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Summary: Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

Background The reported prevalence rate of anxiety disorder in the paediatric population varies widely between different counties. Currently, there is no national epidemiological survey of childhood anxiety disorder in China. This study aims to investigate the national prevalence of anxiety disorder, the distribution profiles of different subtypes and its comorbidity rates among school students.Methods A nationwide epidemiological survey of mental disorders in school students aged 6–16 years was conducted. Participants were randomly recruited from five provinces in China. The Child Behavior Checklist was used to screen students at high risk for mental disorders. The final diagnosis was made based on the Diagnostic and Statistical Manual-IV. The point prevalence and comorbidity rate of anxiety disorder were calculated, and the difference between age, sex and socioeconomic status groups was also compared.Results Generalised anxiety disorder (GAD) was the most common anxiety disorder in school-attending children and adolescents, with a prevalence rate of 1.3% (95% CI: 1.2 to 1.3). Separation anxiety and specific phobia were more common in children than in adolescents. Girls had a higher prevalence of panic disorder (0.3% vs 0.2%, χ2=14.6, p

Gait is impaired in musculoskeletal conditions, such as knee arthropathy. Gait analysis is used in clinical practice to inform diagnosis and monitor disease progression or intervention response. However, clinical gait analysis relies on subjective visual observation of walking as objective gait analysis has not been possible within clinical settings due to the expensive equipment, large-scale facilities, and highly trained staff required. Relatively low-cost wearable digital insoles may offer a solution to these challenges. In this work, we demonstrate how a digital insole measuring osteoarthritis-specific gait signatures yields similar results to the clinical gait-lab standard. To achieve this, we constructed a machine learning model, trained on force plate data collected in participants with knee arthropathy and controls. This model was highly predictive of force plate data from a validation set (area under the receiver operating characteristics curve [auROC] = 0.86; area under the precision-recall curve [auPR] = 0.90) and of a separate, independent digital insole dataset containing control and knee osteoarthritis subjects (auROC = 0.83; auPR = 0.86). After showing that digital insole-derived gait characteristics are comparable to traditional gait measurements, we next showed that a single stride of raw sensor time-series data could be accurately assigned to each subject, highlighting that individuals using digital insoles can be identified by their gait characteristics. This work provides a framework for a promising alternative to traditional clinical gait analysis methods, adds to the growing body of knowledge regarding wearable technology analytical pipelines, and supports clinical development of at-home gait assessments, with the potential to improve the ease, frequency, and depth of patient monitoring.

This paper introduces a hybrid readout system for a cross-strip position-sensitive anode detector that combines a lookup table and weighted averaging. The lookup table approach is used to identify event channels and select appropriate weights based on the corresponding index code for calculating the centroid of the electron cloud. This effectively enhances the readout system’s processing speed while preserving the high-resolution advantage of the cross-strip position-sensitive anode. Simulations were performed to evaluate the performance of the system. Experimental results demonstrate that this readout method achieves an event processing speed exceeding 10 MHz while maintaining a resolution of 17.96 lp/mm.

PurposeThis study aims to retrospectively estimate cumulative reproductive outcomes in women with primary ovarian insufficiency (POI) in assisted reproductive technology (ART) therapy.MethodsA total of 139 patients diagnosed with POI were reviewed in this study. Firstly, they were divided into two groups according to oocyte origin: using their own oocytes (OG group) or accepting oocyte donations (OD I group). Secondly, the patients were split depending on the pregnancy outcome. In the OG group, nine patients decided to use others’ oocytes after a failure of attempting to use their own, and this population was the oocyte donation II group (OD II group).ResultsThere were 88 patients who used their own oocytes, while 51 patients accepted oocyte donations. In the OG group, there are only 10 (7.2%) patients who got pregnant, and patients in the OD group had worse hormone levels (FSH 71.37 ± 4.18 vs. 43.98 ± 2.53, AMH 0.06 ± 0.04 vs. 1.15 ± 0.15, and AFC 0.10 ± 0.06 vs. 1.15 ± 0.15) and more years of infertility (5.04 ± 0.48 vs. 3.82 ± 0.30), which explained why they choose oocyte donation. In all the three groups, baseline characteristics were comparable between pregnant women and non-pregnant women. Of the 10 pregnant patients in the OG group, four of them used luteal-phase short-acting long protocol and had pregnancies successfully in their first cycles.ConclusionOvarian stimulation in POI women requires more cost and time. For those with a stronger desire to have genetic offspring, luteal-phase short-acting long protocol may help them obtain pregnancy rapidly.

Abstract Background and Objectives Previous studies have shown an association between environmental exposure to heavy metals and hearing loss. However, the findings regarding the relationship between exposure to different metals and hearing loss development are inconsistent. To address this, we conducted a meta‐analysis to explore the link between common heavy metal exposures and hearing loss. This study examined the effects of lead (Pb), cadmium (Cd), and mercury (Hg) pollution on hearing loss at various levels, and systematically reviewed the literature on manganese (Mn), barium (Ba), arsenic (As), and hearing loss. Methods We conducted systematic searches in five major databases, including PubMed, Web of Science, Embase, Cochrane Library, and Scopus. In addition, we searched three Chinese digital libraries: CNKI, Wanfang Data, and Wipu. From an initial pool of 649 articles, we carefully screened and selected 15 articles for further analysis. The effect sizes from these selected studies were synthesized through a meta‐analysis to calculate the overall effect size. Results Our findings showed that: (1) There was a significant association between Pb and Cd exposure and hearing loss; (2) There is a proportional relationship between the increase of metal index detected in blood and hearing loss; (3) In the PTA measurement of hearing loss at different frequencies, the 4 kHz high frequency range had a stronger correlation with hearing loss than the low frequency, with OR 1.44 (1.22, 1.71); and (4) There was a more significant correlation between Barium (Ba) levels in nails and hair than in urine. Conclusions The study presented evidence of a significant association between human hearing loss and exposure to lead (Pb) and cadmium (Cd). It not only revealed a positive correlation between blood heavy metal concentrations and the incidence of hearing loss but also highlighted that long‐term exposure indicators of heavy metals were more indicative of the correlation with hearing loss. Lastly, the study recommends utilizing high frequency 4 kHz for the effective assessment and diagnosis of hearing loss caused by exposure to heavy metals.

Introduction Subjective cognitive decline means a decline in the subjective perception of self-cognitive function, which is likely to evolve into mild cognitive impairment and dementia. The number of elderly with subjective cognitive decline has increased, bringing huge burdens and challenges to caregivers and society. With the increase in research on art therapies, some of them have gradually been proven to be effective for cognitive function. Therefore, this study aims to summarise the evidence and identify the best art therapy for elderly with subjective cognitive decline.Methods and analysis We will include published randomised controlled trials written in English and Chinese if the intervention is one of the art therapies and applied in people aged 60 and above with subjective cognitive decline. Eight electronic databases, including the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Elsevier, China BioMedical Literature Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database, will be searched from January 2013 to December 2023. Art therapies will mainly include music therapy, reminiscence therapy, painting therapy, dance therapy, reading therapy, horticultural therapy, museum therapy, calligraphy therapy and so on. The outcome will be cognitive function. Study selection, data extraction and quality assessment will be performed by two reviewers. The risk of bias will be evaluated according to the Cochrane Collaboration’s risk-of-bias tool, and the evidence quality will be assessed with the Grading of Recommendations Assessment, Development and Evaluation. Standard pairwise meta-analysis and Bayesian network meta-analysis will be conducted. The probabilities of each art therapy will be ranked based on the surface under the cumulative ranking curve.Ethics and dissemination Ethical approval is not required for reviewing published studies. To provide important evidence for clinicians and guideline developers, the findings of this study will be submitted to a peer-reviewed journal.PROSPERO registration number CRD42023443773.

