of P. polyphylla var. yunnanensis.