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Abstract Background Epidural labor analgesia (ELA) is widely and safely used for labor pain relief. However, it remains unclear whether ELA affects maternal and neonatal outcomes in women suffering from preeclampsia. Methods This study reviewed the medical records of women with preeclampsia at ≥ 28 weeks of gestation between January 2015 and December 2020. The medical records of women were divided into ELA and no analgesia (NA) groups. The primary endpoint was the cesarean section (CS) rate. Secondary endpoints included hypotension, operative vaginal delivery, fetal distress, neonatal intensive care unit admission, and complications. Using multivariate logistic regression analysis and propensity score matching (PSM), the association between ELA and maternal and neonatal outcomes was examined. Results A total of medical records of 686 women were enrolled, with 242 (35.3%) receiving ELA. Of these, 126 (18.4%) had a higher incidence of CS in the ELA group than in the NA group (22.7% vs. 16.0%, P = 0.020). Multivariable analysis indicated greater risks of CS [adjusted Odds Ratio (aOR) = 1.71; 95% CI, 1.07–2.74; P = 0.025] and operative vaginal delivery (aOR = 2.810; 95% CI, 1.379–5.725; P = 0.004) in the ELA group than that of NA group. In the PSM, ELA did not increase the risk of CS (aOR = 1.56; 95% CI, 0.97–2.52; P = 0.067) and OVD (aOR = 2.048; 95% CI, 0.936–4.484; P = 0.073). The secondary endpoints showed no significant differences between the two groups. Conclusion The study indicates an association between ELA and maternal and neonatal outcomes, supporting the safety of ELA in this population.

Abstract Objectives This study aimed to investigate the diagnostic value of spectral parameters of dual-layer spectral detector computed tomography (DLCT) in distinguishing between low- and high-grade bladder cancer (BCa). Methods This single-center retrospective study included pathologically confirmed BCa patients who underwent preoperative contrast-enhanced DLCT. Patients were divided into low- and high-grade groups based on pathology. We measured and calculated the following spectral CT parameters: iodine density (ID), normalized ID (NID), arterial enhancement fraction (AEF), extracellular volume (ECV) fraction, virtual non-contrast (VNC), slope of the attenuation curve, and Z effective (Zeff). Univariate and multivariable logistic regression analyses were used to determine the best predictive factors in differentiating between low- and high-grade BCa. We used receiver operating characteristic curve analysis to assess diagnostic performance and decision curve analysis to determine the net benefit. Results The study included 64 patients (mean age, 64 ± 11.0 years; 46 men), of whom 42 had high-grade BCa and 22 had low-grade BCa. Univariate analysis revealed that differences in ID and NID in the corticomedullary phase, AEF, ECV, VNC, and Zeff images were statistically significant (p = 0.001–0.048). Multivariable analysis found that AEF was the best predictor of high-grade tumors (p = 0.006). With AEF higher in high-grade BCa, AEF results were as follows: area under the curve (AUC), 0.924 (95% confidence interval, 0.861–0.988); sensitivity, 95.5%; specificity, 81.0%; and accuracy, 85.9%. The cutoff valve of AEF for predicting high-grade BCa was 67.7%. Conclusion Using DLCT AEF could help distinguish high-grade from low-grade BCa. Critical relevance statement This research demonstrates that the arterial enhancement fraction (AEF), a parameter derived from dual-layer spectral detector CT (DLCT), effectively distinguishes between high- and low-grade bladder cancer, thereby aiding in the selection of appropriate clinical treatment strategies. Key Points This study investigated the value of dual-layer spectral detector CT in the assessment of bladder cancer (BCa) histological grade. The spectral parameter arterial enhancement fraction could help determine BCa grade. Our results can help clinicians formulate initial treatment strategies and improve prognostications. Graphical Abstract

Abstract Background Awareness of the characteristics of glial fibrillary acidic protein autoantibody (GFAP-IgG) associated myelitis facilitates early diagnosis and treatment. We explored features in GFAP-IgG myelitis and compared them with those in myelitis associated with aquaporin-4 IgG (AQP4-IgG) and myelin oligodendrocyte glycoprotein IgG (MOG-IgG). Methods We retrospectively reviewed data from patients with GFAP-IgG myelitis at the First Affiliated Hospital of Zhengzhou University and Henan Children’s Hospital from May 2018 to May 2023. AQP4-IgG and MOG-IgG myelitis patients served as controls. Results Thirty-four patients with GFAP-IgG myelitis were included (15 women, 12 children; median age at onset, 28.5 years). Over half experienced prodromal symptoms and required intensive care support. The median Expanded Disability Status Scale (EDSS) score was 4 at admission and 0 at final follow-up (median, 20 months). Cerebrospinal fluid (CSF) analysis showed markedly elevated leukocyte counts in 23 patients, elevated total protein in 28 patients, and decreased glucose levels in 9 patients. Longitudinally sagittal T2 and gadolinium-enhancing spinal cord lesions were detected. Features favoring GFAP-IgG over the other types included presence of fever and neck stiffness, requirement of intensive care and mechanical ventilation, higher monocyte-to-lymphocyte ratio (MLR), presence of hyponatremia, markedly elevated CSF leukocyte counts, increased CSF total protein levels, and decreased CSF glucose levels. Imaging findings more common in GFAP-IgG than in AQP4-IgG myelitis were longer diseased segments, central canal enhancement, and gadolinium-enhancing brain lesions. Higher EDSS scores at discharge distinguished GFAP-IgG from MOG-IgG. Conclusion Clinical, laboratory, imaging, and outcome variables facilitate differential diagnosis of myelitis subtypes.