Pin1 is a member of the peptidyl-prolyl cis/trans isomerase subfamily and is widely expressed in various cell types and tissues. Alterations in Pin1 expression levels play pivotal roles in both physiological processes and multiple pathological conditions, especially in the onset and progression of kidney diseases. Herein, we present an overview of the role of Pin1 in the regulation of fibrosis, oxidative stress, and autophagy. It plays a significant role in various kidney diseases including Renal I/R injury, chronic kidney disease with secondary hyperparathyroidism, diabetic nephropathy, renal fibrosis, and renal cell carcinoma. The representative therapeutic agent Juglone has emerged as a potential treatment for inhibiting Pin1 activity and mitigating kidney disease. Understanding the role of Pin1 in kidney diseases is expected to provide new insights into innovative therapeutic interventions and strategies. Consequently, this review delves into the molecular mechanisms of Pin1 and its relevance in kidney disease, paving the way for novel therapeutic approaches.

Abstract The collective total syntheses of (±)‐hosieines A–C with a cage‐like tetracyclic framework have been realized, which includes the first syntheses of hosieines B‐C. The key strategy of the synthesis employs a one‐pot domino reaction that involves Cu‐catalyzed [3+2] cycloaddition, 1,6‐enone formation, and 1,6‐aza‐Michael addition forming the 5/6/6‐aza‐tricyclic skeleton. Other salient synthetic tactics comprise a challenging double bond migration and a 1,4‐aza‐Michael addition reaction to afford the tetracyclic framework.

ObjectiveThis study aimed to analyze the population characteristics of apheresis platelet donors in Chongqing Province and provide a scientific basis for the development of precise and efficient recruitment strategies. The ultimate goal is to increase the number of regular platelet donors in preparation for public health emergencies.MethodsThis study involved 53,089 blood donors who donated apheresis platelets to the Chongqing Blood Center from 2020 to 2022. Data regarding age, sex, blood type, education level, occupation, and frequency of blood donation were collected and analyzed to identify factors influencing platelet donation.ResultsBetween 2020 and 2022, the majority of apheresis platelet donors in Chongqing were aged 25–35 years, with a male-to-female ratio of 2.6:1. The ABO blood group distribution was O > A > B > AB. The apheresis platelet donors mainly consisted of college students, and the donors who had donated only once accounted for the greatest proportion.ConclusionBased on the population characteristics of apheresis platelet donors in Chongqing, blood collection and supply organizations must refine emergency blood collection and supply plans during public health emergencies. This study underscores the importance of developing precise and efficient recruitment strategies for apheresis platelet donors and expanding the pool of regular apheresis platelet donors. These measures are essential to ensure the timely, safe, and effective use of clinical blood resources during public health emergencies.

Background: Different irrigation methods have variable effects on the physiochemical properties of soils. The predicted widespread replacement of flood irrigation with drip irrigation will alter the micro-environment of the associated soils in terms of migration, transformation, morphology, and toxicology of heavy metals and pesticides. The dynamics of heavy metals in soil under drip irrigation have only been investigated with regard to the use of sewage and reclaimed water; studies comparing these patterns across different irrigation methods are scarce. Purpose: Here, we aimed to investigate the effects of drip and flood irrigation on heavy metal distribution in soil and the related risks in three typical agricultural systems in China. Methods: We used fixed-point sampling, digestion analytical methods, descriptive analyses, one-way analysis of variance (ANOVA), Nemerow pollution index analyses, and correlation analyses to investigate the different effects of drip and flood irrigation on heavy metals (Cd, Cr, Cu, Pb, and Zn) in soils from Hebei, Xinjiang, and Ningxia Provinces, China. Results and Discussion: Analyses of soil samples collected from drip-irrigated fields revealed significant differences in the concentrations of soil heavy metals at depths of 0–60 cm. Drip irrigation had a greater effect on heavy metal content in the soil surface than flood irrigation. In addition, heavy metals likely accumulated at the edges of the wetting fronts following prolonged irrigation. In comparison to drip irrigation, flood irrigation elevated pollution levels in the soil. The amount of fertiliser affected the leaching and migration of heavy metals in the soils by altering the physiochemical characteristics of the drip irrigation solution. Conclusion: Drip irrigation alters the dynamics of heavy metals in soil by influencing their migration and accumulation patterns. This effect can be attributed to the methods of adding water and fertilisers to the soil under drip irrigation. Altering these variables can impact the level of heavy metals that bioaccumulate in crops. This study provides a scientific basis for reducing heavy metal pollution under drip irrigation.

BackgroundStroke is the main disease that causes the burden of neurological disease, leading to upper limb dysfunction and affecting their self-care abilities. Robot-assisted rehabilitation therapy has been gradually used in the rehabilitation of upper limb function after stroke. However, it would be beneficial to explore auxiliary interventions such as reminiscent music therapy, a combination of music and reminiscent, to relieve negative emotions and post-stroke fatigue and improve rehabilitation outcomes. This protocol aims to evaluate the effectiveness of reminiscent music therapy combined with robot-assisted rehabilitation in older stroke patients.MethodsThis trial is a single-blind, three-arm randomized controlled trial. Older stroke patients with upper limb dysfunction will be recruited. Participants will be randomly assigned to receive usual rehabilitation treatment and care, usual rehabilitation treatment and care plus robot-assisted rehabilitation and reminiscent music therapy, or usual rehabilitation treatment and care plus robot-assisted rehabilitation. Robot-assisted rehabilitation will be conducted by rehabilitation doctors five times per week for 3 weeks. In experimental group 1, a reminiscent song list will be played for patients. The primary outcome is activities of daily living. All outcomes will be evaluated at baseline and in the week immediately post-intervention.DiscussionWe are conducting the first randomized controlled trial on the effects of reminiscent music therapy combined with robot-assisted rehabilitation in older stroke patients. It is expected that this study, if proven effective in improving the activities of daily living in older stroke patients with upper limb dysfunction, will provide evidence-based rehabilitation strategies for medical staff.Clinical Trial Registration: ChiCTR2200063738.

IntroductionNeonatal calf diarrhea (NCD) is one of the most common diseases in calves, causing huge economic and productivity losses to the bovine industry worldwide. The main pathogens include bovine rotavirus (BRV), bovine coronavirus (BCoV), and Enterotoxigenic Escherichia coli (ETEC) K99. Since multiple infectious agents can be involved in calf diarrhea, detecting each causative agent by traditional methods is laborious and expensive.MethodsIn this study, we developed a one-step multiplex Real-Time PCR assay to simultaneously detect BRV, BCoV, and E. coli K99+. The assay performance on field samples was evaluated on 1100 rectal swabs of diseased cattle with diarrhea symptoms and compared with the conventional gel-based RT-PCR assay detect BRV, BCoV, and E. coli K99+.ResultsThe established assay could specifically detect the target pathogens without cross-reactivity with other pathogens. A single real-time PCR can detect ~1 copy/µL for each pathogen, and multiplex real-time PCR has a detection limit of 10 copies/µL. Reproducibility as measured by standard deviation and coefficient of variation were desirable. The triple real-time PCR method established in this study was compared with gel-based PT-PCR. Both methods are reasonably consistent, while the real-time PCR assay was more sensitive and could rapidly distinguish these three pathogens in one tube. Analysis of surveillance data showed that BRV and BCoV are major enteric viral pathogens accounting for calves’ diarrhea in China. DiscussionThe established assay has excellent specificity and sensitivity and was suitable for clinical application. The robustness and high-throughput performance of the developed assay make it a powerful tool in diagnostic applications and calf diarrhea research. ​

Summary: Converging studies showed interstitial fluid (ISF) adjacent to blood vessels flows in adventitia along vasculature into heart and lungs. We aim to reveal circulatory pathways and regulatory mechanism of such adventitial ISF flow in rat model. By MRI, real-time fluorescent imaging, micro-CT, and histological analysis, ISF was found to flow in adventitial matrix surrounded by fascia and along systemic vessels into heart, then flow into lungs via pulmonary arteries and back to heart via pulmonary veins, which was neither perivascular tissues nor blood or lymphatic vessels. Under physiological conditions, speckle-like adventitial ISF flow rate was positively correlated with heart rate, increased when holding breath, became pulsative during heavy breathing. During cardiac or respiratory cycle, each dilation or contraction of heart or lungs can generate to-and-fro adventitial ISF flow along femoral veins. Discovered regulatory mechanisms of adventitial ISF flow along vasculature by heart and lungs will revolutionize understanding of cardiovascular system.

