Background:Background: Alcohol-related liver disease (ALD) is the leading cause of liver disease-related deaths globally, necessitating new treatments. This study investigates the role of long intergenic noncoding RNA (lincRNA)-p21 in ALD and explores therapeutic strategies for liver injury. Methods:We identified lncRNAs linked to ethanol-induced liver injury using the Gene Expression Omnibus (GEO) database. Experiments were conducted to assess the function of lincRNA-p21 in ALD both in vivo and in vitro. Autophagy was analyzed through electron microscopy, autophagic flow, and protein expression. Bioinformatics explored underlying mechanisms, focusing on m6A modification of lincRNA-p21 by ALKBH5 using RNA Immunoprecipitation (RIP) and meRIP-PCR. Ferroptosis was induced with erastin, and its levels were measured by cell ROS and viability. A nanoplatform-based system was developed to co-deliver a plasmid encoding lincRNA-p21 and a ferroptosis inhibitor. We developed a nanoplatform-based co-delivery system to deliver a plasmid encoding lincRNA-p21 and the ferroptosis inhibitor ferrostatin-1 (ferr-1/lincRNA-p21@NP) to the liver. Results:LincRNA-p21 protected liver cells against ethanol-induced injury by promoting autophagy. ALKBH5 mediated the m6A demethylation and lincRNA-p21 upregulation. However, we revealed a dual-edged sword function for lincRNA-p21 in ethanol-induced liver injury in mice. LincRNA-p21 reduced acute ethanol-induced cell injury by enhancing autophagy but exacerbated chronic ethanol-induced liver cell injury by increasing ferroptosis. In vivo and in vitro analyses showed favorable therapeutic effects of ferr-1/lincRNA-p21@NPs on ALD. Conclusion:These results show that lincRNA-p21 affects autophagy and ferroptosis, and the ferr-1/lincRNA-p21@NP nanosystem can provide protection against ALD.

Shikonin (SHK) possesses potent antitumor activity; however, its severe non‑selective toxicity greatly limits the feasibility of conventional systemic administration for cancer therapy. Likewise, mild photothermal therapy (PTT) has intrinsic limitations, including inadequate induction of immunogenic cell death (ICD) and compensatory activation of immunosuppressive pathways, such as increased IDO1 activity and PD‑L1 expression. In the present study, low‑dose SHK and gold nanorods were co‑encapsulated within a supramolecular hydrogel (mPECT) and administered by intratumoral injection to achieve localized combination therapy with mild PTT. Mild PTT rapidly triggered antitumor immune activation within the immunosuppressive tumor microenvironment, whereas SHK sustained this response by suppressing PTT‑induced IDO1 activation and PD‑L1 upregulation and by markedly enhancing ICD. The mPECT hydrogel enabled prolonged local retention and controlled release of SHK, minimizing rapid systemic exposure while preserving therapeutic efficacy at the tumor site. This localized combination of SHK and mild PTT elicited a robust adaptive antitumor immune response that not only inhibited primary tumor growth but also suppressed the progression of untreated distant tumors and generated durable antitumor immune memory. These findings indicate that a single intratumoral administration of low‑dose SHK‑loaded hydrogel combined with mild PTT can induce potent systemic antitumor immunity, supporting the further development of localized SHK‑based therapeutic strategies for the treatment of immune‑cold tumors.

Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.

In China, lung cancer stands as the leading cause of cancer-related deaths, often resulting in brain metastases (BM) that severely compromise patients’ quality of life and reduce survival outcomes. The delivery of drugs to the brain is further complicated by the blood-brain barrier (BBB). To address this, we developed EGFR single-chain fragment variable (scFv)-modified macrophage membrane liposomes (scFv-MML) encapsulating LPCAT1 siRNA (scFv-MML@LPCAT1si) as a targeted therapy for non-small cell lung cancer (NSCLC) BM. EGFR scFv-pcDNA3.1(-) plasmids were transfected into RAW 264.7 cells to generate RAW 264.7-scFv cells. Macrophage membranes were isolated from these cells and used to coat liposomes (Lip) encapsulating LPCAT1 siRNA via extrusion. The cellular uptake, LPCAT1 silencing, and anti-tumor efficacy of scFv-MML@LPCAT1si were evaluated in vitro using PC9 lung cancer cells. In vivo studies were performed in a mouse model of NSCLC BM to assess tumor targeting, accumulation, and therapeutic effects. In vitro, scFv-MML@LPCAT1si exhibited superior cellular uptake and silencing of LPCAT1 expression in EGFR-positive PC9 cells compared to control liposomes, leading to increased cell apoptosis and decreased proliferation. In vivo, scFv-MML@LPCAT1si showed improved tumor targeting and accumulation in the brain, effectively slowing tumor growth and reducing body weight loss in mice with NSCLC BM. The biodistribution study revealed sustained tumor fluorescence intensity for more than 24 h after injection, with significant retention of siRNA within the tumor site. No significant systemic toxicity or organ damage was observed in mice treated with scFv-MML@LPCAT1si. Our findings suggest that scFv-MML@LPCAT1si represents a promising targeted therapy for NSCLC BM, leveraging the unique properties of scFv-MML to traverse the BBB and deliver therapeutic payloads to tumor sites with high accuracy and efficiency.

