Vitamin D levels and its influencing factors in pregnant women in mainland China: A systematic review and meta-analysis.

OBJECTIVE: Maternal vitamin D deficiency is a prevalent public health issue worldwide. While isolated reports from certain cities in China have highlighted the existence of maternal vitamin D deficiency, no nationwide investigation has been conducted on this topic. Therefore, we conducted a meta-analysis and systematic review to examine the prevalence and associated influencing factors of maternal vitamin D deficiency in mainland China. This study aims to provide a theoretical foundation for future prevention and supplementation strategies for maternal vitamin D. METHODS: We retrieved relevant Chinese and English literature on the status of maternal vitamin D deficiency in mainland China from databases such as CNKI, Wanfang Data, VIP, CBM, Web of Science, Google Scholar, and PubMed. The literature search and database construction were conducted until September 8, 2023. Data were extracted and synthesized following PRISMA guidelines.After literature screening and quality assessment, we performed meta-analysis, sensitivity analysis, and identified publication bias using RevMan 5.3 software. RESULTS: A total of 26 articles were reviewed, involving 128,820 pregnant women. Among them, 108,768 had vitamin D insufficiency or deficiency, resulting in a prevalence of 84% (95% CI: 81%~88%). Subgroup analysis revealed the highest prevalence of vitamin D deficiency or insufficiency among pregnant women in mainland China to be in the northwest region (94%, 95% CI: 94%~95%). Furthermore, the highest prevalence was observed during the winter and spring seasons (80%, 95% CI: 77%~83%) and in the early stages of pregnancy (93%, 95% CI: 90%~95%). Significant statistical differences (P<0.05) were found among these three subgroups. No publication bias was detected, and sensitivity analysis indicated the stability of the meta-analysis outcome. CONCLUSION: This study provides evidence of the prevalence of vitamin D deficiency or insufficiency among pregnant women in mainland China. To improve the overall health and well-being of the population, relevant health authorities should develop policies aimed at alleviating this phenomenon.

Baicalein triggers ferroptosis in colorectal cancer cells via blocking the JAK2/STAT3/GPX4 axis.

Colorectal cancer (CRC) is a prevalent form of gastrointestinal malignancy with challenges in chemotherapy resistance and side effects. Effective and low toxic drugs for CRC treatment are urgently needed. Ferroptosis is a novel mode of cell death, which has garnered attention for its therapeutic potential against cancer. Baicalein (5, 6, 7-trihydroxyflavone) is the primary flavone extracted from the dried roots of Scutellaria baicalensis that exhibits anticancer effects against several malignancies including CRC. In this study, we investigated whether baicalein induced ferroptosis in CRC cells. We showed that baicalein (1-64 µM) dose-dependently inhibited the viability of human CRC lines HCT116 and DLD1. Co-treatment with the ferroptosis inhibitor liproxstatin-1 (1 µM) significantly mitigated baicalein-induced CRC cell death, whereas autophagy inhibitor chloroquine (25 µM), necroptosis inhibitor necrostatin-1 (10 µM), or pan-caspase inhibitor Z-VAD-FMK (10 µM) did not rescue baicalein-induced CRC cell death. RNA-seq analysis confirmed that the inhibitory effect of baicalein on CRC cells is associated with ferroptosis induction. We revealed that baicalein (7.5-30 µM) dose-dependently decreased the expression levels of GPX4, key regulator of ferroptosis, in HCT116 and DLD1 cells by blocking janus kinase 2 (JAK2)/STAT3 signaling pathway via direct interaction with JAK2, ultimately leading to ferroptosis in CRC cells. In a CRC xenograft mouse model, administration of baicalein (10, 20 mg/kg, i.g., every two days for two weeks) dose-dependently inhibited the tumor growth with significant ferroptosis induced by inhibiting the JAK2/STAT3/GPX4 axis in tumor tissue. This study demonstrates that ferroptosis contributes to baicalein-induced anti-CRC activity through blockade of the JAK2/STAT3/GPX4 signaling pathway, which provides evidence for the therapeutic application of baicalein against CRC.

