Endoplasmic Reticulum-Targeting Self-Assembly Nanosheets Promote Autophagy and Regulate Immunosuppressive Tumor Microenvironment for Efficient Photodynamic Immunotherapy.

The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-TER-Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-TER-Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy.

hucMSCs Treatment Ameliorated Pulmonary Fibrosis via Downregulating the circFOXP1-HuR-EZH2/STAT1/FOXK1 Autophagic Axis.

This study was performed to determine the effect of human umbilical cord mesenchymal stem cells (hucMSCs) treatment on pulmonary fibrosis and investigate the circFOXP1-mediated autophagic mechanism of hucMSCs treatment. Pulmonary fibrosis models were established by spraying bleomycin in mice and TGF-ß1 treatment of MRC-5 cells. Results showed that hucMSCs were retained in lung and hucMSCs treatment alleviated pulmonary fibrosis. Morphological staining indicated that hucMSCs-treated mice had thinner alveolar walls, effectively improved alveolar structure, significantly reduced alveolar inflammation, and decreased collagen deposition than control mice. Fibrotic proteins, including vimentin, α-SMA, collagens I and III, and the differentiation-related protein S100 calcium-binding protein A4 was reduced considerably in the hucMSCs-treated group. The mechanistic study revealed that the inhibition of hucMSCs treatment on pulmonary fibrogenesis depended on downregulating circFOXP1, in which hucMSCs treatment promoted circFOXP1-mediated autophagy process via blocking the nuclear human antigen R (HuR) translocation and promoting the HuR degradation, leading to a marked decrease in autophagy negative regulators EZH2, STAT1, and FOXK1. In conclusion, hucMSCs treatment significantly improved pulmonary fibrosis by downregulating the circFOXP1-HuR-EZH2/STAT1/FOXK1 autophagic axis. hucMSCs can act as an effective treatment for pulmonary fibrosis.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

hnRNPL-activated circANKRD42 back-splicing and circANKRD42-mediated crosstalk of mechanical stiffness and biochemical signal in lung fibrosis.

Increasing circular RNAs (circRNAs) are involved in the progression of idiopathic pulmonary fibrosis (IPF). However, circRNA biogenesis and circRNA-mediated crosstalk between mechanical stiffness and biochemical signals in IPF remain obscure. In this study, a novel circRNA-ankyrin repeat domain 42 (ANKRD42) from peripheral blood of patients with IPF, which participated in pulmonary fibrosis through the close communication of mechanical stiffness and biochemical signals, was identified. Mechanistic studies revealed that the heterogeneous nuclear ribonucleoprotein L (hnRNP L) activated the circANKRD42 reverse splicing biogenesis. The biogenetic circANKRD42 sponged miR-324-5p to promote the AJUBA expression, which blocked the binding between phosphorylated yes-associated protein 1 (YAP1) and large tumor suppressor kinase 1/2 (LATS1/2), leading to increased YAP1 entering the nucleus. circANKRD42 also sponged miR-136-5p to promote the YAP1 translation. Accumulating YAP1 in nucleus bound to TEAD, which initiated the transcription of genes related to mechanical stiffness. Finally, the therapeutic effect of circANKRD42 was evaluated in mice and the association between circANKRD42 and clinicopathological features was analyzed in IPF patients. Our findings supported that circANKRD42 is a promising biomarker and a potential therapeutic target related to cytoskeleton tension for IPF treatment.

Type I Interferon Promotes Humoral Immunity in Viral Vector Vaccination.

