Ultra-high b-value DWI accurately identifies isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas.

OBJECTIVES: To distinguish isocitrate dehydrogenase (IDH) genotypes and tumor subtypes of adult-type diffuse gliomas based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) in 2021 using standard, high, and ultra-high b-value diffusion-weighted imaging (DWI). MATERIALS AND METHODS: This prospective study enrolled 70 patients with adult-type diffuse gliomas who underwent multiple b-value DWI. Apparent diffusion coefficient (ADC) values including ADCb500/b1000, ADCb500/b2000, ADCb500/b3000, ADCb500/b4000, ADCb500/b6000, ADCb500/b8000, and ADCb500/b10000 in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The ADC ratios of TP/NAWM were assessed for correlations with IDH genotypes, tumor subtypes, and Ki-67 status; diagnostic performances were compared. RESULTS: All ADCs were significantly higher in IDH mutant gliomas than in IDH wild-type gliomas (p < 0.01 for all); ADCb500/b8000 had the highest area under the curve (AUC) of 0.866. All ADCs were significantly lower in glioblastoma than in astrocytoma (p < 0.01 for all). ADCs other than ADCb500/b1000 were significantly lower in glioblastoma than in oligodendroglioma (p < 0.05 for all). ADCb500/b8000 and ADCb500/b10000 were significantly higher in oligodendroglioma than in astrocytoma (p = 0.034 and 0.023). The highest AUCs were 0.818 for ADCb500/b6000 when distinguishing glioblastoma from astrocytoma, 0.979 for ADCb500/b8000 and ADCb500/b10000 when distinguishing glioblastoma from oligodendroglioma, and 0.773 for ADCb500/b10000 when distinguishing astrocytoma from oligodendroglioma. Additionally, all ADCs were negatively correlated with Ki-67 status (p < 0.05 for all). CONCLUSION: Ultra-high b-value DWI can reliably separate IDH genotypes and tumor subtypes of adult-type diffuse gliomas using WHO CNS5 criteria. CLINICAL RELEVANCE STATEMENT: Ultra-high b-value diffusion-weighted imaging can accurately distinguish isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas, which may facilitate personalized treatment and prognostic assessment for patients with glioma. KEY POINTS: • Ultra-high b-value diffusion-weighted imaging can accurately distinguish subtle differences in water diffusion among biological tissues. • Ultra-high b-value diffusion-weighted imaging can reliably separate isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas. • Compared with standard b-value diffusion-weighted imaging, high and ultra-high b-value diffusion-weighted imaging demonstrate better diagnostic performances.

[Research hotspots and frontiers of Realgar based on CiteSpace knowledge graph analysis].

This study employed knowledge graph technology to analyze the research status and hot spots of Realgar and provide guidance for clinical application and further research of this drug. The research articles both in English and Chinese involving Realgar were retrieved from five databases including CNKI, Wanfang, VIP, SinoMed, and Web of Science. And NoteExpress, a literature management software was used to screen literature. CiteSpace was utilized for visualized analysis and presentations of the authors, institutions, and keywords. 2 879 articles in Chinese and 194 articles in English were included. China Journal of Chinese Materia Medica and Journal of Ethnopharmacology were the top Chinese and English journals in terms of publication volume. Realgar is widely used in the treatment of skin diseases, blood diseases, and cancer. JIANG Hong was the author who have published more articles in Chinese and English working with teams. School of Public Health of China Medical University and China Academy of Chinese Medical Sciences published the most articles in Chinese and English. The research on Realgar mainly focuses on clinical application, mechanism of action, reduction of toxicity, and enhancement of efficacy. The authors and institutions of Realgar research are mainly concentrated in China. The study on the mechanism of treating hematological diseases and cancer with Realgar, as well as the research on its effects of reducing toxicity and enhancing efficacy, are the current research hotspots. The mechanism of "same treatment for different diseases" in Realgar needs to be further explored. It is urgent to carry out interdisciplinary research on Realgar. This study can provide a refe-rence for the clinical application of Realgar and provide ideas for further research on Realgar.

Does the timing of antibiotic exposure in pregnancy impact the risk of development of pediatric asthma?: A systematic review and meta-analysis.