Prognostic performance of soluble urokinase plasminogen activator receptor for heart failure or mortality in Western and Asian patients with acute breathlessness.

AIMS: The performance of circulating soluble urokinase plasminogen activator receptor (suPAR) for predicting the composite endpoint of subsequent heart failure (HF) hospitalisation and/or death at 1 year was assessed in (i) patients with undifferentiated breathlessness, and generalisability was compared in (ii) disparate Western versus Asian sub-cohorts, and in (iii) the sub-cohort adjudicated with HF. METHODS AND RESULTS: Patients with acute breathlessness were recruited from the emergency departments in New Zealand (NZ, n = 612) and Singapore (n = 483). suPAR measured in the presentation samples was higher in patients incurring the endpoint (n = 281) compared with survivors (5.2 ng/mL vs 3.1 ng/mL, P < 0.0001). The discriminative power of suPAR for endpoint prediction was c-statistic of 0.77 in the combined population, but was superior in Singapore than NZ (c-statistic: 0.83 vs 0.71, P < 0.0001). Although the highest suPAR tertile (>4.37 ng/mL) was associated with risks of >4-fold in NZ, >20-fold in Singapore, and ≥3-fold in HF for incurring the outcome, there was no interaction between country and suPAR levels after adjustment. Multivariable analysis indicated suPAR to be robust in predicting HF/death at 1-year [hazard ratio: 1.9 (95% CI:1.7 to 2.0) per SD increase] and improved risk discrimination for outcome prediction in HF (∆0.06) and for those with NT-proBNP >1000 pg/mL (∆0.02). CONCLUSION: suPAR is a strong independent predictor of HF and/or death at 1 year in acutely breathless patients, in both Asian and Western cohorts, and in HF. suPAR may improve stratification of acutely breathless patients, and in acute HF, for risk of later onset of heart failure or mortality.

Fe-Fe bonding in the rhombic Fe4 cores of the Zintl clusters [Fe4E18]4- (E = Sn and Pb).

We report here the synthesis and characterization of two endohedral Zintl-ion clusters, [Fe4Sn18]4- and [Fe4Pb18]4-, which contain rhombic Fe4 cores. The Fe-Fe bond lengths are all below 2.5 Å, distinctly shorter than in the corresponding Cu clusters, indicating the presence of Fe-Fe bonding. Subtle differences in the structure of the Fe4 core between the two clusters suggest that the change in tetrel element causes a change in electronic ground state, with a very short Fe-Fe bond length of 2.328 Å present across the diagonal of the rhombus in the lead case.

An Investigation of the Immune Microenvironment and Genome during Lung Adenocarcinoma Development.

Background: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are two consecutive pathological processes that occur before invasive lung adenocarcinoma (LUAD). However, our understanding of the immune editing patterns during the progression of LUAD remains limited. Furthermore, we know very little about whether alterations in driver genes are involved in forming the tumor microenvironment (TME). Therefore, it is necessary to elucidate the regulatory role of TME in LUAD development from multiple dimensions, including immune cell infiltration, molecular mutation events, and oncogenic signaling pathways. Methods: We collected 145 surgically resected pulmonary nodule specimens, including 28 cases of AIS, 52 cases of MIA, and 65 cases of LUAD. Immunohistochemistry (IHC) was used to detect the expression of immune markers CD3, CD4, CD8, CD68 and programmed death ligand 1 (PD-L1). Genomic data and TMB generated by targeted next-generation sequencing (NGS). Results: LUAD exhibited higher levels of immune cell infiltration, tumor mutation burden (TMB), and activation of oncogenic pathways compared to AIS and MIA. In LUAD, compared to epidermal growth factor receptor (EGFR) single mutation and wild-type (WT) samples, cases with EGFR co-mutations showed a more pronounced rise in the CD4/CD8 ratio and CD68 infiltration. Patients with low-density lipoprotein (LDL) receptor-related protein 1B (LRP1B) mutation have higher TMB and PD-L1 expression. The transition from AIS to LUAD tends to shift the TME towards the PD-L1+CD8+ subtype (adaptive resistance). Progression-associated mutations (PAMs) were enriched in the lymphocyte differentiation pathway and related to exhausted cells' phenotype. Conclusion: Tumor-infiltrating immune cells tend to accumulate as the depth of LUAD invasion increases, but subsequently develop into an immune exhaustion and immune escape state. Mutations in EGFR and LRP1B could potentially establish an immune niche that fosters tumor growth. PAMs in LUAD may accelerate disease progression by promoting T cell differentiation into an exhausted state.