Summary: Background: Chemoresistance is a critical factor contributing to poor prognosis in clinical patients with cancer undergoing postoperative adjuvant chemotherapy. The role of gut microbiota in mediating resistance to tumour chemotherapy remains to be investigated. Methods: Patients with CRC were categorised into clinical benefit responders (CBR) and no clinical benefit responders (NCB) based on chemotherapy efficacy. Differential bacterial analysis using 16S rRNA sequencing revealed Desulfovibrio as a distinct microbe between the two groups. Employing a syngeneic transplantation model, we assessed the effect of Desulfovibrio on chemotherapy by measuring tumour burden, weight, and Ki-67 expression. We further explored the mechanisms underlying the compromised chemotherapeutic efficacy of Desulfovibrio using metabolomics, western blotting, colony formation, and cell apoptosis assays. Findings: In comparison, Desulfovibrio was more abundant in the NCB group. In vivo experiments revealed that Desulfovibrio colonisation in the gut weakened the efficacy of FOLFOX. Treatment with Desulfovibrio desulfuricans elevates serum S-adenosylmethionine (SAM) levels. Interestingly, SAM reduced the sensitivity of CRC cells to FOLFOX, thereby promoting the growth of CRC tumours. These experiments suggest that SAM promotes the growth and metastasis of CRC by driving the expression of methyltransferase-like 3 (METTL3). Interpretation: A high abundance of Desulfovibrio in the intestines indicates poor therapeutic outcomes for postoperative neoadjuvant FOLFOX chemotherapy in CRC. Desulfovibrio drives the manifestation of METTL3 in CRC, promoting resistance to FOLFOX chemotherapy by increasing the concentration of SAM. Funding: This study is supported by Wuxi City Social Development Science and Technology Demonstration Project (N20201005).

This study aimed to evaluate the usefulness of optical coherence tomography angiography (OCTA) in assessing retinal microvascular structural changes in preterm-born children and compare them with those in term-born children. The Web of Science Library, Cochrane Library, PubMed, Embase, CNKI, Wanfang, VIP, and Sino Med databases were searched systematically to extract studies published till April 25, 2023. Two independent reviewers searched all the literature and completed the data extraction and quality assessment. Mean differences (MDs) with 95% confidence intervals (CIs) were used to assess the continuous estimates. STATA software (v15.1; StataCorp, College Station, TX) was used to analyze the data. Twelve published studies were eligible for inclusion in this study. The meta-analysis revealed that the foveal avascular zone (FAZ) area of preterm-born children was remarkably smaller than that of term-born children, with the laser photocoagulation (LP)-ROP group showing the most pronounced reduction. The foveal superficial capillary plexus vessel density (SCP-VD) and deep capillary plexus vessel density (DCP-VD) were remarkably higher in the preterm-born group than in the control group, with variations in subgroups (LP-ROP, anti-VEGF-ROP, SR-ROP, and Pre-T-ROP). The parafoveal SCP-VD was remarkably lower in preterm-born children compared to that of the controls, while no significant difference was identified in the parafoveal DCP-VD. Preterm-born children had a smaller FAZ area, higher foveal SCP-VD and DCP-VD, and lower parafoveal SCP-VD compared to their term-born counterparts. The parafoveal DCP-VD did not differ substantially between preterm- and term-born children. OCTA is an effective modality for assessing alterations in the retinal microvasculature in preterm children.

The current clinical management of Extranodal NK/T-cell lymphoma (ENKTL) primarily depends on conventional chemotherapy and radiotherapy, underscoring the need for innovative therapeutic strategies. This study explores the clinical significance and therapeutic implication of c-MYC (MYC) in ENKTL. Initially, we identified MYC protein overexpression in approximately 75% of cases within a large cohort of 111 patients. MYC overexpression was strongly correlated with lymphoma cell proliferation and poor clinical outcomes. Intriguingly, integrating MYC expression into the PINK-E prognostic model significantly enhanced its predictive power. Subsequently, we implemented MYC knockdown (KD) in NK malignancy cell lines with MYC overexpression, resulting in significant viability reduction. RNA-sequencing (RNA-seq) used to determine MYC function revealed a high overlap with canonical MYC-regulated genes and enrichment in metabolism and cell cycle regulation. Integrative analysis of the RNA-seq data upon MYC KD with gene expression profiles of primary ENKTL cases identified a subset of genes closely associated with MYC overexpression. Among these, CDK4 emerged as a potential therapeutic target, and its inhibition not only abrogated MYC function but also decreased MYC expression in NK malignancy cells. Furthermore, the clinical-grade CDK4/6 inhibitor palbociclib exhibited a potent anti-tumor effect in xenograft mouse models, especially when combined with gemcitabine. In summary, our study firmly establishes MYC as an oncogene with prognostic significance in ENKTL and highlights CDK4 inhibition as a promising therapeutic strategy for treating ENKTL with MYC overexpression.

BackgroundThe CD16brightCD62Ldim neutrophil subtype is a recently identified neutrophil subtype. The aim of this study was to evaluate changes of peripheral blood CD16brightCD62Ldim neutrophils in patients with sepsis-associated ARDS.MethodsWe prospectively recruited adult patients with sepsis-associated ARDS in the intensive care unit (ICU). Patient demographic data, medical history information, and laboratory data were collected within 48 hours of enrollment, and flow cytometry was applied to analyze the CD16brightCD62Ldim neutrophil subtype in the patients’ peripheral blood. Multifactor COX regression models were used to analyze factors affecting prognosis, and Spearman correlation coefficients were used to analyze clinical and laboratory indicators affecting complications of infection.ResultsOf the 40 patients, 9 patients died by the 28-day follow-up, indicating a mortality rate of 22.5%. Patients in the nonsurvival group had higher CD16brightCD62Ldim neutrophil levels. Patients with sepsis-associated ARDS who had a baseline proportion of CD16brightCD62Ldim neutrophil subtypes to total neutrophils in peripheral blood >3.73% had significantly higher 28-day mortality, while patients with CD16brightCD62Ldim neutrophil subtypes counts >2.62×109/L were also associated with significantly higher 28-day mortality. The percentage of the CD16brightCD62Ldim neutrophil subtype (HR=5.305, 95% CI 1.986-14.165, p=0.001) and IL-8 (HR=3.852, 95% CI 1.561-9.508, p=0.003) were independent risk factors for the development of infectious complications in patients with sepsis-related ARDS. The percentage of CD16brightCD62Ldim neutrophil subtypes predicted an AUC of 0.806 (95% CI 0.147-0.964, P=0.003) for the development of infectious complications, and 0.742 (95% CI 0.589-0.895, P=0.029) for the prediction of death within 28 days.ConclusionWe identified for the first time that CD16brightCD62Ldim neutrophils are elevated in patients with sepsis-associated ARDS and are associated with infectious complications and poor prognosis. The percentage of CD16brightCD62Ldim neutrophil subtypes may serve as a predictor of the development of infectious complications in patients with ARDS.

BackgroundsThe value of circulating microRNA (miR)-155 for breast cancer (BC) diagnosis may differ in different studies. Therefore, we conducted this systematic review and meta-analysis to evaluate the potential application of circulating miR-155 in the diagnosis of BC.MethodsArticles published before December 2023 and in English were searched in these databases: PubMed, Web of Science, Medline, EMBASE and Google Scholar. A summary of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR) were calculated from the true positive (TP), true negative (TN), false positive (FP) and false negative (FN) of each study. Additionally, the summary receive-operating characteristics (SROC) curve was constructed to summarize the TP and FP rates.ResultsThe pooled parameters calculated were as follows: sensitivity, 0.93 (95% CI: 0.83-0.97); specificity, 0.85 (95% CI: 0.74-0.92); PLR, 6.4 (95% CI: 3.4-11.9); NLR, 0.09 (95% CI: 0.04-0.20); and DOR, 74 (95% CI: 22-247). The analysis showed a significant heterogeneity (sensitivity, I2 = 95.19%, p < 0.001; specificity, I2 = 95.29%, p < 0.001; DOR, I2 = 92.9%, p < 0.001). The SROC curve was with an area under curve (AUC) of 0.95 (95% CI: 0.93-0.97).ConclusionCirculating miR-155 has a potential in the diagnosis of BC.