OBJECTIVE: Maternal exposure to antibiotics has been linked to the development of pediatric asthma. However, the impact of the timing of exposure is unclear. We aimed to explore if the risk of pediatric asthma varies with trimester-specific exposure to antibiotics through a systematic review and meta-analysis. METHODS: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched for studies reporting an association between trimester-specific maternal exposure to antibiotics and risk of asthma in the offspring. RESULTS: Eleven studies were included. The total sample size of the included studies was 2,160,216. Meta-analysis revealed a statistically significant increased risk of asthma with first (RR: 1.13 95% CI: 1.10, 1.17 I2 = 59% p < 0.00001), second (RR: 1.14 95% CI: 1.07, 1.21 I2 = 92% p < 0.0001), and third (RR: 1.14 95% CI: 1.08, 1.20 I2=86% p < 0.00001) trimester exposure of antibiotics. The results were stable on sensitivity analysis. On subgroup analysis, we noted that the association for the first and second trimester was significant for studies on children >5 years but not for those on children <5 years of age. The certainty of evidence based on GRADE was low. CONCLUSION: Our results indicate that antibiotics administered during any trimester of pregnancy lead to an increased risk of childhood asthma. The overall risk is small and could be due to confounding. Further studies rigorously adjusting for important confounding variables are needed for stronger evidence.

Mean apparent propagator-MRI in evaluation of glioma grade, cellular proliferation, and IDH-1 gene mutation status.

OBJECTIVES: To evaluate the glioma grade, Ki-67 expression, and IDH-1 mutation status using mean apparent propagator (MAP) MRI. METHODS: Forty enrolled glioma patients underwent structural and diffusion MRI. The diffusion metric values including fractional anisotropy (FA), mean diffusivity (MD), mean squared displacement (MSD), q-space inverse variance (QIV), return-to-origin probability (RTOP), return-to-axis probability (RTAP), and return-to-plane probability (RTPP) in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The TP/NAWM ratios of diffusion metric values were correlated with tumor grades, Ki-67, and IDH-1 mutation statuses, and the diagnostic performance was assessed. RESULTS: QIV were significantly higher, whereas RTAP and RTOP were significantly lower in low-grade gliomas (LGGs) than those in high-grade gliomas (HGGs); QIV and MD were significantly higher, whereas RTAP and RTOP were significantly lower in lower-grade gliomas (grade II and III) than those in grade IV gliomas (p < 0.05 for all). RTAP performed best in grading gliomas. MSD, QIV, and MD were significantly higher, whereas RTAP, RTOP, RTPP, and FA were significantly lower in the IDH-1 mutant gliomas than those in the IDH-1 wild-type ones both for all gliomas and lower-grade gliomas (p < 0.05 for all). RTAP performed best in all gliomas, while QIV performed best in lower-grade gliomas. Additionally, RTAP, RTOP, and FA correlated positively, whereas MSD, QIV, and MD correlated negatively with Ki-67 (p < 0.05 for all). CONCLUSIONS: MAP-MRI is a potent approach in evaluating the microstructural changes in gliomas with different grades, cellular proliferation, and IDH-1 mutation statuses. KEY POINTS: • MAP-MRI, a newly developed diffusion technique, accurately reveals microstructure-related features in the complex white matter by recovering important microstructural tissue parameters. • MAP-MRI is a potent approach in evaluating the glioma grade, IDH-1 mutation status, and Ki-67 expression. • Compared with DTI, MAP-MRI seems to demonstrate higher diagnostic performance.

Comparison of the effects between MPL and JAK2V617F on thrombosis and peripheral blood cell counts in patients with essential thrombocythemia: a meta-analysis.

