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Previous studies showed that the COVID-19 outbreak increased the levels of depression and anxiety in heterogeneous populations. However, none has explored the prevalence and correlates of depression and anxiety among Chinese international students studying in US colleges during the pandemic. This study examines the prevalence of depression and anxiety among Chinese international students enrolled in US universities during the COVID-19 pandemic and identifies the associated factors, including habits, social and psychological support, sleep quality, and remote learning. Between June and July 2020, we conducted a cross-sectional study through Wenjuanxing, a web-based survey platform. Participants were recruited with snowball sampling through 21 Chinese international student associations in US universities. The survey consisted of demographic questions, the Social Support Rating Scale (SSRS), the Insomnia Severity Index (ISI), the Patient Health Questionnaire-9 (PHQ-9), the General Anxiety Disorder-7 (GAD-7), and self-constructed questions on academic performance, financial concerns, use of social media, physical exercise, and psychological support. Cut-off scores of 10 were used for both PHQ-9 and GAD-7 to determine the binary outcomes of depression and anxiety, respectively. Bivariant analyses and multivariable logistic regression analyses were performed to identify the associated factors. Among 1881 participants, we found a prevalence of depression (PHQ-9 score⩾ 10) at 24.5% and that of anxiety (GAD-7 score⩾ 10) at 20.7%. A higher risk of depression was associated with recent exposure to traumatic events, agreement to pandemic's negative impacts on financial status, agreement and strong agreement to the negative impacts of remote learning on personal relationships, and a higher ISI score. A lower risk of depression was associated with disagreement to the negative impacts of remote learning on academic performance and future careers, strong willingness to seek professional help with emotional issues, and a higher SSRS score. In addition, a higher risk of anxiety was associated with recent exposure to traumatic events, a lot of workloads, often staying up for online classes, agreement and strong agreement to the negative impacts of remote learning on personal relationships, and a higher ISI score. A lower risk of anxiety was associated with the willingness and strong willingness to seek professional help with emotional issues, and a higher SSRS score. This study showed a high prevalence of depression and anxiety among Chinese international students studying in US colleges during the COVID-19 pandemic. Multiple correlates-including recent exposure to traumatic events, pandemic-related financial concerns, workload, social support, remote learning, willingness to seek professional help, and sleep quality-were identified. It is critical for future studies to further investigate this student population and for universities to provide more flexible learning options and more access to psychological services.

Background Previous studies showed that the COVID-19 outbreak increased the levels of depression and anxiety in heterogeneous populations. However, none has explored the prevalence and correlates of depression and anxiety among Chinese international students studying in US colleges during the pandemic. Objective This study examines the prevalence of depression and anxiety among Chinese international students enrolled in US universities during the COVID-19 pandemic and identifies the associated factors, including habits, social and psychological support, sleep quality, and remote learning. Methods Between June and July 2020, we conducted a cross-sectional study through Wenjuanxing, a web-based survey platform. Participants were recruited with snowball sampling through 21 Chinese international student associations in US universities. The survey consisted of demographic questions, the Social Support Rating Scale (SSRS), the Insomnia Severity Index (ISI), the Patient Health Questionnaire-9 (PHQ-9), the General Anxiety Disorder-7 (GAD-7), and self-constructed questions on academic performance, financial concerns, use of social media, physical exercise, and psychological support. Cut-off scores of 10 were used for both PHQ-9 and GAD-7 to determine the binary outcomes of depression and anxiety, respectively. Bivariant analyses and multivariable logistic regression analyses were performed to identify the associated factors. Results Among 1881 participants, we found a prevalence of depression (PHQ-9 score⩾ 10) at 24.5% and that of anxiety (GAD-7 score⩾ 10) at 20.7%. A higher risk of depression was associated with recent exposure to traumatic events, agreement to pandemic’s negative impacts on financial status, agreement and strong agreement to the negative impacts of remote learning on personal relationships, and a higher ISI score. A lower risk of depression was associated with disagreement to the negative impacts of remote learning on academic performance and future careers, strong willingness to seek professional help with emotional issues, and a higher SSRS score. In addition, a higher risk of anxiety was associated with recent exposure to traumatic events, a lot of workloads, often staying up for online classes, agreement and strong agreement to the negative impacts of remote learning on personal relationships, and a higher ISI score. A lower risk of anxiety was associated with the willingness and strong willingness to seek professional help with emotional issues, and a higher SSRS score. Conclusion This study showed a high prevalence of depression and anxiety among Chinese international students studying in US colleges during the COVID-19 pandemic. Multiple correlates—including recent exposure to traumatic events, pandemic-related financial concerns, workload, social support, remote learning, willingness to seek professional help, and sleep quality—were identified. It is critical for future studies to further investigate this student population and for universities to provide more flexible learning options and more access to psychological services.