Abstract An ancient and counterintuitive phenomenon known as the Mpemba effect (water can cool faster when initially heated up) showcases the critical role of initial conditions in relaxation processes. How to realize and utilize this effect for speeding up relaxation is an important but challenging task in purely quantum system till now. Here, we experimentally study the strong Mpemba effect in a single trapped ion system in which an exponentially accelerated relaxation in time is observed by preparing an optimal quantum initial state with no excitation of the slowest decaying mode. Also, we demonstrate that the condition of realizing such effect coincides with the Liouvillian exceptional point, featuring the coalescence of both the eigenvalues and the eigenmodes of the systems. Our work provides an efficient strategy to engineer the dynamics of open quantum system, and suggests a link unexplored yet between the Mpemba effect and the non-Hermitian physics.

Abstract Objective This study aims to investigate the clinical application value of the central venous-arterial carbon dioxide partial pressure difference (Pv-aCO2) in postoperative cognitive dysfunction(POCD) in patients with acute aortic dissection. Methods A retrospective analysis was conducted on the general data of 236 patients. Blood gas samples were collected from the arterial and venous lines at various time points during the surgery, including before and after the initiation of cardiopulmonary bypass (CPB), immediately after CPB initiation, before and after deep hypothermic circulatory arrest, 30 min after rewarming, and 5 min before weaning from CPB. The partial PV-aCO2 was calculated. Based on the average PV-aCO2 value, patients were divided into an observation group (PV-aCO2 > 6 mmHg, n = 112) and a control group (PV-aCO2

Abstract This study proved that the curves of carbon monoxide (CO), carbon dioxide (CO2), and CO + CO2 in the off-gas profile were forecastable, and realized a 32-s-ahead forecasting for them. It established a technical foundation for addressing the delay in off-gas profile display and for enabling pre-control in BOF steelmaking based on the forecasted curves’ features. First, a data pre-processing method was proposed based on the characteristics of the off-gas curves, where there are many samples, but each sample contains limited time-steps. It is termed the mixed-batch approach. The importance of the time series’ channels and time-steps were also analyzed by models with attention mechanism. Then, a deep-learning model is proposed to forecast the dynamic off-gas profile, named attention-based convolutional aggregation (ABCA). It incorporates artificial intelligence (AI) techniques, such as aggregation structures, causal dilation convolution, attention mechanisms, residual connections, etc. Its forecasting coefficient of determination (R 2 ) values for the curves of CO, CO2, and CO + CO2 reached 0.9386, 0.8566, and 0.9428, respectively, while the mean squared errors (MSEs) values were 47.3884, 11.9314, and 54.3583, respectively. These results outperform the benchmark state-of-the-art (SOTA) models. Additionally, ABCA was implemented in a forecasting tool for external validation. The results of external validation showed that ABCA has good forecasting accuracy and robustness. What is more, approaches in four aspects of pre-control of BOF steelmaking process with forecasted off-gas profile were also provided as pre-control examples.

Electrospun nanofibrous membranes (eNFMs) have been extensively developed for bio-applications due to their structural and compositional similarity to the natural extracellular matrix. However, the emergence of antibiotic resistance in bacterial infections significantly impedes the further development and applications of eNFMs. The development of antibacterial nanomaterials substantially nourishes the engineering design of antibacterial eNFMs for combating bacterial infections without relying on antibiotics. Herein, a comprehensive review of diverse fabrication techniques for incorporating antibacterial nanomaterials into eNFMs is presented, encompassing an exhaustive introduction to various nanomaterials and their bactericidal mechanisms. Furthermore, the latest achievements and breakthroughs in the application of these antibacterial eNFMs in tissue regenerative therapy, mainly focusing on skin, bone, periodontal and tendon tissues regeneration and repair, are systematically summarized and discussed. In particular, for the treatment of skin infection wounds, we highlight the antibiotic-free antibacterial therapy strategies of antibacterial eNFMs, including (i) single model therapies such as metal ion therapy, chemodynamic therapy, photothermal therapy, and photodynamic therapy; and (ii) multi-model therapies involving arbitrary combinations of these single models. Additionally, the limitations, challenges and future opportunities of antibacterial eNFMs in biomedical applications are also discussed. We anticipate that this comprehensive review will provide novel insights for the design and utilization of antibacterial eNFMs in future research.