Point-of-care ultrasound use in COVID-19: a narrative review.

Background and Objective: The coronavirus disease 2019 (COVID-19) pandemic that began in early 2020 resulted in significant mortality from respiratory tract infections. Existing imaging modalities such as chest X-ray (CXR) lacks sensitivity in its diagnosis while computed tomography (CT) scan carries risks of radiation and contamination. Point-of-care ultrasound (POCUS) has the advantage of bedside testing with higher diagnostic accuracy. We aim to describe the various applications of POCUS for patients with suspected severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the emergency department (ED) and intensive care unit (ICU). Methods: We performed literature search on the use of POCUS in the diagnosis and management of COVID-19 in MEDLINE, Embase and Scopus databases using the following search terms: "ultrasonography", "ultrasound", "COVID-19", "SARS-CoV-2", "SARS-CoV-2 variants", "emergency services", "emergency department" and "intensive care units". Search was performed independently by two reviewers with any discrepancy adjudicated by a third member. Key Content and Findings: Lung POCUS in patients with COVID-19 shows different ultrasonographic features from pulmonary oedema, bacterial pneumonia, and other viral pneumonia, thus useful in differentiating between these conditions. It is more sensitive than CXR, and more accessible and widely available than CT scan. POCUS can be used to diagnose COVID-19 pneumonia, screen for COVID-19-related pulmonary and extrapulmonary complications, and guide management of ICU patients, such as timing of ventilator weaning based on lung POCUS findings. Conclusions: POCUS is a useful and rapid point-of-care modality that can be used to aid in diagnosis, management, and risk stratification of COVID-19 patients in different healthcare settings.

Snap-shots of cluster growth: structure and properties of a Zintl ion with an Fe3 core, [Fe3Sn18]4.

The endohedral Zintl-ion cluster [Fe3Sn18]4- contains a linear Fe3 core with short Fe-Fe bond lengths of 2.4300(9) Å. The ground state is a septet, with significant σ and π contributions to the Fe-Fe bonds. The Sn18 cage is made up of two partially fused Sn9 fragments, and is structurally intermediate between [Ni2CdSn18]6-, where the fragments are clearly separated and [Pd2Sn18]4-, where they are completely fused. It therefore represents an intermediate stage in cluster growth. Analysis of the electronic structure suggests that the presence of the linear Fe-Fe-Fe unit is an important factor in directing reactions towards fusion of the two Sn9 units rather than the alternative of oligomerization via exo bond formation.

Teledermatology in an emergency department: benefits and gaps.