The rising demand for knowledge updates and technological innovations in China has made clinical placement teaching challenging. Reforms for innovative teaching models through pilot classes have shown to improve students' academic performance. This novel integration led to the announcement of healthcare collaboration in the Guangdong-Hong-Kong-Macao Greater Bay Area for projects within China's \"Global-Innovation-Hub\" zones. First Affiliated Hospital (FAH) of Sun Yat-sen University (SYSU) in Guangzhou and the Faculty of Medicine (FMD) of Macau University of Science & Technology (MUST) in Macau have developed an inaugural project for FMD/MUST medical students to perform pre-internships at FAH-SYSU. This study aimed to reflect on students' experiences with collaborative teaching and learning through medical curricular integration in the \"Global-Innovation-Hub\" zones designed by both institutions for developing integrated curriculum. FMD/MUST students attended medical clerkships at FAH-SYSU using a system-integrated curriculum in China's \"Global-Innovation-Hub\" zones, allowing different education systems at different locations. Post-clerkship surveys ranked teaching models in conjunction with written reflections in response to post-clerkship questionnaires for all participating students. The teaching models were defined by the way supervisors' interaction with students, and written reflections in response to the post-clerkship questionnaire were descriptively and semantically analysed. The top-ranked teaching models include first \"Student-led consultation under supervision in observers' chair with discussion\", second \"Observe consultation and discuss with the teacher in-between patients in observers' chair\" and third \"Student-led consultation under supervision in consultants' chair with discussion\". The post-clerkship questionnaires showed positive outcomes. This study demonstrates the successful delivery of collaborative teaching and learning through medical curricular integration in China's \"Global-Innovation-Hub\" zones. This integration enables the development of a consistent and student-preferred teaching model being introduced into clinical placement curriculum. The unique location of China's \"Global-Innovation-Hub\" zones in the Guangdong-Hong-Kong-Macao Greater Bay Area allows this integration to significantly improve students' clinical reasoning learning.

Sarcopenia is defined as a progressive and generalized skeletal muscle disorder characterized by the accelerated loss of muscle mass and function. Current studies have revealed the significant impact of some dietary factors on the development and progression of sarcopenia. However, these studies often focused on single nutrients but little had examined complete dietary strategies. Thus, comprehensive evaluations of diverse dietary factors in larger populations are crucial for effectively adjusting diets to delay sarcopenia progression, enhancing quality of life and independence in the elderly. We conducted a cross-sectional analysis to assess the potential correlation between various dietary factors and sarcopenia based on the population data from the UK Biobank. This analysis employed multivariate logistic regression models adjusted for different covariates (demographic data including age, sex, ethnics, etc., and potential confounders including smoking status, activity group, body mass index, etc.). Furthermore, to evaluate the robustness of our findings, we performed sub-analyses and calculated the Variance Inflation Factor. To investigate the causal influence of dietary factors on sarcopenia-related phenotypes, including low hand grip strength and appendicular lean mass (ALM), we conducted a Mendelian Randomization (MR) analysis. The analytic methods of MR were selected based on the outcomes of sensitivity analyses. In the cross-sectional analysis, a total of 211,027 participants were included in the final analysis, with a mean age of 56 years, comprising 104,271 females and 106,756 males. We identified significant correlations between the frequency and type of food intake and sarcopenia. For probable sarcopenia diagnosed by grip strength, a higher intake frequency of oily fish is negatively correlated with sarcopenia risk, whereas processed meat shows a positive correlation. Preference for FloraPro-Active/Benecol in spreads also relates to a reduced risk. Preliminary findings indicate correlations between tea (OR = 1.02,  < 0.01), coffee (OR = 1.02,  < 0.01), fresh fruit intake (OR = 1.01,  < 0.01), and probable sarcopenia. For confirmed sarcopenia diagnosed by grip strength and ALM, a higher intake frequency of processed meat could increase sarcopenia risk and preference for Bran cereal in cereal type and wholemeal or wholegrain in bread type also related to a reduced risk. The MR analysis revealed that coffee (ground coffee (OR = 3.44,  < 0.0035), instant coffee (OR = 2.69,  < 0.015), decaffeinated coffee (OR = 3.94,  < 0.0004)) intake significantly increased the risk of low grip strength, while water (OR = 1.06,  < 0.000398) and fruit (OR = 1.10,  < 0.0065) intake enhance ALM. Conversely, psychoactive drinks (OR = 0.91,  < 0.00001), alcohol (OR = 0.906,  < 0.0012), and decaffeinated coffee (OR = 0.65,  < 0.0047) decreased ALM. These results have undergone sensitivity analysis validation. Our analysis using UK Biobank data explored associations between dietary factors and sarcopenia. We found strong links between probable sarcopenia and the intake of oily fish, processed meat, lamb, and coffee, whereas processed meat remained significantly related with confirmed sarcopenia. Preference for specific foods, such as FloraPro-Active/Benecol spreads, Bran cereal and wholemeal or wholegrain bread were associated with reduced risk. MR confirmed the causal effects of coffee intake on low hand grip strength and ALM. Our study provides insights for dietary strategies in sarcopenia patients, though further research is needed to validate and explore these mechanisms.

