Evaluation of the Effectiveness of Clinical Pharmacists’ Consultation in the Treatment of Infectious Diseases: A Single-Arm, Prospective Cohort Study

Background: With the implementation of Antimicrobial Stewardship Program, clinical pharmacists’ consultation (CPC) for infectious diseases (ID) is gradually adopted by many hospitals in China. We conducted a cohort study to evaluate the effectiveness of CPC in ID treatment on patient outcomes and potential determinants.Methods: Based on a registry database, a prospective cohort study was conducted in Guizhou Provincial People’s Hospital. The main exposure factor was whether clinician adopted the suggestion from clinical pharmacist. The outcome was effective response rate (ERR) of ID patients. The variables associated with the outcome (e.g., age, gender, severity of infection, liver function, and kidney function) were also prospectively recorded. A multilevel model was performed to analyze the factors related to ERR.Results: A total of 733 ID inpatients were included in the final analysis according to the predesigned inclusion and exclusion criteria. The proportion of clinical pharmacists’ suggestions adopted by clinicians and ERR were 88.13 and 69.03%, respectively. Significant data aggregation (P < 0.05) for individuals at the level of department was observed. According to the two-level variance component model, liver dysfunction (Adjusted Odds Ratio (AOR) = 0.649, 95%Credible Interval (CI): 0.432–0.976), severity of infection (AOR = 0.602, 95%CI: 0.464–0.781), and adopting the suggestion from pharmacist (AOR = 1.738, 95%CI: 1.028–2.940) had significant association with ERR.Conclusion: Our study suggests that the effect of CPC on ID treatment is significant. The policy/decision makers or hospital managers should be cognizant of the critical value of clinical pharmacists in ID treatment

The relative influence of environmental and human factors on seed plant richness at the province scale in China

Seed plant diversity is under threat due to human over-exploitation and changes in land use. There is a need to identify regions where seed plant diversity is most at risk and establish nature reserves to protect the most important species. This study collected province scale seed plant richness data and corresponding environmental, social and, economic data in China in order to assess the impact of environmental and socio-economic factors on seed plant diversity and to quantify the relative importance of climate, human disturbance, and habitat heterogeneity on the distribution of seed plant diversity. A downscaling model was established to map the spatial distribution of seed plant diversity at a 1-km resolution. The results showed that temperature and precipitation seasonality, potential evapotranspiration, humidity index, altitude range, and gross domestic product were important determinants of seed plant diversity. The relative contribution of temperature seasonality was the most important factor (explaining 29.9-36.2% of the variation). Climate, human disturbance, and habitat heterogeneity explained much of the seed plant richness and density variation (about 69.4-71.9%). A scale-down model explained 72% of seed plant richness variation and showed that the center of seed plant species diversity was mainly located in the southeast area of China in the Qing-Tibet Plateau, Yun-Gui Plateau, Hengduan Mountain region, middle of the Sichuan Basins, Taiwan island, and Hainan island. This study improves our understanding of biodiversity hotspot regions and is a useful tool for biodiversity conservation policy and nature reserve management in China

MUC16 C terminal fragment activates YAP1 through Src signaling to promote gallbladder cancer growth

Abstract The Hippo pathway is crucial to organ size control and its dysregulation contributes to tumorigenesis. The aberrant activation of YAP1 was identified in gallbladder cancer (GBC). However, the underlying mechanism and role in GBC remains unclear. The C terminal fragment of Mucin16, also known as carbohydrate antigen 125 (CA125) encoded product, MUC16c, plays extensive roles in tumor initiation and development. Our study showed that MUC16c binding with 14‐3‐3ε disrupted the interaction of 14‐3‐3ε and phosphorylated yes‐associated protein 1 (YAP1), which led to the activation of YAP1 in GBC. Furthermore, MUC16c decreased the phosphorylation of YAP1 at serine 397 (ser397) by inhibiting LATS1, which upregulated YAP1 protein stability. Interestingly, there was a potential Src kinase site in the MUC16c fragment. The MUC16c_del15Y polypeptides with the deletion of the Src kinase site promoted the interaction of YAP1 with 14‐3‐3ε and downregulated the YAP1 protein levels. Consistently, SU6656, a Src kinase inhibitor also blocked the activation of YAP1 by MUC16c. The MUC16c_del15Y polypeptides decreased GBC cell proliferation in vitro and the growth of xenograft tumors in vivo. Our study revealed the underlying mechanism of the activation of MUC16c on YAP1 mediated by Src signaling and the antitumor effect of MUC16c_del15Y, providing a potential target for GBC therapy