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Pulmonary embolism (PE) is a disease caused by blood clots, tumor embolism, and other emboli within the pulmonary arteries. Various scoring scales are used for PE. One such same is the PESI, but it has 12 variables, making it inconvenient for clinical application.The aim of this study was to develop a new simple nomogram model to assess 30-day survival in PE patients. The new nomogram makes it easier and faster for clinicians to assess the prognosis of patients with PE.We collected data about the patients with PE from the Medical Information Mart for Intensive Care-III (MIMIC-III) database and used the receiver operating characteristic (ROC) curve, area under the ROC curve (AUROC), calibration plot, integrated discrimination improvement (IDI), and decision curve analysis (DCA) to evaluate the predictive power of the new model, and compared these with the PESI.According to the multivariable Cox regression model results, alongside the actual clinical conditions, we included the following seven variables: race, bicarbonate, age, tumor, systolic blood pressure (SBP), body temperature, and oxygen saturation (Spo2). The AUROC of the new model was greater than 0.70. Its IDI exceeded 0, but with P-value0.05.The predictive performance of the new model was not worse than the PESI, but the new model only has seven variables, and is therefore more convenient for clinicians to use.

Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in hospitalized HFrEF patients with type 2 diabetes mellitus (T2DM).A total of 463 hospitalized T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after around 12 months. Patients who had an absolute EF improvement ≥10% and a second EF 40% were classified into HFrecEF, and those who did not meet these criteria were defined as persistent HFrEF.During the 12-month follow-up, 44.5% of T2DM patients developed HFrecEF. Patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.5% [IQR 5.8% ∼ 7.2%] vs. 6.7% [IQR 6.1% ∼ 7.8%], P = 0.003), especially in HF of an ischemic etiology. HbA1c levels were inversely correlated with changes in EF during follow-up. After multivariate adjustment, every 1% increase in HbA1c conferred a 17.4% (OR: 0.826 [95% CI 0.701-0.968]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c ≤ 6.2%), those with poor glycemic control (HbA1c 7.1%) had a 52.0% (OR: 0.480 [95% CI 0.281-0.811] decreased likelihood of HFrecEF.This study demonstrates that uncontrolled HbA1c level is associated with compromised development of HFrecEF in T2DM patients with HF, especially in those with an ischemic etiology.

Our patient is a 60-year-old woman of Indian ethnicity with background of diabetes mellitus for 10 years. She presented with persistent vomiting, giddiness and significant weight loss for 1 month. Of note, she had recent hypoglycaemia necessitating gradual reduction in doses of glucose-lowering

Well-established surveillance and monitoring systems for respiratory viruses need to be improved, and epidemiological data on respiratory viruses in China are scarce. This study aimed to investigate the epidemiological characteristics of respiratory viruses among hospitalized children aged ≤2 years with acute respiratory tract infections (ARTIs) in Xiamen, China, from October 2014 to September 2017. The clinical records of 7,248 children hospitalized for ARTIs were retrospectively analyzed. Respiratory syncytial virus (RSV) (22.3%) was the most common virus among hospitalized children aged ≤2 years, followed by parainfluenza (5.0%), adenovirus (3.5%), and influenza (1.7%). RSV-infected children had a higher disease burden, including a higher intensive care unit (ICU) admission rate (12.7%) and higher hospital charges ($635.36). Particularly, infants aged6 months had the highest risk of RSV infection (odds ratio = 2.4; 95% CI, 1.9-2.9) and a higher ICU admission rate (12.1% vs. 4.5%, 4.6%) and hospital cost ($923.3 vs. $785.5, $811.7) than the other age groups. Therefore, infants aged 0-6 months, particularly premature infants and children with congenital diseases, should receive more attention. There is an urgent need to develop effective immunization strategies to protect these infants during the first 6 months of life and in the RSV season.

Singapore was one of the first countries to begin COVID-19 vaccination with the BNT162b2 vaccine for adolescents aged 12-18 years. This study evaluates the incidence of COVID-19 vaccine related attendances to a Pediatric Emergency Department (PED) to understand post-vaccination health behaviors among adolescents.This was a retrospective review of electronic medical records over a 4 month period, from the start of the adolescent vaccination drive to when more than 85% of this group had been fully vaccinated.The incidence of COVID-19 vaccination-related presentations to our PED was 3.1% over 4 months (291 of 9387 PED attendances), with a peak daily incidence of 15.4% (14 of 91 attendances). Presentations were characterized by severity into: severe (3.4%), moderate (7.9%) or mild (88.7%) based on predefined criteria. The most common presenting complaints were chest pain (58.8%), dyspnea (28.2%) and palpitations (22.6%). Hospitalization was required in only 6.2% of attendances. Patients with moderate-severe presentations were 0.7 years older (p = 0.030), more likely to have underlying drug allergies (p = 0.048) and had higher rates of hospitalization (p 0.005) compared to mild presentations. Despite concerns of cardiac inflammation, chest pain related attendances were less likely to be severe (p 0.005) with reduced hospitalization need (p = 0.043) compared to other presentations. Investigations beyond clinical assessment comprised 91% of attendances, but abnormalities were only found in 6.4% cases.Our study supports current evidence that COVID-19 vaccination is safe amongst adolescents. We highlight the health behaviors among adolescents post-vaccination, which is partly driven by media reports on vaccine side effects and an element of anxiety. While most of the presentations were mild, these can have implications on health resource utilization, particularly in an ongoing pandemic. As healthcare workers, we have an ongoing role to ensure accurate information on vaccine safety is communicated effectively to the public.