Abstract Objective This study aims to investigate the distribution characteristics of symptoms in patients with lung cancer during chemotherapy, identify the symptom clusters (SCs) and explore the underlying mechanisms. The findings will provide evidence to assist clinical staff in effectively managing symptoms and SCs. Methods Participants were recruited from the Oncology Department of Guang’anmen Hospital, China Academy of Chinese Medical Sciences, between July 2022 and December 2022. The incidence and severity of symptoms were assessed and SCs were identified. Spearman’s correlation analysis was used to examine the correlation between lung cancer-specific SC and routine blood indices. Results A total of 169 patients participated in the study. The most prevalent and severe symptom was loss of appetite. Based on the occurrence rate and severity of symptoms, SC extraction was performed for mild, moderate, and severe symptoms, resulting in the identification of five SCs: psycho-emotional SC, chemotherapy-related SC, lung cancer-specific SC, urinary-related SC, and gastrointestinal SC. When only the moderate and severe symptoms were considered, two SCs were identified: chemotherapy-related SC and lung cancer-specific SC. Additionally, the lung cancer-specific SC showed a negative correlation with eosinophils. Conclusion Patients with lung cancer undergoing chemotherapy experience complex and diverse symptoms. A total of five SCs were extracted based on mild, moderate and severe symptoms and two SCs were extracted based on moderate and severe symptoms. The results of the study showed that lung cancer-specific SC was negatively correlated with eosinophils. Future research should focus on developing and refining research tools, methodologies, understanding the pathogenesis, and exploring intervention measures for SCs.

Abstract Background Podocyte injury causes proteinuria and accelerates glomerular sclerosis during diabetic kidney disease (DKD). Disruptor of telomeric silencing 1-like (DOT1L), an evolutionarily conserved histone methyltransferase, has been reported in preventing kidney fibrosis in chronic kidney disease models. However, whether DOT1L exerts beneficial effects in diabetes induced podocyte injury and the underlying molecular mechanisms need further exploration. Methods The expression of DOT1L was confirmed by Western blotting in MPC-5 cells and cortex of kidney from db/db mice, as well as immunofluorescence staining in human renal biopsy samples. The effect of DOT1L on podocyte injury was obtained using MPC-5 cells and db/db mice. The potential target genes regulated by DOT1L was measured by RNA-sequencing. Then, a series of molecular biological experiments was performed to investigate the regulation of PLCL1 by DOT1L in MCP-5 cells and db/db mice. Lipid accumulation was assessed by UPLC-MS/MS analysis and Oil Red O staining. Results DOT1L expression was significantly declined in high glucose (HG)-treated MPC-5 cells, podocyte regions of kidney tissues from db/db mice and human renal biopsy samples. Subsequent investigations revealed that upregulation of DOT1L ameliorated HG-induced cell apoptosis in MPC-5 cells as well as primary podocytes. Furthermore, podocyte-specific DOT1L overexpression inhibited diabetic podocyte injury in db/db mice. Mechanistically, we revealed that DOT1L upregulated phospholipase C-like 1 (PLCL1) expression by mediating H3K79me2 at its promoter and PLCL1 silencing suppressed the protective role of DOT1L on podocyte injury. Moreover, DOT1L improved diabetes induced abnormal fatty acid metabolism in podocytes and PLCL1 knockdown reversed its protective effects. Conclusions Taken together, our results indicate that DOT1L protects podocyte injury via PLCL1-mediated fatty acid metabolism and provides new insights into the therapeutic target of DKD.

Abstract We investigate the precessing motion around the the regular black hole with an asymptotically Minkowski core which has a suppression parameter $$\ell $$ ℓ . We obtain the third-order post-Newtonian quasi-Keplerian motion of a test particle in this spacetime and find its relativistic periastron advance. Then, we test this model with the precessing motion of the star S2 and of OJ 287 and determine the upper limits of the dimensionless suppression parameter as $$\ell /m \sim 10^{-3}$$ ℓ / m ∼ 10 - 3 , where m is the mass of the black hole. Compared with the bound given by the shadow of Sgr A*, our bound on $$\ell /m$$ ℓ / m is reduced by 2 orders of magnitude, although our upper limit of $$\ell $$ ℓ still needs further improvement.