BACKGROUND: Teledermatology has provided new avenues through which dermatologists can provide healthcare. Teledermatology was introduced to the Emergency Department (ED) to enable immediate dermatological consult. We aimed to assess the impact of teledermatology on the management of dermatological conditions by emergency medicine physicians and subsequent health resource utilization. METHODS: We conducted a retrospective review of teledermatology referrals from the ED of our tertiary hospital in Singapore from June 2015 to December 2019. The dermatological conditions, the triaging and treatment recommendations were analyzed. Follow-up plans were recorded. RESULTS: Between June 2015 and December 2019, 147 patients were referred from the ED via teledermatology; 11 (7.5%) were admitted, and 136 (92.5%) were recommended to be discharged with a dermatological diagnosis and management plan. If required, a follow-up appointment in the dermatology specialist clinic was arranged. Of the 136 patients who were discharged, 129 (94.9%) patients were provided with outpatient appointment in the dermatology clinic, out of which 110 patients returned for follow-up. 90 (81.8%) patients retained the initial teledermatology diagnoses and 20 (18.2%) patients had their teledermatology diagnoses revised after in-person review. CONCLUSIONS: Teledermatology allows for more efficient triaging of patients with dermatological conditions. Reliability between teledermatology and clinic-based examination is good. Patients may be managed mainly in the outpatient setting with appropriate specialty-directed treatment, return advice, and appropriately-triaged follow-up outpatient appointment.

Dynamic immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in people living with HIV: A longitudinal observational study.

People living with HIV (PLWH) have poor outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); vaccination reduces the associated mortality. The humoral immune response dynamics after booster inactivated vaccinations in PLWH remain unclear. In this longitudinal observational study, 100 PLWH after primary inactivated SARS-CoV-2 vaccination were consecutively recruited and followed up. After booster vaccination (BV), neutralizing antibodies (NAbs) were detected at 1 month from all the PLWH, and the titer increased sixfold compared to that associated with the primary vaccination (PV), similar to that in healthy controls after BV. The NAbs titer declined over time after BV, but remained higher at 6 months than after PV. The NAbs response was elevated after BV with CD4 count <200 cells/µL, it was the poorest among the different CD4 cell count subgroups. Similar results were observed for anti-RBD-IgG responses. Moreover, RBD-specific MBCs were significantly elevated after BV in PLWH. No serious AEs were observed after BV in PLWH. In conclusion, booster inactivated SARS-CoV-2 vaccination is well tolerated and can elicit robust and durable humoral responses in PLWH. PLWH may benefit from a third dose of the inactivated vaccine.

Synthesis and Characterization of [Fe3 (As3 )3 (As4 )]3- , a Binary Fe/As Zintl Cluster With an Fe3 Core.

We report here the synthesis and structural characterization of the first binary iron arsenide cluster anion, [Fe3 (As3 )3 (As4 )]3- , present in both [K([2.2.2]crypt)]3 [Fe3 (As3 )3 (As4 )] (1) and [K(18-crown-6)]3 [Fe3 (As3 )3 (As4 )]⋅en (2). The cluster contains an Fe3 triangle with three short Fe-Fe bond lengths (2.494(1) Å, 2.459(1) Šand 2.668(2) Šfor 1, 2.471(1) Å, 2.473(1) Šand 2.660(1) Šfor 2), bridged by a 2-butene-like As4 unit. An analysis of the electronic structure using DFT reveals a triplet ground state with direct Fe-Fe bonds stabilizing the Fe3 core.

Safety and immunogenicity of inactivated SARS-CoV-2 vaccines in people living with HIV.

