Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study.

BACKGROUND: Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. METHODS: We conducted a multicenter retrospective study to characterize ICI-associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer-Lemeshow test. RESULTS: Forty-four patients were identified, including thirty-five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin-I (cTnI) levels (p < 0.001), higher creatine kinase levels (p = 0.003), higher creatine kinase isoenzyme-MB (CK-MB) levels (p = 0.013), and shorter time to the incidence of adverse cardiovascular events (p = 0.022) after ICI treatment. Twenty-one patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (p = 0.013), higher N-terminal pro-B-type natriuretic peptide levels (p = 0.031), higher creatine kinase levels (p = 0.018), higher CK-MB levels (p = 0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (p = 0.016) compared to non-severe myocarditis patients after ICI treatment. Multivariate logistic regression showed that CK-MB (adjusted odds ratio [OR]: 1.775, 95% confidence interval [CI]: 1.055-2.984, p = 0.031) was the independent risk factor of the development of ICI-associated myocarditis, and cTnI (adjusted OR: 1.021, 95% CI: 1.002-1.039, p = 0.03) and NLR (adjusted OR: 1.890, 95% CI: 1.026-3.483, p = 0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.785 (95% CI: 0.642 to 0.928, p = 0.013) for CK-MB, 0.765 (95% CI: 0.601 to 0.929, p = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, p = 0.016). CONCLUSIONS: Elevated CK-MB after ICI treatment is the independent risk factor for the incidence of ICI-associated myocarditis, and elevated cTnI and NLR after ICI treatment are the independent risk factors for the development of ICI-associated severe myocarditis. CK-MB, cTnI, and NLR demonstrated a promising predictive utility for the identification of ICI-associated myocarditis and severe myocarditis.

Granulation characteristics of anammox sludge in response to different signal-molecule-stimulants; mediated through programmed cell death.

During the anammox process, mitigation of biomass washout to increase sludge retention is an important parameter of process efficiency. Signal molecular stimulants (SMS) initiate the sludge granulations controlled by programmed cell death (PCD) of microorganisms. In this study, the aerobic granular sludge (AGS), cell fragments, extracellular polymeric substances (EPS), and AGS process effluent were tested as SMS to identify their effect on anammox granulation. The results showed that the addition of SMS increased the nitrogen removal efficiency to varying degrees, whereas the addition of AGS process supernatant, as SMS, increased the ammonia removal efficiency up to 96%. The addition of SMS was also found to increase EPS production and contributed to sludge granulation. In this process, the proportion of PCD increased and both Gaiella and Denitratisoma abundance increased from 3.54% to 5.59%, and from 1.8% to 3.42%, respectively. In conclusion, PCD was found important to increase anaerobic ammonia oxidation performance through the granulation mechanism.

Hypoxia-Responsive CAR-T Cells Exhibit Reduced Exhaustion and Enhanced Efficacy in Solid Tumors.

Expanding the utility of chimeric antigen receptor (CAR)-T cells in solid tumors requires improving their efficacy and safety. Hypoxia is a feature of most solid tumors that could be used to help CAR-T cells discriminate tumors from normal tissues. In this study, we developed hypoxia-responsive CAR-T cells by engineering the CAR to be under regulation of hypoxia-responsive elements and selected the optimal structure (5H1P-CEA CAR), which can be activated in the tumor hypoxic microenvironment to induce CAR-T cells with high polyfunctionality. Hypoxia-responsive CAR T cells were in a "resting" state with low CAR expression under normoxic conditions. Compared with conventional CAR-T cells, hypoxia-responsive CAR-T cells maintained lower differentiation and displayed enhanced oxidative metabolism and proliferation during cultivation, and they sowed a capacity to alleviate the negative effects of hypoxia on T-cell proliferation and metabolism. Furthermore, 5H1P-CEA CAR-T cells exhibited decreased T-cell exhaustion and improved T-cell phenotype in vivo. In patient-derived xenograft models, hypoxia-responsive CAR-T cells induced more durable antitumor activity than their conventional counterparts. Overall, this study provides an approach to limit CAR expression to the hypoxic tumor microenvironment that could help to enhance CAR T-cell efficacy and safety in solid tumors. SIGNIFICANCE: Engineering CAR-T cells to upregulate CAR expression under hypoxic conditions induces metabolic reprogramming, reduces differentiation, and increases proliferation to enhance their antitumor activity, providing a strategy to improve efficacy and safety.

