Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial.

BACKGROUND: Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP. METHODS: This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600). FINDINGS: Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed. INTERPRETATION: This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients. FUNDING: Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

WeChat usage and preservation of cognitive functions in middle-aged and older Chinese adults: indications from a nationally representative survey, 2018-2020.

PURPOSE: To investigate the associations between the most popular social media platform WeChat usage and cognitive performance among the middle-aged and older Chinese population using data from a nationally representative survey. METHODS: In total, 17,472 participants (≥ 45 years old) from the China Health and Retirement Longitudinal Study (CHARLS, Wave 4, 2018) were analyzed. Cognitive performance including episodic memory and executive function was assessed using Mini-Mental Status Examination (MMSE). Other confounding variables included socio-economic characteristics, medical status, and lifestyle-related information. Multiple linear regression models were used to test the association between cognitive performance and WeChat usage by introducing covariates hierarchically. Subgroup analyses of age and gender were conducted to estimate the robustness of the primary findings. RESULTS: After adjusting for multiple confounders across all linear models, WeChat usage is significantly associated with executive function, episodic memory, and global cognitive performance (all p values<0.05). Such results remained robust in subgroup analyses, stratified by age and gender, and also verified according to longitudinal analyses. Compared to 'Chat-only' users who only used WeChat for online interpersonal communication, further usage of WeChat functions such as using 'Moments' appeared to be significantly associated with better cognitive performance, especially for episodic memory. CONCLUSION: Social media usage is significantly and positively associated with better cognitive performance among the middle-aged and older Chinese population. Along with point-to-point messaging, using 'Moments' and extended social media platform functions may correlate to better cognitive performance.

Novel anthropometric indices are superior adiposity indexes to portend visual impairment in middle-aged and older Chinese population.

OBJECTIVE: To investigate differential associations of traditional and novel adiposity indices with visual impairment (VI) in the middle-aged and older Chinese population. METHODS AND ANALYSIS: Based on the China Health and Retirement Longitudinal Study, 7750 Chinese older adults aged over 45 were included at baseline 2011, and 4133 participants who accomplished all three interviews from 2011 to 2015 were adapted for longitudinal analyses. We enrolled six adiposity indices, including the body mass index (BMI), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI), a body shape index (ABSI), body roundness index (BRI) and conicity index (ConI). Visual status and other covariates included sociodemographic characteristics, medical supports and lifestyle-related factors. Cross-sectional correlations were assessed using univariate and multivariate logistic regression analyses. For longitudinal analysis, generalised linear models with generalised estimating equations were used to determine the association between time-varying adiposity and visual status. RESULTS: Higher levels of WHtR/WWI/ABSI/BRI/ConI were significantly associated with an increased prevalence of VI, whereas a higher BMI was associated with a decreased prevalence of VI. Only WWI was significantly related to the prevalence of VI after adjustment for multiple confounders in both cross-sectional and longitudinal analyses (all p values <0.05). The multivariable-adjusted OR (95% CI) of VI associated with the highest (vs lowest) quintile of WWI was 1.900 (1.407 to 2.565). CONCLUSION: WWI is a reliable alternative adiposity index that exhibits a dose-response association with the prevalence of VI in the Chinese population. The WWI-VI correlation may eliminate the obesity paradox in the ophthalmic epidemiological area and indicate the detrimental impact of changes in body composition on VI.