It is important to know the safety and efficacy of vaccination in immunocompromised people living with HIV (PLWH), but currently, there is limited data on the inactivated SARS-CoV-2 vaccines' safety and immune responses in PLWH. In this prospective observational study, 139 PLWH and 120 healthy controls were enrolled and monitored for 21-105 days after a two-dose vaccination. The safety, anti-receptor binding domain IgG (anti-RBD-IgG) and anti-spike-IgG responses, and RBD-specific memory B cell (MBC) responses were evaluated. The overall adverse events within seven days were reported in 12.9% (18/139) of PLWH and 13.3% (16/120) of healthy controls. No serious adverse events occurred in both groups. Overall, the seroprevalence of anti-RBD-IgG in PLWH was significantly decreased (87.1% vs. 99.2%; p<0.001). The geometric mean end-point titer (GMT) of anti-RBD-IgG in PLWH was also reduced, especially in patients with CD4 counts <200 cells/µL, regardless of age, gender, or HIV viral load. GMTs of anti-RBD-IgG in both PLWH and healthy controls declined gradually over time. Similar results were also observed in the anti-spike-IgG response. The frequency of RBD-specific MBCs in PLWH decreased (p<0.05), and then remained stable over time. Lastly, through multivariate analysis, we found the factors that predicted a less robust response to inactivated vaccines in PLWH were a low CD4 count and long time interval after vaccination. In conclusion, inactivated vaccines are well-tolerated in PLWH but with low immunogenicity. Therefore, SARS-CoV-2 vaccines and booster doses should be given priority in PLWH, especially in patients with low CD4 counts.Trial registration: ClinicalTrials.gov identifier: NCT05043129..

Macrophage-derived exosomes mediate silica-induced pulmonary fibrosis by activating fibroblast in an endoplasmic reticulum stress-dependent manner.

Macrophages play a key role in silicosis, and exosomes are potent mediators of intercellular communication. This suggests that macrophage-derived exosomes have a potential contribution to the pathogenesis of silicosis. To investigate whether macrophage-derived exosomes promote or inhibit lung fibrosis, in vitro, silica-exposed macrophage-derived exosomes (SiO2 -Exos) were collected and cocultured with fibroblasts. The expression of collagen I and α-SMA was evaluated. Furthermore, the endoplasmic reticulum (ER) stress markers BIP, XBP1s and P-eIF2α were assessed after treatment with or without the ER stress inhibitor 4-PBA. In vivo, mice were pre-treated with the exosome secretion inhibitor GW4869 prior to silica exposure. After sacrifice, lung tissues were histologically examined, and the expression of proinflammatory cytokines (TNF-α, IL-1ß and IL-6) in bronchoalveolar lavage fluid (BALF) was measured. The results showed that the expression of collagen I and α-SMA was up-regulated after treatment with SiO2 -Exos, accompanied by increased expression of BIP, XBP1s and P-eIF2α. Pre-treatment with 4-PBA reversed this effect. More importantly, an in vivo study demonstrated that pre-treatment with GW4869 decreased lung fibrosis and the expression of TNF-α, IL-1ß and IL-6 in BALF. These results suggested that SiO2 -Exos are profibrogenic and that the facilitating effect is dependent on ER stress.

Virtual reality mobile application to improve videoscopic airway training: A randomised trial.

INTRODUCTION: Flexible bronchoscopic intubation (FBI) is an important technique in managing an anticipated difficult airway, yet it is rarely performed and has a steep learning curve. We aim to evaluate if the integration of virtual reality gaming application into routine FBI training for emergency department doctors would be more effective than traditional teaching methods. METHODS: We conducted a randomised controlled trial to compare self-directed learning using the mobile application, Airway Ex* in the intervention group versus the control group without use of the mobile application. All participants underwent conventional didactic teaching and low-fidelity simulation with trainer's demonstration and hands-on practice on a manikin for FBI. Participants randomised to the intervention arm received an additional 30 minutes of self-directed learning using Airway Ex, preloaded on electronic devices while the control arm did not. The primary outcome was time taken to successful intubation. RESULTS: Forty-five physicians (20 junior and 25 senior physicians) were enrolled, with male predominance (57.8%, 26/45). There was no difference in time taken to successful intubation (median 48 seconds [interquartile range, IQR 41-69] versus 44 seconds [IQR 37-60], P=0.23) between the control and intervention groups, respectively. However, the intervention group received better ratings (median 4 [IQR 4-5]) for the quality of scope manipulation skills compared to control (median 4 [IQR 3-4], adjusted P=0.03). This difference remains significant among junior physicians in stratified analysis. CONCLUSION: Incorporating virtual reality with traditional teaching methods allows learners to be trained on FBI safely without compromising patient care. Junior physicians appear to benefit more compared to senior physicians.