This study explores the influence of household technological advancements on children’s nutritional intake, specifically within the context of the Chinese government’s “Home Appliances Going to the Countryside” (HAGC) initiative. Utilizing data from the China Health and Nutrition Surveys of 2006, 2009, and 2011, we employed a Propensity Score Matching Difference-in-Differences (PSM-DID) framework to ascertain the repercussions of enhanced household technology on the dynamics of children’s nutritional consumption patterns. Our analysis reveals that the HAGC-inspired integration of household appliances, including color televisions, washing machines, and refrigerators, has beneficially reshaped the nutritional consumption patterns of children, with a pronounced effect among female children. This finding remains consistent even when employing alternate methodological robustness tests. A deeper examination of the HAGC policy’s mechanisms underscores the pivotal roles of parental time allocation, improved food storage capabilities, and augmented information accessibility as significant drivers bolstering children’s nutritional intake. These insights bear considerable significance for strategizing interventions aimed at elevating the nutritional wellbeing of children in rural settings, offering valuable input for shaping public health policies tailored for such demographies.

Objective: Here, we aimed to explore the effect of LBP in combination with Oxaliplatin (OXA) on reversing drug resistance in colon cancer cells through in vitro and in vivo experiments. We also aimed to explore the possible mechanism underlying this effect. Finally, we aimed to determine potential targets of Lycium barbarum polysaccharide (LBP) in colon cancer (CC) through network pharmacology and molecular docking.Methods: The invasion ability of colon cancer cells was assessed using the invasion assay. The migration ability of these cells was assessed using the migration assay and wound healing assay. Cell cycle analysis was carried out using flow cytometry. The expression levels of phosphomannose isomerase (PMI) and ATP-binding cassette transport protein of G2 (ABCG2) proteins were determined using immunofluorescence and western blotting. The expression levels of phosphatidylinositol3-kinase (PI3K), protein kinase B (AKT), B-cell lymphoma 2 (Bcl-2), and BCL2-Associated X (Bax) were determined using western blotting. Forty BALB/c nude mice purchased from Weitong Lihua, Beijing, for the in vivo analyses. The mice were randomly divided into eight groups. They were administered HCT116 and HCT116-OXR cells to prepare colon cancer xenograft models and then treated with PBS, LBP (50 mg/kg), OXA (10 mg/kg), or LBP + OXA (50 mg/kg + 10 mg/kg). The tumor weight and volume of treated model mice were measured, and organ toxicity was evaluated using hematoxylin and eosin staining. The expression levels of PMI, ABCG2, PI3K, and AKT proteins were then assessed using immunohistochemistry. Moreover, PMI and ABCG2 expression levels were analyzed using immunofluorescence and western blotting. The active components and possible targets of LBP in colon cancer were explored using in silico analysis. GeneCards was used to identify CC targets, and an online Venn analysis tool was used to determine intersection targets between these and LBP active components. The PPI network for intersection target protein interactions and the PPI network for interactions between the intersection target proteins and PMI was built using STRING and Cytoscape. To obtain putative targets of LBP in CC, we performed GO function enrichment and KEGG pathway enrichment analyses.Results: Compared with the HCT116-OXR blank treatment group, both invasion and migration abilities of HCT116-OXR cells were inhibited in the LBP + OXA (2.5 mg/mL LBP, 10 μΜ OXA) group (p < 0.05). Cells in the LBP + OXA (2.5 mg/mL LBP, 10 μΜ OXA) group were found to arrest in the G1 phase of the cell cycle. Knockdown of PMI was found to downregulate PI3K, AKT, and Bcl-2 (p < 0.05), while it was found to upregulate Bax (p < 0.05). After treatment with L. barbarum polysaccharide, 40 colon cancer subcutaneous tumor models showed a decrease in tumor size. There was no difference in the liver index after LBP treatment (p > 0.05). However, the spleen index decreased in the OXA and LBP + OXA groups (p < 0.05), possibly as a side effect of oxaliplatin. Immunohistochemistry, immunofluorescence, and western blotting showed that LBP + OXA treatment decreased PMI and ABCG2 expression levels (p < 0.05). Moreover, immunohistochemistry showed that LBP + OXA treatment decreased the expression levels of PI3K and AKT (p < 0.05). Network pharmacology analysis revealed 45 active LBP components, including carotenoids, phenylpropanoids, quercetin, xanthophylls, and other polyphenols. It also revealed 146 therapeutic targets of LBP, including AKT, SRC, EGFR, HRAS, STAT3, and MAPK3. KEGG pathway enrichment analysis showed that the LBP target proteins were enriched in pathways, including cancer-related signaling pathways, PI3K/AKT signaling pathway, and IL-17 signaling pathways. Finally, molecular docking experiments revealed that the active LBP components bind well with ABCG2 and PMI.conclusion: Our in vitro experiments showed that PMI knockdown downregulated PI3K, AKT, and Bcl-2 and upregulated Bax. This finding confirms that PMI plays a role in drug resistance by regulating the PI3K/AKT pathway and lays a foundation to study the mechanism underlying the reversal of colon cancer cell drug resistance by the combination of LBP and OXA. Our in vivo experiments showed that LBP combined with oxaliplatin could inhibit tumor growth. LBP showed no hepatic or splenic toxicity. LBP combined with oxaliplatin could downregulate the expression levels of PMI, ABCG2, PI3K, and AKT; it may thus have positive significance for the treatment of advanced metastatic colon cancer. Our network pharmacology analysis revealed the core targets of LBP in the treatment of CC as well as the pathways they are enriched in. It further verified the results of our in vitro and in vivo experiments, showing the involvement of multi-component, multi-target, and multi-pathway synergism in the drug-reversing effect of LBP in CC. Overall, the findings of the present study provide new avenues for the future clinical treatment of CC.

ObjectiveTo establish a radiomics model based on intratumoral and peritumoral features extracted from pre-treatment CT to predict the major pathological response (MPR) in patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant immunochemotherapy.MethodsA total of 148 NSCLC patients who underwent neoadjuvant immunochemotherapy from two centers (SRRSH and ZCH) were retrospectively included. The SRRSH dataset (n=105) was used as the training and internal validation cohort. Radiomics features of intratumoral (T) and peritumoral regions (P1 = 0-5mm, P2 = 5-10mm, and P3 = 10-15mm) were extracted from pre-treatment CT. Intra- and inter- class correlation coefficients and least absolute shrinkage and selection operator were used to feature selection. Four single ROI models mentioned above and a combined radiomics (CR: T+P1+P2+P3) model were established by using machine learning algorithms. Clinical factors were selected to construct the combined radiomics-clinical (CRC) model, which was validated in the external center ZCH (n=43). The performance of the models was assessed by DeLong test, calibration curve and decision curve analysis.ResultsHistopathological type was the only independent clinical risk factor. The model CR with eight selected radiomics features demonstrated a good predictive performance in the internal validation (AUC=0.810) and significantly improved than the model T (AUC=0.810 vs 0.619, p

AbstractObjective We aimed to screen and construct a predictive model for pregnancy loss in polycystic ovary syndrome (PCOS) patients through machine learning methods.Methods We obtained the endometrial samples from 33 PCOS patients and 7 healthy controls at the Reproductive Center of the Second Hospital of Lanzhou University from September 2019 to September 2020. Liquid chromatography tandem mass spectrometry (LCMS/MS) was conducted to identify the differentially expressed proteins (DEPs) of the two groups. Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to analyze the related pathways and functions of the DEPs. Then, we used machine learning methods to screen the feature proteins. Multivariate Cox regression analysis was also conducted to establish the prognostic models. The performance of the prognostic model was then evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). In addition, the Bootstrap method was conducted to verify the generalization ability of the model. Finally, linear correlation analysis was performed to figure out the correlation between the feature proteins and clinical data.Results Four hundred and fifty DEPs in PCOS and controls were screened out, and we obtained some pathways and functions. A prognostic model for the pregnancy loss of PCOS was established, which has good discrimination and generalization ability based on two feature proteins (TIA1, COL5A1). Strong correlation between clinical data and proteins were identified to predict the reproductive outcome in PCOS.Conclusion The model based on the TIA1 and COL5A1 protein could effectively predict the occurrence of pregnancy loss in PCOS patients and provide a good theoretical foundation for subsequent research.