Caecal volvulus is a rare cause of intestinal obstruction, of which the caecal bascule is the most uncommonly encountered subtype. Definitive radiological diagnosis of a caecal bascule can be challenging. Lack of familiarity with this rare condition can contribute to delayed diagnosis and treatment, which may result in unnecessary morbidity. This article highlights the case of a patient who presented with a diagnostic challenge, and also discusses the pathogenesis and diagnostic features of caecal bascules. Various options in the surgical management of caecal bascules are reviewed, including the feasibility of laparoscopic-assisted approaches in the emergency setting.

To investigate the relationship between systemic inflammatory response and short-term mortality in patients with non-cirrhotic chronic severe hepatitis (CSH) by using several indicators of inflammation including neutrophil-to-lymphocyte ratio (NLR), neutrophil (NEU), white blood cell (WBC), platelet-to lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR).Data were collected from two prospectively enrolled CATCH-LIFE noncirrhotic cohorts. Cox regression analysis was used to investigate the association between systemic inflammatory biomarkers and 90-day liver transplant (LT)-free mortality. A generalized additive model (GAM) was used to illustrate the quantitative curve relationship between NLR and 90-day LT-free mortality. Kaplan-Meier method was used to estimate the 90-year LT-free survival.The prevalence of CSH was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively, for patients with non-cirrhotic CSH. Patients with no infection accounted for 75.0% of all CSH patients, and NLR was independently associated with 90-day LT-free mortality. NLR of 2.9 might be related to disease deterioration in CSH patients without infection.NLR may be an independent risk factor for 90-day LT-free mortality in patients with non-cirrhotic chronic liver disease. A NLR of 2.9 as the cut-off value can be used to predict disease aggravation in CSH patients without infection.

Liver cirrhosis is the leading cause of liver-related mortality worldwide. It is currently a global health challenge.This research intended to explore and analyse research trends and frontiers in this field during the last 10 years, providing new inspiration for clinical decision-making and scientific research.Publications on hepatic cirrhosis research were retrieved from the Web of Science Core Collection on April 4, 2021. Bibliometric visualisation was conducted through VOSviewer and CiteSpace.The analytic research was based on original articles and reviews. A total of 7775 records of hepatic cirrhosis published from 2011 to 2020 were retrieved. In the past ten years, the number of related annual publications has increased significantly, especially in the United States and China. All publications were distributed among 109 countries. The United States contributed the most (21.95%) and was consistently the leading driving force, with a solid academic reputation in this area. The University of Barcelona distributed the most related articles (177 articles) and was cited the most frequently. TheThis study identified developing trends in the evolution of liver cirrhosis to provide new inspiration for researchers.

Neurogenic sexual dysfunction (NSD) is a common problem in patients after spinal and pelvic trauma. New treatment is needed beyond medicine or psychological therapies. A 24-year-old man who fell from a six-floor building suffered from subsequent NSD. Repetitive transcranial magnetic stimulation (rTMS) was the only method used to treat his NSD caused by multiple spinal and pelvic injuries. The therapy lasted for 3 courses. Motor and sensory conduction, as well as sexual function, were evaluated before and after the rTMS intervention. Improvements on patient's nerve conduction and sexual activity were confirmed at a 1-year follow-up. Our findings indicate that rTMS delivered a novel, positive and low-cost modality treatment to the patient with NSD. Clinical efficacy and potential mechanisms by which rTMS regulate NSD need to be investigated by further clinical trials.

This study aimed to examine changes in electrolytes and acid-base status in primary and secondary hypokalaemic periodic paralysis (HypoPP), which will help early differential diagnosis of HypoPP. A total of 64 HypoPP patients were enrolled and relevant data from clinical records was collected. Overall, 64 patients (mean age 28.2±7.3 years) of which 58(91%) were males, with 39, 11 and 14 patients, respectively, diagnosed as primary HypoPP, thyrotoxic HypoPP, and other secondary HypoPPs at discharge, were assessed. Those with HypoPP secondary to conditions other than hyperthyroidism were more likely to develop acid-base imbalance (p

Suicide in college students is a major public health concern. Suicidal ideation (SI) is associated with childhood trauma, personality, dysfunctional attitudes and depressive symptoms, but how they interact to predict SI remains unclear.Using cross-sectional design and convenience sampling method, a survey was conducted among 565 college students having major depressive disorder (MDD). The Childhood Trauma Questionnaire, Eysenck Personality Questionnaire, Dysfunctional Attitudes Scale and Hamilton Depression Scale assessed participants' psychosocial factors. Chi-square test, t-test, Pearson correlation, and Structural Equation Model were used in data analysis.Overall, 66.02% of participants with MDD had SI. Those with SI showed significant differences in physical abuse, emotional abuse, physical neglect, emotional neglect, psychoticism, neuroticism, extroversion, dysfunctional attitudes and depressive symptoms compared with those without SI. Childhood trauma, psychoticism, neuroticism, extroversion and dysfunctional attitudes affected SI through chain mediation. In addition, depressive symptoms, psychoticism, neuroticism and extroversion directly affected SI.The convenience sampling method may limit the generalizability of the findings. Results may be biased due to the self-report nature of the data collection procedure, the number of research subjects and differences in suicide risk assessment. The cross-sectional study cannot be used to infer causality.The factors of childhood trauma, personality and dysfunctional attitudes affect SI through chain mediation. In addition, depressive symptoms and personality independently predict the occurrence of SI.