Activation of the Unreactive Bond in C70 Fullerene toward Diels-Alder Reaction by Encapsulation of a Lithium Atom.

Diels-Alder cycloaddition reaction is useful for generation of covalent derivatives of fullerenes. Diels-Alder reactions of C70 and dienes usually take place at the carbon-carbon bond that has a short bond length in C70 , while the bonds with long lengths are generally unreactive. In this paper, we investigated the reactivities of Li+ @C70 and Li@C70 toward Diels-Alder reactions with cyclohexadiene by means of density functional theory calculations. We found that the thermodynamic and kinetic reactivities of the fullerene cage are changed significantly after the encapsulation of the lithium ion or atom. The encapsulated lithium ion causes a remarkable decrease of the activation barrier for the cycloaddition reaction, which can be ascribed to the enhanced orbital interaction between cyclohexadiene and the fullerene cage. The unreactive bond with a long length in C70 is activated efficiently after the encapsulation of the lithium atom. According to the activation-strain model analysis, the improved reactivity of the long bond is associated with the small deformation energy and large interaction energy of the reactants. Unlike conventional Diels-Alder reactions that proceed through concerted mechanism, the reaction of Li@C70 and cyclohexadiene undergoes an unusual stepwise mechanism because of the open-shell electronic structure of Li@C70 .

Mid-regional pro-adrenomedullin outperforms N-terminal pro-B-type natriuretic peptide for the diagnosis of acute heart failure in the presence of atrial fibrillation.

AIMS: The performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in diagnosing acute decompensated heart failure (ADHF) among patients presenting with breathlessness is markedly impaired in the presence of atrial fibrillation (AF). We evaluated the diagnostic performance of mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin T as possible alternative markers for discrimination of ADHF in this setting. METHODS AND RESULTS: Breathless patients (n = 1107) were prospectively and contemporaneously recruited in emergency departments in Singapore and New Zealand. The diagnoses of ADHF and presence of AF were adjudicated by two clinician specialists, blinded to MR-proADM, NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) results. MR-proADM exhibited strong discrimination of ADHF with little change in performance irrespective of the presence of AF (area under the curve 0.83 in non-AF vs. 0.76 in AF) compared to NT-proBNP (0.91 vs. 0.71) and hs-cTnT (0.83 vs. 0.62), respectively. The accuracy of MR-proADM (73.3%) for diagnosing ADHF among patients with AF was superior to both NT-proBNP (61.6%) and hs-cTnT (64.6%). The superior performance of MR-proADM remained apparent when data from Singapore and New Zealand were analysed separately. CONCLUSION: In the presence of AF, MR-proADM showed greater discrimination and accuracy, and less impairment in performance compared to that in non-AF cases, for the diagnosis of ADHF, compared to the guideline-endorsed NT-proBNP.

Guideline-based learning for standard plane extraction in 3-D echocardiography.

The extraction of six standard planes in 3-D cardiac ultrasound plays an important role in clinical examination to analyze cardiac function. A guideline-based learning method for efficient and accurate standard plane extraction is proposed. A cardiac ultrasound guideline determines appropriate operation steps for clinical examinations. The idea of guideline-based learning is incorporating machine learning approaches into each stage of the guideline. First, Hough forest with hierarchical search is applied for 3-D feature point detection. Second, initial planes are determined using anatomical regularities according to the guideline. Finally, a regression forest integrated with constraints of plane regularities is applied for refining each plane. The proposed method was evaluated on a 3-D cardiac ultrasound dataset and a synthetic dataset. Compared with other plane extraction methods, it demonstrated an improved accuracy with a significantly faster running time of 0.8 s / volume . Furthermore, it showed the proposed method was robust for a range abnormalities and image qualities, which would be seen in clinical practice.