Comprehensive detection and dissection of interlineage recombination events in the SARS-CoV-2 pandemic.

The global prevalence of the XBB lineage presents a formidable challenge posed by the recombinant SARS-CoV-2 virus. The understanding of SARS-CoV-2's recombination preference assumes utmost significance in predicting future recombinant variants and adequately preparing for subsequent pandemics. Thus, an urgent need arises to establish a comprehensive landscape concerning SARS-CoV-2 recombinants worldwide and elucidate their evolutionary mechanisms. However, the initial step, involving the detection of potential recombinants from a vast pool of over 10 million sequences, presents a significant obstacle. In this study, we present CovRecomb, a lightweight methodology specifically designed to effectively identify and dissect interlineage SARS-CoV-2 recombinants. Leveraging CovRecomb, we successfully detected 135,567 putative recombinants across the entirety of 14.5 million accessed SARS-CoV-2 genomes. These putative recombinants could be classified into 1451 distinct recombination events, of which 206 demonstrated transmission spanning multiple countries, continents, or globally. Hotspot regions were identified in six specific areas, with prominence observed in the latter halves of the N-terminal domain and receptor-binding domain within the spike (S) gene. Epidemiological investigations revealed extensive recombination events occurring among different SARS-CoV-2 (sub)lineages, independent of lineage prevalence frequencies.

Regional health priorities for dementia: a roadmap for the Western Pacific.

In the Western Pacific Region, the prevalence of dementia is expected to increase, however, the diversity of the region is expected to present unique challenges. The region has varying levels of preparedness, with a limited number of countries having a specific national dementia plan and awareness campaigns. Diversity of risk and healthcare services within the region is exerting impact on diagnosis, treatment, care, and support, with most countries being under resourced. Similarly, the ability to monitor dementia-related indicators and progress research, particularly relating to treatment and clinical trial access needs to be addressed. Countries require comprehensive national plans that lay out how resources will be allocated to improve dementia literacy, train, and support carers, mobilise resources to reduce risk factors and improve research capabilities. These plans need to be informed by consumers and tailored to the region to develop an inclusive society for people living with dementia and their families.

Efficacy and safety of visepegenatide as an add-on therapy to metformin in patients with type 2 diabetes: a randomised, double-blind, parallel, placebo-controlled, phase 3 study.

Background: Visepegenatide, a once-weekly glucagon-like peptide-1 receptor agonist injection, demonstrated effective glycaemic control and good tolerability without the requirement of dose titration in the two completed phase 2 studies. We aimed to evaluate the efficacy and safety of visepegenatide in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin monotherapy in this phase 3 clinical study. Methods: This multicentre phase 3 clinical study included a 24-week, randomised, placebo-controlled, double-blind period followed by a 28-week open-label extended treatment period. Patients (N = 620) aged ≥18 and ≤75 years with glycated haemoglobin (HbA1c) ≥7.0% and ≤10.5% [≥53.0 and ≤91.27 mmol/mol], were randomized in a 1:1 ratio to receive visepegenatide 150-µg or placebo once-weekly subcutaneous injection during the double-blind period. Subsequently, the patients in the placebo group were switched to visepegenatide treatment (placebo→visepegenatide group), and the patients in the visepegenatide group continued the same treatment during the open-label extended treatment period. The primary endpoint was the change in HbA1c from baseline to week 24. Findings: At week 24, the placebo-adjusted least squares mean (LSM) change of HbA1c was -0.57% (95% CI -0.71 to -0.43) with visepegenatide (p < 0.001). The proportion of patients achieving HbA1c < 7.0% and ≤6.5% [<53 and ≤ 48 mmol/mol] was higher in the visepegenatide group versus the placebo group (115 [40.5%] vs 50 [17.9%]; p < 0.001, and 60 [21.1%] vs 17 [6.1%]; p < 0.001). Visepegenatide demonstrated a significant reduction in fasting plasma glucose and 2-h postprandial glucose compared with placebo. Trends in the improvement of these variables were maintained during the open-label extended treatment period. No severe gastrointestinal adverse event or severe hypoglycaemia was reported during the 52-week study period. Interpretation: Once-weekly injection of visepegenatide 150 µg as an add-on treatment to metformin therapy significantly improved glycaemic control and was generally well tolerated in Chinese patients with T2DM who were inadequately controlled with metformin monotherapy. Funding: The study was funded by PegBio Co., Ltd, Suzhou, China.

