Hippo dictates signaling for cellular homeostasis and immune defense in Crassostrea hongkongensis hemocytes.

Introduction: The Hippo signaling pathway is an evolutionarily conserved signaling cascade that plays a crucial role in regulating cell proliferation, differentiation, and apoptosis. It has been shown to be a key regulator of cell fate and cellular homeostasis in various immune processes. Despite its well-established functions in vertebrate immunity, its roles in marine invertebrate immunity remain poorly understood. Therefore, our present work provides fresh mechanistic insights into how the Hippo pathway orchestrates hemocytic functions in Crassostrea hongkongensis, with implications for studies on its major forms and modifications in animal evolution. Method: The complete set of Hippo pathway genes, including SAV1, MOB1, LATS, YAP/TAZ, TEAD, and MST, were identified from the C. hongkongensis genome. Quantitative PCR assays were conducted to examine the mRNA expression levels of these genes in different tissues and the levels of these genes in hemocytes before and after bacterial challenges. The study also examined the crosstalk between the Hippo pathway and other immune pathways, such as the AP-1 and p53-dependent p21 signaling cascades. RNA interference was used to knock down MST and TEAD, and MST is a core orchestrator of non-canonical Hippo signaling, to investigate its impact on phagocytosis and bacterial clearance in hemocytes. Result: The results demonstrated that members of the Hippo pathway were highly expressed in hemocytes, with their expression levels significantly increasing following bacterial challenges. Crosstalk between the Hippo pathway and other immune pathways triggered hemocytic apoptosis, which functioned similarly to the canonical Mst-Lats-Yap signaling pathway in Drosophila and mammals. Knocking down MST resulted in increased phagocytosis and boosted the efficiency of bacterial clearance in hemocytes, presumably due to mobilized antioxidant transcription by Nrf for maintaining immune homeostasis. Discussion: This study provides novel insights into the regulatory mechanisms underlying the Hippo pathway in immune responses of C. hongkongensis hemocytes. The study highlights the importance of the Hippo pathway in maintaining immune homeostasis and orchestrating hemocytic functions in oysters. Moreover, this study demonstrates the divergence of the Hippo pathway's roles in marine invertebrate immunity from mammalian observations, indicating the need for further comparative studies across species. These findings have significant implications for future research aimed at elucidating the evolutionary trajectory and functional diversity of the Hippo signaling pathway in animal evolution.

Hemocyte phagosomal proteome is dynamically shaped by cytoskeleton remodeling and interorganellar communication with endoplasmic reticulum during phagocytosis in a marine invertebrate, Crassostrea gigas.

Phagosomes are task-force organelles of innate immune systems, and evolutionary diversity and continuity abound in the protein machinery executing this coordinately regulated process. In order to clarify molecular mechanisms underlying phagocytosis, we studied phagocyte response to beads and Vibrio species, using hemocytes of the Pacific oysters (Crassostrea gigas) as a marine invertebrate model. Phagosomes from different stages of phagocytosis were isolated by density-gradient centrifugation, and more than 400 phagosome-associated proteins were subsequently identified via high-throughput quantitative proteomics. In modeling key networks of phagosomal proteins, our results support the essential roles of several processes driving phagosome formation and maturation, including cytoskeleton remodeling and signal transduction by Rab proteins. Several endoplasmic reticulum (ER)-associated proteins were identified, while live cell imaging confirms an apparent intimate interaction between the ER and phagosomes. In further quantitative proteomic analysis, the signal transducers CgRhoGDI and CgPI4K were implicated. Through experimental validation, CgRhoGDI was shown to negatively regulate actin cytoskeleton remodeling in the formation of oyster phagosomes, while CgPI4K signaling drives phagosome maturation and bacterial killing. Our current work illustrates the diversity and dynamic interplay of phagosomal proteins, providing a framework for better understanding host-microbe interactions during phagosome activities in under-examined invertebrate species.

Establishment of a Quantitative Medical Technology Evaluation System and Indicators within Medical Institutions.