Abstract Background Extended depth of focus (EDOF) and multifocal (Multi) intraocular lenses (IOL) can provide a fixed distance of near vision, which may result in some discomfort for patients who prefer different near distances. The aim of this study was to compare the vision, comfortable near distance (CND) and visual comfort in patients who underwent implantation of EDOF, Multi, and monofocal (Mono) IOLs. Methods A total of 100 eyes were implanted with Tecnis ZXR00, ZMB00 or ZCB00 IOLs. Uncorrected distance, intermediate, and near visual acuity (UDVA, UIVA, and UNVA, respectively), corrected distance visual acuity (CDVA), the fluctuations of CND, the ability to see at comfortable or standard near distance and visual comfort were evaluated at 3-month postoperative. Results At 3 months postoperative, the EDOF and Multi groups showed non-inferiority compared to the Mono group in the UDVA (P > 0.05) and CDVA (P > 0.05) but superiority in the UNVA (P

Abstract Background Robot-assisted radical prostatectomy (RARP) gains increasing popularity in the surgical management of prostate cancer (PCa) but is challenged by its prohibitive expense. A domestic robotic system has been developed to address this issue, but data comparing the self-developed robot with the widely used robot is lacking. We performed a randomized clinical trial to compare KD-SR-01® and DaVinci® robots in terms of perioperative, short-term oncological and functional outcomes in RARP. Materials and methods We prospectively enrolled patients with clinically localized PCa. Patients were randomized to undergo either KD-SR-01®-RARP (K-RARP) or DaVinci®-RARP (D-RARP) by the same surgical team. The baseline, perioperative, short-term oncologic and urinary functional data were collected and compared. Results We enrolled 39 patients, including 20 patients undergoing K-RARP and 19 undergoing D-RARP. Demographic and tumor characteristics were comparable between groups. All surgeries were performed successfully with no conversion to open. The operative time was similar (P = 0.095) and K-RARP offered less volume of intraoperative bleeding (P

Abstract Background Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. Methods We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In this study, we found that extremely low concentrations of GNE-987(2–10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. Conclusions This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Abstract Three-dimensional (3D) imaging of individual atoms is a critical tool for discovering new physical phenomena and developing new technologies in microscopic systems. However, the current single-atom-resolved 3D imaging methods are limited to static circumstances or a shallow detection range. Here, we demonstrate a generic dynamic 3D imaging method to track the extensive motion of single ions by exploiting the engineered point-spread function (PSF). We show that the image of a single ion can be engineered into a helical PSF, thus enabling single-snapshot acquisition of the position information of the ion in the trap. A preliminary application of this technique is demonstrated by recording the 3D motion trajectory of a single trapped ion and reconstructing the 3D dynamical configuration transition between the zig and zag structures of a 5-ion crystal. This work opens the path for studies on single-atom-resolved dynamics in both trapped-ion and neutral-atom systems.

Abstract In the KEYNOTE-811 study, anti-HER2 and immunotherapy treatments resulted in longer survival in HER2-positive gastric cancer patients with CPS ≥ 1, whereas CPS

Mitochondria and lysosomes are critical for neuronal homeostasis, as highlighted by their dysfunction in various neurological diseases. Recent studies have identified dynamic membrane contact sites between mitochondria and lysosomes, independent of mitophagy and the lysosomal degradation of mitochondrial-derived vesicles (MDVs), allowing bidirectional crosstalk between these cell compartments, the dynamic regulation of organelle networks, and substance exchanges. Emerging evidence suggests that abnormalities in mitochondria-lysosome contact sites (MLCSs) contribute to neurological diseases, including Parkinson’s disease, Charcot–Marie-Tooth (CMT) disease, lysosomal storage diseases, and epilepsy. This article reviews recent research advances regarding the tethering processes, regulation, and function of MLCSs and their role in neurological diseases.

Background: Time elapsed from stroke onset and baseline infarct volume is influential on endovascular thrombectomy (EVT) outcomes. Objectives: This study aimed to explore the utility of early infarct growth rate (EIGR) measured by apparent diffusion coefficient (ADC) in predicting symptomatic intracranial hemorrhage (sICH) of ischemic stroke patients after EVT. Methods: We retrospectively analyzed patients from the prospectively maintained stroke registry admitted between January 2019 and March 2023, presenting with large vessel occlusive stroke in the anterior circulation. EIGR was defined as ischemic core volume on magnetic resonance perfusion imaging (ADC ⩽620 × 10 −6 mm 2 /s) divided by the time from stroke onset to imaging. sICH was diagnosed according to the Heidelberg Bleeding Classification within 72 h after the procedure. Results: A total of 315 patients met the inclusion criteria. We observed sICH in 36 (11.4%) patients. After adjusting for the potential confounders, increased EIGR was confirmed to be independently associated with a higher risk of sICH (adjusted odds ratio, 1.033; 95% confidence interval (CI), 1.018–1.048; p = 0.001). Similar results were also confirmed when EIGR was analyzed as a categorical variable. Using a logistic regression model with restricted cubic splines, we found a linear correlation between EIGR and sICH risk ( p = 0.001 for linearity). Furthermore, adding EIGR to a model containing conventional risk factors significantly improved risk reclassification for sICH (category-free net reclassification index, 0.393; 95% CI, 0.227–0.560; p = 0.001; integrated discrimination improvement, 0.245; 95% CI, 0.146–0.343; p = 0.001). Conclusion: Increased EIGR may predict the sICH in ischemic stroke patients who receiving EVT.