Endoscopic Cryoablation Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

BACKGROUND AND OBJECTIVE: Cryoablation is a traditional antitumor therapy with good prospects for development. The efficacy of endoscopic management as a kidney-sparing surgery for high-risk upper tract urothelial carcinoma (UTUC) remains controversial. Our aim was to evaluate the impact of endoscopic cryoablation (ECA) versus radical nephroureterectomy (RNU) on survival outcomes, renal function, and complications. METHODS: We retrospectively analyzed data for 116 patients with newly diagnosed high-risk UTUC who underwent either ECA (n = 13) or RNU (n = 103) from March 25, 2019 to December 8, 2021. Propensity score matching (1:4) using the nearest neighbor method was performed before analysis. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), intravesical recurrence-free survival (RFS), the change in renal function, and treatment-emergent adverse events (TEAEs). KEY FINDINGS AND LIMITATIONS: At median follow-up of 28.2 mo for the ECA group and 27.6 mo for the RNU group, 2-yr OS (82% vs 84%), PFS (73% vs 71%), and intravesical RFS (81% vs 83%) rates after matching did not significantly differ. A decline in renal function was observed after RNU, but not after ECA. Five (41.7%) patients in the ECA group reported six TEAEs, and 17 patients (35.4%) in the RNU group reported 20 TEAEs. CONCLUSIONS AND CLINICAL IMPLICATIONS: In comparison to RNU, ECA for UTUC resulted in noninferior oncological outcomes and superior preservation of renal function. PATIENT SUMMARY: Our study suggests that a treatment called endoscopic cryoablation for high-risk cancer in the upper urinary tract can help in preserving kidney function, with similar survival outcomes to those after more extensive surgery. This option can be considered for selected patients with a strong preference for kidney preservation.

Association of socioeconomic position with sensory impairment among Chinese population: a nationally representative cohort and Mendelian randomization study.

Aims: To investigate the association between socioeconomic position (SEP) and sensory impairments (SIs). Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS) (2015). Logistic regressions estimated the odds ratio for associations of SEP with SIs. In addition, Mendelian randomization (MR) analysis was conducted to assess the causal relationship between them with the inverse variance weighting (IVW) estimator. MR-Egger, simple median, weighted median, maximum likelihood, and robust adjusted profile score were employed for sensitivity analyses. Results: In the observational survey, we enrolled 19,690 individuals aged 45 and above. SEP was negatively associated with SIs. Adjusted odds of vision impairment were higher for illiterate (1.50; 95%CI: 1.19, 1.91), less than elementary school diploma (1.76; 95%CI: 1.39, 2.25), middle school diploma (1.53; 95%CI: 1.21, 1.93) and lower income (all p < 0.001). The odds of hearing impairment were significantly higher for people with less than a high school diploma than those with a college degree or higher diploma, for agricultural workers than non-agricultural workers, and for people in low-income families (p < 0.01). The MR analysis also showed that occupation was associated with HI (1.04, 95%CI: 1.01, 1.09, p < 0.05) using IVW. Conclusion: We found that both observational and causal evidence supports the theory that SEP can result in SIs and that timely discovery, targeted management, and education can prevent SIs among middle-aged and older adults.

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study.

BACKGROUND: The blood-based biomarkers are approaching the clinical practice of Alzheimer's disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. METHODS: Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted. RESULTS: The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001). CONCLUSIONS: Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.

A new triboelectric nanogenerator based on a multi-material stacking structure achieves efficient power conversion from discrete mechanical movement.

Due to its invaluable potential in discrete mechanical energy collection, TENG (triboelectric nanogenerator) is considered to satisfy the power requirements of intelligent electronic devices and drive the development of the Internet of Things (IoT). Nowadays, the promotion of TENGs has been hindered due to the limitation of their output performance and service life. Herein, a brand new triboelectric nanogenerator based on a multi-material stacking structure is proposed. By stacking various triboelectric materials in a specific order, a special charge balance state could be achieved inside the system such that the conductive layer generates more induced charges, and the output performance is significantly enhanced. Besides, due to the usage of the electropositive elastomer PU (polyurethane sponge), the design also effectively alleviates abrasion on the contact surface and adjusts its own output according to different compression environments. The experimental results show that the stacked PTFE/FKM/PU TENG (PFP-TENG) presents a more than 50% increase in transferred charge and almost 5 times the current output compared with the general contact-separation type TENG. When connected to the application circuit, the maximum output power reached 10.2 W m-2 and 145.2 W m-3, and more than 1400 LEDs could be easily lit. Finally, the PFP-TENG was also used to collect mechanical energy from simple motion and realize considerable power generation. This study not only provides new ideas for the design of TENGs by reasoning the theoretical model but also presents improved output performance, thus exemplifying the strong potential of this design in developing a power-generation device that can collect discrete mechanical energy.