Recombinant viral vectors represent an important platform for vaccine delivery. Our recent studies have demonstrated distinct innate immune profiles in responding to viral vectors of different families (e.g., adenovirus versus poxvirus): while human Ad5 vector is minimally innate immune stimulatory, the poxviral vector ALVAC induces strong innate response and stimulates type I interferon (IFN) and inflammasome activation. However, the impact of the innate immune signaling on vaccine-induced adaptive immunity in viral vector vaccination is less clear. Here, we show that Modified Vaccinia Ankara (MVA), another poxviral vector, stimulated a type I IFN response in innate immune cells through cGAS-STING. Using MVA-HIV vaccine as a model, we found that type I IFN signaling promoted the generation of humoral immunity in MVA-HIV vaccination in vivo. Following vaccination, type I IFN receptor-knockout (IFNAR1-/-) mice produced significantly lower levels of total and HIV gp120-specific antibodies compared to wild-type (WT) mice. Consistent with the antibody response, a type I IFN signaling deficiency also led to reduced levels of plasma cells and memory-like B cells compared to WT mice. Furthermore, analysis of vaccine-induced CD4 T cells showed that type I IFN signaling also promoted the generation of a vaccine-specific CD4 T-cell response and a T follicular helper (Tfh) response in mice. Together, our data indicate a role for type I IFN signaling in promoting humoral immunity in poxviral vector vaccination. The study suggests that modulating type I IFN and its associated innate immune pathways will likely affect vaccine efficacy. IMPORTANCE Viral vectors, including MVA, are an important antigen delivery platform and have been commonly used in vaccine development. Understanding the innate host-viral vector interactions and their impact on vaccine-induced immunity is critical but understudied. Using MVA-HIV vaccination of WT and IFNAR1-/- mice as a model, we report that type I IFN signaling promotes humoral immunity in MVA vaccination, including vaccine-induced antibody, B-cell, and Tfh responses. Our findings provide insights that not only add to our basic understanding of host-viral vector interactions but also will aid in improving vaccine design by potentially modulating type I IFN and its associated innate immune pathways in viral vector vaccination.

Characteristics of Interferon-Associated Diabetes Mellitus in Past 30 Years: A Review.

Interferon (IFN) is a broad-spectrum antiviral agent that activates cell surface receptors and causes cells to produce antiviral proteins, inhibiting viral replication. Interferon use has long been associated with diabetes. The PubMed database was searched for articles related to diabetes and interferon from March 30, 2020. Patients were divided into type 1 diabetes group and type 2 diabetes group. We reviewed the relevant literature to compare interferon-associated T1D and interferon-associated T2D differences. Interferon treatment shortened the incubation period of T2D and changed the original T2D to T1D. The onset of interferon-associated T1D required longer periods of IFN treatment than interferon-associated T2D, and the interferon-associated T1D group had higher GADA positive rates, lower BMI, lower fasting blood glucose, and greater insulin dependence (p<0.05). More patients in the T1D group were positive for HLA-DRB1*04, DRB1*03, DRB1*09, DRB1*14, HLA-DQB1*04, HLA-DQB1*02, HLA-DQB1*03, and HLA-DQB1*05. The combined detection of GAD antibodies and HLA alleles may be an effective method to predict the incidence of T1D after IFN treatment.

A study on spinal level, length, and branch type of the inferior mesenteric artery and the position relationship between the inferior mesenteric artery, left colic artery, and inferior mesenteric vein.

BACKGROUND: This study was aimed to explore the clinical application of dual-energy computed tomography (DECT) monoenergetic plus (mono+) imaging to evaluate anatomical variations in the inferior mesenteric artery (IMA). METHODS: The clinical and imaging data of 212 patients who had undergone total abdominal DECT were retrospectively analyzed. The post-processing mono+ technique was used to obtain 40-keV single-level images in the arterial phase. Three-dimensional reconstruction was performed to evaluate the relationship between the IMA root position and the spinal level, IMA length, and IMA branch type, as well as the position of the left colic artery (LCA) and inferior mesenteric vein (IMV) at the IMA root level. RESULTS: The IMA root was located at the L3 level in 78.3% of cases and at the L2/L3 level in 3.3%. The highest vertebral level of IMA origin was L2 (4.2%), and the lowest was L4 (7.1%). The distance from the IMA root to the level of the sacral promontory was 99.58 ± 13.07 mm, which increased with the elevation of the IMA root at the spinal level. Of the patients, 53.8% demonstrated Type I IMA, 23.1% Type II, 20.7% Type III, and 2.4% Type IV. The length of the IMA varied from 13.6 to 66.0 mm. 77.3% of the IMAs belonged to Type A, the adjacent type, and 22.7% to Type B, the distant type. CONCLUSION: DECT mono+ can preoperatively evaluate the anatomical characteristics of the IMA and the positional relationship between the LCA and IMV at the IMA root level, which would help clinicians plan individualized surgery for patients.

A clinical study of inferior mesenteric artery typing in laparoscopic radical resections with left colonic artery preservation of rectal cancer.