Background: ZhuRiHeng Drop Pill (ZRH) is a traditional Mongolian medicinal preparation. Despite its long history of use for the treatment of coronary heart disease, there have been few toxicological studies of the safety profile of ZRH.Purpose: In order to comprehensively elucidate the underlying mechanisms behind the observed toxicity of ZRH on rat livers in the 180-day repeated oral toxicity study, we conducted a comprehensive analysis by integrating transcriptomic and metabolomic data.Methods: High-resolution mass spectrometry was conducted to evaluate the constituents of ZRH. For the acute oral toxicity study, mice were administered a dose of 32 g/(kg·d) of ZRH, while rats were instead orally administered 0.934, 1.868, or 3.736 g/(kg·d) of ZRH over a 180-day period in a 180-day repeated oral toxicity study. Conventional index and organ weights/histology were then monitored to detect any potential ZRH treatment-related toxicity. To identify key genes and metabolites involved in ZRH toxicological processes, we performed transcriptomic and metabolomic analyses of liver tissue upon ZRH treatment using RNA-seq techniques, qPCR and liquid chromatography-mass spectrometry analyses.Results: A total of 60 compounds in ZRH were identified and speculated in positive and negative ion modes. Mice in the acute toxicity study exhibited no signs of ZRH-related toxicity. In a protracted oral toxicity investigation spanning 180 days, discernible elevations in liver ratios were noted in both male and female rats across all three dose cohorts, relative to the control group (p < 0.05 or p < 0.01). Upon subjecting to ZRH treatment, our transcriptomic and qPCR analyses unveiled notable upregulation of crucial genes, exemplified by Abcb1b and Cyp2b2, known for theirs involvement in liver drug transport and metabolism function. Furthermore, our untargeted metabolomic analysis provided supplementary insights, revealing significant regulation in pyrimidine metabolism, as well as alanine, aspartate, and glutamate metabolism pathways.Conclusion: Our study unveils a panoramic understanding of the temporal, dosage-specific, and gene dimensions surrounding the metabolic and transcriptional shifts induced by ZRH exposure. As we peer into the future, recommendations emerge for further exploration, encompassing aspects such as time dynamics, dosage considerations, and gene-centric avenues to enhance therapeutic efficacy.

BackgroundRapid eye movement sleep behavior disorder (RBD) is common in individuals with Parkinson’s disease (PD). In spite of that, the precise mechanism underlying the pathophysiology of RBD among PD remains unclear.ObjectiveThe aim of the present study was to analyze gray matter volumes (GMVs) as well as the changes of functional connectivity (FC) among PD patients with RBD (PD-RBD) by employing a combination of voxel-based morphometry (VBM) and FC methods.MethodsA total of 65 PD patients and 21 healthy control (HC) subjects were included in this study. VBM analyses were performed on all subjects. Subsequently, regions with significant different GMVs between PD patients with and without RBD (PD-nRBD) were selected for further analysis of FC. Correlations between altered GMVs and FC values with RBD scores were also investigated. Additionally, receiver operating characteristic (ROC) curves were employed for the evaluation of the predictive value of GMVs and FC in identifying RBD in PD.ResultsPD-RBD patients exhibited lower GMVs in the left middle temporal gyrus (MTG) and bilateral cuneus. Furthermore, we observed higher FC between the left MTG and the right postcentral gyrus (PoCG), as well as lower FC between the bilateral cuneus (CUN) and the right middle frontal gyrus (MFG) among PD-RBD patients in contrast with PD-nRBD patients. Moreover, the GMVs of MTG (extending to the right PoCG) was positively correlated with RBD severity [as measured by REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score]. Conversely, the FC value between the bilateral CUN and the right MTG in PD-RBD patients was negatively correlated with RBDSQ score.ConclusionThis study revealed the presence replace with GMV and FC changes among PD-RBD patients, which were closely linked to the severity of RBD symptoms. Furthermore, the combination of basic clinical characteristics, GMVs and FC values effectively predicted RBD for individuals with PD.

Abstract A perturbation treatment is derived for weakly deformed microdisk cavities in a more generalized scenario, where both resonant and non‐resonant surface scattering processes coexist. It is proved that the originally developed nondegenerate and degenerate perturbation theories are simplified forms of the generalized theory in special cases. The validity of the perturbation theory is verified by the comparison with a full numerical method for two generic classes of deformed microdisk cavities: locally notched microdisks and smooth globally deformed microdisks. The simulation of these two classes of microdisk cavities using the perturbation theory unveils the distinct characteristics of optical modes from the ones predicted by the original nondegenerate and degenerate perturbation theories in the generalized scenario. Furthermore, a hybrid‐scattering‐based exceptional point is introduced for deformed microdisk cavities in the generalized scenario by using the perturbation theory. The exceptional point exhibits higher nonorthogonality over the originally proposed resonant‐scattering‐based exceptional point, as non‐resonant scattering processes provide an additional degree of freedom. Full numerical simulations demonstrate that the exceptional point is more robust against random surface roughness at cavity boundary than the resonant‐scattering‐based exceptional point.

Summary: There is currently no consensus on the optimal perioperative pain management strategy involving specific opioids. This study aims to compare the postoperative analgesia, the associated side effects between nalbuphine and morphine in children undergoing laparoscopic surgery. One hundred ninety children were randomly assigned to nalbuphine (0.2 mg/kg) or morphine (0.2 mg/kg). Nalbuphine’s analgesic effect was non-inferior to morphine, with similar total rescue analgesic consumption during PACU stay (0.03 ± 0.05mg vs. 0.04 ± 0.06 mg, p > 0.05). Nalbuphine group had a lower incidence of respiratory depression (RR ≤ 10/min) (4.8% vs. 38.6%, p

The combination of urbanization and global warming leads to urban overheating and compounds the frequency and intensity of extreme heat events due to climate change. Yet, the risk of urban overheating can be mitigated by urban green-blue-grey infrastructure (GBGI), such as parks, wetlands, and engineered greening, which have the potential to effectively reduce summer air temperatures. Despite many reviews, the evidence bases on quantified GBGI cooling benefits remains partial and the practical recommendations for implementation are unclear. This systematic literature review synthesizes the evidence base for heat mitigation and related co-benefits, identifies knowledge gaps, and proposes recommendations for their implementation to maximize their benefits. After screening 27,486 papers, 202 were reviewed, based on 51 GBGI types categorized under 10 main divisions. Certain GBGI (green walls, parks, street trees) have been well researched for their urban cooling capabilities. However, several other GBGI have received negligible (zoological garden, golf course, estuary) or minimal (private garden, allotment) attention. The most efficient air cooling was observed in botanical gardens (5.0 ± 3.5°C), wetlands (4.9 ± 3.2°C), green walls (4.1 ± 4.2°C), street trees (3.8 ± 3.1°C), and vegetated balconies (3.8 ± 2.7°C). Under changing climate conditions (2070–2100) with consideration of RCP8.5, there is a shift in climate subtypes, either within the same climate zone (e.g., Dfa to Dfb and Cfb to Cfa) or across other climate zones (e.g., Dfb [continental warm-summer humid] to BSk [dry, cold semi-arid] and Cwa [temperate] to Am [tropical]). These shifts may result in lower efficiency for the current GBGI in the future. Given the importance of multiple services, it is crucial to balance their functionality, cooling performance, and other related co-benefits when planning for the future GBGI. This global GBGI heat mitigation inventory can assist policymakers and urban planners in prioritizing effective interventions to reduce the risk of urban overheating, filling research gaps, and promoting community resilience.