To assess the effects between MPL and JAK2V617F on the thrombosis risk and peripheral blood cell counts in patients with essential thrombocythemia (ET), we identified eligible studies from PubMed, Embase, and the Cochrane Library. Seven studies were ultimately included in this meta-analysis. All studies reported the peripheral blood cell counts of ET patients, and three of them reported the eligible thrombotic events. In comparing the effect of MPL versus JAK2V617F on thrombosis, 1257 ET patients (73 MPL + and 1184 JAK2V617F +) were included. MPL-positive (MPL +) ET patients had a higher risk of thrombosis than JAK2V617F-positive (JAK2V617F +) ET patients [RR = 1.80 (1.08-3.01), P = 0.025]. And 3453 ET patients (138 MPL + and 3315 JAK2V617F +) were included in the comparison of peripheral blood cell counts. Platelet counts of MPL + ET patients were higher than that of JAK2V617F + ET patients [WMD = 81.18 (31.77-130.60), P = 0.001]. MPL + ET patients had lower hemoglobin [WMD = - 11.66 (- 14.32 to - 9.00), P = 0.000] and white blood cell counts [WMD = - 1.01 (- 1.47 to - 0.56), P = 0.000] than JAK2V617F + ET patients. These findings indicate that the MPL mutation is a high-risk factor for thrombosis in ET patients, and it may be rational to include MPL mutation in the revised IPSET as a criterion for thrombosis prediction scores. And given the differences in peripheral blood, it is necessary to further study whether MPL + ET patients differ from JAK2V617F + ET patients in bleeding and survival.

Prognostic value of ASXL1 mutations in patients with primary myelofibrosis and its relationship with clinical features: a meta-analysis.

Additional sex combs like 1 (ASXL1) mutations are one of the most common molecular biological abnormalities in patients with primary myelofibrosis (PMF), and the effect of these mutations on prognosis remains controversial. Hence, we conducted a meta-analysis to assess the prognostic value and clinical characteristics of ASXL1 mutations in PMF patients. Eligible studies were systematically searched from PubMed, Embase, and the Cochrane Library. We extracted the hazard ratios (HRs) and their 95% confidence intervals (CIs) of overall survival (OS) and leukemia-free survival (LFS), the number of patients transformed to acute leukemia, and clinical characteristics to carry out a meta-analysis by fixed effect model or random effect model according to the heterogeneity between studies. A total of 4501 PMF patients from 16 cohorts of 14 studies were included in this meta-analysis. The results revealed that ASXL1 mutations might predict a shorter OS (HR = 2.30, 95% CI: 1.79-2.94, P < 0.00001) and a higher probability of transformation to acute leukemia (LFS: HR = 1.77, 95% CI: 1.30-2.42, P = 0.0003; the rate of acute leukemia transformation: OR = 2.06, 95% CI: 1.50-2.83, P < 0.00001). Furthermore, ASXL1 mutations were correlated with patients older than 65 years old, male, a lower level of platelet counts, and a higher risk of the international prognostic score system. These findings indicate that ASXL1 mutations have a significant adverse impact on the prognosis of PMF patients and may contribute to risk stratification and prognostic assessment for PMF patients.

FAM134B-Mediated ER-Phagy in Mg2+-Free Solution-Induced Mitochondrial Calcium Homeostasis and Cell Death in Epileptic Hippocampal Neurons.

Mitochondrial-associated endoplasmic reticulum (ER) membranes (MAMs) regulate calcium (Ca2+) homeostasis via Ca2+ transport-related proteins such as inositol-1,4,5-triphosphate receptor (IP3R). FAM134B-mediated ER-phagy plays an important role in ER homeostasis. However, it remains unknown whether FAM134B-mediated ER-phagy affects mitochondrial Ca2+ homeostasis and cell death through MAMs. In this study, we demonstrated that colocalization degree of FAM134B with LC3 and the LC3-II/LC3-I ratio were elevated in the hippocampal neuronal culture (HNC) model of acquired epilepsy (AE), which indicate an increased level of autophagy. In this model, FAM134B overexpression enhanced ER-phagy, while FAM134B downregulation had the opposite effect. Additionally, FAM134B overexpression significantly reversed the increases in IP3R expression and mitochondrial Ca2+ concentration and the decrease in the ER Ca2+ concentration in this model. FAM134B overexpression also ameliorated the AE-induced ultrastructural damage in neuronal mitochondria, decrease in mitochondrial membrane potential (mMP), cytochrome c (CytC) release and caspase-3 activation, while FAM134B downregulation induced the opposite effects. Altogether, our data indicate that FAM134B-mediated ER-phagy can attenuate AE-induced neuronal apoptosis, possibly by modulating the IP3R in MAMs to alter Ca2+ exchange between ER and mitochondria and thus inhibit mitochondrial structural damage, a decrease in mMP, release of CytC and mitochondrial apoptosis.

Sensitive pH-responsive point-of-care electrochemical immunoassay for influenza A (H1N1) virus using glucose oxidase-functionalized Ti3C2-MXene nanosheets.

