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Background: During intraoperative monitoring for scoliosis surgery, we have previously elicited ipsilateral and contralateral motor evoked potentials (MEP) with cross scalp stimulation. Ipsilateral MEPs, which may have comprised summation of early ipsilaterally conducted components and transcallosally or deep white matter stimulated components, can show larger amplitudes than those derived purely from contralateral motor cortex stimulation. We tested this hypothesis using two stimulating positions. We compared intraoperative MEPs in 14 neurologically normal subjects undergoing scoliosis surgery using total intravenous anesthetic regimens. Methods: Trancranial electrical stimulation was applied with both cross scalp (C3C4 or C4C3) or midline (C3Cz or C4Cz) positions. The latter was assumed to be more focal and result in little transcallosal/deep white matter stimulation. A train of 5 square wave stimuli 0.5 ms in duration at up to 200 mA was delivered with 4 ms (250 Hz) interstimulus intervals. Averaged supramaximal MEPs were obtained from the tibialis anterior bilaterally. Results: The cross scalp stimulating position resulted in supramaximal MEPs that were of significantly higher amplitude, shorter latency and required lower stimulating intensity to elicit overall (Wilcoxon Signed Rank test, p < 0.05 for all), as compared to the midline stimulating position. However, no significant differences were found for all 3 parameters comparing ipsilaterally and contralaterally recorded MEPs (p > 0.05 for all), seen for both stimulating positions individually. Conclusions: Our findings suggest that cross scalp stimulation resulted in MEPs obtained ipsilaterally and contralaterally which may be contributed to by summation of ipsilateral and simultaneous transcallosally or deep white matter conducted stimulation of the opposite motor cortex. Use of this stimulating position is advocated to elicit MEPs under operative circumstances where anesthetic agents may cause suppression of cortical and spinal excitability. Although less focal in nature, cross scalp stimulation would be most suitable for infratentorial or spinal surgery, in contrast to supratentorial neurosurgical procedures. [ABSTRACT FROM AUTHOR]

Background. Soft tissue injury imposes major public health burdens worldwide. The positive effect of China's Tibetan medicine and the Lamiophlomis rotata-based herbal Pain Relieving Plaster (PRP) on healing closed soft tissue injury (CSTI) has been reported. The herbs contained in Plaster are also referred as 'blood-activating and stasis-dispelling' in herbal medicine. The formula of the plaster contains four China's Tibetan medical herbs, including Lamiophlomis rotata, Oxytropis falcate Bunge, Curcuma longa Linn, and Myricaria bracteata. Two of these herbs (Lamiophlomis rotate; Curcuma longa Linn) are commonly used in different formulae of Chinese medicine. The objective of this study is to use an interdisciplinary approach to test the hypothesis that the formula and its components influence the process of CSTI.Methods. In vivo models have been established in 30 rabbit ear pinnae and studied for: (1) blood flow velocity (BFV) which was affected by pressure of 21.2 kg/cm2 for 30 second over the local rabbit ear tissue; (2) edema formation of the closed soft tissue injury; (3) in vivo local temperature change.Results. The results of in vivo studies indicated that CSTI significantly increased the velocity of blood flow and increased edema formation within the control group. The PRP extracts for 5 hours significantly slowed down the BFV of CSTI in rabbit ears, markedly decreased the elevated edema level from the 3rd to the 5th day.Conclusion. The ingredients contained in the formula have positive effects in healing CSTI and further study is worth exploring. [ABSTRACT FROM AUTHOR]