Background. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in the treatment of hypertension. Hypertension is often accompanied by osteoporosis. However, the relationship between ACEI/ARB and fractures remains controversial. The purpose of this meta-analysis was to update the potential relationship between ACEI/ARB and fractures. Methods. This meta-analysis was identified through PubMed, EMBASE, Cochrane Library, and Web of Science. Related studies about ACEI/ARB with the risk of fracture were published from inception to June 2022. Results. Nine qualified prospective designed studies, involving 3,649,785 subjects, were included in this analysis. Overall, the RRs of ACEI compared with the nonusers were 0.98 (95% CI: 0.88, 1.10; P < 0.001 ) for composite fractures and 0.96 (95% CI: 0.87, 1.05; P = 0.048 ) for hip fractures; the RRs of ARB compared to the nonusers were 0.82 (95% CI: 0.73, 0.91; P < 0.001 ) for composite fractures and 0.85 (95% CI: 0.74, 0.97; P = 0.028 ) for hip fractures. Furthermore, in the subgroup analysis, male may benefit from ARB (RR = 0.65, 95% CI: 0.49, 0.89, P = 0.028 ), and the European may also benefit from ARB (RR = 0.86, 95% CI: 0.80, 0.93, P = 0.015 ). Conclusions. ACEI usage will not decrease the risk of osteoporosis fracture. On the contrary, ARB usage can decrease the risk of total fracture and hip fracture, especially for males and Europeans. Compared with ACEI, for patients at higher risk of fracture in cardiovascular diseases such as hypertension, the protective effect of ARB should be considered.

Aims: This trial explored the safety and efficacy of neoantigen-specific T cells (Nas-Ts) combined with anti-PD-1 (Nas-T + anti-PD-1). Patients & methods: This non-randomized trial recruited participants with solid tumors treated with at least two prior systemic treatment lines. For comparison, 1:1-matched controls who received anti-PD-1 alone were recruited. The primary end point was safety. Results: 15 participants were enrolled in the Nas-T + anti-PD-1 group, the objective response rate was 33.3%, and the disease control rate was 93.3%. The median progression-free survival was significantly different between the Nas-T + anti-PD-1 and control groups (13.8 vs 4.2 months; p = 0.024), but no difference in overall survival was found (p = 0.126). The most common adverse events were maculopapular skin reaction (53.3%), rash (53.3%), hepatotoxicity (53.3%) and fever (53.3%) in the Nas-T + anti-PD-1 group. No serious safety issues were experienced. Conclusion: Nas-Ts combined with anti-PD-1 could be more effective than anti-PD-1 alone in prolonging progression-free survival, with good safety.

Context Circulating proteomes may provide intervention targets for type 2 diabetes (T2D). Objective We aimed to identify proteomic biomarkers associated with incident T2D and assess its joint effect with dietary or lifestyle factors on the T2D risk. Methods We established 2 nested case-control studies for incident T2D: discovery cohort (median 6.5 years of follow-up, 285 case-control pairs) and validation cohort (median 2.8 years of follow-up, 38 case-control pairs). We integrated untargeted mass spectrometry-based proteomics and interpretable machine learning to identify T2D-related proteomic biomarkers. We constructed a protein risk score (PRS) with the identified proteomic biomarkers and used a generalized estimating equation to evaluate PRS-T2D relationship with repeated profiled proteome. We evaluated association of PRS with trajectory of glycemic traits in another non-T2D cohort (n = 376). Multiplicative interactions of dietary or lifestyle factors with PRS were evaluated using logistic regression. Results Seven proteins (SHBG, CAND1, APOF, SELL, MIA3, CFH, IGHV1-2) were retained as the proteomic biomarkers for incident T2D. PRS (per SD change) was positively associated with incident T2D across 2 cohorts, with an odds ratio 1.29 (95% CI, 1.08-1.54) and 1.84 (1.19-2.84), respectively. Participants with a higher PRS had a higher probability showing unfavored glycemic trait trajectory in the non-T2D cohort. Red meat intake and PRS showed a multiplicative interaction on T2D risk in the discovery (P = 0.003) and validation cohort (P = 0.017). Conclusion This study identified proteomic biomarkers for incident T2D among the Chinese populations. The higher intake of red meat may synergistically interact with the proteomic biomarkers to exaggerate the T2D risk.

Newer generation durable polymer drug-eluting stents (DP-DES) and biodegradable polymer DES (BP-DES) have similar efficacy with dual-antiplatelet therapy (DAPT) duration of 6 months. However, this difference in outcomes have not been well studied in shorter DAPT regime. This study compares the safety and efficacy profiles of DP-DES and BP-DES based on short-term (1-3 months), intermediate-term (4-6 months) and standard DAPT (6-12 months) durations. A search was conducted on Embase and Medline for Randomized Controlled Trials (RCTs) comparing stent types, and DAPT durations. Primary endpoints include cardiac death, myocardial infarction (MI), definite stent thrombosis, stroke, target vessel revascularization (TVR) and major bleeding. Network analysis was conducted to summarize the evidence. A total of 15 RCTs involving 43,875 patients were included. DP-DES was associated with significantly lower major bleeding rates compared to BP-DES (RR 0.44, Crl 0.22-0.83) in short-term DAPT. Among DP-DES patients, short-term DAPT was associated with lower major bleeding risk compared to standard DAPT (RR 0.47, CrI 0.32-0.69). This favorable bleeding profile with short DAPT was not found in BP-DES patients. Cardiac death, MI, definite stent thrombosis, stroke and TVR rates were similar across the various DAPT durations and stent types. Our preliminary findings demonstrated comparable efficacy and safety outcomes between BP-DES and newer generation BP-DES across various DAPT durations. In patients requiring short DAPT, DP-DES had more favourable major bleeding profile compared to BP-DES, without compromising anti-thrombotic efficacy.