Current treatment strategies for high-grade gliomas have a limited overall patient benefit. Here, Methylated RNA immunoprecipitation sequencing (MeRIP-seq) of glioma was conducted to screen the lncRNA regulated by m6A modification in glioma, and provide an innovative chemotherapeutic strategy to improved the therapeutic efficacy. To elucidate the impact and the molecular mechanism of ALKBH5/SH3RF3-AS1/SH3RF3 regulation on glioma malignancy, proliferation phenotypic assays, MeRIP-qPCR, RIP-qPCR and western blotting were used. Expressions and clinical significances of ALKBH5, SH3RF3-AS1, and SH3RF3 were assessed in tissue chip. Furthermore, we designed a nanodrug (NanoPCPT/siRNA@U251) for the targeted co-delivery of CPT (targeting type Ⅰ topoisomerase) and si-SH3RF3-AS1 (inhibiting SH3RF3, a Rac1-JNK activator) in glioma treatment. SH3RF3-AS1 was demethylated and overexpressed in glioma. We elucidated the mechanistic link between ALKBH5-mediated N6-methyladenosine (m6A) modification and SH3RF3-AS1 expression, and the cis-regulation of SH3RF3-AS1 to SH3RF3. Clinically, the ALKBH5, SH3RF3-AS1, and SH3RF3 expression increased with increasing glioma grade, high SH3RF3-AS1 expression correlated with unfavorable 5-year overall survival and progression-free survival in a cohort of 148 glioma patients. SH3RF3-AS1 drived glioma progression and promoted chemoresistance to camptothecin (CPT). We designed a nanodrug (NanoPCPT/siRNA@U251) for the targeted co-delivery of CPT (targeting type Ⅰ topoisomerase) and si-SH3RF3-AS1 (inhibiting SH3RF3, a Rac1-JNK activator) in glioma treatment, and it effectively suppressed glioma cell growth both in vivo and in vitro models. Our findings provide valuable insights into the roles of m6A demethylation-mediated upregulation of SH3RF3-AS1 in supporting glioma proliferation and demonstrate the potential of NanoPCPT/siRNA@U251 as an innovative chemotherapeutic strategy for glioma.

[This corrects the article DOI: 10.3389/fgene.2024.1293668.].

Background Blended learning comprised with flipped classroom (FC) and "internet plus" is a new learning strategy that reverses the position of teacher and students in class, and provides abundant learning resources before and after class. This study aimed to assess the impact of blended learning on learning outcomes in evidence-based medicine course, and compare with traditional learning method.Methods The participants of the two groups were from two difference cohorts in Air force medical university in China. The two groups toke the same pre-test before class and then were given the teaching of same chapters of evidence-based medicine with two different learning strategy. In the blended learning group, the participants were required to create a debriefing slide about their learning outcomes and the answers of questions given in advance after study the learning material sent by teacher a week before class, and the teacher gave a detailed summary based on the common problems, and distributed multimedia resources for review. After the experiment was carried out, learning outcomes including mastering knowledge, learning satisfaction, and self-evaluation were compared.Results 37 and 39 participants were enrolled to blended learning and traditional learning groups, respectively, and no statistically significant difference were found in baseline information and pre-test grades. Statistically significant differences were found in learning outcomes including post-test score (t = 2.90, p = 0.005), changes of scores between pre-test and post-test (t = 2.49, p = 0.022), learning satisfaction (t = 12.41, p = 0.001), and self-evaluation of the two groups (t = 7.82, p = 0.001). Especially, the changes of scores between pre-test and post-test of blended learning and traditional learning groups were 4.05 (4.26), and 2.00 (2.85), respectively.Conclusions This study showed that compared with traditional learning strategy, blended learning can effectively enhanced participants' acquisition of knowledge, learning satisfaction, and self-evaluation in evidence-based medicine. Using blended learning method including "internet plus" and flipped classroom is recommended in the teaching of evidence-based medicine course.

