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 retrospectively analyze the laborotary test results and clinical data of 31 patients with mixed phenotype acute leukemia (MPAL) in order to summarize and discuss the biological characteristics, curative effect, and prognosis of each subtype of MPAL based on immunophenotype results. METHODS: MPAL patients diagnosed and treated in our hospital from July 2013 to January 2019 were selected to analyze the data of cell morphology, immunophenotyping, cytogenetics, molecular biology (MICM), and routine blood at initial diagnosis. Follow-up was carried out until the last discharge time. RESULTS: Among 31 patients, there were 19 males and 12 females, with a median age of 41(12-76) years old. According to the results of immunophenotyping and EGIL score, there were 16 cases of myeloid-T lymphoid mixed phenotype (myeloid-T group), 9 cases of myeloid-B lymphoid mixed phenotype (myeloid-B group), 5 cases of T-B lymphoid mixed phenotype (T-B group), and 1 case of myeloid-T-B lymphoid mixed phenotype. Compared between different subtypes, the antigen expression characteristics were the highest positive rate and expression rate of HLA-DR in myeloid-B group, and the positive rate of CD2 in T-B group was significantly higher than that in the myeloid-T group. Meanwhile, the expression rates of CD7 and cCD3 (cytoplasmic CD3) in T-B group were higher than those in myeloid-T group, and cCD79a was positive in all cases of myeloid-B group and T-B group. The median WBC of T-B group was 81.92×10⁹/L, which was significantly higher than that of the other two groups (P<0.05). The quantitative results of WT1 were higher than 10^-4 in 92.6% of the patients, and the WT1 expression level in myeloid-B group was significantly lower than the other two groups (P<0.01). Among the 9 patients with myeloid-B mixed phenotype, 5 cases showed BCR-ABL positive. Among 28 patients followed up, 21 cases achieved complete remission (CR), the median time to first obtain CR was 32.5(9-75) days, and the median follow-up time was 16 months (range from 21 days to 6 years). The CR rate and median overall survival (OS) time in myeloid-B group were 88.9% and 40 months, which were higher than the other two groups. The CR rate and 3-year OS rate in T-B group were relatively lower (50.0%, 0). CONCLUSION WT1 gene is highly expressed in patients with MPAL, and each subgroup of MPAL based on immuophenotype has its unique antigen expression characteristics. Compared with myeloid-T group and T-B group, myeloid-B group can acquire higher remission rate and have better prognosis.
Acute Disease ; Female ; HLA-DR Antigens ; Humans ; Immunophenotyping ; Leukemia ; Male ; Phenotype ; Prognosis ; Retrospective Studies

Objective: To detect the SMO mutations in odontogenic keratocyst (OKC) and to explore the mechanism behind. Methods: Patients with OKC who received treatment in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology,Peking University, from September 2012 to June 2017 were enrolled. OKC samples from 10 patients diagnosed as naevoid basal cell carcinoma syndrome (NBCCS)-related OKC (4 females and 6 males) and 20 patients diagnosed as sporadic OKC (7 females and 13 males) were collected. Genomic DNAs were extracted from fibrous capsules and epithelial lining respectively. SMO mutations were detected and analyzed by Sanger sequencing. Results: Three SMO mutations were found in one NBCCS-associated OKC who carrying c.2081C>G (p.P694R) mutation) and two sporadic OKC who carrying c.907C>T (p.L303F) mutation and c.1247_1248delinsAA (p.G416E), respectively), among which the first two mutations were novel mutations that had not been reported before. Besides, two mutations in sporadic OKC were not paired with PTCH1 mutations. Conclusions: In addition to PTCH1 gene mutations, SMO gene mutations also exist in OKC which might be related to the development of OKC.
Basal Cell Nevus Syndrome/genetics* ; Female ; Humans ; Male ; Mutation ; Odontogenic Cysts/genetics* ; Odontogenic Tumors/genetics* ; Smoothened Receptor/genetics*

The study is aimed through field experiments to study the effect of combined application of organic and chemical fertilizers on the growth and quality of Salvia miltiorrhiza, provide ideas for reducing fertilization while increasing the efficiency as well as improving the quality of produces. The experiment included 6 treatments viz., no fertilization(CK), full application of chemical fertilizer(F), 25% orga-nic fertilizer with 75% chemical fertilizer(M25), 50% organic fertilizer with 50% chemical fertilizer(M50), 75% organic fertilizer with 25% chemical fertilizer(M75), and fully apply organic fertilizer(M100). The results showed that:(1)from the perspective of yield and economic benefits, M75 was the best and M100 second;(2)for effective components, the combined application of organic and chemical fertilizers increased the content of main water-soluble components and the total content of effective components, among which M25 and M50 were better.
Agriculture ; Fertilizers/analysis* ; Nitrogen ; Salvia miltiorrhiza ; Soil