Both people living in the COVID-19 epicenter and those who have recently left are at a higher risk of loneliness.

There is little empirical data on the heightened risk of loneliness among individuals residing in the COVID-19 epicenter or those who have recently left. This study compared the risk of loneliness in individuals residing in Wuhan, the COVID-19 epicenter in China, and those who had recently left during the initial outbreak period to those living in non-epicenter regions. During the COVID-19 outbreak in China in 2020, three samples were obtained using snowball sampling. The samples included 2882 epicenter residents, 1028 left residents, and 2963 non-epicenter residents. Loneliness was assessed using the six-item De Jong Gierveld Loneliness Scale, with a score of two or more indicating the presence of loneliness. 53.5% and 55.2% of epicenter and recently left residents, respectively, experienced loneliness, which was significantly higher than the 43.9% observed in non-epicenter residents. After adjusting for covariates, the risk of loneliness remained statistically significant for both epicenter and left residents (OR = 1.35, P < 0.001 and OR = 1.20, P = 0.017, respectively), when compared to non-epicenter residents. Individuals residing in the COVID-19 epicenter, as well as those who have recently left, are at a heightened risk of loneliness during the outbreak. These individuals need psychosocial support to mitigate their risk of loneliness and promote their psychological wellbeing.

Loneliness in older Chinese adults amid the COVID-19 pandemic: Prevalence and associated factors.

INTRODUCTION: Data on loneliness among older adults in China during the COVID-19 pandemic are still scarce. This study aimed to examine the prevalence of loneliness and identify its associated factors among older Chinese adults during the COVID-19 pandemic. METHODS: During the COVID-19 pandemic, 1268 older Chinese adults (aged 50+ years) were recruited through snowball sampling. The Chinese version of the validated six-item De Jong Gierveld Loneliness Scale was used to assess participants' recent feelings of loneliness, and a cut-off score of two or more was used to indicate the presence of loneliness. RESULTS: Loneliness was experienced by 37.9% of the participants in recent days. Factors significantly associated with loneliness included male sex (vs. female, OR: 1.62, p < .001), an education level of middle school and below (vs. college and above, OR: 1.50, p = .007), residing in the COVID-19 epicenter (vs. other provinces, OR: 1.48, p = .004), concern about contracting COVID-19 (OR: 1.68, p = .001), poor knowledge of COVID-19 (OR: 2.39, p = .012), and physical health problems (OR: 1.65, p < .001). DISCUSSION: Loneliness is common among older Chinese adults amid the COVID-19 pandemic. Targeted intervention programs may be more effective in reducing loneliness among older adults who are worried about contracting COVID-19, have poor COVID-19 knowledge, and experience physical health problems.

Screening and characterization of the scFv for chimeric antigen receptor T cells targeting CEA-positive carcinoma.