TTMV::RARA is a recently reported fusion gene associated with acute promyelocytic leukemia (APL), caused by the integration of torque teno mini virus (TTMV) genomic fragments into the second intron of the RARA gene. Currently, there have been only six documented cases, with clinical presentations showing significant variability. Although initial responses to all-trans retinoic acid (ATRA) treatment may be observed in patients with TTMV::RARA-APL, the overall prognosis remains unfavorable among infrequent reported cases. This article presents a pediatric case that manifested as PML::RARA-negative APL with central nervous system involvement at onset. The patient experienced both intramedullary and extramedullary relapse one year after undergoing allogeneic hematopoietic stem cell transplantation. Upon identification as TTMV::RARA-APL and subsequent administration of two rounds of ATRA-based treatment, the patient rapidly developed multiple RARA ligand-binding domain mutations and demonstrated extensive resistance to ATRA and various other therapeutic interventions. Additionally, the patient experienced ARID1A mutant clone expansion and progressed MYC-targeted gene activation. This case represents the first documentation of extramedullary involvement at both the initial diagnosis and relapse stages, emphasizing the intricate clinical features and challenges associated with the rapid accumulation of multiple ATRA-resistant mutations in TTMV::RARA-APL, characterizing it as a distinct and complex sub-entity of atypical APL.

Transglutaminase (TGase) was added to soy protein isolate (SPI) dispersion after the combination treatment of high intensity ultrasound (HIU) and high hydrostatic pressure (HHP) to catalyze the formation of cold gel, which was used to encapsulate riboflavin. The structure, physicochemical properties and in vitro digestion characteristics of riboflavin-loaded SPI cold gel were investigated. HIU-HHP combined treatment enhanced the strength, water retention, elastic property, thermal stability and protein denaturation degree of riboflavin-loaded SPI cold gels, and improved the gel network structure, resulting in a higher encapsulation efficiency of riboflavin and its chemical stability under heat and light treatment. HIU-HHP combined treatment reduced the erosion and swelling of SPI cold gel in simulated gastrointestinal fluid, and improved the sustained release effect of SPI gel on riboflavin by changing the digestion mode and rate of gel. In addition, HIU-HHP combined treated gels promoted the directional release of riboflavin in the simulated intestinal fluid, thereby improving its bioaccessibility, which was related to the secondary structure orderliness, tertiary conformation tightness and aggregation degree of protein during the gastrointestinal digestion. Therefore, HIU-HHP combined treatment technology had potential application value in improving the protection, sustained/controlled release and delivery of SPI cold gels for sensitive bioactive compounds.

Glycated proteins are effective materials for improving the environmental stability and bioavailability of biologically active chemicals. The whey protein concentrate (WPC)-xylose (D) conjugates produced by the Maillard process were used to load and protect purple sweet potato anthocyanins in this study. Response surface optimization was used to determine the best parameters for preparing WPC-D conjugates. Glycation altered the secondary structure of proteins, according to structural studies, which also had an impact on their functional characteristics, which showed better antioxidant activity before and after simulated gastrointestinal (GI) digestion (p

Acute lung injury (ALI) is a clinically prevalent inflammatory disorder that still needs to be developed with more accurate diagnostic biomarkers and more satisfactory therapies. This study intended to explore the therapeutic material basis and molecular mechanisms of a classical traditional Chinese medicinal prescription, Sang Ju Yin (SJY), against ALI, focusing on the chemical components of formula composition, the disturbance of host genes/metabolites and the dysbiosis of intestinal flora. First, based on liquid chromatography-mass spectrometry (LC-MS) component analysis, 212 in vitro and 44 in vivo compounds were identified respectively in SJY. Then, network pharmacology was adopted to calculate potential anti-ALI compounds in SJY and predict that CXCR2, PI3K-Akt signaling and arachidonic acid (AA) metabolism could be potential targets. Subsequently, integrative multi-omics techniques were employed to elaborate deeper systematic molecular mechanisms. Metabolomic data combining both 1H NMR and LC-MS techniques illustrated that 146 pulmonary and 75 fecal biomarkers, associated with AA and other metabolisms, were recuperated by SJY’s intervention. Transcriptomic analyses suggested that SJY could significantly regulate genes and signaling pathways involved with inflammation and apoptosis, such as PI3K-Akt. Further the obtained key targets (IL-10, LCAT, CXCR2 and C5) were verified by qRT-PCR and their relative compound-target interaction were validated by molecular docking. Notably, the disturbance of intestinal microbial community (such as the abundance of Lactobacillus, etc.) was detected through 16S rRNA gene sequencing, that could be effectively reshaped by SJY. Collectively, our integrated work showed SJY could regulate the crosstalk of metabolite-target-pathway-microflora along the gut-microbiota-lung axis on the whole. Noteworthy, our study provided fundamental and new insights into how molecular networks connected different types of components, genes, metabolites, microbes and potential pathways to map an endogenous functional landscape for clinical ALI diagnosis and SJY application.

Environmental pollution has emerged as a global concern due to its detrimental effects on human health. One of the critical aspects of this concern is the impact of environmental pollution on sperm quality in males. Male factor infertility accounts for approximately 40%− 50% of all infertility cases. Nonobstructive azoospermia (NOA) is the most severe type of male infertility. Human umbilical cord mesenchymal stem cell (hUCMSC) exosomes enhance proliferation and migration, playing crucial roles in tissue and organ injury repair. However, whether hUCMSC exosomes impacting on NOA caused by chemotherapeutic agents remains unknown. This study aimed to explore the functional restoration and mechanism of hUCMSC exosomes on busulfan-induced injury in GC-1 spg cells and ICR mouse testes. Our results revealed that hUCMSC exosomes effectively promoted the proliferation and migration of busulfan-treated GC-1 spg cells. Additionally, oxidative stress and apoptosis were significantly reduced when hUCMSC exosomes were treated. Furthermore, the injection of hUCMSC exosomes into the testes of ICR mice treated with busulfan upregulated the expression of mouse germ cell-specific genes, such as vasa, miwi, Stra8 and Dazl. Moreover, the expression of cellular junction- and cytoskeleton-related genes, including connexin 43, ICAM-1, β-catenin and androgen receptor (AR), was increased in the testicular tissues treated with exosomes. Western blot analysis demonstrated significant downregulation of apoptosis-associated proteins, such as bax and caspase-3, and upregulation of bcl-2 in the mouse testicular tissues injected with hUCMSC exosomes. Further, the spermatogenesis in the experimental group of mice injected with exosomes showed partial restoration of spermatogenesis compared to the busulfan-treated group. Collectively, these findings provide evidence for the potential clinical applications of hUCMSC exosomes in cell repair and open up new avenues for the clinical treatment of NOA.

Variations in the quality of brewing water profoundly impact tea flavor. This study systematically investigated the effects of four common water sources, including pure water (PW), mountain spring water (MSW), mineral water (MW) and natural water (NW) on the flavor of Tieguanyin tea infusion. Brewing with MW resulted in a flat taste and turbid aroma, mainly due to the low leaching of tea flavor components and complex interactions with mineral ions (mainly Ca2+, Mg2+). Tea infusions brewed with NW exhibited the highest relative contents of total volatile compounds, while those brewed with PW had the lowest. NW and MSW, with moderate mineralization, were conducive to improving the aroma quality of tea infusion and were more suitable for brewing both aroma types of Tieguanyin. These findings offer valuable insights into the effect of brewing water on the sensory and physicochemical properties of oolong teas.

Abstract Background Tregs are key drivers of immunosuppression in solid tumors. As an important chemokine receptor on Tregs, the regulatory effect of CCR8 on tumor immunity has received more and more attention. However, the current research on CCR8 in the immune microenvironment of ovarian cancer has not been clear. Methods Bioinformatics analysis was used to compare the transcriptome differences between CD4+ T cells in the peripheral circulation and infiltrated in ovarian tumor tissues. RT-PCR was used to detect the expression levels of chemokine receptor-related differential genes on CD4+ T cells in peripheral blood and ovarian tumor tissues. Multiparameter flow cytometry was used to detect the proportion and phenotypic characteristics of CD4+CCR8+ Tregs and CD4+CCR8− Tregs in different sample types. The expression level of CCR8 ligands was detected at multiple levels. To explore the important role of CCR8-CCL1 and CCR8-CCL18 axis in the migration and invasion of CD4+CCR8+ Tregs into ovarian tumor tissues by establishing a chemotaxis system in vitro. Results In this study, significantly different gene expression profiles were found between peripheral circulating CD4+ T cells and infiltrating CD4+ T cells in ovarian tumor tissues, in which chemokine-chemokine receptor signaling pathway was significantly enriched in all three groups of differential genes. The expression level of CCR8 in infiltrating CD4+ T cells of ovarian cancer tissue was significantly higher than that in peripheral blood of healthy controls and ovarian cancer patients, and high expression of CCR8 was significantly correlated with advanced tumor stage and poor differentiation. CD4+CCR8+ Tregs are the main type of infiltrating CD4+ Tregs in ovarian tumor tissues, which have stronger immunosuppressive phenotypes, secrete more inhibitory cytokines and have stronger proliferation ability. The ligands CCL1 and CCL18 corresponding to CCR8 were significantly overexpressed in ovarian tumor tissues, and the CCR8-CCL1 and CCR8-CCL18 axis played a key role in the migration and infiltration of CD4+CCR8+ Tregs into ovarian tumor tissues. Conclusions The results of this study may help to understand the phenotypic characteristics and recruitment process of Tregs in the tumor, and provide new ideas for improving the immunosuppressive status of the ovarian cancer microenvironment.