Pancreatic Cancer: An Exocrine Tumor with Endocrine Characteristics.

OBJECTIVE: To examine the characteristics of pancreatic cancer patients with long-term survival. BACKGROUND: Although pancreatic cancer is a highly lethal malignancy, a minority of patients experience long-term survival. The characteristics of these patients remain largely unidentified. METHODS: An indolent subgroup was established using carbohydrate antigen 19-9 (CA19-9), which is the best-validated biomarker for pancreatic cancer. Of 1558 patients, 13.9% were included in the CA19-9-normal (≤ 37 U/mL) subgroup. RESULTS: A normal A19-9 level was an independent variable for overall survival (median survival, 18.1 vs. 9.7 months, hazard ratio = 0.53, P < 0.001). The 5-year survival of patients with stage IV CA19-9-normal cancer was higher than that of patients with stage I-IV CA19-9-high cancer (22.4% vs. 6.8%, P = 0.034). The CA19-9-normal subgroup exhibited reduced levels of circulating glucose (P < 0.001) and increased expression of insulin (P < 0.001) compared with the CA19-9-high subgroup. Glucose was a substrate for CA19-9 biosynthesis through the hexosamine biosynthesis pathway. In addition, in pancreatic cancer animal models of diabetes, glucose control decreased CA19-9 levels and improved overall survival. In a clinical trial (NCT05306028) of patients before undergoing major anticancer treatments, glucose control decreased CA19-9 levels in 90.9% of the patients. CONCLUSIONS: CA19-9-normal pancreatic cancer is a strikingly indolent subgroup with low glucose and high insulin. Glucose control is a promising therapeutic strategy for pancreatic cancer.

Phosphorus balance calculator: an individualized tool for treatment of hyperphosphatemia in hemodialysis patients.

BACKGROUND AND HYPOTHESIS: Lack of evaluations of the dietary phosphorus and dialysis phosphorus removal in daily clinical practice are the common obstacle to assess phosphorus balance and control phosphorus in hemodialysis patients. We aimed to investigate whether the individualized therapy using phosphorus balance calculator improves phosphorus control. METHODS: A randomized, open-label, multicenter, 4-week clinical trial was conducted. 119 maintenance hemodialysis patients aged 18 to 85 years old and with serum phosphorus level higher than 1.45mmol/l from 3 university teaching hospitals in Shanghai were enrolled. Patients were randomized in a 1:1 ratio to individualized therapy (n=60), or conventional therapy (n=59). The primary outcome was the serum phosphorus concentration after 4-week treatment. Secondary outcomes included the serum calcium and parathyroid hormone (PTH) concentrations, changes in serum phosphorus, calcium and PTH concentrations, and the proportion of patients achieving target ranges of serum phosphorus, calcium and PTH after 4-week treatment. RESULTS: Among 119 randomized participants (mean age, 62 years; 68 male[57%]), 116 completed the trial. By using the phosphorus balance calculator, the individualized group achieved a better phosphorus balance state, significantly reduced the serum phosphorus (1.62±0.45mmol/l versus 1.85±0.45 mmol/l, P=0.006), increased the proportions of patients achieving target serum phosphorus range (41% versus 18%, P=0.006), and had greater adjusted mean difference in change in serum phosphorus over the 4 weeks (-0.47 versus -0.23mmol/l, P=0.010) when compared to conventional therapy. No significant changes were observed in serum calcium and PTH levels, the proportion of patients achieving target serum calcium or PTH levels, and adjusted mean difference of serum calcium and PTH levels over the treatment period. CONCLUSION: Phosphorus balance calculator was proved to improve serum phosphorus control in patients undergoing maintenance hemodialysis, offering a new tool for managing hyperphosphatemia.

Progress in diagnosis and treatment of difficult-to-treat asthma in children.

At present, medications containing inhaled corticosteroids (ICS-containing) are the keystones of asthma treatment. The majority of asthmatic children can significantly improve clinical outcomes with little worsening by standardized inhaled glucocorticoid treatment, but there is still a small proportion of children who are unable to achieve good symptom control even after the maximum standardized treatment, known as 'children with difficult-to-treat asthma (DA)'. The high heterogeneity of DA makes therapy challenging and expensive, which poses a serious risk to children's health and makes it extremely difficult for clinical physicians to accurately identify and treat children with DA. This article reviews the definition, evaluation, and treatment of this asthma in order to provide a reference for optimal clinical decision-making.