Introduction: Chimeric antigen receptor T (CAR-T) cell therapy presents a promising treatment option for various cancers, including solid tumors. Carcinoembryonic antigen (CEA) is an attractive target due to its high expression in many tumors, particularly gastrointestinal cancers, while limited expression in normal adult tissues. In our previous clinical study, we reported a 70% disease control rate with no severe side effects using a humanized CEA-targeting CAR-T cell. However, the selection of the appropriate single-chain variable fragment (scFv) significantly affects the therapeutic efficacy of CAR-T cells by defining their specific behavior towards the target antigen. Therefore, this study aimed to identify the optimal scFv and investigate its biological functions to further optimize the therapeutic potential of CAR-T cells targeting CEA-positive carcinoma. Methods: We screened four reported humanized or fully human anti-CEA antibodies (M5A, hMN-14, BW431/26, and C2-45), and inserted them into a 3rd-generation CAR structure. We purified the scFvs and measured the affinity. We monitored CAR-T cell phenotype and scFv binding stability to CEA antigen through flow cytometry. We performed repeated CEA antigen stimulation assays to compare the proliferation potential and response of the four CAR-T cells, then further evaluated the anti-tumor efficacy of CAR-T cells ex vivo and in vivo. Results: M5A and hMN-14 CARs displayed higher affinity and more stable CEA binding ability than BW431/26 and C2-45 CARs. During CAR-T cell production culture, hMN-14 CAR-T cells exhibit a larger proportion of memory-like T cells, while M5A CAR-T cells showed a more differentiated phenotype, suggesting a greater tonic signal of M5A scFv. M5A, hMN-14, and BW431/26 CAR-T cells exhibited effective tumor cell lysis and IFN-γ release when cocultured with CEA-positive tumor cells in vitro, correlating with the abundance of CEA expression in target cells. While C2-45 resulted in almost no tumor lysis or IFN-γ release. In a repeat CEA antigen stimulation assay, M5A showed the best cell proliferation and cytokine secretion levels. In a mouse xenograft model, M5A CAR-T cells displayed better antitumor efficacy without preconditioning. Discussion: Our findings suggest that scFvs derived from different antibodies have distinctive characteristics, and stable expression and appropriate affinity are critical for robust antitumor efficacy. This study highlights the importance of selecting an optimal scFv in CAR-T cell design for effective CEA-targeted therapy. The identified optimal scFv, M5A, could be potentially applied in future clinical trials of CAR-T cell therapy targeting CEA-positive carcinoma.

The Role of Two Factors of Negative Symptoms and Cognition on Social Functioning in Male Patients with Schizophrenia: A Mediator Model.

OBJECTIVE: This study aims to compare the cognitive function and social functioning in male patients with deficit syndrome (DS) and non-DS, and to explore whether cognitive function serves as a mediator in the relationship between the two factors of negative symptoms (motivation and pleasure (MAP) and expressivity (EXP) deficits, and social functioning in schizophrenia patients. METHODS: One hundred and fifty-six male patients with schizophrenia and 109 age- and education-matched normal controls were enrolled in the current study. The Chinese version of a Schedule for Deficit Syndrome (SDS) was used for DS and non-DS categorization. The Brief Psychiatric Rating Scale (BPRS) and the Brief Negative Symptoms Scale (BNSS) were used to assess psychotic and negative symptoms in patients. The Social-Adaptive Functioning Evaluation (SAFE) was adopted to evaluate patients' social functioning, and a battery of classical neurocognitive tests was used to assess cognition, including sustained vigilance/attention, cognitive flexibility, ideation fluency, and visuospatial memory. RESULTS: We found that male patients with DS performed worse in all four cognitive domains and social functioning compared to non-DS patients. Both total negative symptoms and its two factors were significantly associated with all four domains of cognition and social functioning in male patients. Interestingly, our results indicate that only cognitive flexibility mediates the relationship between negative symptoms and social functioning in schizophrenia patients, but there were no differences between EXP and MAP negative factors in this model. CONCLUSION: Our findings suggest that DS patients may represent a unique clinical subgroup of schizophrenia, and the integrated interventions targeting both negative symptoms and cognition, especially cognitive flexibility, may optimally improve functional outcomes in schizophrenia patients.

Associations of Insomnia With Insulin Resistance Traits: A Cross-sectional and Mendelian Randomization Study.