Rhein induces apoptosis of AGS and MGC803 cells by regulating the Ras/PI3K/AKT and p38/MAPK signaling pathway.

OBJECTIVES: Rhein is one of the main bioactive compounds in the Polygonaceae plant, and has been proven to have anti-cancer activity in some reports. But the mechanism of Rhein in the treatment of gastric cancer (GC) is limited reported. In this research, network pharmacology combined with in vitro experiments was used for systematically studying the mechanism of Rhein. METHODS: Network pharmacology confirmed the major effect signaling pathway and key targets of Rhein in the treatment of GC. Cell viability assay, colony formation assay, fluorescence probe assay, apoptosis assay, western blot and qRT-PCR verified the mechanism of Rhein in the treatment of GC cells (AGS and MGC803 cells). KEY FINDINGS: The results showed that Rhein significantly induced the apoptosis process of AGS and MGC803 cells by regulating the Ras/phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and the p38/mitogen-activated protein kinase signaling pathways. The AKT activator (SC79) and p38 inhibitor (SB202190) inhibited Rhein-induced apoptosis. CONCLUSIONS: All results proved that Rhein could be recognized as a potential natural drug for the treatment of GC.

Visual reading for [18F]Florzolotau Tau PET scans in progressive supranuclear palsy.

PURPOSE: The identification of tau accumulation within living brains holds significant potential in facilitating accurate diagnosis of progressive supranuclear palsy (PSP). While visual assessment is frequently employed, standardized methods for tau positron emission tomography (PET) specifically in PSP are absent. We aimed to develop a visual reading algorithm dedicated to the evaluation of [18F]Florzolotau PET in PSP. METHODS: 148 PSP and 30 healthy volunteers were divided into a development set (for the establishment of the reading rules; n = 89) and a testing set (for the validation of the reading rules; n = 89). For differential diagnosis, 55 α-synucleinopathies were additionally included into the testing set. The visual reading method was established by an experienced assessor (Reader 0) and was then validated by Reader 0 and two additional readers on regional and overall binary manners. A positive binding in both midbrain and globus pallidus/putamen regions was characterized as a PSP-like pattern, whereas any other pattern was classified as non-PSP-like. RESULTS: Reader 1 (94.4%) and Reader 2 (93.8%) showed excellent agreement for the overall binary determination against Reader 0. The regional binary determinations of midbrain and globus pallidus/putamen showed excellent agreement among readers (kappa > 0.80). The overall binary evaluation demonstrated reproducibility of 86.1%, 94.4% and 77.8% for three readers. The visual reading algorithm showed high agreement with regional standardized uptake value ratios and clinical diagnoses. CONCLUSION: Through the application of the suggested visual reading algorithm, [18F]Florzorotau PET imaging demonstrated a robust performance for the imaging diagnosis of PSP.

Prediction of testicular histology in azoospermia patients through deep learning-enabled two-dimensional grayscale ultrasound.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.

Mettl1 knockdown alleviates cardiac I/R injury in mice by inactivating the Mettl1-CYLD-P53 positive feedback loop.

The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H2O2-treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury.

A highly potential Zn biofortification tool: MTP1 in Triticum aestivum.