OBJECTIVES: An investigation of the effects of different types of the inferior mesenteric artery (IMA) on laparoscopic left colic artery (LCA) radical resection of rectal cancer was conducted. METHODS: Clinical data were collected from 92 patients who underwent laparoscopic radical resection of rectal cancer with preservation of the LCA at Nantong University's Second Affiliated Hospital. All patients underwent full-abdominal dual-energy CT enhancement examination before surgery and 3D post-processing reconstruction of the IMA. Two radiologists with >3 years of experience in abdominal radiology jointly conducted the examination. A total of three types of IMA were identified among the patients: IMA type I (the LCA arising independently from the IMA), type II (LCA and sigmoid colon artery [SA] branching from a common trunk from IMA), and type III (LCA, SA, and superior rectal artery [SRA] branching from the IMA at the same point). The baseline data, pathological results, and intra-operative and post-operative indicators of the groups were analyzed. RESULTS: The proportions of type I, type II, and type III IMA were 58.70% (54/92), 18.48% (17/92), and 22.82% (21/92), respectively. IMA typing was consistent with the preoperative CT evaluation results. The intra-operative blood loss of type III IMA patients [median (interquartile spacing), M (P25, P75): 52.00 (39.50, 68.50) ml] was higher than that of type I and II IMA patients [35.00 (24.00, 42.00) and 32.00 (25.50, 39.50) ml, respectively] (P<0.05). The incidence of anastomotic fistula in type III IMA patients (4 cases, 19.05%) was higher than that in non-type III IMA patients (1 case, 1.41%) (X2=6.679, P=0.010). The incidence of postoperative complications among the three types of IMA was not significantly different (P>0.05). CONCLUSIONS: Among rectal cancer patients undergoing laparoscopic LCA preservation, type III IMA patients had more intraoperative bleeding and a higher incidence of postoperative anastomotic fistula. However, this did not increase the risk of overall postoperative complications.

Exosomal miR-145-5p derived from orthohantavirus-infected endothelial cells inhibits HTNV infection.

Human infection of orthohantavirus can cause potentially fatal diseases, such as hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) in Eurasia. Exosomes are new carriers for information exchange between cells. Cumulative findings suggest that exosomes released from parental infected cells can block or promote viral infection in recipient cells, but the role of exosomes in hantavirus infection is poorly understood. In our study, we identified the exosomes derived from HTNV-infected human vascular endothelial cells (HUVECs) (Exo-HV) and found the antiviral properties of Exo-HV in the uninfected recipient cells. High-throughput sequencing revealed the distinctly expressed miRNAs transcriptomes in Exo-HV. MiR-145-5p, one of the abundant miRNAs packaged into Exo-HV, was found to be able to transferred to recipient cells and functioned by directly targeting M RNA of HTNV 76-118 and inducing type I interferon (IFN-I) response, thus, blocking the viral replication. Concluding, this study indicated that exosomes released by HTNV-infected HUVECs were able to transfer active molecules, miR-145-5p as a proving sample, to mediate novel anti-HTNV activity in the neighboring uninfected cells, which will help us to explore new strategies for the treatment of infectious disease utilizing exosomes with miRNA.

Delirium in Older Patients after Combined Epidural-General Anesthesia or General Anesthesia for Major Surgery: A Randomized Trial.

BACKGROUND: Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery. METHODS: Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days. RESULTS: Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 [1.8%] of 857 patients) than in the general anesthesia group (43 [5.0%] of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 [49%] vs. 288 [33%]; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 [58%] vs. 387 [45%]; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001). CONCLUSIONS: Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension.

Comparison of the caregivers' and community health professionals' views on home health care services for disabled older adults: a cross-sectional study in Beijing, China.