CONTEXT: Insomnia is associated with insulin resistance (IR) in observational studies; however, whether insomnia is causally associated with IR remains unestablished. OBJECTIVE: This study aims to estimate the causal associations of insomnia with IR and its related traits. METHODS: In primary analyses, multivariable regression (MVR) and 1-sample Mendelian randomization (1SMR) analyses were performed to estimate the associations of insomnia with IR (triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol [TG/HDL-C] ratio) and its related traits (glucose level, TG, and HDL-C) in the UK Biobank. Thereafter, 2-sample MR (2SMR) analyses were used to validate the findings from primary analyses. Finally, the potential mediating effects of IR on the pathway of insomnia giving rise to type 2 diabetes (T2D) were examined using a 2-step MR design. RESULTS: Across the MVR, 1SMR, and their sensitivity analyses, we found consistent evidence suggesting that more frequent insomnia symptoms were significantly associated with higher values of triglyceride-glucose index (MVR, ß = 0.024, P < 2.00E-16; 1SMR, ß = 0.343, P < 2.00E-16), TG/HDL-C ratio (MVR, ß = 0.016, P = 1.75E-13; 1SMR, ß = 0.445, P < 2.00E-16), and TG level (MVR, ß = 0.019 log mg/dL, P < 2.00E-16, 1SMR: ß = 0.289 log mg/dL, P < 2.00E-16) after Bonferroni adjustment. Similar evidence was obtained by using 2SMR, and mediation analysis suggested that about one-quarter (25.21%) of the association between insomnia symptoms and T2D was mediated by IR. CONCLUSIONS: This study provides robust evidence supporting that more frequent insomnia symptoms are associated with IR and its related traits across different angles. These findings indicate that insomnia symptoms can be served as a promising target to improve IR and prevent subsequent T2D.

RUNX3 improves CAR-T cell phenotype and reduces cytokine release while maintaining CAR-T function.

CAR-T therapy has shown successful in the treatment of certain types of hematological malignancy, while the efficacy of CAR-T cell in treating solid tumors has been limited due to the exhaustion of CAR-T caused by the tumor microenvironment in solid tumors. Therefore, improving the exhaustion of CAR-T cell is one of the inspiring strategies for CAR-T treatment of solid tumors. As an important regulator in T cell immunity, the transcription factor RUNX3 not only negatively regulates the terminal differentiation T-bet gene, reducing the ultimate differentiation of T cells, but also increases the residency of T cells in non-lymphoid tissues and tumors. By overexpressing RUNX3 in CAR-T cells, we found that increasing the expression of RUNX3 maintained the low differentiation of CAR-T cells, further improving the exhaustion of CAR-T cells during antigen stimulation. In vitro, we found that RUNX3 could reduce the release of cytokines while maintaining CAR-T cells function. In re-challenge experiments, CAR-T cells overexpressing RUNX3 (Runx3-OE CAR-T) were safer than conventional CAR-T cells, while RUNX3 could also maintain the anti-tumor efficacy of CAR-T cells in vivo. Collectively, we found that Runx3-OE CAR-T cells can improve CAR-T phenotype and reduce cytokines release while maintaining CAR-T cells function, which may improve the safety of CAR-T therapy in clinical trials.

A study of the Rashba effect in two-dimensional ternary compounds ABC monolayers (A = Sb, Bi; B = Se, Te; C = Br; I).

The structure and electronic and spintronic properties of two-dimensional (2D) ternary compounds ABC (A = Sb, Bi; B = Se, Te; C = Br; I) monolayers are investigated using the first-principles method. The ABC monolayers possess typical Janus structures with a considerable potential gradient normal to the surface, inducing intrinsic Rashba spin splitting (RSS) at the conduction band minimum near the Γ point. Among them, the splitting strength of the BiSeI monolayer is the largest and its Rashba coefficient can reach 1.84 eV Å. The projected energy band of the BiSeI monolayer suggests that the RSS state is mainly rooted in the Bi-pz orbital. The RSS strength can be modulated by applying the in-plane strain. The tensile strain can improve the RSS strength, which is ascribed to the increase of the potential gradient normal to the surface. These results indicate that these 2D ternary compounds have great potential for application in tunable spintronic devices.

An investigation of low-protein diets' qualification rates and an analysis of their short-term effects for patients with CKD stages 3-5: a single-center retrospective cohort study from China.