TaMTPs belong to metal tolerance proteins (MTPs) family in common wheat and have significant potential to address the "hidden hunger" caused by inadequate dietary intake of a key micronutrient (Zn). In this study, a total of 33 MTP members in Triticum aestivum were identified, among which six TaMTP1-likes were closely related to Arabidopsis thaliana MTP1 and were designated as TaMTP1-A/B/D and TaMTP1.1-A/B/D. When heterologously expressed in yeast mutants, TaMTP1-likes complemented their hypersensitivity to Zn and Co, and three of the most metal-resistant members, TaMTP1-A, TaMTP1-D and TaMTP1.1-B, were selected for further subcellular localization and functional experiment in Arabidopsis and rice. The results showed that all three proteins were localized in the vacuole membrane, that TaMTP1-D was more resistant to Zn and less resistant to Co than other TaMTP1-like members, and that TaMTP1-D was expressed at a higher level in the endosperm than other members. All results reveal that the use of TaMTP1-D for biofortification can substantially increase the content of Zn in the edible part of wheat and avoid the overaccumulation of Co, suggesting that TaMTP1-D is a potential Zn biofortifier / bioreinforcement.

Monocytes perturbation implicated in the association of stress hyperglycemia with postoperative poor prognosis in non-diabetic patients with Stanford type-A acute aortic dissection.

OBJECTIVES: The study aimed to investigate the interaction of intraoperative stress hyperglycemia with monocyte functions and their impact on major adverse events (MAEs) in acute aortic dissection (AAD) patients who underwent open repair surgery. METHODS: A total of 321 adults who underwent open surgery for AAD at two tertiary medical centers in China were enrolled in the study. The primary endpoint was defined as the incidence and characteristics of perioperative stress hyperglycemia. The secondary endpoints included the incidence of postoperative MAEs, postoperative monocyte counts and inflammatory cytokine expression. Multi-logistic, linear regression and receiver operating characteristic (ROC) curve analyses were used to establish relationships between intraoperative time-weighted average glucose (TWAG), day-one postoperative monocyte counts, serum inflammatory cytokines and postoperative outcomes. In addition, in vitro experiments were conducted to evaluate changes in the inflammatory features of monocytes under high glucose conditions. RESULTS: Intraoperative hyperglycemia, as indicated by a TWAG level over 142 mg/dL, was associated with elevated postoperative monocyte counts and inflammatory cytokines, which correlated with extended intensive care unit (ICU) stays and worsened outcomes. In vitro, high glucose treatment induced mitochondrial impairment in monocytes, increased the release of inflammatory cytokines and the proportion of classical monocytes from AAD patients. CONCLUSIONS: Intraoperative stress hyperglycemia, in combination with day-one postoperative monocyte counts, were clinically significant for predicting adverse outcomes in AAD patients undergoing open repair surgery. Elevated glucose concentrations shaped the inflammatory features of monocytes in AAD by impairing mitochondrial functions.

A case report of cardiac rehabilitation in coronary artery aneurysm combined with acute ST segment elevation myocardial infarction.

Coronary artery aneurysm (CAA), marked by diffuse or localized dilation of artery, can cause life-threatening complications in acute coronary syndrome. This report presents a case of CAA combined with acute ST-segment elevation myocardial infarction, successfully treated with cardiac rehabilitation exercise therapy, offering insights for clinical practice.

Perfluorobutane-Enhanced CEUS in Intrahepatic Cholangiocarcinoma: Correlating Imaging Features With Liver Backgrounds and Tumor Sizes.