Introduction Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation.Methods For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments.Results Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland.Conclusion Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.

BackgroundTriage is an initial important step in emergency medical rescues for mass casualty incidents, and different triage systems are used in practice. However, quantitative analysis-based evidence comparing these triage systems in mass casualty incidents is limited.ObjectiveTo compare the performance of three triage systems, simple triage and rapid treatment (START), abbreviated scoring method for combat casualty (ASMcc), and sort assess lifesaving interventions treatment/transport (SALT) system, for simulated disaster patients, as assessed by medical undergraduate students.MethodsMedical undergraduates were recruited and randomly divided into three groups to evaluate the performance of the three triage systems by using simulated disaster patient cards. The triage time, accuracy, and overtriage and undertriage rates were analyzed among groups. Furthermore, a questionnaire survey was used to investigate the responses of the participants regarding learning, practice, and satisfaction among the three triage systems.ResultsA total of 30 participants were included in the study. The participants were male medical undergraduate students with a mean age of 20.73 ± 0.45 years. ASMcc had the highest accuracy of 75% with the lowest over-triage rate of 20%, SALT had the lowest undertriage rate of 19%, and START had the shortest triage time of 12.68 ± 4.96 min (all P < 0.05). Furthermore, the results of the questionnaire survey showed that START was easy to learn and recall with high efficiency and, among the three systems, had the highest satisfaction ratings from the participants.ConclusionThe results of the study showed that the three triage systems had their own characteristics and advantages, and they are all suitable for use in mass casualty incidents. Further studies involving more triage systems with data based on real conditions are recommended.

Purpose POSTN as an ECM protein and M2-polarized TAMs exhibit pro-tumor roles. However, having little knowledge of the influence of POSTN on the proliferation of HNSCC cells and the crosstalk between POSTN and M2-skewed macrophages in HNSCC. Materials and Methods We applied the public database to analyze the association of this differential expression gene with the survival rate and CD206 in HNSCC. Through IHC staining, we further explored the protein expression of POSTN and its correlation with CD206 via linear regression analysis. We explored the effect of POSTN on the proliferation of HNSCC cells and the regulatory mechanism of POSTN for macrophages by lentivirus infection, Western blotting, CCK-8, plate clone formation assay, immunofluorescence staining, Transwell, Western blotting, and qRT-PCR experiments. Results We uncovered that the mRNA and protein expression levels of POSTN were overexpressed in HNSCC tissues and it was decreased as the survival rate elevated. We discovered the mRNA expression level of CD206 is up-regulated in HNSCC tissues, which showed a conspicuously positive correlation with POSTN in mRNA and protein levels. IHC analysis demonstrated the association between high POSTN protein expression and lymph node metastasis. Our study suggested that POSTN promoted HNSCC cell proliferation and also fostered chemotactic migration and the activation of M2 likely mediated by integrinβ3. Conclusion Our study suggested POSTN as an oncogene in tumor progression, revealed the crosstalk of it between tumor cells and macrophages probably through the interaction with integrinβ3, and emphasized the possibility of treating HNSCC by targeting POSTN or POSTN-mediated TAM recruitment.

This study aimed to evaluate the diagnostic value of chemiluminescence immunoassay (CLIA), passive particle agglutination (PPA), and indirect immunofluorescence assay (IFA) in detecting Mycoplasma pneumoniae infection in children. Serum samples from 165 children with acute community-acquired respiratory tract infections were examined using CLIA, PPA, and IFA, and consistency coefficient, specificity, and sensitivity were analyzed. Compared with the PPA (titer ≥ 1:160), the consistency coefficients of the immunoglobulin(Ig)M-CLIA, immunoglobulin(Ig)G-CLIA and IgM-IFA methods were 93.94%, 75.76%, and 83.64%, respectively. The positive likelihood ratio (PLR) and specificity of IgM-CLIA was 19.40 and 95.49%, respectively. The consistency coefficient of (IgM+IgG)-CLIA and PPA (titer ≥ 1:160) was 89.1%, and the sensitivity and negative predictive value of (IgM+IgG)-CLIA were 96.88% and 98.94%, respectively. CLIA MP-IgM has high concordance with PPA, and its specificity and sensitivity are higher than those of CLIA MP-IgG and IFA MP-IgM, suggesting its better diagnosis of early MP infection. The sensitivity and negative predictive value of CLIA MP (IgM+IgG) were higher than those of PPA or IFA, indicating that it should be considered as a priority in the diagnosis of MP infection.