Objective To investigate the effect of platelet‐rich plasma on tendon‐bone healing after anterior cruciate ligament reconstruction. Methods This retrospective study included 85 patients (range, 18–50 years; mean age, 33.95 ± 10.53 years; male/female, 49/36) who underwent anterior cruciate ligament reconstruction using autologous hamstring tendons between August 2017 and June 2019 at our institute. The participants in the study group (n = 42) were injected with platelet‐rich plasma at both ends of the tendon graft, while those in the control group (n = 43) received an injection of normal saline. Magnetic resonance imaging signal/noise quotient values of the femoral and tibial ends, knee Lysholm scores, and International Knee Documentation Committee scores were compared at 3, 6, and 12 months postoperatively. Results The signal/noise quotient values of the femoral and tibial ends in both groups were higher at 6 months than at 3 and 12 months postoperatively. The signal/noise quotient values of the tibial end were significantly lower in the platelet‐rich plasma group than in the normal saline group at all follow‐up time points (P, Preparation of PRP fluid and woven autologous hamstring tendon. (A) Image of the PRP fluid. (B) In the study group, 2.5 mL of PRP was injected into the tibial and femoral ends of the graft. (C) The graft was positioned properly after anterior cruciate ligament reconstruction.

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. Diagnostic challenges remain in this highly time-sensitive condition. Using capillary electrophoresis-laser-induced fluorescence, we analyzed the blood plasma N-glycan profile in a cohort study comprising 103 patients with AMI and 69 controls. Subsequently, the data generated was subjected to classification modeling to identify potential AMI biomarkers. An area under the Receiving Operating Characteristic curve (AUCROC) of 0.81 was obtained when discriminating AMI vs. non-MI patients. We postulate that the glycan profile involves a switch from a pro- to an anti-inflammatory state in the AMI pathophysiology. This was supported by significantly decreased levels in galactosylation, alongside increased levels in sialylation, afucosylation and GlcNAc bisection levels in the blood plasma of AMI patients. By substantiating the glycomics analysis with immunoglobulin G (IgG) protein measurements, robustness of the glycan-based classifiers was demonstrated. Changes in AMI-related IgG activities were also confirmed to be associated with alterations at the glycosylation level. Additionally, a glycan-biomarker panel derived from glycan features and current clinical biomarkers performed remarkably (AUCROC = 0.90, sensitivity = 0.579 at 5% false positive rate) when discriminating between patients with ST-segment elevation MI (n = 84) and non-ST-segment elevation MI (n = 19). Moreover, by applying the model trained using glycomics information, AMI and controls can still be discriminated at 1 and 6 months after baseline. Thus, glycomics biomarkers could potentially serve as a valuable complementary test to current diagnostic biomarkers. Additional research on their utility and associated biomechanisms via a large-scale study is recommended.

This study evaluates the cost-effectiveness of daratumumab (D) in combination with lenalidomide and dexamethasone (Rd) for treatment of relapsed and/or refractory multiple myeloma in patients who have received at least one prior therapy in Singapore. A 3-state partitioned survival model was developed to evaluate the cost-effectiveness of lenalidomide and dexamethasone with or without daratumumab from a healthcare system perspective over 10 years. Clinical inputs were obtained from the POLLUX trial. Health state utilities were derived from the literature and direct medical costs obtained from public healthcare institutions. Sensitivity and scenario analyses were conducted to explore uncertainties. DRd was associated with a high base-case incremental cost-effectiveness ratio (ICER) of US$576,247 per quality-adjusted life year (QALY) gained, compared with Rd. According to one-way sensitivity analysis, ICER was most heavily influenced by time horizon, discount rate for outcomes, progression-free utility and cost of daratumumab. Regardless of the variation, DRd remained not cost-effective. Even when the cost of both daratumumab and lenalidomide dropped by 20% and 80%, the ICERs remained high at US$470,400 and US$152,860 per QALY gained. At current prices, the addition of daratumumab to lenalidomide and dexamethasone does not represent cost-effective use of healthcare resources in Singapore.

The purpose of this study was to examine 1) the relationship between apathy and leisure activity participation in nursing home residents with Alzheimer disease (AD) and 2) the moderator effect of the severity of dementia on this relationship. Data were collected from 290 residents with AD using the Apathy Evaluation Scale-informant version (AES-I), Leisure Activities Questionnaire (LAQ), and Clinical Dementia Rating scale (CDR). The multiple linear regression model showed that leisure activity participation (β=-0.452, p0.001) was negatively associated with apathy, while the severity of dementia (β=0.515, p0.001) was positively associated with apathy. The severity of dementia moderated the effect of leisure activity participation on apathy (β=-0.108, p=0.015). The results indicate that the effects of leisure activity participation on apathy diminish with the aggravation of AD. The severity of dementia should be considered when designing and delivering leisure activity interventions to manage apathy in nursing home residents with AD.

Introduction: Surgical resection of the primary and metastatic tumour is increasingly recommended in suitable patients with metastatic colorectal cancer (CRC). While the role of metastasectomy is well studied and established in colorectal liver metastasis, evidence remains limited in pulmonary metastases. This systematic review was conducted to examine the current evidence on the role of lung metastasectomy (LUM) in CRC. Methods: Three databases were systematically searched, to identify studies that compared survival outcomes of LUM, and factors that affected decision for LUM. Results: From a total of 5,477 records, 6 studies were eventually identified. Two papers reported findings from one randomised controlled trial and 4 were retrospective reviews. There was no clear survival benefit in patients who underwent LUM compared to those who did not. When compared against patients who underwent liver metastasectomy, there was also no clear survival benefit. Patients who underwent LUM were also more likely to have a single pulmonary tumour, and metachronous disease. Conclusion: The evidence suggests a role for LUM, but is limited by inherent selection bias in retrospective reviews, and the single randomised clinical trial performed was not completed. More prospective studies are required to understand the true effect of LUM on outcomes in metastatic CRC. Keywords: Colorectal cancer, pulmonary metastasectomy, pulmonary metastases, survival