BACKGROUND: The feasibility and efficacy of low-protein diets (LPD) treatment in chronic kidney disease (CKD) is controversial. Based on the characteristics of the Chinese diet, we observe the qualification rates and short-term clinical effects of LPD for CKD patients in our center. METHODS: This is a retrospective cohort study. CKD stages 3-5 patients who were regularly followed up 5 times (over 2 years) and treated with LPD were included. We collected clinical data to observe the changes in LPD qualification rates and divided patients into LPD and non-LPD group according to the average dietary protein intake (DPI) of 5 follow-up time points and compared the changes in primary and secondary outcome measures between the two groups. RESULTS: We analyzed data from 161 eligible CKD stages 3-5 patients. From baseline to the 5th follow-up time point, the LPD qualification rates of all patients were 11.80%, 35.40%, 47.82%, 53.43% and 54.04%, respectively. For primary outcome measures, the urine protein/creatinine ratio (UPCR) decreased more in the LPD group than in the non-LPD group [Median (interquartile range, IQR) of the difference between the 5th follow-up time point and baseline: 0.19 (- 0.01-0.73) vs. 0.10 (- 0.08-0.27), P < 0.001]. We constructed three classes of mixed linear models (model I, II, III). The UPCR slopes were all negative in the LPD group and positive in the non-LPD group (P < 0.001). Meanwhile, in model I, the estimate glomerular filtration rate(eGFR) decline slope in the LPD group was lower than that in the non-LPD group [slope (standard error): - 1.32 (0.37) vs. - 2.35 (0.33), P = 0.036]. For secondary outcome measures, body mass index (BMI) triglycerides (TG), body weight, and fat free mass (FFM) showed stable statistical differences in the comparison of LPD and non-LPD groups, with greater declines in the former. CONCLUSION: The results of this study suggest that LPD treatment can reduce UPCR in patients with CKD stages 3-5, and may also delay the decline in eGFR. Meanwhile, it also reduces BMI, TG, body weight, and FFM, thus the need to prevent malnutrition in clinical implementation.

Simultaneous editing of TCR, HLA-I/II and HLA-E resulted in enhanced universal CAR-T resistance to allo-rejection.

Introduction: The major challenge for universal chimeric antigen receptor T cell (UCAR-T) therapy is the inability to persist for a long time in patients leading to inferior efficacy clinically. The objective of this study was to design a novel UCAR-T cell that could avoid the occurrence of allo-rejection and provide effective resistance to allogeneic Natural Killer (NK) cell rejection, together with the validation of its safety and efficacy ex vivo and in vivo. Methods: We prepared T-cell receptor (TCR), Human leukocyte antigen (HLA)-I/II triple-edited (TUCAR-T) cells and evaluated the anti-tumor efficacy ex vivo and in vivo. We measured the resistance of exogenous HLA-E expressing TUCAR-T (ETUCAR-T) to NK rejection by using an enhanced NK. Furthermore, we established the safety and efficacy of this regimen by treating Nalm6 tumor-bearing mice with a repeated high-dose infusion of ETUCAR-T. Moreover, we analyzed the effects of individual gene deficiency CAR-T on treated mice and the changes in the transcriptional profiles of different gene-edited T cells via RNA-Seq. Results: Data showed that HLA-II editing didn't impair the anti-tumor efficacy of TUCAR-T ex vivo and in vivo and we found for the first time that HLA-II deficiency could facilitate the persistence of CAR-T. Contrastively, as the most commonly eliminated target in UCAR-T, TCR deficiency was found to be a key disadvantageous factor for the shorter-term anti-tumor efficacy in vivo. Our study demonstrated ETUCAR-T could effectively resist allogeneic NK rejection ex vivo and in vivo. Discussion: Our research provided a potential and effective strategy for promoting the persistence of UCAR-T cells in clinical application. And it reveals the potential key factors of the poor persistence of UCAR-T along with new insights for future development.