Objective To study the preference relation between residence, sex, age and causes of accidental death of Chinese residents. Methods In this study, 72 residence-sex-age groups and 8 causes of accidental death were qualitatively and quantitatively analyzed by correspondence analysis using the official statistical yearbook issued from 2014 to 2018, and the preference values were calculated. Results Among the 576 pairs of correspondences between the residence-sex-age groups and causes of accidental death, 352 pairs （61.11%） showed a preference relation （preference value>0）. In terms of residence and sex, accidental death preference among Chinese residents was higher in rural areas than in urban areas, and males were higher than females. In terms of the causes of accidental death, the overall risk of accidental mechanical asphyxia and motor vehicle accidents was the highest among all age groups of Chinese residents. In terms of age, with the increase of age, the preference value of accidental death of Chinese residents showed a trend of first increasing and then decreasing. The comparative analysis results of the preference values of various causes of accidental death in different age groups showed that motor vehicle traffic accidents, accidental poisoning, death by crush and electric shock were more likely to occur in the working age group between 20 and 59 years old, accidental fall and fire were more likely to occur in the elderly group over 80 years old, and drowning and accidental mechanical asphyxia were more likely to occur in the minor group between 1 and 19 years old. Conclusion There are different preference relations between residence-sex-age groups and causes of accidental death in China. Therefore, effective control strategies and measures should be formulated for Chinese residents with preference for accidental death.
Accidental Falls ; Accidents, Traffic ; Adult ; Aged ; Asphyxia/etiology* ; China/epidemiology* ; Drowning ; Female ; Humans ; Male ; Middle Aged ; Young Adult

This paper summarized the effects of ecological planting on secondary metabolism firstly and pointed out that ecological planting can increase the content of secondary metabolites in plants, especially the content of defensive secondary metabolites. The possible mechanism was analyzed subsequently. Then, we reviewed the induction and utilization of secondary metabolism in the ecological planting of Chinese materia medica from the perspectives of biological control of pests and diseases, promotion of beneficial microorganism accumulation, optimization of mixed planting, regulation of no-tillage and straw cover. In this article, we pointed out that paying close attention to secondary metabolism is the most important feature of ecological planting of Chinese materia medica. Ecological planting can promote the accumulation of secondary metabolites of Chinese materia medica which means can improve the quality of Chinese materia medica, beneficial to the prevention and control of diseases, insects and weeds. Furthermore, lacking of systemic researches,the extensive verifications and systematic in-depth researches on the ecological planting of Chinese materia medica should be carry out urgently.
Drugs, Chinese Herbal ; Materia Medica ; Medicine, Chinese Traditional ; Plants, Medicinal ; Secondary Metabolism

As an environment-friendly agriculture, ecological agriculture of Chinese materia medica(CMM) is being implemented in all parts of the country. Due to the stronger dependence on natural environmental conditions, ecological agriculture of CMM shows obvious regional differences in production practice. More mature CMM ecological planting patterns representative of each region were collected. It was found that common types of patterns in various regions of the country mainly included intercropping,intercropping,rotation planting mode, undergrowth planting mode, wild tending planting mode and landscape ecological planting mode. Based on the Construction Plan of National Dao-di Herbs Production Base(2018-2025) and Chinese Medicine Division, this paper systematically sorts out the pattern of ecological planting of CMM in the 8-avenue medicinal materials production areas according to the varieties and regions. The specific pattern of ecological planting of CMM included the ginseng undergrowth planting pattern in northeastern China, the bionics wild ecological planting of the Forsythia suspensa in northern China, the Fritillaria thunbergii-rice rotation in eastern China, the imitation wild planting pattern under the Polygonatum cyrtonema in central China, the planting pattern of the Fructus amomi under forest in southern China, the Ligusticum chuanxiong-rice rotation pattern in the Southwest, wild tending of Glycyrrhiza uralensis in the Northwest, and rhubarb imitation wild planting pattern in Qinghai-Tibet area. Finally, it is expected to provide reference for the screening and popularization of ecological planting patterns of other CMMs in various distribution areas.
China ; Drugs, Chinese Herbal ; Ligusticum ; Materia Medica ; Medicine, Chinese Traditional ; Tibet

The ecological agriculture of Chinese materia medica(CMM) has become the most dynamic and promising new field in the global ecological agriculture. The development of ecological planting of CMM has become the national strategy of Chinese traditional medicine agriculture. It has been highly valued and has flourished throughout the country, and has formed some more mature ecological planting models of CMM. Based on the system level, this paper sorts out the common ecological cultivation patterns of CMM, and obtains five basic patterns: landscape pattern at the ecological landscape level, circulation pattern at the ecosystem level, stereo model at the bio-community level, biodiversity patterns at the level of biological populations and well-established models at the level of biological individuals. On this basis, eight common ecological planting techniques of CMM were obtained, includingwild tending techniques, fine agricultural farming techniques, directional cultivation techniques, soil improvement techniques, soil testing and fertilization techniques, mycorrhizal cultivation techniques, green control technology for pests and diseases and facility cultivation techniques.This paper aims to provide theoretical basis for scientific research and popularization and application of CMM ecological planting.
Agriculture ; Drugs, Chinese Herbal ; Ecosystem ; Humans ; Materia Medica ; Medicine, Chinese Traditional