Background The circulating concentration of 1α,25-dihydroxyvitamin D [1α,25(OH)2D] is very low, and the presence of multiple isomers may lead to inaccurate quantitation if not separated prior to analysis. Antibody-based immunoextraction procedures are sometimes used to remove structurally related isomers of 1α,25(OH)2D prior to an LC-MS/MS analysis. However, immunoextraction increases sample preparation time and cost. In addition, some dihydroxyvitamin D metabolites are not completely removed by immunoextraction. Method We developed an HPLC method using a phenyl-hexyl column to investigate interfering isomers of 1α,25(OH)2D. Result Using this method, 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) derivatization product of 1α,25(OH)2D was found to be present as 2 epimers, which were separated chromatographically with an area ratio of 2:1. PTAD derivatized metabolite of 25-hydroxyvitamin D3 [i.e., 4β,25-dihydroxyvitamin D3 (4β,25(OH)2D3)] eluted out between 6R and 6S epimers of derivatized 1α,25(OH)2D3. If not chromatographically resolved, 4β,25(OH)2D can affect 1α,25(OH)2D quantitation. In a method comparison study, it was found that the presence of 4β,25(OH)2D produced positive bias up to 127% on 1α,25(OH)2D3 quantitation. Conclusion The LC-MS/MS method we developed without an immunoextraction procedure was able to resolve the major interference peak from 1α,25(OH)2D and achieved reliable quantitation of 1α,25(OH)2D.

Background Resistance to conventional dose schemes and radiotoxicity of healthy tissue is a clinical challenge in the radiation therapy of large locally advanced drug-resistant gastrointestinal stromal tumor (LADR-GIST). This study aimed to assess the feasibility of using multi-shell Simultaneous Integrated Boost Intensity-Modulated modality (SIB-IMRT) strategy to provide a safe and effective escalation dose regimen for LADR-GIST. Methods 7 patients with LADR-GIST were selected in this study. The modified SIB-IMRT plans for all patients were generated by delivering different escalation-dose gradients to four ring shaped regions (shells) within the gross tumor volume (GTV). The doses of the central volume of the tumor (GTVcenter) were escalated up to 70–92.5 Gy (25 fractions), while the doses of planning target volume (PTV) and shell-1 were kept at 50.0 Gy. Based on different escalation-dose gradients, the modified SIB-IMRT plans were divided into four groups (SIB-IMRT groups). For comparison purposes, plans obtained by conventional IMRT technique (Con-IMRT) with 50 Gy (25 fractions) were also generated for all patients (Con-IMRT group). All plans were normalized to cover 95% of the PTV with the prescribed dose of 50.0 Gy. The equivalent uniform dose (EUD), relative equivalent uniform dose (rEUD), dose volume histogram (DVH), dose profile, conformity index (CI) and monitor unit (MU) were evaluated in five groups. The Friedman Test was performed to determine whether there were significant differences (P Results Compared with the Con-IMRT group, the EUD of GTV (EUDGTV) and rEUD of SIB-IMRT groups were improved when escalation-dose gradient was increased, and the improvement became significant when the escalation-dose gradient reached 20% of the prescription dose. The rEUD tended to be stable as the escalation-dose gradient went up to 25% of the prescription dose. There were no significant differences in CIs and DVH metrics for OARs between the Con-IMRT group and any SIB-IMRT group, but the significant differences were observed between the SIB10-IMRT group and the SIB25-IMRT group. For the SIB-IMRT groups, as the dose gradient became steeper in the dose profiles, the higher dose was mainly accumulated in the inner part of GTV accompanied with a higher MU. Conclusions The proposed multi-shell SIB-IMRT strategy is feasible in dosimetry for LADR-GIST and can acquire higher therapeutic gain without sacrifice of healthy tissues. It appears that the scheme of delivering 20% of the prescribed escalation-dose gradient to the target volume can provide satisfactory dose irradiation for LADR-GIST, and it should be evaluated in future clinical study.

Refereed/Peer-reviewed Cell membrane-coated nanoparticles are emerging as a new type of promising nanomaterials for immune evasion and targeted delivery. An underlying premise is that the unique biological functions of natural cell membranes can be conferred on the inherent physiochemical properties of nanoparticles by coating them with a cell membrane. However, the extent to which the membrane protein properties are preserved on these nanoparticles and the consequent bio-nano interactions are largely unexplored. Here, we synthesized two mesenchymal stem cell (MSC) membrane-coated silica nanoparticles (MCSNs), which have similar sizes but distinctly different stiffness values (MPa and GPa). Unexpectedly, a much lower macrophage uptake, but much higher cancer cell uptake, was found with the soft MCSNs compared with the stiff MCSNs. Intriguingly, we discovered that the soft MCSNs enabled the forming of a more protein-rich membrane coating and that coating had a high content of the MSC chemokine CXCR4 and MSC surface marker CD90. This led to the soft MCSNs enhancing cancer cell uptake mediated by the CD90/integrin receptor-mediated pathway and CXCR4/SDF-1 pathways. These findings provide a major step forward in our fundamental understanding of how the combination of nanoparticle elasticity and membrane coating may be used to facilitate bio-nano interactions and pave the way forward in the development of more effective cancer nanomedicines.