A Bibliometric-Based Analytical Framework for the Study of Smart City Lifeforms in China.

Smart cities are the future development direction of cities and are a comprehensive expression of the development of the organic life body of cities. The organic life form of a smart city relates to viewing the city as an organic life self-organizing system based on the wholeness and systemic nature of the smart city life form itself, to construct a holistic spatial linkage of the functions and mechanisms of the city life system, and to enhance the overall vitality of the space. This study is based on the literature of "smart city" research in the China National Knowledge Infrastructure (CNKI) database, and the current situation and related themes of smart city research in China are discussed through co-word analysis and cluster analysis using software such as SPSS and VOSviewer, among which there are four themes in co-word cluster analysis, namely, intelligent technology supporting smart city research; research on the integration of the social system of a smart city; research on the top-level strategic design and planning and construction of a smart city; and research on the development, evaluation, and concrete practice of smart city construction. Four conclusions are drawn from the development of smart city research in China: Firstly, smart city research has attracted the attention of multiple disciplines, and the research themes are scattered and integrated across disciplinary systems. Secondly, smart city construction, development rules, and characteristics need to be further explored, and the problems, future trends, and policy support for the modernization of China's cities and towns have been focused on engineering and technology, with a lack of practical research in non-technical areas such as humanities and ethics. Thirdly, the philosophical humanism and ecological ethics of smart cities need to be systematized, and their construction and development needs to be humanistic, systematic, and comprehensive, thus contributing to the sustainability, livability, ecology, and wisdom of future urban development. Fourthly, the development of the smart city system is supported by theories related to global cities and innovative cities, and the world city, a product of globalization, is undergoing a transformation into a digital and intelligent organic urban life form.

Clinical insomnia among elderly primary care attenders in Wuhan, China: A multicenter cross-sectional epidemiological study.

Background and objectives: Integrating sleep health into primary care is a promising approach to narrow the treatment gap for insomnia in older adults but data regarding the epidemiological characteristics of insomnia among elderly primary care attenders (EPCAs) are very limited. This study examined the prevalence and correlates of clinical insomnia among Chinese EPCAs. Methods: By using two-stage consecutive sampling method, a total of 757 EPCAs were recruited from seven urban and six rural primary care centers in Wuhan, China. The Insomnia Severity Index (ISI) and the Geriatric Depression Scale (15 item version) were administered to assess insomnia severity and depressive symptoms, respectively. Results: The two-week prevalence of clinical insomnia (ISI score ≥ 15) was 28.9%. Significant correlates of clinical insomnia were: female sex (vs. male, OR = 2.13, P < 0.001), fair and poor family relationship (vs. good, OR = 1.59, P = 0.028), hypertension (OR = 1.67, P = 0.004), heart disease (OR = 1.73, P = 0.048), arthritis (OR = 2.72, P = 0.001), and depressive symptoms (OR = 4.53, P < 0.001). Conclusion: The high prevalence of clinical insomnia among Chinese EPCAs suggests a high level of sleep health need in older patients in China's primary care settings. Considering the many negative outcomes associated with insomnia, it is necessary to integrate sleep health into primary care in China.

Anxiety symptoms in older Chinese adults in primary care settings: Prevalence and correlates.

Background: Integrating mental health services into primary care is a potentially cost-effective way to decrease the treatment gap for anxiety in older adults but data on the epidemiology of anxiety symptoms in older Chinese adults in primary care settings have been very limited. This study investigated the prevalence and correlates of anxiety symptoms in Chinese older primary care patients. Methods: A total of 753 older primary care patients (≥65 years) were consecutively recruited from 13 primary care clinics in Wuhan, China, and interviewed with the validated Chinese version of the short form of the Geriatric Anxiety Inventory (GAI-SF). Results: The prevalence of anxiety symptoms (GAI-SF ≥ 3) in older primary care patients was 21.1%. Statistically significant correlates of anxiety symptoms were female sex (vs. male, OR = 1.85, P = 0.002), poor economic status (vs. good, OR = 2.31, P = 0.013), fair and poor family relationship (vs. good, OR = 1.85, P = 0.006), hypertension (OR = 2.01, P < 0.001), chronic gastric ulcer (OR = 6.82, P < 0.001), and Parkinson's disease (OR = 7.83, P = 0.031). Conclusions: Anxiety symptoms are prevalent among older adults attending primary care clinics. Efforts for preventing or reducing anxiety symptoms in older primary care patients may be more useful to target those who are women, have poor financial status, don't have a good family relationship, suffer from hypertension, have chronic gastric ulcer, and suffer from Parkinson's disease.