OBJECTIVE: To investigate Sonazoid contrast-enhanced ultrasound (CEUS) features of intrahepatic cholangiocarcinoma (ICC) based on liver backgrounds and tumor sizes. METHODS: A retrospective analysis was conducted on patients with histopathologically diagnosed ICC at two centers. Patients underwent Sonazoid CEUS examination at a dose of 0.0165 mL/kg before surgery or biopsy. Continuous imaging was recorded for the first 70 s, followed by intermittent scanning every 15-20 s for 5 min, with a Kupffer phase captured after an 8-min delay. Patients were categorized by liver backgrounds and tumor sizes. Two ultrasound experts evaluated the enhancement patterns of ICCAs during the arterial, portal, delayed, and Kupffer phases according to current guidelines. RESULTS: From February 2019 to July 2022, a total of 85 ICC lesions were included. ICCs were categorized into normal liver (n = 24), chronic liver disease with fibrosis (n = 40), and cirrhosis (n = 21) groups based on different liver backgrounds, and into groups measuring ≤30 mm (n = 22), 31-50 mm (n = 32), and >50 mm (n = 31) based on tumor sizes. Most ICCs in liver fibrosis or liver cirrhosis tended to show non-rim enhancement in arterial phase (p = 0.022) and relatively later washout (39.9 ± 8.5 s vs. 39.7 ± 13.0 s) compared with those on a normal liver background (28.1 ± 5.6 s) (p < 0.001). Based on CEUS Liver Imaging Reporting and Data System, the diagnostic performance of LR-M criteria showed an accuracy of 100% in our high-risk populations. ICCs of ≤30 mm more commonly showed non-rim enhancement in arterial phase (p = 0.003) and relatively later washout (41.3 ± 12.5 s) compared with larger ICCs (p = 0.046). In the Kupffer phase, all ICCs showed marked washout with sharp margin delineation on Sonazoid CEUS, regardless of liver backgrounds and tumor sizes. CONCLUSION: Sonazoid CEUS features of ICCs differ according to different liver backgrounds and tumor sizes. Arterial phase non-rim enhancement and relatively later washout were more commonly observed in ICCs on liver fibrosis or cirrhosis background or smaller ICCs (≤30 mm).

Multi-platform analysis revealed the substance basis and mechanism of Wei-Tong-Xin in ameliorating ENS dysfunction for dyspepsia treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Duodenal motility disorder is a contributing factor to dyspepsia. The traditional Chinese medicine (TCM) formula Wei-Tong-Xin (WTX), originated from the famous ancient Chinese formula "Wan Ying Yuan", has been demonstrated efficacy in alleviating dyspepsia. AIM OF THE STUDY: The current study aims to elucidate the chemical composition of WTX to establish the pharmacodynamic material basis. On the basis of component, in depth to illuminate the mechanism by which WTX treats dyspepsia via constructing the comprehensive analysis of multi-platform. MATERIALS AND METHODS: The chemical constituents of WTX were systematically analyzed by UHPLC-Q-TOF-MS/MS data processing methods. Based on this, network pharmacology was employed to predict the mechanism by which WTX improved dyspepsia. The dyspepsia mouse model was constructed, and histopathology as well as intestinal permeability were assessed using H&E staining, PAS staining and FITC-dextran assay. Protein expression was detected using Western blot, immunofluorescence, immunohistochemistry and ELISA kits. RESULTS: A total of 100 chemical components of WTX were preliminarily identified. Network pharmacological analysis indicated that the therapeutic mechanism of WTX in treating dyspepsia may be related to the regulation of inflammation and oxidative stress-related signaling pathways. In vivo studies showed that WTX mitigated duodenal inflammation and oxidative stress responses, repairing the intestinal mucosal barrier damaged by cisplatin (CIS). Additionally, WTX restored the number of glial cells diminished by inflammatory damage, and ameliorated the serotoninergic neuronal dysfunction caused by insufficient secretion of glia-derived neurotrophic factor (GDNF), and enhanced intestinal transit. CONCLUSIONS: In this study, a total of 100 components of the WTX extract were identified through literature review and mass spectrometry database search. Utilizing computer technology, in conjunction with pharmacodynamic and mechanistic studies, WTX has been found to restore serotoninergic neuronal function by reducing intestinal mucosal inflammatory and oxidative damage, ultimately promoting intestinal transport and treating dyspepsia.

Treatment of pediatric refractory or relapsed Epstein-Barr virus-associated hemophagocytic syndrome with PD-1 inhibitors.