Blood-based biomarkers have been considered as a promising method for the diagnosis of Alzheimer's disease (AD). The reliability and accuracy of plasma core AD biomarkers, including phosphorylated tau (P-tau181), total tau (T-tau), Aβ42, and Aβ40, have also been confirmed in diagnosing AD and predicting cerebral β-amyloid (Aβ) deposition in Western populations, while fewer research studies have ever been conducted in China's Han population. In this study, we investigated the capability of plasma core AD biomarkers in predicting cerebral Aβ deposition burden among the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort consisting of cognitively normal (CN), mild cognitive impairment (MCI), AD dementia, and non-Alzheimer's dementia disease (Non-ADD). Body fluid (plasma and CSF) AD core biomarkers were measured via single-molecule array (Simoa) immunoassay. The global standard uptake value ratio (SUVR) was then calculated by

Objective This study aims to analyze the association between preoperative LDL/HDL ratio and new-onset atrial fibrillation (AF) after on-pump coronary artery bypass grafting (on-pump CABG), evaluate the clinic value of preoperative LDL/HDL ratio to identify postoperative rhythm. Methods A retrospective study of consecutive patients (n = 2052) who underwent on-pump CABG at TEDA International Cardiovascular Hospital (Tianjin, China), from June 1, 2020, to December 30, 2021, was conducted. The association between preoperative LDL/HDL and new-onset POAF was analyzed by Lowess curve and univariate logistic regression. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the identification capacity of preoperative LDL/HDL level for new-onset POAF. Results In studied populations, the incidence of new-onset POAF was about 29.24%. The lowess curve showed that the association between preoperative LDL/HDL ratio and POAF after on-pump CABG was similar to a linear relationship. With the increasement of preoperative LDL/HDL ratio, the incidence of POAF increased simultaneously. ROC analysis showed that preoperative LDL/HDL ratio could identify postoperative arrhythmia after on-pump CABG (AUC = 0.569,95% CI = 0.529–0.608, P = 0.006) among female patients, the best preoperative LDL/HDL ratio cutoff of 2.11, which was considered a predictive factor of incident POAF, showed a sensitivity of 83.60% (95% CI = 0.775–0.886) and a specificity of 30.02% (95% CI = 0.257–0.346). Conclusion Preoperative LDL/HDL ratio is associated with new-onset POAF, but there is a difference in different sex. Preoperative LDL/HDL level can help to identify postoperative rhythm in females.

Allergic rhinitis(AR) is a chronic inflammatory disorder of nasal mucosa induced by allergen exposure triggering IgE-mediated inflammation. With frequent recurrence, it is difficult to be cured. Zixin Biqiu Granules is developed based on the 60-year clinical experience of CHAO En-xiang, a master of national medicine of China-Japan Friendship Hospital. At present, phase Ⅲ multicenter clinical trial is being prepared, but the mechanism is unclear. Therefore, this study explored the mechanism of Zixin Biqiu Granules against AR based on network pharmacology and molecular docking. First, the chemical components and targets of Zixin Biqiu Granules were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of AR from GeneCards and Online Mendelian Inheritance in Man(OMIM). Then the common targets of the two were screened out and thequot;Chinese medicine-component-targetquot; network was constructed. Afterward, the common targets were imported into the STRING to obtain the interaction of them, and Cytoscape was employed to establish the protein-protein interaction(PPI) network. Through topological analysis, the core targets were obtained. DAVID was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Thequot;key target-pathway-biological processquot; network was constructed to explore the anti-AR mechanism of Zixin Biqiu Granules. Finally, the core targets were selected for molecular docking with the key components of Zixin Biqiu Granules to verify the mechanism. The results showed that there were 151 components and 97 targets in thequot;Chinese medicine-component-targetquot; network. We obtained 20 core targets, 488 biological processes and 147 pathways in topological, GO, and KEGG enrichment analysis of the protein interaction network, and in the comprehensive analysis, it was found that Zixin Biqiu Granules mainly exerted the therapeutic effect through anti-inflammation and immunoregulation. Serine/threonine-protein kinase 1(AKT1) and tumor necrosis factor(TNF) were docked with the key components of Zixin Biqiu Granules, and the results showed that the key components of Zixin Biqiu Granules had high binding affinity to the core targets. This study preliminarily discussed the anti-AR mechanism of Zixin Biqiu Granules, which laid a scientific basis for its clinical application.

Cancer is a major cause of morbidity and mortality worldwide and therefore there has been interest in discovering the phytoconstituents of medicinal plants exhibiting anticancer activities.

Emerging pollutants have drawn global concerns under rapid urbanization and industrialization. However, research has been relatively independent on specific groups of pollutants due to the limitation of the discipline. In this study, from the perspective of interdisciplinary research, taking the fluorochemical industry as an example, two major categories of emerging pollutants, per-and polyfluoroalkyl substances (PFAS) and ozone-depleting substances (ODS), were discussed regarding their co-emission. The co-production mechanism of the two types of pollutants were discussed from the production processes to reveal their internal relationship; their differences and cross-processes in the emission routes were analyzed, as well as the technical approaches and challenges required in sample collection, pretreatment, and instrumental analysis. The eco-environmental effects, including ecological and human health risks, ozone depletion, and global warming effects caused by the two types of pollutants in different media were comprehensively summarized. We also further expanded the perspectives of stakeholder analysis, life cycle analysis, and mass balance analysis to provide suggestions for further research and management of emerging pollutant co-emissions.

