An Investigation of the Magnitude of the Role of Different Plant Species in Grassland Communities on Species Diversity, China.

In this study, we selected four grassland plots in Altai forest area and used the field survey method of "two-valued occurrence" to obtain the occurrence data of each plant species in the plots so as to calculate the species diversity index value of the community as a whole and the species diversity index value of each plant species not present in the community and to make use of the difference between these two diversity indices to determine the role of each plant species in the overall species diversity of the community. The difference between these two diversity indices was used to investigate the role of each plant species in the overall species diversity of the community. The results show the following: (1) In the grassland of the Altai forest area in Xinjiang, Asteraceae, Poaceae, Fabaceae, Polygonaceae, and Rosaceae are the dominant families, among which the genera Puccinellia Parl, Taraxacum, Pharbitis, Lactuca, Geranium, and Alchemilla are the dominant genera. (2) The plant species with the greatest contribution to species diversity in the four grassland samples was not the first dominant species of the community, but rather the plant species whose dominance was in the second to sixth position. (3) The first dominant species was overwhelmingly dominant in the four sample plots, and it served to increase the overall diversity of the community. (4) The overall trend in the size of the role of species in diversity is unimodal, i.e., logarithmically increasing to a maximum as species dominance decreases and then exponentially or linearly decreasing and eventually converging to zero. The synthesis showed that it was not the first dominant species that played the largest role in species diversity in the different grassland communities and that the overwhelmingly dominant species reduced the species diversity of the community.

Identification of a Group of Therapeutic Targets and Prognostic Biomarker for Triple Negative Breast Cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. Mining differentially expressed genes of TNBC is helpful to explore new therapeutic targets. This study aimed to investigate diagnostic biomarker genes in TNBC compared to normal tissue. Additionally, we explored the functions and prognostic value of these key genes as well as potential targeted drugs that could affect these genes. METHODS: Differential gene expression analysis was conducted using the R software with data from the Gene Expression Omnibus (GEO) database. Then, the identified differentially expressed genes (DEGs) were used to construct a protein-protein interaction (PPI) network using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. The mRNA expression levels of key genes were analyzed using the UALCAN database with data from The Cancer Genome Atlas (TCGA). Enrichment and survival analyses were performed using R software. In addition, potential compounds showing sensitivity to key genes were identified by gene set cancer analysis (GSCA). RESULTS: Compared with normal tissues, a total of 203 DEGs were upregulated in TNBC. These DEGs participated in various biological processes including nuclear division, microtubule binding, cell cycle, and the p53 signaling pathway. Through the PPI network analysis, ten key genes were identified, among which four genes showed significant correlation with poor progression-free interval (PFI) in patients with TNBC. Moreover, the four survival-related genes were found to act as sensitive therapeutic targets. CONCLUSION: The identified four key genes were considered new biomarkers for diagnosis and prognosis and also potential therapeutic targets for TNBC.

Safety, tolerability, pharmacokinetics and immunogenicity of an antibody-drug conjugate (SHR-A1201) in patients with HER2-positive advanced breast cancer: an open, phase I dose-escalation study.

SHR-A1201 is an antibody-drug conjugate (ADC) that combines trastuzumab with DM1 (a chemotherapeutic agent) using a chemical connector. This phase I study investigated the safety, tolerability and pharmacokinetics of SHR-A1201 in patients with human epidermal growth factor receptor 2-positive advanced breast cancer. This phase I study enrolled patients in a traditional 3 + 3 dose-escalation design to receive a single dose of SHR-A1201 (1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg or 4.8 mg/kg). The observation period of dose-limiting toxicity (DLT) was 21 days. A total of 12 patients were enrolled and received SHR-A1201. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity, with elevated aspartate aminotransferase (75%), thrombocytopenia (75%), and nausea (66.7%) being reported most frequently. The common grade 3 TEAEs were thrombocytopenia and decreased lymphocyte count, and there were no grade 4 or above TEAEs. There were no serious adverse events or drug-related deaths. One DLT occurred in one patient treated with SHR-A1201 4.8 mg/kg (asymptomatic grade 3 increased γ-glutamyltransferase). The maximum tolerated dose of SHR-A1201 was not lower than that of T-DM1 (3.6 mg/kg). A total of 8.3% (1/12) of patients had ADA-positive reactions 504 h after administration, but no differences were observed in the type, incidence, or severity of TEAEs between patients with and without ADA. SHR-A1201 exhibited the pharmacokinetics characteristics of typical ADCs. An encouraging antitumor effect was observed in the 4.8 mg/kg dose group. SHR-A1201 was well tolerated and safe in patients with advanced HER2-positive breast cancer. The pharmacokinetics parameters showed a linear trend, and the immunogenicity results met the clinical expectations.