Abstract Background Ovarian cancer is commonly associated with a poor prognosis due to metastasis and chemoresistance. PINK1 (PTEN-induced kinase 1) is a serine/threonine kinase that plays a crucial part in regulating various physiological and pathophysiological processes in cancer cells. Methods The ATdb database and "CuratedOvarianData" were used to evaluate the effect of kinases on ovarian cancer survival. The gene expression in ovarian cancer cells was detected by Western blot and quantitative real-time PCR. The effects of gene knockdown or overexpression in vitro were evaluated by wound healing assay, cell transwell assay, immunofluorescence staining, immunohistochemistry, and flow cytometry analysis. Mass spectrometry analysis, protein structure analysis, co-immunoprecipitation assay, nuclear-cytoplasmic separation, and in vitro kinase assay were applied to demonstrate the PINK1-PTEN (phosphatase and tensin homolog) interaction and the effect of this interaction. The metastasis experiments for ovarian cancer xenografts were performed in female BALB/c nude mice. Results PINK1 was strongly associated with a poor prognosis in ovarian cancer patients and promoted metastasis and chemoresistance in ovarian cancer cells. Although the canonical PINK1/PRKN (parkin RBR E3 ubiquitin protein ligase) pathway showed weak effects in ovarian cancer, PINK1 was identified to interact with PTEN and phosphorylate it at Serine179. Remarkably, the phosphorylation of PTEN resulted in the inactivation of the phosphatase activity, leading to an increase in AKT (AKT serine/threonine kinase) activity. Moreover, PINK1-mediated phosphorylation of PTEN impaired the nuclear import of PTEN, thereby enhancing the cancer cells’ ability to resist chemotherapy and metastasize. Conclusions PINK1 interacts with and phosphorylates PTEN at Serine179, resulting in the activation of AKT and the inhibition of PTEN nuclear import. PINK1 promotes ovarian cancer metastasis and chemotherapy resistance through the regulation of PTEN. These findings offer new potential therapeutic targets for ovarian cancer management.

Abstract Background Post-traumatic growth is a positive psychological change that may aid recovery in individuals experiencing trauma. Owing to the lack of research in the area of parental care for premature infants, we decided to explore the levels and factors influencing post-traumatic growth among parents of premature infants in neonatal intensive care units. We believe that these findings will help reassess existing care practices so that healthcare providers can promptly identify negative emotions and take necessary measures to help develop the potential to enhance post-traumatic growth. Methods A cross-sectional survey was conducted using convenience sampling between February and September 2022. Data were analysed using independent sample t-tests and one-way analysis of variance (ANOVA). Bivariate correlations were analysed using the Pearson’s or Spearman’s method, and related factors were analysed using multiple linear regression. We followed the SRQR checklist throughout the study period. Results A total of 217 patients were effectively treated, with a recovery rate of 98.64%. Univariate analysis showed that the length of hospital stay, presence of only one child, parents’ age, marital status, education level, working status, and per capita monthly familial income were influencing factors. Bivariate analysis showed that post-traumatic growth was moderately and positively correlated with perceived social support, rumination, and family resilience. Multiple linear regression showed that purposeful contemplation, family resilience, education, family support, age, and marital status entered into the regression equation and together accounted for 47.4% of the total variation. Conclusions It is necessary to pay attention to post-traumatic growth and familial stability in these families, provide aid in building a good support system, and encourage parents to mobilise their family and favourable factors to increase post-traumatic growth levels.

Groundwater reservoirs play an important role in regional water volume balance. In order to ensure the efficiency of a groundwater reservoir and obtain its maximum value, it is necessary to figure out its characteristics, such as minimum water level, normal water level, and maximum water level. The characteristics not only determined the storage capacity but also influenced the water allocation and utilization. Therefore, this paper took a groundwater reservoir built in an alluvial fan as an example to assess its storage capacity and the influence on water dynamic control. The alluvial fan was located in the front of Lao River, where there were an alluvial-diluvial fan, groundwater storage space, and natural impervious boundary. Therefore, it was an ideal place for constructing a groundwater reservoir. Through theoretical analysis and numerical simulation, the storage capacity was determined, and the influence of groundwater reservoir characteristics on water dynamic control was analyzed. On this basis, the water-supply method in the research area was confirmed. This paper will present a new method for repairing the groundwater system and protecting the ecological environment. HIGHLIGHTS Groundwater reservoir built in an alluvial fan could balance the water contradiction.; Groundwater reservoir characteristics have a great influence on water dynamic control.; Groundwater reservoir capacity and its characteristics were calculated.;

Abstract Objective Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj. Methods A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed. Results Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support. Conclusion The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.

Abstract Background Fraction of functional sequence in the human genome remains a key unresolved question in Biology and the subject of vigorous debate. While a plethora of studies have connected a significant fraction of human DNA to various biochemical processes, the classical definition of function requires evidence of effects on cellular or organismal fitness that such studies do not provide. Although multiple high-throughput reverse genetics screens have been developed to address this issue, they are limited to annotated genomic elements and suffer from non-specific effects, arguing for a strong need to develop additional functional genomics approaches. Results In this work, we established a high-throughput lentivirus-based insertional mutagenesis strategy as a forward genetics screen tool in aneuploid cells. Application of this approach to human cell lines in multiple phenotypic screens suggested the presence of many yet uncharacterized functional elements in the human genome, represented at least in part by novel exons of known and novel genes. The novel transcripts containing these exons can be massively, up to thousands-fold, induced by specific stresses, and at least some can represent bi-cistronic protein-coding mRNAs. Conclusions Altogether, these results argue that many unannotated and non-canonical human transcripts, including those that appear as aberrant splice products, have biological relevance under specific biological conditions.

Abstract Background Abnormal foetal tissue chromosome karyotypes are one of the important pathogenic factors for spontaneous abortion (SA). To investigate the age and abnormal foetal karyotypes of 1903 couples who experienced SA. Methods A retrospective multicentre study collected age and foetal tissue karyotypes CNV-seq data of 1903 SA couples from 6 hospitals in 5 regions from January 2017 to March 2022. The distribution and correlation of abnormal foetal tissue karyotypes were evaluated by using regions and age. Results In our study, 1140 couples (60.5% of the total) had abnormal foetal tissue chromosome karyotypes in all regions. We found that there were differences in the number of abnormal foetal tissue chromosome karyotypes, of which the incidence of trisomy was higher. At the same time, the populations situated in the eastern region had a more triploid (15.5%) distribution, trisomy (58.1%) in the southern region, mosaicism (14.8%) and microduplication (31.7%) in the southwestern region, microdeletion (16.7%) in the northern region. There are variances across areas, and it is more common in the north. The incidence risk of prenatal chromosomal abnormalities varied according to age group. Conclusion The findings of this study suggest that the karyotypes of patients with abnormal foetal tissue chromosome abortion in different regions were different. Meanwhile, patients ≥ 35 years old had a higher risk of abnormal foetal tissue chromosome abortion.