Background There is a raising concern of a higher infectious Omicron BA.2 variant and the latest BA.4, BA.5 variant, made it more difficult in the mitigation process against COVID-19 pandemic. Our study aimed to find optimal control strategies by transmission of dynamic model from novel invasion theory. Methods Based on the public data sources from January 31 to May 31, 2022, in four cities (Nanjing, Shanghai, Shenzhen and Suzhou) of China. We segmented the theoretical curves into five phases based on the concept of biological invasion. Then, a spatial autocorrelation analysis was carried out by detecting the clustering of the studied areas. After that, we choose a mathematical model of COVID-19 based on system dynamics methodology to simulate numerous intervention measures scenarios. Finally, we have used publicly available migration data to calculate spillover risk. Results Epidemics in Shanghai and Shenzhen has gone through the entire invasion phases, whereas Nanjing and Suzhou were all ended in the establishment phase. The results indicated that Rt value and public health and social measures (PHSM)-index of the epidemics were a negative correlation in all cities, except Shenzhen. The intervention has come into effect in different phases of invasion in all studied cities. Until the May 31, most of the spillover risk in Shanghai remained above the spillover risk threshold (18.81–303.84) and the actual number of the spillovers (0.94–74.98) was also increasing along with the time. Shenzhen reported Omicron cases that was only above the spillover risk threshold (17.92) at the phase of outbreak, consistent with an actual partial spillover. In Nanjing and Suzhou, the actual number of reported cases did not exceed the spillover alert value. Conclusions Biological invasion is positioned to contribute substantively to understanding the drivers and mechanisms of the COVID-19 spread and outbreaks. After evaluating the spillover risk of cities at each invasion phase, we found the dynamic zero-COVID strategy implemented in four cities successfully curb the disease epidemic peak of the Omicron variant, which was highly correlated to the way to perform public health and social measures in the early phases right after the invasion of the virus. Graphical Abstract

Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.

To analyze and sum up clinical application regularities of Chengshan (BL57) acupoint in ancient Chinese literature.The bookA total of 196 articles meeting our inclusion standards of the present study, involving 61 ancient books which contain 174 related terms covering 56 diseases or syndromes of internal medicine, surgery, pediatrics, ophthalmology and otorhinola-ryngology, etc.. Among them, the most frequently attending disease treated by single BL57 or acupoints combination was limb meridian disorders, and the most frequently used auxiliary acupoint was Kunlun (BL60). The most frequently used auxiliary meridian was the Bladder Meridian of Foot Taiyang. In addition, a total of 71 terms involved the acupuncture and moxibustion techniques of BL57, covering 7 treatment methods. In terms of the treatment methods, the dose of moxibustion was five cones in each session, and the depth of acupuncture needle insertion was about seven fen.BL57 is widely used in various clinical departments, especially for limb meridian diseases.

Accurate discrimination of amyloid-β (Aβ) peptides containing familial point mutations would advance the knowledge of their roles in early-onset Alzheimer's disease. Herein, we simultaneously identified the mutant A21G, E22G, E22Q, and the wild-type (WT) Aβ

Background The COVID-19 pandemic has affected patients with ST-segment elevation myocardial infarction (STEMI) requiring primary percutaneous coronary intervention (PCI) worldwide. In this review we examine the global effect of the COVID-19 pandemic on incidence of STEMI admissions, and relationship between the pandemic and door to balloon time (D2B), all-cause mortality, and other secondary STEMI outcomes. Methods We performed a systematic review and meta-analysis to primarily compare D2B time and in-hospital mortality of STEMI patients who underwent primary PCI during and before the pandemic. Subgroup analyses were performed to investigate the influence of geographical region and income status of a country on STEMI care. An online database search included studies that compared the aforementioned outcomes of STEMI patients during and before the pandemic. Results In total, 32 articles were analyzed. Overall, 19,140 and 68,662 STEMI patients underwent primary PCI during and before the pandemic, respectively. Significant delay in D2B was observed during the pandemic (weighted mean difference, 8.10 minutes; 95% confidence interval [CI], 3.90-12.30 minutes; P = 0.0002; I2 = 90%). In-hospital mortality was higher during the pandemic (odds ratio [OR], 1.27; 95% CI, 1.09-1.49; P = 0.002; I2 = 36%), however this varied with factors such as geographical location and income status of a country. Subgroup analysis showed that low–middle-income countries observed a higher rate of mortality during the pandemic (OR, 1.52; 95% CI, 1.13-2.05; P = 0.006), with a similar but insignificant trend seen among the high income countries (OR, 1.17; 95% CI, 0.95-1.44; P = 0.13). Conclusions The COVID-19 pandemic is associated with worse STEMI performance metrics and clinical outcome, particularly in the Eastern low–middle-income status countries. Better strategies are needed to address these global trends in STEMI care during the pandemic.

Lack of knowledge adversely affects one's attitude toward organ donation. To increase understanding, Singapore informs each citizen and permanent resident turning 21 years old through information mailers sent to their place of residence. This study measured the current knowledge on organ donation of 106 polytechnic students (aged 16-24 years) and their reception toward 3 versions of the information mailers (current, revised version 1, and version 2). It was found that 69% of respondents were unaware of the Human Organ Transplant Act. The current mailer also lacks appeal, with only 3.8% of respondents preferring the current version, compared with 42% to 44% who preferred revised version 1 and 52% to 55% who preferred revised version 2. Qualitative responses suggest that the assimilation of elements in both new versions (ie, visuals, layout, and font) will likely lead to better appeal. Findings therefore reinforced the need for revision of current information mailers to captivate young adults to find out about organ donation in Singapore and make informed end-of-life decisions. Further research should consider eliciting more detailed qualitative responses in a conducive setting under a wider time frame.