Non-operative treatment strategy for appendiceal abscess in children under 3 years old: a retrospective observational study.

Background: There are few studies on appendiceal abscess with appendicolith in children under 3 years old. This study aims to explore the success rate of non-surgical treatment of appendiceal abscess and assess the potential influence of an appendicolith on non-surgical treatment outcomes in children under 3 years old. Methods: The clinical data of children under 3 years old who were diagnosed with appendiceal abscess at the Wuhan Children's Hospital, China, from February 2013 to May 2020 were collected. According to the findings of ultrasonography and CT imaging, they were divided into two groups, namely, the appendicolith group and the non-appendicolith group. Results: A total of 94 children with appendiceal abscess were identified, meeting the specified study criteria, and categorized into two groups, namely, the appendicolith group (n = 51, 54.3%) and the non-appendicolith group (n = 43, 45.7%). Non-surgical treatment was unsuccessful in six out of the 94 children, yielding an overall success rate of 93.6% for non-surgical management of appendiceal abscess in children under 3 years old. The success rate for non-surgical treatment in the appendicolith subgroup was 90.2%, whereas that for the non-appendicolith subgroup was 97.7%. No statistically significant distinction was observed between the two groups (P = 0.292). Likewise, there were no significant differences in gender, age, duration of symptoms, fever, vomiting, diarrhea, rebound pain, white blood cell count, C-reactive protein level, and abscess cross-sectional area between the appendicolith group and the non-appendicolith group. However, there is a statistical difference in tenderness in the right lower abdomen. Conclusion: Non-surgical treatment of appendiceal abscess has a high success rate and can be considered an effective treatment strategy. In pediatric patients under 3 years old without evidence of complete intestinal obstruction or diffuse peritonitis, non-surgical treatment may be considered for appendiceal abscess.

Corrigendum: The prevalence, incidence, and persistence of self-reported visual impairment among Chinese population with diabetes mellitus: evaluation from a nationally representative survey, 2015-2018.

[This corrects the article DOI: 10.3389/fpubh.2023.978457.].

Association of preoperative aneurysmal wall enhancement with relief of chronic headache after surgical clipping of unruptured intracranial aneurysms.

OBJECTIVE: To investigate the association between chronic headache outcome and aneurysmal wall enhancement (AWE) on high-resolution vessel wall imaging (HR-VWI) in patients with unruptured intracranial aneurysms (UIAs) who underwent microsurgical clipping. METHODS: Two hundred seventy-four UIA patients were retrospectively analyzed. Patients were grouped according to presence of AWE. AWE was subclassified as focal or uniform. Clinical and imaging data were recorded. Headache was evaluated using the 10-point numerical rating scale and Headache Impact Test-6 before and 6 months after surgery. RESULTS: The proportions of patients reporting chronic headache in the no AWE, focal wall enhancement (FWE), and uniform wall enhancement (UWE) groups were 5.7%, 24.8%, and 41.8%, respectively. All patients in the UWE group who reported headache before surgery experienced headache improvement after surgery. Decrease in headache severity was greater in the UWE group than in the FWE group. Multivariate binary logistic regression showed that FWE (odds ratio (OR) 0.490; 95% confidence interval (CI), 0.262-0.917; p = 0.026) and small intraluminal thrombus (OR 0.336; 95% CI, 0.142-0.795; p = 0.013) were independent factors protective against preoperative headache. FWE (OR 0.377; 95% CI, 0.195-0.728; p = 0.004) and small intraluminal thrombus (OR 0.235; 95% CI, 0.088-0.630; p = 0.004) were independent predictors of no headache relief after surgery. CONCLUSIONS: AWE on HR-VWI is associated with relief of chronic headache after surgical clipping in patients with UIAs. Incidence of chronic headache was highest in patients exhibiting UWE. These patients also experienced the greatest improvement in headache after surgical clipping. CLINICAL RELEVANCE STATEMENT: This study revealed that high-resolution vessel wall imaging can demonstrate aneurysmal wall plaque and intraluminal thrombus, which may be prognostic imaging markers for chronic headache in patients with unruptured intracranial aneurysms. KEY POINTS: • Aneurysmal wall enhancement may be associated with chronic headache. • Incidence of chronic headache was highest in patients with aneurysms exhibiting uniform wall enhancement. • Patients with aneurysms exhibiting uniform wall enhancement experienced the greatest improvement in headache after clipping.