Abstract Background This study aimed to assess the predictive value of endometrial blood flow branches on pregnancy outcomes after hormone replacement therapy-frozen embryo transfer (HRT-FET). Methods This prospective observational study involved 292 reproductive-aged women who underwent endometrial receptivity assessment in a tertiary care academic medical center in southwest China using power Doppler ultrasonography during HRT-FET. Three-dimensional power Doppler ultrasound was performed on the day of endometrial transformation and the day before embryo transfer. The endometrial blood flow branches of the endometrial and subendometrial regions were compared in the non-pregnant and pregnant groups at the two time points mentioned above. Results The endometrial blood flow branches were higher in pregnant patients than in non-pregnant patients on the day of endometrial transformation (P = 0.009) and the day before embryo transfer (P = 0.001). Changes in endometrial blood flow pattern and endometrial blood flow branches at the two time points did not differ among the pregnancy outcome samples. After adjusting for age, antral follicles, and embryos transferred, the endometrial blood flow branches on the day before embryo transfer was the independent factor influencing the chance of clinical pregnancy, with an odds ratio of 3.001 (95% confidence interval: 1.448 − 6.219, P = 0.003). Conclusions Endometrial blood flow perfusion during the peri-transplantation period of the HRT-FET cycle is a good indicator of pregnancy outcomes, suggesting that valuation of endometrial branches via power Doppler ultrasound is a simple and effective approach for achieving indicator measurements.

Abstract The pandemic of COVID-19 was a major public health events and had a deeply impact on the healthcare acquired by patients with inflammatory bowel disease (IBD). The purpose of this study was to evaluate the long-term impacts on healthcare service in Chinese IBD patients under the dynamic zero-COVID strategy. The study was performed in the Inflammatory Bowel Disease Quality of Care Centers in mainland China in 2021. The data about the healthcare was collected by a 44-item questionnaire. Totally 463 were from ulcerative colitis (UC) patients and 538 from Crohn’s disease (CD) patients were included in the study. The pandemic impacted 37.5% patients on their treatment, and the biggest problem was unable to follow up timely (77.9%). There was a significant increase in healthcare costs in CD (P

Abstract Solitary fibrous tumors (SFTs) are rare mesenchymal tumors with unpredictable evolution and with a recurrence or metastasis rate of 10-40%. Current medical treatments for relapsed SFTs remain ineffective. Here, we identify potential therapeutic targets and risk factors, including IDH1 p.R132S, high PD-L1 expression, and predominant macrophage infiltration, suggesting the potential benefits of combinational immune therapy and targeted therapy for SFTs. An integrated risk model incorporating mitotic count, density of Ki-67+ cells and CD163+ cells, MTOR mutation is developed, applying a discovery cohort of 101 primary non-CNS patients with negative tumor margins (NTM) and validated in three independent cohorts of 210 SFTs with the same criteria, and in 36 primary CNS SFTs with NTM. Compared with the existing models, our model shows significantly improved efficacy in identifying high-risk primary non-CNS and CNS SFTs with NTM for tumor progression.Our findings hold promise for advancing therapeutic strategies and refining risk prediction in SFTs.

Abstract Lipin family members in mammals include lipins 1, 2, and 3. Lipin family proteins play a crucial role in lipid metabolism due to their bifunctionality as both transcriptional coregulators and phosphatidate phosphatase (PAP) enzymes. In this review, we discuss the structural features, expression patterns, and pathophysiologic functions of lipins, emphasizing their direct as well as indirect roles in cardiovascular diseases (CVDs). Elucidating the regulation of lipins facilitates a deeper understanding of the roles of lipins in the processes underlying CVDs. The activity of lipins is modulated at various levels, e.g., in the form of the transcription of genes, post-translational modifications, and subcellular protein localization. Because lipin characteristics are undergoing progressive clarification, further research is necessitated to then actuate the investigation of lipins as viable therapeutic targets in CVDs.

As an infrastructure, the railway stations' roof and platform canopy have considerable space potential for deploying photovoltaic power generation systems. In order to study the feasibility of installing PV systems in railway stations, this paper analyzes the PV potential and techno-economic characteristics of China's high-grade railroad stations by combining a three-dimensional digital earth system (LSV) and PV plant calculation methods. The results show that the total installed PV capacity of Chinese high-grade railway stations, which are mainly used for passenger transportation, can reach 820 MW, and the total annual PV power generation capacity can reach 1111GWh. The self-sufficiency rate of each station is affected by the scale of the station building, the number of canopies on the passenger platform and the architectural design factors. The smaller the scale of the station building, the larger the area of the platform canopy, the smaller the overlap between the station building and the station canopy, the easier the railway station to achieve self-sustaining. The payback period is the time it takes for the total return on PV power generation to equal the investment in PV construction. 63% of the stations can realize full payback of their investment within 4–7 years under the operation strategy of full self-consumption of power generation. In addition the photovoltaic systems in railroad stations can generate considerable ecological benefits, reducing carbon dioxide emissions by 820,000 tons per year, which is about the carbon emissions of 304,000 cars in one year.

During winter of 2021/2022, the temperature in China is characterized by a warm-to-cold transition, and the average temperature anomaly in February 2022 is −1.6 °C, the coldest February in 2013–2022. We revealed the circulation regimes and physical mechanisms associated with this reversal event and demonstrated the advantage of a regional model downscaling over the use of the global model alone in predicting. In early winter, the warm anomalies are mainly related to an anomalous anticyclonic system downstream of a PNA-like (Pacific–North America) Rossby-wave train induced by La Niña. In late winter, due to the circulation response to the central Pacific warming and negative tropical Indian Ocean Dipole (TIOD), two ‘−＋−’ Rossby-wave trains from high latitudes and the tropical Indian Ocean jointly lead to an anomalous cyclonic system in China. Meanwhile, an anticyclonic blocking system on the northern side of Baikal brings strong and cold air to China. These two systems together cause a significant drop in surface air temperature anomaly in China during the late winter. The Beijing Climate Center climate system model (BCC_CSM1.1 m) can essentially predict this temperature reversal in China about five months in advance. However, the reversal amplitude is weaker due to warm deviations over the tropical Pacific Ocean and equatorial Indian Ocean. Using dynamic downscaling, a regional Climate–Weather Research and Forecasting (CWRF) model correctly predicts the cold SAT anomalies in late winter 2021/2022. The regional model depicts more realistic circulation patterns in East Asia; the anomalous cyclonic system in Inner Mongolia accompanied by the northerly anomalies contribute to a lower-than-normal SAT over China. This study reveals the cooperative effect of wave trains from high latitudes and the tropics on the subseasonal temperature reversal and demonstrates a possible solution to improve the forecast skill by dynamic downscaling according to precise characterization of local surface information.

Abstract Bupivacaine (BPV) can cause severe central nervous system toxicity when absorbed into the blood circulation system. Rapid intravenous administration of lipid emulsion (LE) could be used to treat local anaesthetic toxicity. This study aimed to investigate the mechanism by which the BDNF-TrkB/proBDNF-p75NTR pathway regulation by LE rescues BPV induced neurotoxicity in hippocampal neurons in rats. Seven- to nine-day-old primary cultured hippocampal neurons were randomly divided into 6 groups: the blank control group (Ctrl), the bupivacaine group (BPV), the lipid emulsion group (LE), the bupivacaine + lipid emulsion group (BPV + LE), the bupivacaine + lipid emulsion + tyrosine kinase receptor B (TrkB) inhibitor group (BPV + LE + K252a), the bupivacaine + lipid emulsion + p75 neurotrophic factor receptor (p75NTR) inhibitor group (BPV + LE + TAT-Pep5). All hippocampal neurons were incubated for 24 h, and their growth state was observed by light microscopy. The relative TrkB and p75NTR mRNA levels were detected by real-time PCR. The protein expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, TrkB, p75NTR and cleaved caspase-3 were detected by western blotting. The results showed that primary hippocampal neuron activity was reduced by BPV. As administration of LE elevated hippocampal neuronal activity, morphology was also somewhat improved. The protein expression and mRNA levels of TrkB and p75NTR were decreased when BPV induced hippocampal neuronal toxicity, while the expression of BDNF was increased. At the same time, BPV increased the original generation of cleaved caspase-3 protein content by hippocampal neurons, while the content of cleaved caspase-3 protein in hippocampal neurons cotreated with LE and BPV was decreased. Thus, this study has revealed LE may reduce apoptosis and promote survival of hippocampal neurons by regulating the BDNF-TrkB pathway and the proBDNF-p75NTR pathway to rescue BPV induced central neurotoxicity in rats.