Background: Patients with coronavirus disease 2019(COVID-2019) infections may still experience long-term effects, with fatigue being one of the most frequent ones. Clinical research on the long COVID in the Chinese population after infection is comparatively lacking. Objective: To collect and analyze the long-term effects of non-severe COVID-19 infection patients and to develop a model for the prediction of fatigue symptoms. Methods: 223 non-severe COVID-19 patients admitted to one designated hospital were enrolled after finish all the self-designed clinical information registration form and nine-month follow-up. We explored the frequency and symptom types of long COVID. Correlation analysis was done on the neuropsychological scale results. After cluster analysis, lasoo regression and logistic regressions, a nomogram prediction model was produced as a result of investigating the risk factors for fatigue. Results: A total of 108 (48.4%) of the 223 non-severe COVID-19 patients reported sequelae for more than 4 weeks, and of these, 35 (15.7%) had fatigue sequelae that were scale-confirmed. Other sequelae of more than 10% were brain fog (n = 37,16.6%), cough (n = 26,11.7%) and insomnia (n = 23,10.3%). A correlation between depression and fatigue was discovered following the completion of neuropsychological scale. The duration of hospitalization, the non-use of antiviral medications in treatment, IL-6 and CD16+CD56+ cell levels in blood are the main independent risk factors and predictors of fatigue sequelae in long COVID. Additionally, the neurology diseases and vaccination status may also influence the fatigue sequelae. Conclusion: Nearly half of the patients infected with COVID-19 Omicron variant complained of sequelae, and fatigue was the most common symptom, which was correlated with depression. Significant predictors of fatigue sequelae included length of hospitalization, non-use of antiviral drug, and immune-related serum markers of IL-6 and CD16+CD56+ NK cell levels. The presence of neurology diseases and a lack of vaccination could also predict the occurrence of fatigue sequelae.

BackgroundEndometriosis (EMs) results in approximately 50% of reproductive-age women facing infertility. Currently, no precise model is available to predict successful postoperative pregnancy.MethodsThis study involved 81 patients with severe EMs (stages III and IV) and 38 controls with benign gynecological conditions, matched by age and BMI, diagnosis at Fujian Maternity and Child Health Hospital from January 2018 to December 2019. Relative expression levels of ERRβ and ERRγ mRNA in ectopic and ectopic endometrial tissues were measured using fluorescence quantitative PCR. Serum levels of ERRβ, ERRγ, and fertility-related hormones (AMH, FSH, LH, CA125) were assessed. Correlations were analyzed, and the predictive value of ERRγ for postoperative pregnancy was evaluated using a nomogram based on LASSO and multivariate logistic regression. Internal validation using bootstrapping techniques assessed the nomograms performance, including calibration and DCA.ResultsERRβ and ERRγ mRNA levels from ectopic tissues were significantly reduced in patients with severe EMs compared to controls. High serum CA125 correlated with increased ERRγ mRNA expression in ectopic tissues. ERRγ mRNA expression in ectopic endometrial tissues was negatively correlated with age, BMI, and FSH levels, and positively with AMH and LH/FSH ratio. ERRγ mRNA and FSH were significant predictors of postoperative pregnancy, with the nomogram model showing a Brier score of 0.175 and a consistency statistic of 0.811.ConclusionsERRβ and ERRγ are downregulated in ectopic tissues from severe EMs. Elevated ERRγ mRNA expression and lower FSH levels are predictive factors for successful postoperative pregnancy.

In this article, the behaviors of both flow and generated output of photovoltaic pump, the characteristics of both water pumping efficiency and output frequency, and the feature of charge capacity in accumulators have been tested through experiments, based on the integrated application system for water pumping, energy storage and illumination by photovoltaic pump, and in combination with composition and operation performance of photovoltaic water pumping system. According to the experimental results and under a constant delivery head, the photovoltaic pump and accumulator energy storage system with a total measured power of 1.8375 kWp in a photovoltaic array produces a daily water output of 13.1 m 3 and an average water output of 1.93 m 3 /h; the maximum water pumping efficiency of the system is 12.7% and the average water pumping efficiency is 11.1%; meanwhile, the energy storage capacity of accumulators by charging in three time periods throughout a day is 1.01 kWh, which accounts for about 9.72% of the photovoltaic array's all-day generated energy, namely 10.3 kWh. Those conclusions have certain practical implications for the optimal configuration of photovoltaic water pumping system.