BACKGROUND: In an era of an increasingly ageing society, part of healthcare for older adults can be provided in patients' homes, and the need for home health care services (HHCSs) is increasing. This study sought to determine whether a gap exists between the views of community health professionals and the caregivers of disabled older adults towards HHCSs in Beijing, China. METHODS: A cross-sectional study with two comparative questionnaire surveys was conducted in Beijing, China. One survey was administered to the caregivers of disabled older adults, and the other was administered to health professionals in community health service institutions (CHSIs). T-tests and Wilcoxon signed-rank tests were used to explore potential differences between the views of caregivers and community health professionals towards HHCSs. RESULTS: We received 370 valid questionnaires from caregivers and 224 questionnaires from health professionals. Of the 370 caregivers, 314 (84.9%) were willing to apply for HHCSs for the older adults, but only 20.5% (N = 76) received HHCSs. Over 80% of the caregivers accepted out-of-pocket costs less than 100 yuan per visit. Caregivers' demands on home nursing services were significantly higher than those of health guidance services (Z = - 7.725, P < 0.001). Most of the 224 health professionals chose "health professionals' personal safety cannot be guaranteed" as a problem limiting the provision of HHCSs (N = 151, 40.8%). The health professionals' attitudes towards home nursing services were significantly less positive than those towards health guidance services (Z = - 10.081, P < 0.001). For home nursing services, health professionals' attitude scores were lower than the caregivers' demand scores (Z = - 4.960, P < 0.001), while for health guidance services, health professionals' attitude scores were higher than the caregivers' demand scores (Z = - 8.373, P < 0.001). CONCLUSIONS: Gaps exist between the views of caregivers and health professionals on HHCSs. Compared to health professionals with a higher willingness to provide health guidance services, caregivers need home nursing services. Feasible policies should be implemented to safeguard the rights and interests of health professionals, and qualified health professionals should be trained for HHCSs.

Health education services utilization and its determinants among migrants: a cross-sectional study in urban-rural fringe areas of Beijing, China.

BACKGROUND: Domestic migration poses a challenge for China as migrants have little access to preventive healthcare services and are vulnerable to certain risks and diseases. This research sought to unveil and explore the determinant factors associated with health education utilization as a key aspect in basic public health services for migrants in Beijing, China. METHODS: A sample of 863 inter-provincial migrants, 18 years old and above, was selected by three-stage stratified cluster sampling method in urban-rural fringe areas of Beijing during 2016 to 2017. Face-to-face structured interviews were conducted in the questionnaire survey. The effects of the explanatory variables on health education utilization from predisposing, enabling, health behaviors and need variables were used to demonstrate by Anderson health service utilization model. RESULTS: The study revealed that 61.6% migrants desired to receive health education, while only 53.8% of them received in the past year. There were differences in the utilization and needs of health education among the migrants in different ages and genders. Many migrants desired to gain access to various types of health education information from the internet. Chi-square independence test lists such major determinant factors in migrants whole health education as age, "Hukou" registration system, marital status, education level, long-term residence plan in Beijing, one or more children in Beijing, employment status, housing source, average daily working time, exercises, health knowledge, smoking, self-rated health. The binary logistic regression indicates that the migrants with younger age, high education level, one or more children in Beijing, exercises and good self-rated health were more likely to receive whole health education. The results also show that average daily working time of enabling variables and exercise of health behavior variables were the strong and consistent determinants of three types of health education utilization, including communicable, non-communicable and occupational diseases. CONCLUSION: Gaps exist between the needs and utilization in health education and more attention should be given to the migrants with heavy workload and low education level. Feasible policies and measures, such as multiple health information channels, should be vigorously implemented to ensure equitable and easy access to health education for migrants.

Development of a competency model for general practitioners after standardized residency training in China by a modified Delphi method.

BACKGROUND: The "5 + 3" residency training is the main stream general practitioner training program in China. However, a competency model is absent for evaluating the clinical competence attained by general practitioners after training. This study was conducted to develop a consensus set of competencies for general practitioners after standardized residency training in China. METHODS: A modified Delphi process was deployed to develop the competency model, including two stages: (1) generation of an initial set of competencies derived from literature review, behavioral observation of GP-patient consultations, and critical incidents interview of GPs; (2) a 2-round, web-based Delphi survey of experts in general practice, selected using purposive sampling, to prioritize and gain consensus on the essential competencies of GPs. RESULTS: From literature review, behavioral observation, and critical incidents interview, 46 competencies in 7 domains were identified. After two rounds of Delphi survey of 28 participants (the mean age was 47.9 [9.3] years and 64.3% were women) representing a range of health professionals (GPs, managers, and researchers), a consensus was reached on 50 competencies categorized into 7 domains. CONCLUSION: A consensus-based competency model for general practitioners in China has been identified which may be used to evaluate the general practitioners' clinical competence after standardized training.

MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6.