Pertuzumab combined with trastuzumab compared to trastuzumab in the treatment of HER2-positive breast cancer: A systematic review and meta-analysis of randomized controlled trials.

Objective: Although dual anti-HER2 therapy, namely, pertuzumab plus trastuzumab, has shown promising results in patients with HER2-positive breast cancer (BC), it is still unclear whether dual therapy will increase adverse effects (AEs) while ensuring the efficacy compared with trastuzumab monotherapy. We conducted a systematic review and meta-analysis to compare the efficacy and safety of combined therapy with monotherapy. Methods: A systematic search was performed to identify eligible randomized controlled trials (RCTs) that evaluated the administration of dual anti-HER2 therapy [pertuzumab plus trastuzumab or trastuzumab emtansine (T-DM1)] versus monotherapy (trastuzumab or T-DM1). The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: Fourteen RCTs (8,378 patients) were identified. Compared to monotherapy, dual therapy significantly improved the OS (HR = 0.77, 95% CI: 0.59-0.99) and PFS (HR = 0.74, 95% CI: 0.63-0.86) in advanced BC. In neoadjuvant therapy, dual blockade has a higher ORR rate than monotherapy. Grade 3 or higher febrile neutropenia, diarrhea, and anemia as well as heart failure were more frequently reported in dual therapy compared to monotherapy. No significant difference in serious AEs was observed between the two groups. In the subgroup analysis, compared to single-target therapy, dual-target therapy has higher OS and PFS rates in Asian patients with advanced therapy; however, total grade ≥3 AEs and serious AEs were significantly higher in the dual group in Asian patients. Conclusions: Our study confirms that the combination of pertuzumab and trastuzumab therapy could substantially improve the outcome of patients with HER2-positive breast cancer and was well tolerated compared to trastuzumab monotherapy.

Bioequivalence and safety evaluation of two preparations of metformin hydrochloride sustained-release tablets (Boke® and Glucophage®-XR) in healthy Chinese volunteers: a randomized phase I clinical trial.