ABSTRACT Objectives Whether to perform local radiotherapy on metastatic bone for primary bone‐only oligometastatic nasopharyngeal carcinoma (NPC) patients remains unclear. Therefore, we analyzed the treatment methods and their survival and developed a prognostic model to predict outcomes and guide personalized treatment. Materials and Methods We studied 308 primary bone‐only oligometastatic NPC patients who were treated with either palliative chemotherapy (PCT) alone, PCT combined with locoregional radiotherapy (LRRT), or PCT, LRRT, and radiotherapy to metastatic bones (bRT). The primary endpoint was overall survival (OS). Cox regression was utilized to identify independent prognostic factors, leading to the construction of a nomogram model. Patients were stratified into two risk groups based on median prognostic scores, and treatment modalities were compared using log‐rank test while employing the inverse probability of treatment weighting (IPTW) to balance baseline characteristics and adjust for sample size differences between risk groups. Results The best OS was observed in the group treated with PCT, LRRT, and bRT (HR = 0.60, 95% CI: 0.45–0.81, p = 0.002). Multivariable analysis revealed that age, N stage, pre‐treatment levels of LDH, and EBV DNA were independent prognostic factors for OS. In total, 155 patients were in low‐risk group while 153 were in high‐risk group. Before and after IPTW, the high‐risk group benefited from the PCT, LRRT, and bRT regimen (adjusted HR = 0.53, 95% CI: 0.42–0.67, p

Objectives: Deletion of Fscn2 gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells. Cisplatin, an antitumor drug, can cause various side effects, including ototoxicity. The aim of this study was to investigate the effects of Fscn2 on cisplatin-induced hearing impairment in mice and to explore the possible mechanism. Methods: Two-week-old Fscn2+/+ mice and Fscn2−/− mice were treated with two doses of cisplatin, with a 3-day recovery period in between. ABR (auditory evoked brain stem response) thresholds were measured and cochlear pathology was observed at 3 weeks of age. Results: Both Fscn2+/+ and Fscn2−/− mice showed hearing loss under the effect of cisplatin, but the impairment was more severe in Fscn2−/− mice. Further experiments showed that the percentages of outer hair cell (OHC) and spiral ganglion neuron (SGN) loss were significantly higher in cisplatin-treated Fscn2−/− mice compared to Fscn2+/+ mice. Additionally, knockdown of Fscn2 in HEI-OC1 cells worsened cisplatin-induced cell apoptosis. Conclusion: FSCN2 mediates reduction of CDDP induced ototoxicity by inhibiting cell apoptosis.

Abstract Considerable attention has been directed towards exploring the potential efficacy of miR-155 in the realm of cancer immunotherapy. Elevated levels of miR-155 in dendritic cells (DCs) have been shown to enhance their maturation, migration, cytokine secretion, and their ability to promote T cell activation. In addition, overexpression of mir155 in M2 macrophages boost the polarization towards the M1 phenotype. Conversely, miR-155 has the propensity to induce the accumulation of immunosuppressive cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor tissue. To account for this discrepancy, it is imperative to get help from a drug that could deal with immunosuppressive effect. Curcumin (CUR) exhibits the capacity to prompt Tregs converse into T helper 1 cells, fostering the polarization of M2 tumor-associated macrophage towards the M1 phenotype, and impeding the recruitment and aggregation of MDSCs within the tumor microenvironment. Nonetheless, CUR is known to exert an immunosuppressive impact on DCs by hindering the expression of maturation markers, cytokines, and chemokines, thereby prevent DCs response to immunostimulatory agents. Hence, a reactive oxygen species/glutathione dual responsive drug conveyance platform (CUR/miR155@DssD-Hb NPs) was devised to co-deliver CUR and miR155, with the aim of exploring their synergistic potential in bolstering a sustained and robust anti-tumor immune response. In vitro and in vivo results have suggested that CUR/miR155@DssD-Hb NPs can effectively inhibit the viability of 4T1 and B16F10 tumor cells, trigger the release of damage associated molecular patterns, stimulate DCs maturation, subsequent activation of CD8+ T cells, diminish immunosuppressive cell populations (MDSCs, Tregs, M2 TAMs and exhausted T cells), promote the formation of long-term immunity and lessen the formation of metastatic nodules in the lungs. In summary, the co-delivery system integrating CUR and miR155 (CUR/miR155@DssD-Hb NPs) demonstrates promise as a promising strategy for the immunotherapy of melanoma and triple negative breast cancer. Graphical abstract

Abstract When traditional statistical quality control protocols, represented by the Westgard protocol were applied to infectious disease serology, the rejection limits were questioned because of the high rejection probability. We first define the probability of false rejection (Pfr) and error detection (Ped) for infectious disease serology. QC data in 6 months were collected and the Pfr of each rule in the Westgard protocol and Rilibak protocol was evaluated. Then, as improvements, we chose different rules for negative and positive QC data to constitute an asymmetric protocol, furthermore, while reagent lot changes, the mean value of QC protocol is reset with the first 15 QC results of new lot reagent. QC materials and Standard Reference Materials were tested synchronously in the next 6 months, to verify whether the Pfr and Ped of the asymmetric protocol could meet the requirement. Protocol 1 exhibited the higher level of rejection rate among the two protocols, especially after reagent lot changes; Pfr below the lower control limit (LCL) was 1.39–21.78 times higher than the upper control limit (UCL); false rejections were more likely to occur in negative QC data, with Pfr-total of 27–65%. The asymmetric protocol can significantly reduce the proportion of analytes with Pfr by over 20%. Systematic error due to reagent lot changes and random error due to routine QC data variation were considered potential factors for excessive Pfr. Asymmetric QC protocol that can reduce Pfr by different control limits for negative and positive QC data.