Background: Axillary lymph node dissection (ALND) is a standard procedure for early-stage breast cancer (BC) patients with three or more positive sentinel lymph nodes (SLNs). However, ALND can lead to significant postoperative complications without always providing additional clinical benefits. This study aims to develop machine-learning (ML) models to predict non-sentinel lymph node (non-SLN) metastasis in Chinese BC patients with three or more positive SLNs, potentially allowing the omission of ALND., Methods: Data from 2217 BC patients who underwent SLN biopsy at Shantou University Medical College were analyzed, with 634 having positive SLNs. Patients were categorized into those with ≤ 2 positive SLNs and those with ≥ 3 positive SLNs. We applied nine ML algorithms to predict non-SLN metastasis. Model performance was evaluated using ROC curves, precision-recall curves, and calibration curves. Decision Curve Analysis (DCA) assessed the clinical utility of the models., Results: The RF model showed superior predictive performance, achieving an AUC of 0.987 in the training set and 0.828 in the validation set. Key predictive features included size of positive SLNs, tumor size, number of SLNs, and ER status. In external validation, the RF model achieved an AUC of 0.870, demonstrating robust predictive capabilities., Conclusion: The developed RF model accurately predicts non-SLN metastasis in BC patients with ≥ 3 positive SLNs, suggesting that ALND might be avoided in selected patients by applying additional axillary radiotherapy. This approach could reduce the incidence of postoperative complications and improve patient quality of life. Further validation in prospective clinical trials is warranted., (© 2024. The Author(s).)

Background: Diabetic nephropathy (DN) is a major contributor to chronic kidney disease. This study aims to identify immune biomarkers and potential therapeutic drugs in DN., Methods: We analyzed two DN microarray datasets (GSE96804 and GSE30528) for differentially expressed genes (DEGs) using the Limma package, overlapping them with immune-related genes from ImmPort and InnateDB. LASSO regression, SVM-RFE, and random forest analysis identified four hub genes (EGF, PLTP, RGS2, PTGDS) as proficient predictors of DN. The model achieved an AUC of 0.995 and was validated on GSE142025. Single-cell RNA data (GSE183276) revealed increased hub gene expression in epithelial cells. CIBERSORT analysis showed differences in immune cell proportions between DN patients and controls, with the hub genes correlating positively with neutrophil infiltration. Molecular docking identified potential drugs: cysteamine, eltrombopag, and DMSO. And qPCR and western blot assays were used to confirm the expressions of the four hub genes., Results: Analysis found 95 and 88 distinctively expressed immune genes in the two DN datasets, with 14 consistently differentially expressed immune-related genes. After machine learning algorithms, EGF, PLTP, RGS2, PTGDS were identified as the immune-related hub genes associated with DN. In addition, the mRNA and protein levels of them were obviously elevated in HK-2 cells treated with glucose for 24 h, as well as their mRNA expressions in kidney tissues of mice with DN., Conclusion: This study identified 4 hub immune-related genes (EGF, PLTP, RGS2, PTGDS), as well as their expression profiles and the correlation with immune cell infiltration in DN., (© 2024. The Author(s).)

Objective: As there are no substantial selection criteria for determining the lowest instrumented vertebra (LIV) in adolescent idiopathic scoliosis (AIS) Lenke 5C/6C, thus, many surgeons base their selection on experience. The study aims to compare the selection of the lowest instrumented vertebrae (LIV) lumbar vertebra three (L3) with the use of direct vertebrae rotation (DVR) to the lowest instrumented vertebrae (LIV) lumbar vertebra four (L4) with the use of non-DVR for the correction of adolescent idiopathic scoliosis (AIS) Lenke 5C/6C when the lower end vertebrae (LEV) is at lumbar vertebrae four (L4)., Methods: This prospective study involved 101 patients who were divided into two groups based on different techniques. The patients were prospectively followed up for at least four years. All patients included in the study had a lower end vertebra (LEV) at L4, while patients older than 18 years and patients with prior surgical procedures were excluded. The DVR group consisted of 49 patients, and the non-DVR group included 51 patients., Results: The preoperative mean LIV disc angle was 3.1 ± 3 and 3.1 ± 1, P = 0.097, which corrected to 1.2 ± 0 and 1.1 ± 0 in both groups at 4-year follow-up without statistical significance. The LIVDA and LIVT were statistically insignificant at the preoperative, and there were no significant differences at the follow-up visitation. The DVR group achieved a satisfactory coronal and Cobb's angle correction compared to the NDVR group; however, there were no statistical differences at the follow-up visitations. Both groups achieve a satisfactory correction rate without substantial significance in clinical and radiological outcomes. Furthermore, no post-surgical complications were recorded in either group., Conclusions: DVR is suitable for selecting L3 as the LIV in AIS Lenke 5C/6C compared to L4 in non-DVR. DVR preserved more segments without substantial complications during the follow-up visitations. Nevertheless, both groups will continue to be followed up to prevent adding-on post-surgical complications., (© 2024. The Author(s).)