BACKGROUND: As per the National Medical Products Administration (NMPA) requirements, the quality and efficacy of generic drugs must be consistent with those of the innovator drug. We aimed to evaluate the bioequivalence and safety of generic metformin hydrochloride sustained-release (MH-SR) tablets (Boke®) developed by Beijing Wanhui Double-crane Pharmaceutical Co. Ltd., China and the innovator product metformin hydrochloride extended-release tablets (Glucophage®-XR) manufactured by Bristol-Myers Squibb Company, New York, NY, in healthy Chinese volunteers. MATERIALS AND METHODS: We performed a bioequivalence and safety assessment of MH-SR (500 mg/tablet) and Glucophage®-XR (500 mg/tablet) tablets in a randomized, open-label, two-period, two-sequence crossover, single-dose oral study in 48 healthy Chinese adult participants under fasting conditions (Chinese Clinical Trial Registration No. CTR20171306). The washout period was seven days. Bioequivalence (80.00-125.00%) was assessed using adjusted geometric mean ratios (GMRs) and two-sided 90% confidence intervals (CIs) of the area under the curve (AUC) and maximum concentration (Cmax) for each component. RESULTS: The 90% CIs of the test/reference preparation for key pharmacokinetic parameters were 97.36-108.30% for AUC0→t, 97.26-108.09% for AUC0→∞ and 96.76-111.37% for Cmax. No severe adverse events (AEs) were observed. However, 38 adverse drug reactions (ADRs) occurred, including metabolic or nutritional conditions (n = 8), infections (n = 2), gastrointestinal conditions (n = 10) and abnormal inspection (n = 18). No significant difference was observed between MH-SR (23 ADRs, 10 participants) and Glucophage®-XR (15 ADRs, 12 participants) (p = .500). Bioequivalence was concluded since the 90% CIs of the main pharmacokinetic parameters were within the equivalence interval (80.00-125.00%). CONCLUSIONS: MH-SR (500 mg/tablet) and Glucophage®-XR (500 mg/tablet) were found to be bioequivalent and safe under fasting conditions in healthy Chinese participants. Thus, the market demand for MH-SR tablets (500 mg/tablet) can be met using the generic alternative.KEY MESSAGESGeneric MH-SR tablets (500 mg, Beijing Wanhui Double-crane Pharmaceutical Co. Ltd., Beijing, China) and innovator MH-SR tablets (Glucophage®-XR, 500 mg, Bristol-Myers Squibb Company, New York, NY, USA) were bioequivalent and safe in healthy Chinese volunteers under single-dose administration and fasting conditions.The main goal of this study is to support an increase in the supply of MH-SR tablets in China by proving the efficacy and safety of a generic alternative.Although no sugar was administered in the BE trial of the MH-SR tablets under fasting conditions, no hypoglycaemic event occurred. The method used in this study is expected to serve as a reference for BE studies of different MH-SR formulations.

Phase I, randomized, double-blind, single-dose study to assess the pharmacokinetics, safety, and immunogenicity of the proposed biosimilar SCT630 and adalimumab in healthy Chinese subjects.

We aimed to compare the pharmacokinetics, safety, and immunogenicity of the adalimumab biosimilar SCT630 with those of its reference (adalimumab, Humira®). This study involved a randomized, double-blind, parallel-controlled design; healthy subjects (N = 146) were randomly distributed into two groups to receive a single-dose subcutaneous injection of 40 mg SCT630 or 40 mg adalimumab, with a 71-day follow up. The bioequivalence of the primary pharmacokinetic parameters (AUC0-t) and maximum observed serum concentration (Cmax) between SCT630 and adalimumab were the primary endpoints; safety and immunogenicity of SCT630 compared with those of adalimumab were the secondary endpoints. The geometric mean Cmax ratio of SCT630 to adalimumab and its 90% confidence interval (CI) were 116.02% and 108.66%-123.88%, AUC0-t ratio and 90% CI were 109.47% and 99.80%-120.08%, and AUC0-∞ ratio and 90% CI were 109.24% and 99.80%-120.78%. These PK parameters fulfilled the equivalence criterion of 80.00%-125.00%. Treatment-emergent adverse events (TEAEs) occurred in 62 (84.9%) and 61 (83.6%) subjects; mild and moderate drug-related TEAEs were observed in 60 (82.2%) and 59 (80.8%) subjects in the adalimumab and SCT630 groups, respectively. On day 71, 69 (95.8%) subjects in the adalimumab group and 66 (93%) in the SCT630 group reported positive anti-drug antibodies. Among them, 15 (21.7%) and 11 (16.7%) subjects showed positive neutralizing antibodies, with no significant difference. SCT630 was well tolerated and demonstrated PK and safety profiles similar to adalimumab. The profiles support the initiation of further confirmatory study to demonstrate the clinical similarity of SCT630 to adalimumab.

A multicenter randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Caelyx ® in advanced breast cancer.