BACKGROUND: The human myxovirus resistance 2 (Mx2/MxB) protein was originally found to regulate cytoplasmic-nuclear transport but was recently reported to restrict HIV-1 replication by binding to HIV-1 capsid (CA), preventing uncoating, the nuclear import of pre-integration complex (PIC) and viral DNA integration. This work explores the mechanisms of MxB-mediated HIV-1 inhibition. RESULTS: We demonstrated that MxB represses NUP358-mediated PIC nuclear import and HIV-1 replication. Moreover, MxB's effects on PIC nuclear import and HIV-1 replication depend critically on cofactor cleavage and polyadenylation specificity factor subunit 6 (CPSF6). MxB binds nucleoporin NUP358, blocks NUP358-CA interaction, thereby impeding the nuclear import of HIV-1 PIC with CPSF6 binding to PIC. More intriguingly, CPSF6's role in nuclear import depends on MxB, being a facilitator of HIV-1 nuclear import on its own, but becoming an inhibitor when MxB is present. CONCLUSIONS: Our work establishes that MxB impedes the NUP358-mediated HIV-1 nuclear import and viral replication cooperatively with CPSF6.

Awareness, utilization and influencing factors of social supports for main informal caregivers of schizophrenia patients: a cross-sectional study in primary care settings in Beijing, China.

BACKGROUND: Most schizophrenia patients are supported by main informal caregivers at home in China. This study aims to investigate the further needs of social supports for main informal caregivers of schizophrenia patients and to analyze influencing factors on the awareness and utilization of social supports in Beijing. The results of this study could potentially act as reference for health professionals to implement appropriate and effective support programs. METHODS: A mixed-methods approach was used in this study. Awareness, utilization and influencing factors of social supports for main informal caregivers were investigated using questionnaires in 6 urban districts in Beijing. Meanwhile, individual in-depth interviews with 10 main informal caregivers from the urban districts of Beijing were conducted to identify the caregivers' perspective on social supports and their further needs. RESULTS: Quantitative results showed that although the government provided multi-channel resources for schizophrenia patients and their families, awareness and utilization of the resources such as rehabilitation and relevant subsidies were less than 10.0 and 5.0% respectively. Most caregivers in in-depth interviews expressed that they had negative experiences with respect to obtaining social supports, and they emphasized that more support would be needed in terms of financial support, respect, and rehabilitation institutions. CONCLUSIONS: The awareness and utilization of social supports are low for main informal caregivers of schizophrenia patients. More services and improved public attitudes are needed for schizophrenia patients and their caregivers.

Knowledge, attitudes and skills of dementia care in general practice: a cross-sectional study in primary health settings in Beijing, China.

BACKGROUND: General practitioners (GPs) play a significant role in dementia care. However, the knowledge and attitudes of them towards dementia care are poorly characterized. The present study aimed to investigate GPs' knowledge, attitudes and skills of dementia care in primary health settings in Beijing. METHODS: A cross-sectional survey was conducted in 27 community health service centers (CHSCs) in Beijing. The GPs' knowledge, attitudes and skills were assessed utilizing the Alzheimer's Disease Knowledge Scale (ADKS), Dementia Care Attitude Scale (DCAS) and self-designed questionnaire, respectively. RESULTS: A total of 341 participants returned the questionnaire. The overall mean score of GPs' dementia knowledge measured by the ADKS was 21.42 (SD = 2.73) out of 30 (71.4%), GPs' attitudes to dementia care was 36.25 (SD = 5.12) out of 50 (72.5%), and GPs' self-confidence on dementia care skills was 53.93 (SD = 9.57) out of 75 (71.9%). GPs' overall knowledge towards dementia care was limited and the attitudes were generally positive. They had low level recognition of their roles towards dementia care. The majority of GPs believed that dementia care was within a specialist's domain not that of general practice. CONCLUSION: GPs demonstrate low levels of dementia knowledge and skills, but express generally positive attitudes towards dementia in this study. It is much needed to translate detailed dementia care handbook, and adequate dementia knowledge training for GPs into practice to improve care outcomes for people with dementia in China. In addition, dementia management should be covered in the national basic package of public health services in primary care.

Development of type 2 diabetes mellitus quality indicators in general practice by a modified Delphi method in Beijing, China.