Prevalence of post-traumatic stress disorder among residents of Shanghai standardized training programs during the COVID-19 outbreak: a cross-sectional study.

Background: The COVID-19 pandemic may have increased the prevalence of psychiatric disorders, such as anxiety, depressive disorders, and post-traumatic stress disorder (PTSD), among healthcare workers. Purpose: This study aims to investigate the prevalence of PTSD and its risk factors among residents in the standardized residency training programs (SRTPs) in Shanghai during the COVID-19 outbreak. Participants and methods: An online cross-sectional survey was conducted between December 17, 2021, and January 7, 2022, among SRPT residents from 15 hospitals in Shanghai, China. Questionnaires comprising general information, medical-related traumatic event experiences, the PTSD Checklist (PCL-5), and the perceived social support scale (PSSS) were distributed to the participants using the online Questionnaire Star electronic system. Results: We included 835 valid responses for the analysis. In total, 654 residents (78.3%) had experienced at least one traumatic event, and 278 residents (33.3%) were found to have PTSD symptoms. The age 26-30 years old, female sex, and increased resident working hours were identified as the risk factors for PTSD (p < 0.05), and perceived social support had a significant negative association with PTSD (p < 0.05). Conclusion: During the COVID-19 pandemic, there was a high prevalence of PTSD among SRTPs residents in Shanghai. The age 26-30 years old, female sex, and increased resident working hours were identified as risk factors for PTSD, while perceived social support was identified as a protective factor against PTSD. The present findings can be applied in STRPs management and provide useful information for designing special interventions and protocols for SRTPs residents.

Microbial signature of intestine in children with allergic rhinitis.

Introduction: Previous studies have found that unique patterns of gut microbial colonization in infancy associated with the development of allergic diseases. However, there is no research on the gut microbiota characteristics of AR children in Chinese Mainland. Objective: To investigate the changes of gut microbial of AR children in Chinese Mainland and evaluate the correlation between gut microbial and clinical indexes. Methods: In this clinical study, fecal samples from 24 AR children and 25 healthy control children (HCs) were comparative via next generation sequencing of the V3-V4 regions of the 16S rRNA gene. Analyzed the relationship between clinical features and gut microbial using Spearman correlation. Results: Compared to HCs, AR children showed significant decreases in Shannon index and significant increases in Simpson index at both the family and genera levels (all p < 0.05). In terms of bacterial composition, at the phylum level, AR children had higher abundance of Bacteroidetes than that in the HCs group (p < 0.05) and were significantly positively correlated with TNSS (p < 0.05). At the family level, AR children had higher abundance of Prevotellaceae and Enterobacteriaceae higher than that in the HCs group (all p < 0.05) and had a significantly positive correlation with TNSS, eosinophils (EOS) and total immunoglobulin E (tIgE) (all p < 0.05). At the genus level, reduced abundance of Agathobacter, Parasutterella, Roseburia and Subdoligranulum were also observed in the AR cohorts compared to HCs (all p < 0.05) and significantly negatively associated with TNSS, EOS, tIgE, QOL, and FeNO (all p < 0.05). Conclusion: AR children in Chinese Mainland were characterized by reduced microbial diversity and distinguished microbial characteristics in comparison with HCs. The observations of this study offer proof that distinctive gut microbiota profiles were present in AR children and necessitate further investigation in the form of mechanistic studies.

The prevalence, incidence, and persistence of self-reported visual impairment among Chinese population with diabetes mellitus: evaluation from a nationally representative survey, 2015-2018.