Background Increasing studies have shown a vital fact that long non-coding RNAs (lncRNAs) play a considerable regulatory role in hepatocellular carcinoma (HCC) progression. However, whether ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sialyltransferase 6 antisense RNA 1 (ST8SIA6-AS1) affects the development of HCC is unclear. Methods The target genes in HCC cell lines were quantified via utilzing quantitative real-time polymerase chain reaction (RT-qPCR) analysis and western blot. Effects of ST8SIA6-AS1 on proliferative, apoptosis and migratory ability of HCC cells were proved by a series of function experiments. The cellular distribution of ST8SIA6-AS1 was examined through fluorescent in situ hybridization (FISH) assay and subcellular fractionation experiments. RNA pulldown assay was implemented to explore the target of ST8SIA6-AS1. RNA Binding Protein Immunoprecipitation (RIP) and luciferase reporter assays were performed to identify the specific relationships between miR-338-3p and ST8SIA6-AS1/ non-POU domain containing octamer binding (NONO). Results The expression of ST8SIA6-AS1 was apparently elevated in HCC cell. Silenced ST8SIA6-AS1 reduced proliferative, migratory and invasive ability of HCC cells. Moreover, ST8SIA6-AS1 targeted miR-338-3p to modulate the expression of NONO in HCC cells. Conclusions ST8SIA6-AS1 enhances the progression of HCC via miR-338-3p/NONO axis in vitro.

Keloid is a fibroproliferative disorder resulting from trauma, characterized by abnormal activation of keloid fibroblasts and excessive deposition of extracellular matrix (ECM). It affects life quality of patients and lacks of effective therapeutic targets. Protein tyrosine phosphatase 1B (PTP1B) belongs to the protein tyrosine phosphatases and participates in many cellular processes such as metabolism, proliferation and motility. It has been reported that PTP1B negatively regulated diabetic wound healing and tumor progression. However, its effects in keloid remain unclear. Here, we aimed to evaluate the effects of PTP1B on keloid fibroblasts which play essential roles in keloids pathogenesis. Our results revealed that PTP1B expression was decreased both in keloid tissues and in keloid fibroblasts compared to healthy controls. Keloid fibroblasts (KFs) showed higher cell proliferation, motility, ECM production and ERK activity than normal fibroblasts (NFs). Overexpression of PTP1B in KFs and NFs inhibited cell proliferation, motility, ECM synthesis and the MAPK/ERK signalling pathway while knockdown of PTP1B showed converse effects. The rescue experiments with ERK inhibitor further verified that MAPK/ERK signalling pathway involved in PTP1B regulatory network. Taken together, our findings indicated that overexpression of PTP1B suppressed keloid fibroblasts bio-behaviours and promoted their phenotype switch to normal cells via inhibiting the MAPK/ERK signalling pathway, suggesting it may be a potential anti-keloid therapy.

Background Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. Methods and Results A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow‐up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2‐IR). The median HOMA2‐IR level was 1.05 (interquartile range [IQR], 0.67–1.63) in our cohort of patients with HF who were nondiabetic. During follow‐up, 121 (odds ratio [OR], 46.2% [95% CI 40.2–52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2‐IR levels (0.92 [IQR, 0.61–1.37] versus 1.14 [IQR, 0.75–1.78], P =0.007), especially in nonischemic HF. Log 2 ‐transformed HOMA2‐IR was inversely correlated to improvements in EF (Pearson's r =−0.25, P Conclusions This study reveals that IR is independently associated with compromised development of HFrecEF in patients who are nondiabetic.

This study aimed to develop a vaccine that targets mutation-derived neoantigen in Chinese non-small-cell lung cancer (NSCLC).A cohort of 1862 Chinese NSCLC patients who underwent targeted sequencing with a 1021-gene panel was investigated. HLA typing was done using OptiType v1.0 and neoantigens were predicted by netMHCpan v4.0. HLA LOH was inferred using the lohhla algorithm and TMB were quantified by counting the total number of non-synonymous ones based on our panel data. CIBERSORT was utilized to estimate the TME in differentHLA-A*11:01(42.59%) was the top one allele and HLA-A*33:03(12.94%) ranked 12th.Our study identified that

Dialysis adequacy is a known risk factor for mortality in maintenance hemodialysis (MHD) patients. However, the optimal dialysis dose remains controversial. Therefore, we aimed to explore the relationship between dialysis dose and all-cause and cardiovascular disease (CVD) mortality among MHD. We examined the associations of dialysis dose with mortality in a cohort (n = 558) of MHD patients from 31 December 2015 to 31 December 2020. Dialysis adequacy was assessed using baseline Single-pool Kt/Vurea (spKt/V), which was categorized into three groups, and the lowest dose group was used as the reference category. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 214 patients died (64.5% for CVD). Compared with the low-dose group, high-dose group could reduce the risk of all-cause mortality by 33% (HR = 0.67, 95% CI: 0.47–0.98). Of note, when stratification by age, high-dose group was associated with both lower all-cause (HR = 0.46, 95% CI: 0.26–0.81) and CVD mortality (HR = 0.42, 95% CI: 0.20–0.88) among patients with age below 65 years. When stratification by dialysis age, high-dose group was associated with decreased risk of CVD mortality (HR = 0.43, 95% CI: 0.20–0.91) among patients with dialysis age over 60 months. spKt/V is a simple index of hemodialysis dose used in clinical practice and a useful modifiable factor in predicting the risk of death, especially in MHD patients under 65 years old or dialysis age more than 60 months.

Heme proteins play vital roles in regulating the reactive oxygen/nitrogen species (ROS/RNS) levels in cells. In this study, we overexpressed human wild-type (WT) myoglobin (Mb) and its double mutant, F43H/H64A Mb with enhanced nitrite reductase (NIR) activity, in the typical representative triple-negative breast cancer cell, MDA-MB-231 cells. The results showed that the overexpression of F43H/H64A Mb increased the level of nitric oxide (NO) and the degree of oxidative stress, and then activated Akt/MAPK mediated apoptotic cascade, whereas WT Mb showed the opposite effect. This study indicates that Mb plays an important role in maintaining the balance of the cellular redox system and could thus be a valuable target for cancer therapy.