BACKGROUND: The development and application of medical technologies reflect the medical quality and clinical capacity of a hospital. It is also an effective approach in upgrading medical service and core competitiveness among medical institutions. This study aimed to build a quantitative medical technology evaluation system through questionnaire survey within medical institutions to perform an assessment to medical technologies more objectively and accurately, and promote the management of medical quality technologies and ensure the medical safety of various operations among the hospitals. METHODS: A two-leveled quantitative medical technology evaluation system was built through a two-round questionnaire survey of chosen experts. The Delphi method was applied in identifying the structure of evaluation system and indicators. The judgment of the experts on the indicators was adopted in building the matrix so that the weight coefficient and maximum eigenvalue (λ max), consistency index (CI), and random consistency ratio (CR) could be obtained and collected. The results were verified through consistency tests, and the index weight coefficient of each indicator was conducted and calculated through analytical hierarchy process. RESULTS: Twenty-six experts of different medical fields were involved in the questionnaire survey, 25 of whom successfully responded to the two-round research. Altogether, 4 primary indicators (safety, effectiveness, innovativeness, and benefits), as well as 13 secondary indicators, were included in the evaluation system. The matrix is built to conduct the λ max, CI, and CR of each expert in the survey, and the index weight coefficients of primary indicators were 0.33, 0.28, 0.27, and 0.12, respectively, and the index weight coefficients of secondary indicators were conducted and calculated accordingly. CONCLUSIONS: As the two-round questionnaire survey of experts and statistical analysis were performed and credibility of the results was verified through consistency evaluation test, the study established a quantitative medical technology evaluation system model and assessment indicators within medical institutions based on the Delphi method and analytical hierarchy process. Moreover, further verifications, adjustments, and optimizations of the system and indicators will be performed in follow-up studies.

Cost Analysis of Cervical Cancer Patients with Different Medical Payment Modes Based on Gamma Model within a Grade A Tertiary Hospital.

BACKGROUND: Cervical cancer shows a growing incidence and medical cost in recent years that has increased severe financial pressure on patients and medical insurance institutions. This study aimed to investigate the medical economic characteristics of cervical cancer patients with different payment modes within a Grade A tertiary hospital to provide evidence and suggestions for inpatient cost control and to verify the application of Gamma model in medical cost analysis. METHODS: The basic and cost information of cervical cancer cases within a Grade A tertiary hospital in the year 2011-2016 were collected. The Gamma model was adopted to analyze the differences in each cost item between medical insured patient and uninsured patients. Meanwhile, the marginal means of different cost items were calculated to estimate the influence of payment modes toward different medical cost items among cervical cancer patients in the study. RESULTS:: A total of 1321 inpatients with cervical cancer between the 2011 and 2016 were collected through the medical records system. Of the 1321 cases, 65.9% accounted for medical insured patients and 34.1% were uninsured patients. The total inpatient medical expenditure of insured patients was RMB 29,509.1 Yuan and uninsured patients was RMB 22,114.3 Yuan, respectively. Payment modes, therapeutic options as well as the recurrence and metastasis of tumor toward the inpatient medical expenditures between the two groups were statistically significant. To the specifics, drug costs accounted for 37.7% and 33.8% of the total, surgery costs accounted for 21.5% and 25.5%, treatment costs accounted for 18.7% and 16.4%, whereas the costs of imaging and laboratory examinations accounted for 16.4% and 15.2% for the insured patient and uninsured patients, respectively. As the effects of covariates were controlled, the total hospitalization costs, drug costs, treatment costs as well as imaging and laboratory examination costs showed statistical significance. The total hospitalization costs, drug costs, treatment costs as well as imaging and laboratory examination costs of insured patient were 1.33, 1.42, 1.52, and 1.44 times of uninsured patients. CONCLUSIONS: The analysis of different payment modes toward the medical economic characteristics based on Gamma model is basically rational. Medical payment modes are having certain influence toward the hospitalization expenses of cervical cancer patients in an extent, as drug costs, treatment costs, and examination costs appear to be the main causes.

Research of Medical Expenditure among Inpatients with Unstable Angina Pectoris in a Single Center.