Aims: Our aim was to investigate the prevalence, incidence, and persistence of visual impairment (VI) and their correlates among the Chinese population with diabetes mellitus (DM) over 3 years. Materials and methods: The China Health and Retirement Longitudinal Survey is the first nationally representative longitudinal survey of the Chinese population. A cross-sectional analysis of prevalent VI in 2015 consisted of 2,173 participants with DM. A longitudinal observation of incident and persistent VI consisted of 1,633 participants from 2015 to 2018. Risk factors of VI were identified via univariate and multivariate logistic regression analyses. Results: Among our study population with DM, 11.8% reported VI in 2015, 4.5% had persistent VI from 2015 to 2018, and 8.9% developed VI in 2018. Factors identified to be correlated to VI (p < 0.05) were older age, being a woman, lower educational attainment, living in a rural area, application of DM medication and non-pharmacological treatment, receiving DM-related tests, use of spectacles, and poorer health status. Conclusion: This most recent national data provides a baseline for future public health initiatives on VI among the Chinese population with DM. With multiple risk factors identified, these could provide concurrent targets for various public health strategies and interventions with the aim of reducing the burden of VI among the population with DM in China.

Best medical management versus intravenous thrombolysis for mild non-disabling ischemic stroke: A prospective noninferiority registry study.

OBJECTIVES: The efficacy and safety of intravenous thrombolysis uncertain in patients with non-disabling mild ischemic stroke. Our aim was to investigate whether best medical management only is noninferior to intravenous thrombolysis plus best medical management therapy for achieving favorable functional outcome at 90 days. MATERIALS AND METHODS: In a prospective acute ischemic stroke registry from 2018 through 2020, 314 non-disabling mild ischemic stroke patients received best medical management only and 638 underwent intravenous thrombolysis plus best medical management. The primary outcome was modified Rankin Scale ≤1 at Day 90. The noninferiority margin was -5%. Secondary outcomes of hemorrhagic transformation, early neurologic deterioration and mortality were also evaluated. RESULTS: The best medical management only was noninferior to the combined therapy of intravenous thrombolysis and best medical management with regard to the primary outcome (unadjusted risk difference, 1.16%; 95% CI, -3.48% âˆ¼ 5.8%; p = 0.0046 for noninferiority; adjusted risk difference, 3.01%; 95% CI, -3.39% âˆ¼ 9.41%). After propensity score matching, p < 0.0001 for noninferiority. RD, 4.03%; 95% CI, -1.59% âˆ¼ 9.69%. p < 0.0001 for noninferiority. Adjusted RD, 5.23%; 95% CI, -1.88% âˆ¼ 9.97%. The occurrence of hemorrhagic transformation was significantly increased in the group of combination therapy (OR, 4.26; 95% CI, 1.30 to 13.99; p = 0.008), while no significant difference was detected in early neurologic deterioration (OR, 1.11; 95% CI, 0.49-2.52; p = 0.808) and mortality (OR, 0.57; 95% CI, 0.20 to 1.69; p = 0.214) between groups. CONCLUSIONS: In the present study, we found the best medical management only was noninferior to the combination therapy of intravenous thrombolysis plus best medical management for non-disabling mild ischemic stroke within 4.5 h after onset. Best medical management may be a treatment of choice for non-disabling mild ischemic stroke patients. Further randomized controlled studies are warranted.

Diabetes remission in drug-naïve patients with type 2 diabetes after dorzagliatin treatment: A prospective cohort study.