Influenza A (H1N1) virus is a serious health threat and potential leading cause of death around the world during the processes of immunity and inflammation. Herein a sensitive pH-responsive point-of-care (POC) electrochemical immunoassay was designed for the quantitative monitoring of H1N1 influenza virus using glucose oxidase (GOx) and secondary antibody-functionalized Ti3C2-MXene nanosheets. The assay was carried out on the basis of the sandwich-type immunoreaction in the capture antibody-coated microplate. Two-dimensional (2D) Ti3C2-MXene nanosheets with a large surface area could efficiently enhance the loading amount of GOx molecules, thereby resulting in the signal amplification. Accompanying the formed immunocomplexes, labeled GOx molecules catalyzed glucose into gluconic acid and hydrogen peroxide. The generated gluconic acid caused a pH change of the detection solution, which was quantitatively determined on a handheld pH meter. Two labeling strategies with and without Ti3C2-MXene nanosheets were investigated to determine the target H1N1 influenza virus, and improved properties were acquired with the Ti3C2-MXene-labeled system. Under optimum conditions, the Ti3C2-MXene-based immunoassay gave good dynamic responses toward the target H1N1 influenza virus from 0.01 µg mL-1 to 100 µg mL-1 with a detection limit of 1.3 ng mL-1. Good reproducibility, high specificity, and acceptable stability were also achieved in the analysis of the target H1N1 influenza virus. Significantly, measurements of the H1N1 influenza virus from clinical human samples were demonstrated to further confirm the method reliability and accuracy of the Ti3C2-MXene-based electrochemical immunoassay. Importantly, such a pH-meter-based immunoassay can be suitable for use in point-of-care applications and opens new opportunities for diagnostics.

cydA, spdC, and mroQ are novel genes involved in the plasma coagulation of Staphylococcus aureus.

Coagulation is a critical pathogenic process in Staphylococcus aureus. Although the agglutination of S. aureus has been studied for a long time, the genes involved in this process are not completely clear. We performed tube agglutination and dynamic turbidimetry tests to identify novel genes involved in reduced plasma coagulation. A total of 15 genes were identified, including coa, clfA, vwbp, saeS, agrA, trpC, spdC, mroQ, cydA, qoxC, sucC, pyrP, menH, threonine aldolase, and truncated transposase for IS1272. The functions of these genes include bicomponent regulation, membrane transport, energy metabolism and biosynthesis, respectively. cydA, spdC, and mroQ genes were further studied by gene knockout and complementation. Results of gene knockout and complementation and real-time-qPCR proved that cydA, spdC, and mroQ genes are necessary for plasma coagulation. Furthermore, the survival ability of 7 day mice decreased significantly when cydA, spdC, and mroQ genes had been knocked out.

Pregnancy outcomes of infertile women with ultrasound-diagnosed adenomyosis for in vitro fertilization and frozen-thawed embryo transfer.

OBJECTIVE: This study aimed to investigate the effect of ultrasound-diagnosed adenomyosis on assisted pregnancy outcomes, i.e., in vitro fertilization-embryo transfer (IVF-ET). METHODS: This was a retrospective cohort study of 18,568 women who had received their first frozen-thawed ET cycle in Center of Reproductive Medicine, Children's Hospital of Shanxi and Women Health Center of Shanxi and the Reproductive Medicine Center of Tianjin Central Obstetrics and Gynecology Hospital from January 2014 to May 2019. A total of 5,087 patients met the inclusion and exclusion criteria, and they were divided into two groups: adenomyosis with tubal factor infertility (study group, n = 193) and only tubal factor infertility (control group, n = 4894). After a 1:1 propensity score match (caliper value = 0.005), 360 cases were matched in the end. RESULT: There was no statistical difference in the embryo implantation rate, clinical pregnancy rate, or multiple pregnancy rate between the two groups (28.4% vs. 31.7%, 42.2% vs. 42.8%, and 11.7% vs. 12.8%, respectively; P > 0.05). However, the early miscarriage rate in the adenomyosis group was significantly higher than that in the control group (13.3% vs. 5.6%, respectively; P = 0.012). The live birth rate was 22.8% in the women with adenomyosis and was observed to be significantly lower than 33.3% in the control group (P = 0.026). The patients with adenomyosis had a higher incidence of pregnancy complications than those without (4.4% vs. 0.6%, respectively; P = 0.018), but the neonatal birth weight was not related to adenomyosis. CONCLUSION: Women with adenomyosis should be treated as being at high risk of early miscarriage. However, maternal adenomyosis has no effect on the birth weight of the newborn.