OBJECTIVE:Atrial fibrillation is the most common arrhythmia of clinical significance and hypertension is one of its major risk factors. This study aimed to evaluate the diagnostic accuracy of an automated oscillometric blood pressure (BP) monitor with the function of atrial fibrillation detection for atrial fibrillation screening. MATERIALS AND METHODS:Patients attending outpatient cardiology clinics were recruited for atrial fibrillation screening by the BP monitor with triplicate BP measurements for atrial fibrillation detection. Furthermore, a single-lead ECG was recorded simultaneously for comparison as the reference standard. The diagnostic test's evaluation index were analyzed, including sensitivity, specificity, and receiver operator characteristic (ROC) analysis. RESULTS:A total of 295 participants were analyzed including 166 males and 129 females, with an average age of 72.5 ± 5.9 years. The sensitivity and specificity for atrial fibrillation detection by the device were 1.000 and 0.904, respectively, with the area under the ROC curve of 0.952 (95% confidence interval: 0.929-0.975, P  < 0.001). Furthermore, the device had a Kappa-value of 0.781 ( P  < 0.001) with the single-lead ECG in detecting atrial fibrillation. CONCLUSION:The automated oscillometric BP monitor (G.LAB MD41A0) with atrial fibrillation detection function has high sensitivity and specificity with good accuracy for atrial fibrillation screening, which could be used as a reliable screening tool for the early detection of atrial fibrillation with potential benefits.

BackgroundMachine learning (ML) models provide more choices to patients with diabetes mellitus (DM) to more properly manage blood glucose (BG) levels. However, because of numerous types of ML algorithms, choosing an appropriate model is vitally important. ObjectiveIn a systematic review and network meta-analysis, this study aimed to comprehensively assess the performance of ML models in predicting BG levels. In addition, we assessed ML models used to detect and predict adverse BG (hypoglycemia) events by calculating pooled estimates of sensitivity and specificity. MethodsPubMed, Embase, Web of Science, and Institute of Electrical and Electronics Engineers Explore databases were systematically searched for studies on predicting BG levels and predicting or detecting adverse BG events using ML models, from inception to November 2022. Studies that assessed the performance of different ML models in predicting or detecting BG levels or adverse BG events of patients with DM were included. Studies with no derivation or performance metrics of ML models were excluded. The Quality Assessment of Diagnostic Accuracy Studies tool was applied to assess the quality of included studies. Primary outcomes were the relative ranking of ML models for predicting BG levels in different prediction horizons (PHs) and pooled estimates of the sensitivity and specificity of ML models in detecting or predicting adverse BG events. ResultsIn total, 46 eligible studies were included for meta-analysis. Regarding ML models for predicting BG levels, the means of the absolute root mean square error (RMSE) in a PH of 15, 30, 45, and 60 minutes were 18.88 (SD 19.71), 21.40 (SD 12.56), 21.27 (SD 5.17), and 30.01 (SD 7.23) mg/dL, respectively. The neural network model (NNM) showed the highest relative performance in different PHs. Furthermore, the pooled estimates of the positive likelihood ratio and the negative likelihood ratio of ML models were 8.3 (95% CI 5.7-12.0) and 0.31 (95% CI 0.22-0.44), respectively, for predicting hypoglycemia and 2.4 (95% CI 1.6-3.7) and 0.37 (95% CI 0.29-0.46), respectively, for detecting hypoglycemia. ConclusionsStatistically significant high heterogeneity was detected in all subgroups, with different sources of heterogeneity. For predicting precise BG levels, the RMSE increases with a rise in the PH, and the NNM shows the highest relative performance among all the ML models. Meanwhile, current ML models have sufficient ability to predict adverse BG events, while their ability to detect adverse BG events needs to be enhanced. Trial RegistrationPROSPERO CRD42022375250; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375250

铁死亡作为一种新型程序性细胞死亡方式,通过脂质过氧化作用引起细胞死亡.靶向铁死亡成为肿瘤治疗的新策略.越来越多研究表明肿瘤细胞铁死亡和免疫细胞铁死亡能够参与调节肿瘤微环境,影响肿瘤免疫治疗效果.本文主要阐述铁死亡与肿瘤细胞和淋巴系、骨髓系免疫细胞之间的信息交流和相互作用,旨在为肿瘤免疫治疗与靶向铁死亡途径的联合策略提供理论基础.