PURPOSE: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a type of pediatric HLH that occurs frequently in Asia. Although immunochemotherapy based on etoposide and hormone has improved survival rates, there are still about 30% of HLH patients that do not respond. The objective of the article is to examine the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors for children with relapsed/refractory (r/r) EBV-HLH. METHODS: A retrospective case note review of four pediatric patients with r/r EBV-HLH who were treated with PD-1 inhibitors at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. RESULTS: All four patients responded to PD-1 inhibitors and achieved partial response after their first infusion. Plasma EBV DNA copy number and HLH-related monitoring indicators decreased in all of these patients. All patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and two were still alive at the last follow-up on December 30, 2022. Two patients died because of transplantation-related complications. Serious side effects included increased liver enzymes and edema in two patients. CONCLUSION: PD-1 inhibitors are an effective salvage therapy and can provide a bridge to allo-HSCT for pediatric patients with r/r EBV-HLH. However, side effects should be monitered.

Neural encoding for spatial release from informational masking and its correlation with behavioral metrics.

The central auditory system encompasses two primary functions: identification and localization. Spatial release from masking (SRM) highlights speech recognition in competing noise and improves the listening experience when a spatial cue is introduced between noise and target speech. This assessment focuses on the integrity of auditory function and holds clinical significance. However, infants or pre-lingual subjects sometimes provide less reliable results. This study investigates the value of cortical auditory evoked potentials (CAEPs) onset and acoustic change complex (ACC) as an objective measurement of SRM. Thirty normal-hearing young adults (11 males) were recruited. We found the spatial separation of signals and noise (±90° symmetrically) resulted in a signal-to-noise ratio (SNR) improvement of 9.00 ± 1.71 dB behaviorally. It significantly enhanced cortical processing at all SNR levels, shortened CAEP latencies, and increased amplitudes, resulting in a greater number of measurable peaks for ACC. SRM showed mild to moderate correlations with the differences between two conditions in CAEP measures. The regression model combining N1'-P2' amplitude at 5 dB SNR (R2 = 0.26), P1 amplitude at 0 dB SNR (R2 = 0.14), and P1 latency at -5 dB SNR (R2 = 0.15), explained 45.3% of the variance in SRM. Our study demonstrates that introducing spatial cues can improve speech perception and enhance central auditory processing in normal-hearing young adults. CAEPs may contribute to predictions about SRM and hold potential for practical application.NEW & NOTEWORTHY The neural encoding of spatial release from masking (SRM) can be observed in normal-hearing young adults. Spatial separation between target and masker improves speech perception in noise and enhances central auditory processing. The behavioral results showed mild-to-moderate correlations with electrophysiological measures, with acoustic change complex (ACC) amplitude being a better indicator than onset components. Cortical auditory evoked potentials (CAEPs) may contribute to predictions about spatial release from masking, especially when behavioral tests are less reliable.

Establishment of predictive models and determinants of preoperative gastric retention in endoscopic retrograde cholangiopancreatography.

BACKGROUND: Study on influencing factors of gastric retention before endoscopic retrograde cholangiopancreatography (ERCP) background: With the wide application of ERCP, the risk of preoperative gastric retention affects the smooth progress of the operation. The study found that female, biliary and pancreatic malignant tumor, digestive tract obstruction and other factors are closely related to gastric retention, so the establishment of predictive model is very important to reduce the risk of operation. AIM: To analyze the factors influencing preoperative gastric retention in ERCP and establish a predictive model. METHODS: A retrospective analysis was conducted on 190 patients admitted to our hospital for ERCP preparation between January 2020 and February 2024. Patient baseline clinical data were collected using an electronic medical record system. Patients were randomly matched in a 1:4 ratio with data from 190 patients during the same period to establish a validation group (n = 38) and a modeling group (n = 152). Patients in the modeling group were divided into the gastric retention group (n = 52) and non-gastric retention group (n = 100) based on whether gastric retention occurred preoperatively. General data of patients in the validation group and modeling group were compared. Univariate and multivariate logistic regression analyses were performed to identify factors influencing preoperative gastric retention in ERCP patients. A predictive model for preoperative gastric retention in ERCP patients was constructed, and calibration curves were used for validation. The receiver operating characteristic (ROC) curve was analyzed to evaluate the predictive value of the model. RESULTS: We found no statistically significant difference in general data between the validation group and modeling group (P > 0.05). The comparison of age, body mass index, hypertension, and diabetes between the two groups showed no statistically significant difference (P > 0.05). However, we noted statistically significant differences in gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction between the two groups (P < 0.05). Multivariate logistic regression analysis showed that gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction were independent factors influencing preoperative gastric retention in ERCP patients (P < 0.05). The results of logistic regression analysis revealed that gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction were included in the predictive model for preoperative gastric retention in ERCP patients. The calibration curves in the training set and validation set showed a slope close to 1, indicating good consistency between the predicted risk and actual risk. The ROC analysis results showed that the area under the curve (AUC) of the predictive model for preoperative gastric retention in ERCP patients in the training set was 0.901 with a standard error of 0.023 (95%CI: 0.8264-0.9567), and the optimal cutoff value was 0.71, with a sensitivity of 87.5 and specificity of 84.2. In the validation set, the AUC of the predictive model was 0.842 with a standard error of 0.013 (95%CI: 0.8061-0.9216), and the optimal cutoff value was 0.56, with a sensitivity of 56.2 and specificity of 100.0. CONCLUSION: Gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction are factors influencing preoperative gastric retention in ERCP patients. A predictive model established based on these factors has high predictive value.