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia’s severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia. Here, the authors provide evidence that SARS-CoV-2 N protein leads to autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inducing DNA damage and proteotoxic stress, eventually causing pneumonia. The small-molecule drug PJ34 or anastrozole alleviates N protein-induced pneumonia.

PurposeThe aim of this study was to investigate the expression levels of plasma miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p and their relationship to dexmedetomidine efficacy and adverse effects in pediatric patients.MethodsThe expression levels of miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p were measured by qRT-PCR in plasma of 133 pediatric patients receiving dexmedetomidine for preoperative sedation. We analyzed the relationship between miRNA abundance and dexmedetomidine response, including sedative effect and adverse effects, and assessed the predictive power of miRNAs for drug response.ResultsAmong 133 pediatric patients, 111 patients were dexmedetomidine responders (UMSS ≥ 2) and 22 patients were non-responders (UMSS < 2). We observed higher expression levels of miR-101-3p and miR-140-3p in dexmedetomidine responders compared with non-responders (P < 0.05, P < 0.0001). In contrast, there was no significant difference in the expression levels of miR-30a-5p and miR-141-3p between responders and non-responders (P > 0.05). The plasma levels of miR-101-3p and miR-30a-5p were markedly downregulated in patients who experienced hypotension and bradycardia, respectively (P < 0.05). MiR-101-3p and miR-140-3p demonstrated a potential discriminatory ability between dexmedetomidine responders and non-responders, with AUC of 0.64 (P < 0.05) and 0.77 (P < 0.0001), respectively. The AUC of miR-101-3p in distinguishing patients without hypotension was 0.63 (P < 0.05). The AUC of miR-30a-5p in distinguishing patients without bradycardia was 0.74 (P < 0.05).ConclusionOur study demonstrated that circulating miR-101-3p, miR-140-3p and miR-30a-5p might be used as a blood-based marker for dexmedetomidine efficacy and safety in pediatric patients.

The incidence of hemodynamic instability associated with dexmedetomidine (DEX) sedation has been reported to exceed 50%, with substantial inter-individual variability in response. Genetic factors have been suggested to contribute significantly to such variation. The aim of this study was to identify the clinical, pharmacokinetic, and genetic factors associated with DEX-induced hemodynamic instability in pediatric anesthesia patients. A cohort of 270 pediatric patients scheduled for elective interventional surgery received an intranasal dose of 3 mcg·kg of dexmedetomidine, and subsequent propofol induction was conducted when patients had a UMSS of 2-4. The primary endpoint was hemodynamic instability-defined as a composite of hypotension and/or bradycardia, which is characterized by a 20% reduction from age-specific baseline values. Plasma concentrations of dexmedetomidine were determined, and single-nucleotide polymorphisms (SNPs) were genotyped. A validated population pharmacokinetic model was used to estimate pharmacokinetic parameters. LASSO regression was used to identify significant factors, and a Cox's proportional hazards model-derived nomogram for hemodynamic instability was developed. Hemodynamic instability was observed in 52 out of 270 patients (209 events), resulting in a cumulative incidence of 16.30% at 90 min, as estimated by Kaplan-Meier estimation, and it was associated with a median time to event of 35 min. The interval time between DEX initiation and propofol induction was 16 min (IQR: 12-22 min). The cumulative incidence was 8.2% within 22 min after DEX initiation. The identified significant risk factors for DEX-associated hemodynamic instability included weight, DEX clearance, concomitant propofol use, and the following gene variants rs1841042 (hazard ratio (HR):1.41, 95% confidence interval (CI): 1.12-1.79), rs8192733 (HR:0.28, 95%CI:0.09-0.88), rs3813662 (HR:1.39,95%CI:1.02-1.89), rs2236957 (HR:1.46, 95%CI:1.09-1.96), rs3814057 (HR:0.64, 95%CI:0.43-0.95), and rs10764319 (HR:1.40,95%CI:1.05-1.87). The areas under the curve for the training and test cohorts were 0.881 and 0.762, respectively. The calibration curve indicated excellent agreement. The predictive nomogram, which incorporates genetic variants ( , and ) along with clinical factors such as weight, DEX clearance, and propofol use, may help prevent DEX-associated hemodynamic instability. Delayed hemodynamic instability is likely to occur after 35-min DEX initiation in patients with lower DEX clearance after propofol induction.