Objective To investigate the clinical manifestations and imaging characteristics of pulmonary cryptococcosis, and discuss its guidance in diagnosing. Methods The clinical data of patients diagnosed with cryptococcosis in our hospital from January 2014 to May 2020 were collected and retrospectively analyzed. Patients were divided into the immunocompromised group and the immunocompetent group. The symptomatic features, laboratory examination, imaging manifestations, and curative effect were analyzed. Results The most common symptoms of patients were cough and sputum production, followed by fever. The immunocompetent group has a significantly higher accident rate of cough and fever than the immunocompromised group, while the immunocompromised group has a significantly higher accident rate of headache and dizziness ( P < 0.05). The positive rate of serum cryptococcal capsular antigen (CrAg) test of the two groups were 83.33% and 86.96%, respectively. While the positive rate of CrAg test in cerebrospinal fluid of the immunocompromised group was significantly higher than that of the immunocompetent group ( P < 0.05). The lesions of pulmonary cryptococcosis were predominantly present in the lower part of the lung periphery and significantly distributed in the right lung ( P < 0.05). The most common imaging finding of pulmonary cryptococcosis was halo sign (64.58%), followed by multiple nodules, and trachea sign was significantly more common in the immunocompetent group. Conclusions Cryptococcosis has an insidious onset, which can infect healthy people as well. Conducting a CrAg test is good for screening and diagnosing cryptococcosis. We should be alert for the high risk of cryptococcal meningoencephalitis in patients with compromised immune function.

Gliomas are the most common central cancer with high aggressive-capacity and poor prognosis, remaining to be the threat of most patients. With the blood–brain barrier and highly malignant progression, the efficacy of high-intensity treatment is limited. The N6-methyladenine (m6A) modification is found in rRNA, snRNA, miRNA, lncRNA, and mRNA, influencing the metabolism and translation of these RNAs and consequently regulating the proliferation, metastasis, apoptosis, etc. of glioma cells. The key role that m6A modification in gliomas has played makes it a prospective target for diagnosis and treatment. However, with studying deeper in m6A modification and gliomas, the conclusion and mechanism are abundant and complex. This review focused on the dysregulation of m6A regulators and m6A modification of key genes and pathways in Hallmarks of gliomas. Furthermore, the potential of exploiting m6A modification for gliomas diagnosis and therapeutics was also discussed. This review will summarize the recent studies about m6A modification, revealing that m6A modification plays an important role in the malignant progression, angiogenesis, microenvironment, and genome instability in gliomas by exploring the interaction and network between m6A modification-related regulators and classical tumor-related genes. And it might provide some clue for the molecular mechanism, diagnosis, and treatment of gliomas.

OBJECTIVES:To systematically evaluate the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in ALK-rearranged positive non-small cell lung cancer (NSCLC) with brain metastases, and update the overall survival (OS) outcomes of the second-generation and third-generation ALK (ALK-2ndG/3rdG) inhibitors versus first-generation (ALK-1stG) inhibitors. DESIGN:The study is in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Randomised controlled trials (RCTs) published up to 3 November 2021 were retrieved from PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov. SETTING:RCTs from any country and healthcare setting. PARTICIPANTS:Patients with advanced ALK-positive NSCLC with or without brain metastases. INTERVENTIONS AND COMPARISONS:The interventions were ALK-2ndG/3rdG; the control arm was ALK-1stG or crizotinib. PRIMARY AND SECONDARY OUTCOME MEASURES:Primary outcomes included median progression-free survival and median OS. Secondary outcomes included systemic objective response rate, intracranial response rate and rate of grade ≥3 adverse events (AEs). RESULTS:A total of 12 RCTs involving 3156 patients were analysed. Compared with ALK-1stG (crizotinib), ALK-2ndG (alectinib, brigatinib, ceritinib and ensartinib) significantly improved the OS (HR: 0.72, 95% CI: 0.57 to 0.90, p=0.004) and intracranial response of patients with any brain metastases, especially with measurable (diameter ≥10 mm) brain metastases. Network meta-analysis demonstrated that ALK-3rdG (lorlatinib) had superior efficacy for patients with brain lesions, but performed a distinct side-effect profile. Moreover, alectinib showed superior efficacy and lower toxicity in ALK-positive NSCLC. CONCLUSION:Treatment with ALK-2ndG inhibitors significantly improved OS compared with crizotinib, and alectinib has less severe AEs than any other ALK inhibitors with moderate-high efficacy. The limited OS follow-up and inadequate sample sizes might contribute to having no statistically significant difference in OS of lorlatinib versus crizotinib. More high-quality and longer follow-up RCTs are warranted to prove our findings. PROSPERO REGISTRATION NUMBER:CRD42021292245.