[Oral Mucosal Diffuse Large B-cell Lymphoma Caused by Long-term Oral Methotrexate:Report of One Case].

A case of primary oral mucosal diffuse large B-cell lymphoma(DLBCL)due to long-term use of methotrexate(MTX)for the treatment of rheumatoid arthritis(RA)was admitted to the Department of Hematology,Fujian Medical University Union Hospital.We analyzed and discussed the clinical features,diagnosis and treatment,and prognosis of specific malignant lymphoma induced by MTX in this RA patient.Our purpose is to improve the awareness and knowledge of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of clinicians and pathologists.This study provides a new reference for the clinical diagnosis and treatment of MTX-associated DLBCL.

Non-canonical WOX11-mediated root branching contributes to plasticity in Arabidopsis root system architecture.

Lateral roots (LRs), which originate from the growing root, and adventitious roots (ARs), which are formed from non-root organs, are the main contributors to the post-embryonic root system in Arabidopsis However, our knowledge of how formation of the root system is altered in response to diverse inductive cues is limited. Here, we show that WOX11 contributes to root system plasticity. When seedlings are grown vertically on medium, WOX11 is not expressed in LR founder cells. During AR initiation, WOX11 is expressed in AR founder cells and activates LBD16LBD16 also functions in LR formation and is activated in that context by ARF7/19 and not by WOX11 This indicates that divergent initial processes that lead to ARs and LRs may converge on a similar mechanism for primordium development. Furthermore, we demonstrated that when plants are grown in soil or upon wounding on medium, the primary root is able to produce both WOX11-mediated and non-WOX11-mediated roots. The discovery of WOX11-mediated root-derived roots reveals a previously uncharacterized pathway that confers plasticity during the generation of root system architecture in response to different inductive cues.

Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to.

Ruxolitinib is a targeted drug to treat myelofibrosis (MF). Ruxolitinib has significant advantages in spleen reduction and increasing 5-year overall survival (OS), and ruxolitinib-based combinations might provide more benefits than ruxolitinib monotherapy. In this review, we focus on the data of ruxolitinib-based combinations therapies and treatment-related adverse events (AEs) and safety. We analyzed and summarized the data of ruxolitinib-based combinations. Ruxolitinib combined with prednisone + thalidomide + danazol (TPD), panobinostat, pracinostat, azacytidine, or hydroxyurea has well reduced spleen. Ruxolitinib combined with danazol or TPD had well therapies in improvement of hemoglobin (Hgb) and platelets (PLT). Most ruxolitinib-based combinations therapies showed a superior benefit on reduced treatment-related AEs than ruxolitinib monotherapy. Treatment-related AEs and dose modification affect the safety and tolerability of ruxolitinib-based combinations. Genetic testing before treatment is recommended. To provide better clinical guidance, comparisons of these randomized controlled trials with the trials of ruxolitinib alone are necessary. This review suggests that the clinical application of ruxolitinib-based combinations is worth waiting for.