Background HOXD9, a Hox family member, is involved in cancer growth and metastasis. But, its regulation mechanism at the molecular level particularly in colorectal cancer (CRC), is mostly unknown. Methods The HOXD9 protein expression levels were analyzed using immunofluorescence, immunohistochemistry (IHC) assays, and western blot. The in vivo and in vitro roles of HOXD9 in CRC were determined using colony formation and EdU incorporation, CCK‐8, wound scratch and transwell invasion assay, and animal models. Results Expression of HOXD9 was higher in CRC than in matched healthy tissues. High expression of HOXD9 has significantly associated with the American Joint Committee on Cancer (AJCC) stages, tumor differentiation, lymph node metastasis, and other serious invasions, and it had a poor prognosis. In vitro, HOXD9 encouraged proliferation, movement and EMT processes in cells of CRC. Also, TGF‐β1 promoted the expression of HOXD9 and this effect was dependent on the dose and downregulation of HOXD9 repressed TGF‐β1 ‐induced EMT. In vivo, HOXD9 promoted the invasive and metastasis of CRC cells via orthotopic implantation. Conclusions The ectopic expression of HOXD9 promoted the invasion metastasis in cells of the colorectal tumor by induction of EMT in vitro and vivo. HOXD9 is overexpressed in CRC and increases tumorigenicity and tumor proliferation. Also, ectopic HOXD9 expression influences EMT and tumor spread both in vivo and in vitro. Therefore, the HOXD9 gene could act as an assuring therapeutic approach for treating patients suffering from CRC.

Pentagon Copying Test (PCT) is commonly used to assess visuospatial deficits, but the neural substrates underlying pentagon copying are not well understood. The Qualitative Scoring Pentagon Test (QSPT), an optimized scoring system, classifies five categories of errors patients make in pentagons copying and grades them depending on the errors’ severity. To determine the strategic brain regions involved in the PCT, we applied the QSPT system to evaluate the visuospatial impairment of 136 acute ischemic stroke patients on the PCT and used Support Vector Regression Lesion-Symptom Mapping to investigate relevant brain regions. The total QSPT score was correlated with the right supramarginal gyrus. The angle number errors and closure errors were principally associated with lesions of the posterior temporoparietal cortex, including the right middle occipital gyrus and middle temporal gyrus, while the intersection errors and rotation errors were related to the more anterior part of the right temporoparietal lobe with the additional frontal cortex. In conclusion, the right temporoparietal cortex is the strategic region for pentagon copying tasks. The angle number and closure represent the visuospatial processing of within-object features, while intersection and rotation require between-object manipulation. The posterior-anterior distinction in the right temporoparietal region underlies the differences of within-object and between-object processing.

Age is a major risk factor for coronavirus disease (COVID-19)-associated severe pneumonia and mortality; however, the underlying mechanism remains unclear. Herein, we investigated whether age-related deregulation of RNAi components and RNA splicing factors affects COVID-19 severity. Decreased expression of RNAi components (Dicer and XPO5) and splicing factors (SRSF3 and hnRNPA3) correlated with increased severity of COVID-19 and SARS-CoV-2 nucleocapsid (N) protein-induced pneumonia. N protein induced autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, repressing miRNA biogenesis and RNA splicing and inducing DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 were downregulated with age in mouse lung tissues. Older mice experienced more severe N protein-induced pneumonia than younger mice. However, treatment with a poly(ADP-ribose) polymerase inhibitor (PJ34) or aromatase inhibitor (anastrozole) relieved N protein-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.