AIM: To investigate the post-treatment effect of dorzagliatin in drug-naïve patients with type 2 diabetes (T2D) regarding the achievement of stable glycaemic control and drug-free diabetes remission. MATERIALS AND METHODS: Patients who completed dorzagliatin treatment in the SEED trial and achieved stable glycaemic control were enrolled in this 52-week study without any antidiabetic medication. The primary endpoint was the diabetes remission probability at week 52 using the Kaplan-Meier method. The potential factors that contribute to stable glycaemic control and diabetes remission based on the characteristics of patients before and after treatment with dorzagliatin were analysed. A post hoc sensitivity analysis of diabetes remission probability using the American Diabetes Association (ADA) definition was conducted. RESULTS: The Kaplan-Meier remission probability was 65.2% (95% CI: 52.0%, 75.6%) at week 52. Based on the ADA definition, the remission probability was 52.0% (95% CI: 31.2%, 69.2%) at week 12. The significant improvements in the insulin secretion index ΔC30/ΔG30 (41.46 ± 77.68, P = .0238), disposition index (1.22 ± 1.65, P = .0030), and steady-state variables of HOMA2-ß (11.49 ± 14.58, P < .0001) and HOMA2-IR (-0.16 ± 0.36, P = .0130) during the SEED trial were important factors in achieving drug-free remission. A significant improvement in time in range (TIR), a measure of glucose homeostasis, in the SEED trial from 60% to more than 80% (estimated treatment difference, 23.8%; 95% CI: 7.3%, 40.2%; P = .0084) was observed. CONCLUSIONS: In drug-naïve patients with T2D, dorzagliatin treatment leads to stable glycaemic control and drug-free diabetes remission. Improvements in ß-cell function and TIR in these patients are important contributors to diabetes remission.

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. Patients who died before follow-up; patients for whom follow-up would be difficult because of psychotic disorders, dementia, or readmission to hospital; those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism; those who declined to participate; those who could not be contacted; and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5-6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received SARS-CoV-2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 years (IQR 47·0-65·0) and 897 (52%) were male and 836 (48%) were female. The follow-up study was done from June 16 to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 days (175·0-199·0). Fatigue or muscle weakness (52%, 855 of 1654) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1616) of patients. The proportions of 6-min walking distance less than the lower limit of the normal range were 17% for those at severity scale 3, 13% for severity scale 4, and 28% for severity scale 5-6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5-6, and median CT scores were 3·0 (IQR 2·0-5·0) for severity scale 3, 4·0 (3·0-5·0) for scale 4, and 5·0 (4·0-6·0) for scale 5-6. After multivariable adjustment, patients showed an odds ratio (OR) of 1·61 (95% CI 0·80-3·25) for scale 4 versus scale 3 and 4·60 (1·85-11·48) for scale 5-6 versus scale 3 for diffusion impairment; OR 0·88 (0·66-1·17) for scale 4 versus scale 3 and OR 1·76 (1·05-2·96) for scale 5-6 versus scale 3 for anxiety or depression, and OR 0·87 (0·68-1·11) for scale 4 versus scale 3 and 2·75 (1·61-4·69) for scale 5-6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with an estimated glomerular filtration rate (eGFR) of 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Sensory impairments and subjective well-being status in middle-aged and older Chinese population: Cross-sectional and longitudinal analyses of a nationally representative survey.

Purpose: To investigate the impacts of sensory impairments (SIs) including single vision impairment (SVI), single hearing impairment (SHI) and dual sensory impairment (DSI) on subjective wellbeing measurements including life expectancy (LE), life satisfaction (LS) and self-rated health (SRH) in middle-aged and older Chinese population. Methods: We obtained data from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 9,293 Chinese middle-aged and older adults aging over 45 were included at baseline 2011 in this study, and 3,932 participants who accomplished all 4 interviews from 2011 to 2018 were adapted for longitudinal analyses. Sensory status and subjective wellbeing measurements were collected. Other covariates included socio-demographic characteristics, medical condition and lifestyle-related factors. The impacts of baseline sensory status on LE, LS and SRH were assessed using univariate and multivariate logistic regression analyses. A linear regression analysis with generalized estimating equations (GEE) was used to assess the association between time-varying sensory statuses with LE, LS and SRH over 8 years after being adjusted with multi-confounding factors. Results: Participants with SIs had significantly lower level of LE, LS, and SRH, compared to those who were free of SI. All kinds of SIs were significantly associated with LE, LS, and SRH according to cross-sectional data. The correlations between SIs and LE or SRH over 8 years were also noticed. However, only SHI and DSI were found to be significantly associated with LS according to longitudinal data (all p values < 0.05). Conclusion: Sensory impairments had explicitly detrimental effects on subjective wellbeing status over time among middle-aged and older Chinese population.