Objective To evaluate the accuracy of the KANG KC-2850 ambulatory blood pressure monitor (ABPM) for clinical blood pressure (BP) measurement according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) universal standard (ISO 81060-2:2018). Methods BP was sequentially measured and compared with a standard mercury sphygmomanometer in 85 eligible participants. A standard adult cuff (22–3232 cm) was used for test device measurements. A total of 255 comparison pairs were obtained and analyzed according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO universal standard. Results The standard requirements were followed precisely. For the validation Criterion 1, the mean ± SD of the differences between the test device and reference BP readings was −1.12 ± 5.01 and −0.33 ± 4.52 mmHg for SBP and DBP, respectively. For Criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 3.59 and 3.60 mmHg for SBP and DBP, respectively. Conclusion The KANG KC-2850 ABPM met all the requirements for validation by the AAMI/ESH/ISO universal standard and can be recommended for clinical use in general population.

Context The potential anti-inflammatory bioactivities of β-hydroxyisovalerylshikonin (β-HIVS) remain largely unknown.Objective This study investigated the anti-inflammatory effects and underlying mechanisms of β-HIVS.Materials and methods RAW 264.7 cells stimulated with LPS (100 ng/mL) for 24 h were treated with the non-cytotoxic doses of β-HIVS (0.5 or 1 μM, determined by MTT and Trypan blue staining), qRT-PCR and FCM assay were used to examine macrophage polarization transitions. Western blotting was used to evaluate the activation of the AMPK/Nrf2 pathway. In vivo, C57BL/6 mice were randomly divided into vehicle control, LPS (10 mg/kg), and β-HIVS (2.5 mg/kg) combined with LPS (10 mg/kg) groups, blood samples, BALF, and lung tissues of mice were subjected to ELISA, qRT-PCR, FCM, and H&E staining.Results β-HIVS (1 μM) inhibited LPS-induced expression of M1 macrophage markers (TNF-α: 0.29-fold, IL-1β: 0.32-fold), promoted the expression of M2 macrophage markers (CD206: 3.14-fold, Arginase-1: 3.98-fold) in RAW 264.7 cells; mechanistic studies showed that β-HIVS increased the expression of nuclear Nrf2 (2.04-fold) and p-AMPK (3.65-fold) compared with LPS group (p < 0.05). In vivo, β-HIVS decreased the levels of pro-inflammatory cytokines (TNF-α: 1130.41 vs. 334.88 pg/mL, IL-1β: 601.89 vs. 258.21 pg/mL in serum; TNF-α: 893.07 vs. 418.21 pg/mL, IL-1β: 475.22 vs. 298.54 pg/mL in BALF), decreased the proportion of M1 macrophages (77.83 vs. 68.53%) and increased the proportion of M2 macrophages (13.55 vs. 19.56%) in BALF, and reduced lung tissue damage and septic mice survival (p < 0.05).Conclusions These results indicate that β-HIVS may be a new potential anti-inflammatory agent.

Objective The objective of this study is to determine the accuracy of the G.LAB MD41A0 upper-arm oscillometric blood pressure (BP) monitor for self/home BP measurement in patients with diabetes according to the Association for the Advancement of Medical Instrumentation /European Society of Hypertension /International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018). Methods Patients with diabetes were recruited according to AAMI/ESH/ISO Universal Standard using the same arm sequential BP measurement method. The standard cuff of the test device was used for arm circumference 22-44 cm. Results A total of 92 patients with diabetes were recruited and 85 were analyzed with an average age of 55.1 +/- 17.7 years, 48 men, and arm circumference of 32.0 +/- 6.0 cm. For the validation Criterion 1, the mean +/- SD of the differences between the test device and reference BP readings was 0.89 +/- 6.04/-0.84 +/- 5.11 mmHg (systolic/diastolic). For Criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 4.23/4.19 mmHg (systolic/diastolic). Conclusion The G.LAB MD41A0 upper arm BP monitor fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in patients with diabetes and can be recommended for self/home use.