BACKGROUND: The service capacity of primary care has improved in China. General practice also takes growing responsibility in the management of type 2 diabetes mellitus, but there are concerns about the paucity of evidence of the quality of care delivered. And there is an absence of systematic quality indicators of type 2 diabetes mellitus in general practice in China. This study aimed to develop a set of type 2 diabetes mellitus quality indicators to facilitate quality measurement in general practice in China. METHODS: Preliminary quality indicators were generated and refined by literature review and an expert consultation meeting. Two rounds of email-based Delphi survey and a consensus meeting were carried out to identify quality indicators. Delphi questionnaires with 43 indicators were sent to 30 participants in the first round. There were 16 general practitioners and 10 community health service center leaders from primary care, 3 endocrinologists and a primary care researcher in the first round. And 27 out of the 30 participants participated in the second round. The consensus meeting was held among 9 participants to refine the indicators and a last round of rating was carried out in the meeting. The indicators were rated in terms of importance and feasibility. The agreement criteria were defined as median ≥ 7.0 and ≥ 85.0% of ratings in the 7-9 tertile for importance; median ≥ 7.0 and ≥ 65.0, 70.0, 75.0% of ratings in the 7-9 tertile for feasibility respectively in the three rounds of rating. RESULTS: After 2 rounds of Delphi survey and the consensus meeting, total 38 indicators achieved consensus for inclusion in the final set of indicators. The final set of indicators were grouped into 7 domains: access (5 indicators), monitoring (12 indicators), health counseling (7 indicators), records (2 indicators), health status (7 indicators), patient satisfaction (2 indicators) and self-management (3 indicators). CONCLUSIONS: A set of 38 potential quality indicators of type 2 diabetes mellitus in general practice were identified by an iterative Delphi process in Beijing, China. Preliminary approach for measurement and data collection were described. However, the indicators still need to be validated by testing in a further study.

A global coexpression network of soybean genes gives insights into the evolution of nodulation in nonlegumes and legumes.

A coexpression network is a powerful tool for revealing genes' relationship with many biological processes. Mass transcriptomic and genomic data from different plant species provide the foundation for understanding the evolution of nodulation across the Viridiplantae at a systematic level. We used weighted coexpression network analysis (WGCNA) to mine a nodule-related module (NRM) in Glycine max. Comparative genomic analysis of 78 green plant species revealed that NRM genes are recruited from different evolutionary nodes along with gene duplication events. A set of core coexpressed genes within legumes may play vital roles in regulating nodule environments essential for nitrogen fixation, including oxygen concentrations, sulfur transport, and iron homeostasis (such as GmCHY). The regulation of these genes occurred mainly at the transcription level, although some of them, such as sulfate transporters, may also undergo positive selection at protein level. We revealed that ancient orthologs and duplication events before the origin of legumes were preadapted for symbiosis. Conserved coregulated genes found within legumes paved the way for nodule formation and nitrogen fixation. These findings provide significant insights into the evolution of nodulation and indicate promising candidates for identifying other key components of legume nodulation and nitrogen fixation.

Interactions of WRKY15 and WRKY33 transcription factors and their roles in the resistance of oilseed rape to Sclerotinia infection.

WRKY transcription factors are known to participate in the defence responses of higher plants. However, little is known about the roles of such proteins, especially regarding their functions in the resistance of oilseed rape (Brassica napus) to Sclerotinia sclerotiorum, a necrotrophic fungal pathogen that causes stem rot. In this study, we identified BnWRKY33 as a S. sclerotiorum-responsive gene that positively regulates resistance to this pathogen by enhancing the expression of genes involved in camalexin synthesis and genes regulated by salicylic acid (SA) and jasmonic acid (JA). We also identified a S. sclerotiorum-responsive region in the promoter of BnWRKY33, which we revealed to be a relatively conserved W-box region in the promoters of homologous genes in different species. Using this S. sclerotiorum-responsive region as bait in a yeast one-hybrid assay, we identified another WRKY transcription factor, BnWRKY15, and observed that both BnWRKY15 and BnWRKY33 could bind to this region. In addition, BnWRKY15 overexpression simultaneously increased the susceptibility of B. napus to S. sclerotiorum and down-regulated BnWRKY33 after different durations of infection. Furthermore, BnWRKY15, which contains a transcriptional repression domain, exhibited reduced transactivation ability and could reduce the transactivation ability of BnWRKY33 in Arabidopsis protoplast assays. Therefore, we suggest that the increased susceptibility of BnWRKY15-overexpressing plants results from reduced BnWRKY33 expression, which is due to the inhibition of BnWRKY33 transcriptional activation by BnWRKY15.