Objectives: Seeking a noninvasive predictor for BRAF V600E mutation status of pleomorphic xanthoastrocytomas (PXAs) is essential for their prognoses and therapeutic use of BRAF inhibitors. We aimed to noninvasively diagnose BRAF V600E-mutated PXAs using MRI morphologic, DWI and clinical parameters., Methods: The clinical findings, anatomical MRI characteristics, and diffusion parameters of 36 pathologically confirmed PXAs were retrospectively analyzed, and BRAF V600E-mutated (n = 16) and wild-type (n = 20) groups were compared. A binary logistic-regression analysis was performed, and a ROC curve was calculated to determine the independent predictors of BRAF V600E mutation status, diagnostic accuracy, and optimal cut-off value., Results: A comparison of findings between groups showed that BRAF V600E-mutated PXAs were more frequent in children and young adults (≤ 35 years; P = 0.042) who often had histories of seizures (P = 0.004). Furthermore, BRAF V600E-mutated PXAs generally presented as solitary masses (P = 0.024), superficial locations with meningeal attachment (P < 0.001), predominantly cystic with mural nodules (P = 0.005), and had greater minimal ADC ratio (ADC ratio ) values of the tumor and peritumoral edema (P < 0.001). Binary logistic regression showed that age ≤ 35 years, solitary mass, superficial locations with meningeal attachment, and a greater minimal ADC ratio of the tumor were independent predictors of BRAF V600E-mutated PXAs. The combination of all four independent predictors resulted in the highest sensitivity (100%) and specificity (90%), with AUC = 0.984., Conclusion: The BRAF V600E mutation status of PXAs could be noninvasively predicted using clinical and MRI characteristics., Critical Relevance Statement: The noninvasive diagnostic criteria for BRAF V600E-mutated PXAs could offer guidance for the administration of BRAF V600E mutation inhibitors in the future., (© 2024. The Author(s).)

Introduction: Early screening and identification are crucial for fall prevention, and developing a new method to predict fall risk in the elderly can address the current lack of objectivity in assessment tools., Methods: A total of 132 elderly individuals over 80 years old residing in some nursing homes in Shanghai were selected using a convenient sampling method. Fall history information was collected, and gait data during a 10-meter walk were recorded. Logistic regression was employed to establish the prediction model, and a nomogram was used to assess the importance of the indicators. The Bootstrap method was utilized for internal validation of the model, while the verification set was used for external validation. The predictive performance of the model was evaluated using the area under the ROC curve, calibration curve, and decision curve analysis (DCA) to assess clinical benefits., Results: The incidence of falls in the sample population was 36.4%. The Tinetti Gait and Balance Test (TGBT) score (OR = 0.832, 95% CI: 0.734,0.944), stride length (OR = 0.007, 95% CI: 0.000,0.104), difference in standing time (OR = 0.001, 95% CI: 0.000,0.742), and mean stride time (OR = 0.992, 95% CI:0.984,1.000) were identified as significant factors. The area under the ROC curve was 0.878 (95% CI: 0.805, 0.952), with a sensitivity of 0.935 and specificity of 0.726. The Brier score was 0.135, and the Hosmer-Lemeshow test (χ 2  = 10.650, P = 0.222) indicated a good fit and calibration of the model., Conclusion: The TGBT score, stride length, difference in standing time, and stride time are all protective factors associated with fall risk among the elderly. The developed risk prediction model demonstrates good discrimination and calibration, providing valuable insights for early screening and intervention in fall risk among older adults., (© 2024. The Author(s).)