Introduction: The use of the dorsal hamate as a free osteochondral bone graft or vascularized bone flap has become the mainstay for large, comminuted middle phalanx volar lip fractures. To date, few studies have been conducted in the assessment of donor site morbidity for the hemi-hamate graft or flap, and none have discussed modes of repair or reconstruction of this donor site. Methods: A retrospective analysis of 14 hemi-hamate arthroplasty (HHA) procedures, including 6 vascularized and 8 non-vascularized grafts, from two surgeons was performed. Four hamate defect reconstruction techniques were utilized: no formal reconstruction, autologous bone grafting, gel foam, or synthetic bone substitute. The dorsal capsule was repaired with either extensor retinaculum grafting or by direct closure. Wrist range of motion, pain scores, and radiographic alignment were assessed. Results: At 6 months follow-up, all patients achieved full, pain-free wrist motion compared to the uninjured side, with visual analog scale pain scores of 0. Serial radiographs showed maintained carpal alignment without instability or subluxation. No differences based on the hamate defect reconstruction method or capsular repair technique was demonstrated. Conclusion: Safe return to pain free, unrestricted wrist function is achievable after HHA, regardless of hamate donor site management. Adequate dorsal capsular repair appears critical to prevent instability. Further study is needed to compare techniques, but choice may be guided by surgeon preference in the absence of clear evidence.

Abstract The vertical settling of plastic debris in oceans is poorly understood. A large share of low-density microplastics (LDMPs) are largely absent from sea surfaces. The present study employs a model that considers the potential of an overlooked microbially induced calcium carbonate precipitation (MICP) process and new motion equations for irregular LDMPs. Here we show that the motion of LDMPs in the present model, exhibiting a damped oscillation pattern, is quite different from that in biofouling models. Furthermore, LDMPs in the size range of 10–200 µm are most likely to gain sufficient density at the biofouling/MICP stage to independently sink to the ocean floor with relatively small drag coefficients, potentially explaining the selective enrichment of LDMPs in the oceanic sediment. The size and shape exhibit strong non-linear effects on the settling patterns of LDMPs. Overall, the present study highlights the importance of calcite-mediated sinking of LDMPs in open oceans.

Abstract Background Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. Methods Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin–eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. Results The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. Conclusions LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions. Graphical Abstract

Abstract Background Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. Methods and results A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P

ObjectiveTo explore the status of knowledge graph-based research into breast cancer microenvironment and to predict future research hotspots. MethodsThe literature related to breast cancer microenvironment in recent 20 years was retrieved from CNKI and Web of Science Core Collection database and analyzed with CiteSpace and VOSviewer. ResultsA total of 825 Chinese articles and 16,221 English articles were retrieved. Visual analysis showed that research focus has gradually shifted from cellular research to molecular research and drug innovation. Cancer stem cells, PD-1, PD-L1, immune checkpoint inhibitors, and nanoparticles are the main subjects of interest in research on breast cancer microenvironment, and the United States has the largest number of studies on breast cancer microenvironment, followed by China and Italy. ConclusionCurrent research mainly focuses on tumor stemness, immunotherapy, and nanodelivery. Owing to deepening research in this field, the targeting of the breast cancer microenvironment for the prevention of tumor development and metastasis and improvement of tumor prognosis has emerged as a new research direction.

Abstract Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen–glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.

Introduction. Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. Objective. To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). Materials and methods. Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. Results. The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT

Abstract Background Gastric cancer patients with peritoneal metastasis (GCPM) experience a rapidly deteriorating clinical trajectory characterized by therapeutic resistance and dismal survival, particularly following the development of malignant ascites. However, the intricate dynamics within the peritoneal microenvironment (PME) during the treatment process remain largely unknown. Methods Matched samples from primary tumours (PT), peritoneal metastases (PM), and paired pre‐treatment and post‐chemo/immunotherapy (anti‐PD‐1/PD‐L1) progression malignant ascites samples, were collected from 48 patients. These samples were subjected to single‐cell RNA sequencing (n = 30), multiplex immunofluorescence (n = 30), and spatial transcriptomics (n = 3). Furthermore, post hoc analyses of a phase 1 clinical trial (n = 20, NCT03710265) and an in‐house immunotherapy cohort (n = 499) were conducted to validate the findings. Results Tracing the evolutionary trajectory of epithelial cells unveiled the terminally differentially MUC1+ cancer cells with a high epithelial‐to‐mesenchymal transition potential, and they demonstrated spatial proximity with fibroblasts and endothelial cells, correlating with poor prognosis. A significant expansion of macrophage infiltrates, which exhibited the highest proangiogenic activity, was observed in the ascites compared with PT and PM. Besides, higher C1Q+ macrophage infiltrates correlated with significantly lower GZMA+ T‐lymphocyte infiltrates in therapeutic failure cases, potentially mediated by the LGALS9‐CD45 and SPP1‐CD44 ligand–receptor interactions. In the chemoresistant group, intimate interactions between C1Q+ macrophages and fibroblasts through the complement activation pathway were found. In the group demonstrating immunoresistance, heightened TGF‐β production activity was detected in MUC1+ cancer cells, and they were skewed to interplay with C1Q+ macrophages through the GDF15‐TGF‐βR2 axis. Ultimately, post hoc analyses indicated that co‐targeting TGF‐β and PDL1 pathways may confer superior clinical benefits than sole anti‐PD‐1/PD‐L1 therapy for patients presenting with GCPM at the time of diagnosis. Conclusions Our findings elucidated the cellular differentiation trajectories and crucial drug resistance features within PME, facilitating the exploration of effective targets for GCPM treatment. Highlights MUC1+ cancer cells with a high epithelial‐to‐mesenchymal transition potential and exhibiting spatial proximity to fibroblasts and endothelial cells constitute the driving force of gastric cancer peritoneal metastasis (GCPM). Higher C1Q+ macrophage infiltrates correlated with significantly lower GZMA+ T‐lymphocyte infiltrates within the peritoneal microenvironment in therapeutic failure cases. Co‐targeting TGF‐β and PDL1 pathways may confer superior clinical benefits than sole anti‐PD‐1/PD‐L1 therapy for patients presenting with GCPM at diagnosis.

ObjectiveThis study aims to analyze the association between the weight-adjusted waist index (WWI) and the risk of gynecologic cancers, using data collected from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016.MethodsWe employed multiple logistic regression analysis to investigate the relationship between WWI and risk of gynecologic cancers. Subsequent subgroup analyses were performed on specific populations of interest. A restricted cubic spline model was used to explore potential non-linear relationships. Additionally, the effectiveness of WWI in predicting sarcopenia was assessed through Receiver Operating Characteristic (ROC) curve analysis. K-fold cross-validation was applied for model assessment.ResultsAmong the 4,144 participants, 98 self-reported having gynecologic cancers. In the fully adjusted model, WWI was significantly associated with the prevalence of gynecologic cancers (OR = 1.38, 95% CI: 1.02–1.88, p = 0.0344). Our findings indicate a linear positive association between WWI and the risk of gynecologic cancers. Subgroup analysis revealed that WWI had the strongest association with cervical cancer (OR = 1.46, 95% CI: 0.97–2.18, p = 0.0354) and endometrial cancer (OR = 1.39, 95% CI: 0.81–2.39, p = 0.0142). No significant association was found between WWI and the risk of ovarian cancer (OR = 1.16, 95% CI: 0.48–2.72, p = 0.5359). Restricted cubic spline analysis confirmed a linear relationship between WWI and the risk of cervical, endometrial, and ovarian cancers. ROC curve analysis demonstrated that WWI had superior predictive capability for gynecologic cancers.ConclusionElevated levels of WWI were significantly associated with an increased risk of gynecologic cancers in American women, displaying a stronger association than other obesity markers. Therefore, WWI may serve as a distinct and valuable biomarker for assessing the risk of gynecologic cancers, particularly cervical and endometrial cancers.

Abstract Over the years, microbiome research has achieved tremendous advancements driven by culture‐independent meta‐omics approaches. Despite extensive research, our understanding of the functional roles and causal effects of the microbiome on phenotypes remains limited. In this study, we focused on the rumen metaproteome, combining it with metatranscriptome and metabolome data to accurately identify the active functional distributions of rumen microorganisms and specific functional groups that influence feed efficiency. By integrating host genetics data, we established the potentially causal relationships between microbes‐proteins/metabolites‐phenotype, and identified specific patterns in which functional groups of rumen microorganisms influence host feed efficiency. We found a causal link between Selenomonas bovis and rumen carbohydrate metabolism, potentially mediated by bacterial chemotaxis and a two‐component regulatory system, impacting feed utilization efficiency of dairy cows. Our study on the nutrient utilization functional groups in the rumen of high‐feed‐efficiency dairy cows, along with the identification of key microbiota functional proteins and their potentially causal relationships, will help move from correlation to causation in rumen microbiome research. This will ultimately enable precise regulation of the rumen microbiota for optimized ruminant production.