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

Investigation of biofilm production and its association with genetic and phenotypic characteristics of OM (osteomyelitis) and non-OM orthopedic Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is a primary pathogen of orthopedic infections. By mediating antimicrobial resistance, S. aureus biofilm plays an important role in the recalcitrance of orthopedic infections, especially for the intractable osteomyelitis (OM). This study investigated the relationship between biofilm production and various genetic or phenotypic characteristics among orthopedic S. aureus strains. METHODS: A total of 137 orthopedic S. aureus isolates were enrolled and divided into OM and non-OM groups. Biofilm production was evaluated using the crystal violet assay. Genetic and phenotypic characteristics including MRSA identification, MLST and spa typing, carriage of virulence genes, drug resistance, and patients' inflammatory responses indicators were characterized. The relationship between biofilm production and above-mentioned features was respectively analyzed among all isolates and compared between OM and non-OM isolates. RESULTS: Biofilm production presented no significant difference between OM (including 9 MRSA isolates) and non-OM (including 21 MRSA isolates) strains. We found that ST88, t377 and ST630-MSSA-t377 strains produced very strong biofilms, while MLST types of ST15, ST25, ST398, ST5, ST59 and spa types of t002, t2325, t437 tended to produce weaker biofilms. Strains with the following profiles produced stronger biofilms: fib(+)-hlgv(+)-lukED(+)-sei(-)-sem(-)-seo(-) for all isolates, sei(-)-sem(-)-seo(-) for OM isolates, and cna (+)-fib (+)-hlgv (+)-lukED (+)-seb(-)-sed(-) for non-OM isolates. In addition, not any single drug resistance was found to be related to biofilm production. We also observed that, among OM patients, strains with stronger biofilms caused weaker inflammatory responses. CONCLUSION: Some genetic or phenotypic characteristics of orthopedic strains were associated with biofilm production, and this association could be different among OM and non-OM strains. The results are of great significance for better understanding, evaluating and managing different kinds of biofilm-associated orthopedic infections, and provide potential targets for biofilm clearance.

Effect of inappropriate admissions on hospitalization performance in county hospitals: a cross-sectional study in rural China.

BACKGROUND: Inappropriate admissions cause excessive utilization of health services compared with outpatient services. However, it is still unclear whether inappropriate admissions cause excessive use of health services compared with appropriate admissions. This study aims to clarify the differences in the hospitalization performances between appropriately admitted inpatients and inappropriately admitted inpatients. METHODS: A total of 2575 medical records were obtained after cluster sampling in three counties. Admission appropriateness was assessed by appropriateness evaluation protocol (AEP). The propensity score matching (PSM) was computed to match patients in treatment and control group with similar characteristics, and to examine the differences in the utilization of hospitalization services between the two groups. The samples were matched in two major steps in this study. In the first step, total samples were matched to examine the differences in the utilization of hospital services between the two groups using 15 individual covariates. In the second step, PSM was computed to analyze the differences between the two groups in different disease systems using 14 individual covariates. RESULTS: For the whole sample, the inappropriate group has lower expenditure of hospitalization (EOH) (difference = - 0.12, p = 0.003) and shorter length of stay (LOS) (difference = - 0.73, p = 0.016) than the appropriate group. For number of clinical inspection (NCI), it has no statistically significant difference (difference = - 0.39, p = 0.082) between the two groups. Among different disease systems, no significant differences were observed between the two groups among EOH, LOS and NCI, except that the EOH was lower in the inappropriate group than that in the appropriate group for surgical disease (difference = - 0.169, p = 0.043). CONCLUSION: Inappropriate admissions have generated excessive health service utilization compared with appropriate admissions, especially for internal diseases. The departments in charge of medical services and hospital managers should pay high attention to the health service utilization of the inappropriately admitted inpatients. Relevant medical policies should be designed or optimized to increase the appropriateness in health care service delivery and precision in clinical pathway management.

Determinants of inappropriate admissions of children to county hospitals: a cross-sectional study from rural China.

BACKGROUND: The incidence of inappropriate admissions in China has become the shackle of its' service supply system. This research aims to assess the level of children's inappropriate admissions to county hospitals in rural China and identify the characteristics and determinants of children's inappropriate admissions. METHODS: A retrospective review was conducted on data of children aged 0-14 years. A total of 771 children medical records in four county hospitals was collected by stratified random sampling in Midwestern China and was evaluated through the Rural Appropriateness Evaluation Protocol. A questionnaire survey was conducted among doctors whose names were shown in medical records. Chi-square test was used to analyse the characteristics of inappropriate admissions, and a binary logistic regression model was used to examine the determinants of inappropriate admissions. RESULTS: Inappropriate admissions indicate that patients who could have been treated as outpatients received services as inpatients. The average rate for inappropriate admissions of children in county hospitals was 61.35%. The highest rate of inappropriate admissions was found among children aged 1-5 years (68.42%). Inappropriate admissions mostly occurred in children with respiratory diseases (72.45%), circulatory diseases (72.22%) and certain infectious diseases and parasitic diseases (70.37%). Binary logistic regression analysis showed that county, normal health status, treating department, disease, the length of hospital stay and the doctor's self-evaluation on the understanding about the degree of the patient's feelings were determinants for children's inappropriate admissions. CONCLUSIONS: County hospitals have a high rate of inappropriate admissions of children. The relationship of children's inappropriate admissions to age distribution and the insurance compensation is affected by disease and hospitalisation expenses, respectively. The determinants of children's inappropriate admissions are directly related to the weak level of primary care services in the health service system, the initial requirements requested by children's admission decision makers and the interests among medical institutions and doctors.