Prevalence and correlates of suspected dementia in older adults receiving primary healthcare in Wuhan, China: A multicenter cross-sectional survey.

Background: Integrating the management of dementia into primary healthcare is a cost-effective way to reduce the burden of dementia but the clinical epidemiology of dementia in primary healthcare settings remains unclear. This study investigated the prevalence and correlates of suspected dementia in Chinese older adults receiving primary healthcare. Methods: In this multicenter cross-sectional survey, a total of 773 older adults (≥65 years) were consecutively recruited from seven urban and six rural primary care clinics in Wuhan, China, and interviewed with the validated Chinese version of the Brief Community Screening Instrument for Dementia (BCSI-D). Participants with suspected dementia were those who were screened positive on the BCSI-D. Results: The prevalence of suspected dementia in older primary healthcare adults was 26.8%. Factors significantly associated with suspected dementia were female sex (OR = 1.95, P < 0.001), age-group of 75+ (OR = 1.68, P = 0.004), poor financial status (OR = 4.79, P < 0.001), rural residence (OR = 1.47, P = 0.032), no regular physical exercise (OR = 1.74, P = 0.002), and stroke and other cerebrovascular diseases (OR = 1.97, P = 0.015). Conclusions: Chinese older adults receiving primary healthcare are at high risk of suspected dementia. Screening and intervention efforts for dementia in primary healthcare settings may be more useful to target older adults who are women, are 75 years and above, have poor economic status, are rural residents, have no exercise habit, and suffer from cerebrovascular diseases.

Depressive disorders in older Chinese adults with essential hypertension: A classification tree analysis.

Background: Although there has been accumulating evidence on the elevated risk of depression in hypertensive patients, data regarding depressive disorders in older adults with hypertension and the interplay between factors associated with depression in this population are very limited. Disentangling the mutual influences between factors may help illuminate the pathways involved in the pathogenesis of the comorbidity of depression in hypertension. This study investigated the prevalence of depressive disorders in older Chinese adults with hypertension and examined major correlates of depressive disorders and the interactions between correlates by using classification tree analysis (CTA). Methods: In total, 374 older adults with essential hypertension were enrolled from seven urban and six rural primary care centers in Wuhan, China, and interviewed with the Chinese Mini-international Neuropsychiatric Interview 5.0. Family relationship and feelings of loneliness were assessed with standardized questions. A checklist was used to assess the presence of six major medical conditions: diabetes mellitus, heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, chronic gastric ulcer, and arthritis. Results: The 1-month prevalence rate of depressive disorders was 25.7%. The CTA model identified four major correlates of depressive disorders: loneliness was the most salient, followed by arthritis, family relationship, and heart disease. There were statistically significant interactions between loneliness and arthritis, loneliness and family relationship, and arthritis and heart disease. Conclusion: Over one out of every four older Chinese adults with hypertension suffer from depressive disorders. Collaborative multidisciplinary management services are needed to reduce the burden of depression in hypertensive older adults, which may include social work outreach services to promote family relationship, mental health services to relive loneliness, and primary care services to manage arthritis and heart disease.

Prevalence and correlates of suicidal ideation among older adults attending primary care clinics in Wuhan, China: A multicenter cross-sectional study.