Background: It is known that the neurodevelopmental disorder associated gene, Satb2, plays important roles in determining the upper layer neuron specification. However, it is not well known how this gene regulates other neocortical regions during the development. It is also lack of comprehensive delineation of its spatially regulatory pathways in neocortical development., Results: In this work, we utilized spatial transcriptomics and immuno-staining to systematically investigate the region-specific gene regulation of Satb2 by comparing the Satb2 +/+ and Satb2 -/- mice at embryonic stages, including the ventricle zone (VZ) or subventricle zone (SVZ), intermediate zone (IZ) and cortical plate (CP) respectively. The staining result reveals that these three regions become moderately or significantly thinner in the Satb2 -/- mice. In the cellular level, the cell number increases in the VZ/SVZ, whereas the cell number decreases in the CP. The spatial transcriptomics data show that many important genes and relevant pathways are dysregulated in Satb2 -/- mice in a region-specific manner. In the VZ/SVZ, the key genes involved in neural precursor cell proliferation, including the intermediate progenitor marker Tbr2 and the lactate production related gene Ldha, are up-regulated in Satb2 -/- mice. In the IZ, the key genes in regulating neuronal differentiation and migration, such as Rnd2, exhibit ectopic expressions in the Satb2 -/- mice. In the CP, the lineage-specific genes, Tbr1 and Bcl11b, are abnormally expressed. The neuropeptide related gene Npy is down-regulated in Satb2 -/- mice. Finally, we validated the abnormal expressions of key regulators by using immunofluorescence or qPCR., Conclusions: In summary, our work provides insights on the region-specific genes and pathways which are regulated by Satb2 in neocortical development., (© 2024. The Author(s).)

Background: The Chiari network, a remnant of fetal anatomy, consists of a mesh-like structure within the right atrium. With advancements in cardiac interventions, complications associated with the Chiari network have increasingly been reported. However, there are few reports about guidewire or catheter entrapment in the Chiari network during the insertion of a dialysis catheter., Case Presentation: A 46-year-old male with end-stage renal disease was hospitalized and underwent a digital subtraction angiography-assisted catheterization of the right internal jugular vein tunnel-cuffed dialysis catheter. When the guide wire entered a depth of about 20 cm, it was difficult to advance, manifested as resistance when twisting the guide wire and inability to enter the inferior vena cava. After the peelable sheath was inserted, it was difficult to pull out the guide wire. After repeated attempts to rotate the guide wire, the guide wire was finally pulled out. A fibrous tissue was wrapped around the tip of the guide wire. Its length was 6 cm, with a smooth surface and tough texture. We considered that the tissue we pulled out was most likely a part of a Chiari network., Conclusions: This case highlights the potential for the Chiari network to complicate surgical procedures, including difficulty with guidewire and catheter manipulation. Attention should be paid to Chiari networks. Echocardiography can be used to identify the Chiari network. During the surgery, forcefully pulling out a stuck guidewire is not suggested, to avoid the risk of tearing the atrial wall and causing pericardial tamponade. An urgent consultation with ultrasound doctors and cardiac surgeons might be helpful in such cases., (© 2024. The Author(s).)

Background: The treatment for bilateral synchronous multiple primary lung cancers (MPLC) remains challenging. Simultaneous bilateral video-assisted thoracic surgery (VATS) may be an optimal treatment with curative intent, but its safety and feasibility are controversial., Methods: One hundred and fifty-eight patients who underwent simultaneous bilateral VATS (simultaneous group) and 79 who underwent two-staged bilateral VATS (two-staged group) were included in this study. Their medical records were retrospectively reviewed and analyzed., Results: The majority of patients were female and non-smokers. The most common surgical plan was lobectomy and contralateral wedge resection in both groups. There was no significant difference in the postoperative complication rate between the simultaneous groups and two-staged group (13.3% vs. 11.4%, p = 0.73). Patients who underwent simultaneous bilateral resection had shorter hospital stays, shorter anesthesia time and less chest drainage compared with those who underwent two-staged resection. Advanced TNM stage, complicated surgical plan and aggressive lymph node resection were risk factors for postoperative complications in simultaneous bilateral VATS. Patients in two groups had similar overall survival and disease free survival (p = 0.2)., Conclusions: Simultaneous bilateral VATS for bilateral lung nodule resection is as safe and feasible as two-staged bilateral VATS. Patients who underwent simultaneous bilateral resection had similar or even better outcomes compared to that of the two-staged group. Simultaneous bilateral VATS is potentially an optimal treatment option for patients with erarly cTNM stage and good physical condition., (© 2024. The Author(s).)