BACKGROUND: With the rising incidence as well as the medical expenditure among patients with unstable angina pectoris, the research aimed to investigate the inpatient medical expenditure through the combination of diagnosis-related groups (DRGs) among patients with unstable angina pectoris in a Grade A tertiary hospital to conduct the referential standards of medical costs for the diagnosis. METHODS: Single-factor analysis and multiple linear stepwise regression method were used to investigate 3933 cases between 2014 and 2016 in Beijing Hospital (China) whose main diagnosis was defined as unstable angina pectoris to determine the main factors influencing the inpatient medical expenditure, and decision tree method was adopted to establish the model of DRGs grouping combinations. RESULTS: The major influential factors of inpatient medical expenditure included age, operative method, therapeutic effects as well as comorbidity and complications (CCs) of the disease, and the 3933 cases were divided into ten DRGs by four factors: age, CCs, therapeutic effects, and the type of surgery with corresponding inpatient medical expenditure standards setup. Data of nonparametric test on medical costs among different groups were all significant (P < 0.001, by Kruskal-Wallis test), with R2 = 0.53 and coefficient of variation (CV) = 0.524. CONCLUSIONS: The classification of DRGs by adopting the type of surgery as the main branch node to develop cost control standards in inpatient treatment of unstable angina pectoris is conducive in standardizing the diagnosis and treatment behaviors of the hospital and reducing economic burdens among patients.

Research on 2041 Cases of High Inpatient Expenditure and Influence Factors during 3 Years in a Single Center.

BACKGROUND: The study was to explore the causes of high inpatient expenditure through analyzing the distribution characteristics as well as the influence factors of high inpatient expenditure cases during 3 years within a Grade-A tertiary hospital through various aspects and multiple angles, thus identifying the major influence factors for high medical expenditure to develop further research. METHODS: We retrospectively studied 2041 inpatient cases which cost more than RMB 100,000 Yuan per case in a Grade-A tertiary hospital from 2013 to 2015. We analyzed the compositions of the medical cost to evaluate the major factors that cause the high inpatient expenditure. All the data and materials were collected from medical record system, and the statistical methods included t-test, variance of analysis, and multivariate linear regression. RESULTS: The average cost of the 2,041 cases was RMB 152,173 Yuan for medicines and materials of medical costs, which respectively accounted for 33.03% and 32.32% of the total cost; and the average length of hospital stay was 28.39 days/person. Diseases of skeletal and muscular system, circulatory system, and tumor were the top three disease categories of high inpatient expenditure, which accounted for 39.00%, 33.46%, and 18.03%, respectively. Complications, criticality of the disease, gender of the patients, the occurrence of death, and the excessive length of hospital stay all had great impacts on average medical expenditure, while age, hospital infection, and surgery showed no significant impact on average medical cost. CONCLUSIONS: The main factors for high inpatient expenditure included the inadequate use of high-value medicines and materials, lacking cost control measures within the hospital, the excessive length of hospital stay for inpatients, and the unnecessary treatment for the patients.

Evolving Healthcare Quality in Top Tertiary General Hospitals in China during the China Healthcare Reform (2010-2012) from the Perspective of Inpatient Mortality.

Healthcare reforms (HR) initiated by many countries impacts on healthcare systems worldwide. Being one of fast developing countries, China launched HR in 2009. Better understanding of its impact is helpful for China and others in further pursuit of HR. Here we evaluate inpatient mortality, a proxy to healthcare quality, in 43 top tertiary hospitals in China during this critical period. This is a hospital-based observational study with 8 million discharge summary reports (DSR) from 43 Chinese hospitals from 2010-2012. Using DSRs, we extract the vita status as the outcome, in addition to age, gender, diagnostic codes, and surgical codes. Nearly all hospitals have expanded their hospitalization capacities during this period. As of year 2010, inpatient mortality (IM) across hospitals varies widely from 2‰ to 20‰. Comparing IM of year 2011 and 2012 with 2010, the overall IM has been substantially reduced (OR = 0.883 and 0.766, p-values<0.001), showing steady improvements in healthcare quality. Surgical IM correlates with the overall IM (correlation = 0.60, p-value <0.001), but is less uniform. Over these years, surgical IM has also been steadily reduced (OR = 0.890 and 0.793, p-values<0.001). Further analyses of treatments on five major diseases and six major surgeries revealed that treatments of myocardial infarction, cerebral hemorrhage and cerebral infarction have significant improvement. Observed temporal and spatial variations demonstrate that there is a substantial disparity in healthcare quality across tertiary hospitals, and that these hospitals are rapidly improving healthcare quality. Evidence-based assessment shed light on the reform impact. Lessons learnt here are relevant to further refining HR.