The Diagnostic and Therapeutic Value of Anti CCP Antibodies and Double Stranded DNA in Rhupus Syndrome.

BACKGROUND: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. METHODS: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. RESULTS: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of ˃ 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. CONCLUSIONS: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome.

Macrophage-mediated mechanisms of lung injury in the sensitization reaction to Echinococcus granulosus.

Objective: In this study, the impact of inhibiting the PI3K/AKT/NF-κB pathway on lung oxidative damage induced by Echinococcus granulosus cyst fluid was investigated. Methods: Twenty-four mice were randomly assigned to four groups. Three months after inoculation with hydatid cyst segments, mice in group A were treated with intraperitoneal and intratracheal saline injections; mice in group B were administered a caudal vein injection of a PI3K inhibitor, followed by cyst fluid sensitization; mice in group C received an AKT inhibitor via caudal vein, followed by cyst fluid sensitization; and mice in group D were subjected to cyst fluid sensitization without any inhibitor treatment. Cellular changes in lung tissues across all groups were evaluated, including pathological section analysis. Analysis of pulmonary tissue and serum from these mice included the assessment of PI3K/AKT/NF-κB pathway proteins, inflammatory factors, and related mRNA levels. Results: Mice in groups B and C exhibited a higher proportion of M2-type macrophages and significantly lower levels of PI3K/AKT/NF-κB pathway proteins, inflammatory factors (interleukin-6 [IL-6]/tumor necrosis factor-α [TNF-α]), and oxidative markers in lung tissues compared to mice in group D (P < 0.05). Conclusion: Our results in this study indicate that activation of the PI3K/AKT/NF-κB pathway contributed to an increase in the M1 macrophage phenotype, leading to enhanced secretion of peroxidases and inflammatory factors. This mechanism plays a crucial role in the oxidative and inflammatory lung damage associated with allergic reactions to E. granulosus cyst fluid.

Dietary pattern trajectories in early childhood and their associations with patterns of maternal feeding practices in a multi-ethnic Asian cohort.