Purpose: To compare the pharmacokinetic (PK) bioequivalence (BE) and safety of a generic pegylated liposomal doxorubicin (PLD) formulation with the reference product Caelyx®. Methods: A multicenter, single-dose, open-label, randomized, two-way crossover study was conducted in patients with breast cancer. For each period, the patients were administered with the test or the reference PLD intravenously at a dose of 50 mg/m2. Cmax, AUC0-t and AUC0-∞ for free, and encapsulated doxorubicin (doxorubicin) and partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin were evaluated in 17 blood samples taken predose, and increasing time intervals over the following 14 days in each period. A washout period of 28-35 days was observed before crossing over. Results: 48 patients were enrolled and randomised, of which 44 were included and analysed in bioequivalence set (BES). The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of Cmax, AUC0-t and AUC0-∞ for free doxorubicin and encapsulated doxorubicin all fall within the bioequivalent range of 80% to 125%. The 90% CIs of GMR of partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin also fall within the bioequivalent range. 48 patients were all included in the safety set (SS). The incidence of treatment-emergent adverse events (TEAEs) related to T and R was 95.8% (46/48) and 97.8% (45/46) respectively. The highest incidence of TEAEs was various laboratory abnormalities. 2 patients withdrew due to T-drug-related AEs. Only one patient experienced serious adverse events and no death occurred in this study. There were no significant differences between the safety profiles of the generic formulation and Caelyx®. Conclusions: Bioequivalence between the test and the reference products was established for free and encapsulated doxorubicin. Clinical trial registration: http://www.chinadrugtrials.org.cn, identifier [CTR20210375].

Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a Monoclonal Antibody (SCTA01) Targeting SARS-CoV-2 in Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, Phase I Study.

SCTA01 is a novel monoclonal antibody with promising prophylactic and therapeutic potential for COVID-19. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of SCTA01 in healthy adults. This was a randomized, double-blind, placebo-controlled, dose escalation phase I clinical trial. Healthy adults were randomly assigned to cohort 1 (n = 5; 3:2), cohort 2 (n = 8; 6:2), cohort 3, or cohort 4 (both n = 10; 8:2) to receive SCTA01 (5, 15, 30, and 50 mg/kg, respectively) versus placebo. All participants were followed up for clinical, laboratory, PK, and immunogenicity assessments for 84 days. The primary outcomes were the dose-limiting toxicity (DLT) and maximal tolerable dose (MTD), and the secondary outcomes included PK parameters, immunogenicity, and adverse events (AE). Of the 33 participants, 18 experienced treatment-related AEs; the frequency was 52.0% (13/25) in participants receiving SCTA01 and 62.5% (5/8) in those receiving placebo. All AEs were mild. There was no serious AE or death. No DLT was reported, and the MTD of SCTA01 was not reached. SCTA01 with a dose range of 5 to 50 mg/kg had nearly linear dose-proportional increases in Cmax and AUC parameters. An antidrug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50 mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional. (This study has been registered at ClinicalTrials.gov under identifier NCT04483375.).

Pharmacokinetics and Bioequivalence of Rasagiline Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions: An Open, Randomized, Single-Dose, Double-Cycle, Two-Sequence, Crossover Trial.

Objective: This study evaluated the pharmacokinetics, safety, and bioequivalence (BE) of two formulations of rasagiline tablets in healthy Chinese subjects under fasting and fed conditions. Methods: An open, randomized, single-dose, double-cycle, two-sequence, self-crossover pharmacokinetic study in healthy Chinese subjects under fasting and high-fat postprandial conditions was performed. A total of 108 healthy subjects (36 in the fasting group and 72 in the postprandial group) were recruited. In each cycle of the study under both conditions, subjects received a single oral dose of 1 mg of a test or reference preparation of rasagiline tablets (1 mg each). A washout period of 3 days was observed. Blood samples were obtained up to 10 h post-intake. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0-t and AUC0-∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters. Results: The 90% confidence interval (CI) of the geometric mean ratio (GMR) of the test drug vs. the reference drug for rasagiline was 94.16-105.35% for the AUC0-t under fasting conditions and 99.88-107.07% under postprandial conditions. The 90% CIs for the AUC0-∞ were 93.55-105.01% and 99.59-107.05% under fasting and postprandial conditions, respectively. The 90% CIs for the Cmax were 88.26-108.46% and 89.54-118.23% under fasting and postprandial conditions, respectively. The 90% CIs for the test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80-1.25) for BE. In this BE study, there were no serious adverse events (AEs). Conclusion: BE between the test and the reference products was established in both fasting and postprandial conditions. The two formulations of rasagiline showed good tolerability and a similar safety profile. Clinical Trial Registration: chinaDrugtrials.org.cn, identifier CTR20181466.