Changes in inpatients' distribution and benefits under institution level-based quota payment for specific diseases in rural China: An interrupted time-series analysis.

The distribution of patients is increasingly disordered in China, which leads to the waste of medical resources, increase in inpatients' economic burden, and decrease in benefits from health insurance. Institution level-based quota payment for specific diseases represents a typical payment-system reform mode in rural China that rationalizes the distribution of rural inpatients. The aim of this study is to evaluate the effectiveness of this mode by estimating rural inpatients' distribution among hospitals at different levels, per capita cost of hospitalization, and actual compensation ratio and then to provide suggestions to advance this mode. Interrupted time-series analysis was applied to evaluate the effect of the reform mode in the study, and Weiyuan County, Gansu Province, was selected as our sample. Institution level-based quota payment for specific diseases in Weiyuan County has rationalized the distribution of rural inpatients and improved their benefit levels. Further research should be conducted to evaluate the appropriateness of medical services, the health outcomes of rural inpatients, and the sustainability and replicability of the policy.

Safe Staphylococcal Platform for the Development of Multivalent Nanoscale Vesicles against Viral Infections.

Many viruses often have closely related yet antigenically distinct serotypes. An ideal vaccine against viral infections should induce a multivalent and protective immune response against all serotypes. Inspired by bacterial membrane vesicles (MVs) that carry different protein components, we constructed an agr locus deletion mutant of the Staphylococcus aureus strain (RN4220-Δagr) to reduce potential toxicity. Nanoscale vesicles derived from this strain (ΔagrMVs) carry at least four major components that can deliver heterologous antigens. These components were each fused with a triple FLAG tag, and the tagged proteins could be incorporated into the ΔagrMVs. The presentation levels were (3.43 ± 0.73)%, (5.07 ± 0.82)%, (2.64 ± 0.61)%, and (2.89 ± 0.74)% of the total ΔagrMV proteins for Mntc-FLAG, PdhB-FLAG, PdhA-FLAG, and Eno-FLAG, respectively. With two DENV envelope E domain III proteins (EDIIIconA and EDIIIconB) as models, the DENV EDIIIconA and EDIIIconB delivered by two staphylococcal components were stably embedded in the ΔagrMVs. Administration of such engineered ΔagrMVs in mice induced antibodies against all four DENV serotypes. Sera from immunized mice protected Vero cells and suckling mice from a lethal challenge of DENV-2. This study will open up new insights into the preparation of multivalent nanosized viral vaccines against viral infections.

The WOX11-LBD16 Pathway Promotes Pluripotency Acquisition in Callus Cells During De Novo Shoot Regeneration in Tissue Culture.

De novo shoot regeneration in tissue culture undergoes at least two phases. Explants are first cultured on auxin-rich callus-inducing medium (CIM) to produce a group of pluripotent cells termed callus; the callus is then transferred to cytokinin rich shoot-inducing medium (SIM) to promote the formation of shoot progenitor cells, from which adventitious shoots may differentiate. Here, we show that the Arabidopsis thaliana transcription factor gene LATERAL ORGAN BOUNDARIES DOMAIN16 (LBD16) is involved in pluripotency acquisition in callus cells. LBD16, which is activated by WUSCHEL RELATED HOMEOBOX11 (WOX11), is specifically expressed in the newly formed callus on CIM and its expression decreases quickly when callus is moved to SIM. Blocking the WOX11-LBD16 pathway results in the loss of pluripotency in callus cultured on CIM, leading to shooting defects on SIM. Further analysis showed that LBD16 may function in the establishment of the root primordium-like identity in the newly formed callus, indicating that the root primordium-like identity is the cellular nature of pluripotency in callus cells. Additionally, LBD16 promotes cell division during callus initiation. Our study clarified that the WOX11-LBD16 pathway promotes pluripotency acquisition in callus cells.