BACKGROUND: Maternal feeding practices play a major role in children's dietary intakes. However, there is limited data on the associations between trajectories of dietary patterns (DPs) and patterns of maternal feeding practices during early childhood. METHODS: Using data from a multi-ethnic Asian cohort study, namely the Growing Up in Singapore Towards healthy Outcomes (GUSTO), dietary intakes were measured using Food Frequency Questionnaires in children at 18 months, 5 and 7 years of age. Maternal feeding practices were assessed using validated questionnaires at 15 months, 3 and 5 years of age. Principal component analysis was used to derive 2 major DPs at all time-points as well as patterns of maternal feeding practices. Group-based trajectory modelling was used to identify trajectory groups for the derived DPs. Multivariable logistic regression examined associations between patterns of maternal feeding practices and DP trajectory groups. RESULTS: Two DPs, namely the 'healthy' and 'less healthy' were consistently derived at 18 months, 5 and 7 years of age. From each DP, 2 stable DP trajectory groups were further identified between 18 months and 7 years of age. For the 'healthy' DP trajectory, majority of the children (Group 1) formed a consistent average adherence trajectory group (91.8%) while the remaining children (Group 2) showed a higher but decreasing adherence (8.2%) to this DP. For the 'less healthy' DP trajectory, most children (Group 1) formed a consistent average adherence trajectory (95.5%), while the remainder (Group 2) showed consistent higher adherence to this 'less healthy' DP (4.5%). Two patterns of maternal feeding practices were derived and labelled as 'structured with autonomy support' and 'coercive control', respectively, at ages 15 months, 3 and 5 years. Children whose mothers showed high adherence to the structured with autonomy support feeding practices at age 5 years were significantly more likely to be associated with the higher but decreasing 'healthy' DP trajectory group [OR = 3.62 (95% CI: 1.64, 7.99)]. CONCLUSIONS: A small number of children in this multi-ethnic study showed high adherence to the 'healthy' or 'less healthy' DP trajectory groups, respectively, while the majority showed average adherence to either of these trajectories. The positive association between structured with autonomy support maternal feeding practices and higher z-scores for the healthy DP trajectory highlights the importance of guiding parents on appropriate feeding practices.

Pralsetinib as neoadjuvant therapy for RET-Altered differentiated thyroid cancer: Two case reports.

BACKGROUND: 5-10% of thyroid cancers are at locally advanced stage. Neoadjuvant targeted therapy will likely create surgical opportunities for these patients with unresectable or borderline resectable tumors. Pralsetinib, a RET inhibitor, has been approved for advanced or metastatic RET-altered thyroid cancer. However, there is no evidence on the efficacy of pralsetinib as neoadjuvant therapy in locally advanced RET-altered thyroid cancer. CASE REPORT: Two patients with locally advanced pappilary thyroid carcinoma (PTC) were treated with pralsetinib (400 mg daily) to reduce tumor size and increase the chance of R0 resection. Both PTCs, characterized by RET-fusion, underwent successful R0 resection without major surgical complications after 4-months neoadjuvant pralsetinib. CONCLUSION: There is a potential for pralsetinib as a neoadjuvant treatment in PTC with RET-fusion.

Association Between Systolic Blood Pressure and in-Hospital Mortality Among Congestive Heart Failure Patients with Chronic Obstructive Pulmonary Disease in the Intensive Care Unit: A Retrospective Cohort Study.

Background: There has been a growing body of research focusing on patients with Congestive Heart Failure (CHF) and chronic obstructive pulmonary disease (COPD) admitted to the intensive care unit (ICU). However, the optimal blood pressure (BP) level for such patients remains insufficiently explored. This study aimed to investigate the associations between systolic blood pressure (SBP) and in-hospital mortality among ICU patients with both CHF and COPD. Methods: This retrospective cohort study enrolled 6309 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. SBP was examined as both a continuous and categorical variable, with the primary outcome being in-hospital mortality. The investigation involved multivariable logistic regression, restricted cubic spline regression, and subgroup analysis to determine the relationship between SBP and mortality. Results: The cohort consisted of 6309 patients with concurrent CHF and COPD (3246 females and 3063 males), with an average age of 73.0 ± 12.5 years. The multivariate analysis revealed an inverse association between SBP and in-hospital mortality, both as a continuous variable (odds ratio = 0.99 [95% CI, 0.99~1]) and as a categorical variable (divided into quintiles). Restricted cubic spline analysis demonstrated an L-shaped relationship between SBP and mortality risk (P nonlinearity < 0.001), with an inflection point at 99.479 mmHg. Stratified analyses further supported the robustness of this correlation. Conclusion: The relationship between SBP and in-hospital mortality in patients with both CHF and COPD follows an L-shaped pattern, with an inflection point at approximately 99.479 mmHg.