Background: Primary care represents an ideal setting for screening for and managing suicidal older adults but the clinical epidemiology of suicidal ideation in Chinese older primary care patients remains unclear. This study investigated the prevalence and correlates of suicidal ideation in older Chinese adults receiving primary care. Methods: This multicenter cross-sectional survey included a total of 769 older adults (≥65 years) from seven urban and six rural primary care clinics in Wuhan, China. The presence of depressive symptoms and suicidal ideation was assessed with the Geriatric Depression Scale and a single-item question "In the past 12 months, did you think about ending your life?," respectively. Results: The 12-month prevalence of suicidal ideation in older primary care patients was 16.6%. Significant correlates of suicidal ideation were poor economic status (vs. good, OR = 2.80, P = 0.008), heart disease (OR = 2.48, P = 0.005), chronic gastric ulcer (OR = 3.55, P = 0.012), arthritis (OR = 2.10, P = 0.042), and depressive symptoms (OR = 11.29, P < 0.001). Conclusions: Suicidal ideation is common among older adults attending Chinese primary care clinics. It is necessary to integrate psychological crisis intervention into primary care to prevent late-life suicide.

Machine learning algorithms' accuracy in predicting kidney disease progression: a systematic review and meta-analysis.

BACKGROUND: Kidney disease progression rates vary among patients. Rapid and accurate prediction of kidney disease outcomes is crucial for disease management. In recent years, various prediction models using Machine Learning (ML) algorithms have been established in nephrology. However, their accuracy have been inconsistent. Therefore, we conducted a systematic review and meta-analysis to investigate the diagnostic accuracy of ML algorithms for kidney disease progression. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Chinese Biomedicine Literature Database, Chinese National Knowledge Infrastructure, Wanfang Database, and the VIP Database for diagnostic studies on ML algorithms' accuracy in predicting kidney disease prognosis, from the establishment of these databases until October 2020. Two investigators independently evaluate study quality by QUADAS-2 tool and extracted data from single ML algorithm for data synthesis using the bivariate model and the hierarchical summary receiver operating characteristic (HSROC) model. RESULTS: Fifteen studies were left after screening, only 6 studies were eligible for data synthesis. The sample size of these 6 studies was 12,534, and the kidney disease types could be divided into chronic kidney disease (CKD) and Immunoglobulin A Nephropathy, with 5 articles using end-stage renal diseases occurrence as the primary outcome. The main results indicated that the area under curve (AUC) of the HSROC was 0.87 (0.84-0.90) and ML algorithm exhibited a strong specificity, 95% confidence interval and heterogeneity (I2) of (0.87, 0.84-0.90, [I2 99.0%]) and a weak sensitivity of (0.68, 0.58-0.77, [I2 99.7%]) in predicting kidney disease deterioration. And the the results of subgroup analysis indicated that ML algorithm's AUC for predicting CKD prognosis was 0.82 (0.79-0.85), with the pool sensitivity of (0.64, 0.49-0.77, [I2 99.20%]) and pool specificity of (0.84, 0.74-0.91, [I2 99.84%]). The ML algorithm's AUC for predicting IgA nephropathy prognosis was 0.78 (0.74-0.81), with the pool sensitivity of (0.74, 0.71-0.77, [I2 7.10%]) and pool specificity of (0.93, 0.91-0.95, [I2 83.92%]). CONCLUSION: Taking advantage of big data, ML algorithm-based prediction models have high accuracy in predicting kidney disease progression, we recommend ML algorithms as an auxiliary tool for clinicians to determine proper treatment and disease management strategies.

Review of Digital Economy Research in China: A Framework Analysis Based on Bibliometrics.

This article combs the present situation and future development trend of digital economy research in China by means of literature measurement. On the one hand, China's digital economy presents a framework system of industrial digitization, digital industrialization, digital governance, and data value. On the other hand, digital economics has gradually become a dominant science and is constantly challenging the traditional economic research framework. Data are no longer the traditional data, and the data-driven economic and social innovation development model is the future trend. Data privacy, data protection, data ethics, data assets, and so on will become the focus of academic research.