Independent factors associated with pneumonia among hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease.

Acute exacerbations (AE) affect the prognosis of hospitalized patients with chronic obstructive pulmonary disease (COPD). Pneumonia further affects their prognosis and early diagnosis of pneumonia in AECOPD is important to initiate treatments. This study aimed to examine the differences between hospitalized AECOPD patients with and without pneumonia in order to identify risk factors of pneumonia among hospitalized patients with AECOPD.This was a retrospective case-control study of patients with COPD hospitalized at the respiratory ward of Beijing Shijitan Hospital, Capital Medical University, from October 2010 to October 2013. Patients were divided into the pneumonia and nonpneumonia groups based on exudations or opacities on chest computed tomography (CT) at admission. Data were analyzed using the chi-square test and independent 2-sample ANOVA in SPSS 20.0. Logistic regression analysis was used to identify the factors independently associated with pneumonia. P < .05 was considered statistically significant.A total of 164 patients were included. Smoking history (OR = 2.646, 95%CI 1.153-6.074, P = .022), use of drugs during the stable stage (OR = 0.435, 95%CI 0.216-0.877, P = .020), D-dimer levels (OR = 1.001, 95%CI 1.000-1.002, P = .049), percentage of neutrophils (OR = 0.271, 95%CI 0.078-0.940, P = .040), and magnitude of neutrophils increase (OR = 0.946, 95%CI 0.896-0.999, P = .046) were independently associated with pneumonia in patients with AECOPD. For severe and very severe COPD patients, smoking history (OR = 4.426, 95%CI 1.458-13.435, P = .009), use of drugs during the stable stage (OR = 0.384, 95%CI 0.168-0.877, P = .042), and fever (OR = 0.426, 95%CI 0.187-0.969, P = .023) were independently associated with pneumonia.Smoking history, use of drugs during the stable stage, and percentage of neutrophils are independently associated with CT-diagnosed pneumonia among hospitalized AECOPD patients.

Influence of casein hydrolysates on exopolysaccharide synthesis by Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus.

BACKGROUND: A lot of interesting research has been undertaken to enhance the yield of exopolysaccharides (EPS) produced by lactic acid bacteria (LAB). The objective of this study was to determine the influence of casein hydrolysates (CH) with molecular weight less than 3 kDa on cell viability, EPS synthesis and the enzyme activity involved in EPS synthesis during the co-culturing of Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus in MRS broth for 72 h at 37 ± 0.1 °C. RESULTS: The highest EPS yield (150.1 mg L⁻¹) was obtained on CH prepared with papain (CHP) at 48 h. At 24 h, EPS were composed of galactose, glucose and rhamnose in a molar ratio of 1.0:2.4:1.5. The monosaccharide composition changed with extension of the fermentation time. The activities of α-phosphoglucomutase, uridine 5'-diphosphate (UDP)-glucose pyrophosphorylase and UDP-galactose 4-epimerase were associated with EPS synthesis. Moreover, the activities of ß-phosphoglucomutase and deoxythymadine 5'-diphosphate (dTDP)-glucose pyrophosphorylase involved in rhamnose synthesis were very low at the exponential growth phase and could not be detected during other given periods. CONCLUSION: The influence of different CH (<3 kDa) on LAB viability, EPS production, EPS monomeric composition and activity levels of key metabolic enzymes was distinct. Besides, their influence was related to the distribution of amino acids.