Objectives: Thoracic surgery is a complex field requiring advanced technical skills and critical decision-making. Surgical education must evolve to equip trainees with proficiency in new techniques and technologies., Methods: This bibliometric analysis systematically reviewed 113 articles on thoracic surgery skills training published over the past decade, retrieved from databases including Web of Science. Publication trends, citation analysis, author and journal productivity, and keyword frequencies were evaluated., Results: The United States contributed the most publications, led by pioneering institutions. Simulation training progressed from basic to sophisticated modalities and virtual reality emerged with transformative potential. Minimally invasive techniques posed unique learning challenges requiring integrated curricula., Conclusion: Ongoing investments in educational research and curriculum innovations are imperative to advance thoracic surgery training through multidisciplinary strategies. This study provides an evidentiary foundation to optimize training and address the complexities of modern thoracic surgery., (© 2024. The Author(s).)

Objective: The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke., Methods: Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China., Results: A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0-2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947-0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807-0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869-0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665-0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991-0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705-25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke., Conclusion: Younger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke., Chinese Clinical Trial Registry Identifier: ChiCTR-IOR-17014167., (© 2024. The Author(s).)

Objectives: The goal of this research is to pinpoint the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer., Methods: We identified the top 100 most frequently referenced studies on sublobectomy for non-small cell lung cancer by searching the Web of Science database. We extracted key information from the selected studies, including the author, journal, impact factor, type of article, year of publication, country, organization, and keyword., Results: To the best of our understanding, this is the inaugural bibliometric study on sublobectomy for non-small cell lung cancer. The publication years of the top 100 most frequently referenced studies span from 1994 to 2022, with citation counts ranging from 51 to 795. The majority of the included studies are original (93/100) and primarily retrospective studies (82/93). The United States leads in terms of published articles and citations, with the Annals of Thoracic Surgery being the most frequently sourced journal (n = 27). High-density keywords primarily originate from limited resection, lobectomy, survival, carcinoma, recurrence, randomized trial, radiotherapy, lung cancer, outcome, 2 cm, as revealed by CiteSpace analysis., Conclusions: Our research compiles and analyzes the top 100 most frequently referenced studies in the field of sublobectomy for non-small cell lung cancer. The United States has the most published and cited works on this topic. Currently, the hot keywords for sublobectomy research are gradually shifting towards prognosis and obtaining better evidence-based medical evidence to demonstrate its value in the treatment of non-small cell lung cancer., (© 2024. The Author(s).)

Background: For prostate electrosurgery, where real-time surveillance screens are relied upon for operations, manual identification of the prostate capsule remains the primary method. With the need for rapid and accurate detection becoming increasingly urgent, we set out to develop a deep learning approach for detecting the prostate capsule using endoscopic optical images., Methods: Our method involves utilizing the Simple, Parameter-Free Attention Module(SimAM) residual attention fusion module to enhance the extraction of texture and detail information, enabling better feature extraction capabilities. This enhanced detail information is then hierarchically transferred from lower to higher levels to aid in the extraction of semantic information. By employing a forward feature-by-feature hierarchical fusion network based on the 3D residual attention mechanism, we have proposed an improved single-shot multibox detector model., Results: Our proposed model achieves a detection precision of 83.12% and a speed of 0.014 ms on NVIDIA RTX 2060, demonstrating its effectiveness in rapid detection. Furthermore, when compared to various existing methods including Faster Region-based Convolutional Neural Network (Faster R-CNN), Single Shot Multibox Detector (SSD), EfficientDet and others, our method Attention based Feature Fusion Single Shot Multibox Detector (AFFSSD) stands out with the highest mean Average Precision (mAP) and faster speed, ranking only below You Only Look Once version 7 (YOLOv7)., Conclusions: This network excels in extracting regional features from images while retaining the spatial structure, facilitating the rapid detection of medical images., (© 2024. The Author(s).)

Background: Complete fractures and dislocations of the lower cervical spine are usually associated with severe spinal cord injury. However, a very small number of patients do not have severe spinal cord injury symptoms, patients with normal muscle strength or only partial nerve root symptoms, known as "lucky fracture dislocation". The diagnosis and treatment of such patients is very difficult. Recently, we successfully treated one such patient., Case Presentation: A 73-year-old male patient had multiple neck and body aches after trauma, but there was sensory movement in his limbs. However, preoperative cervical radiographs showed no significant abnormalities, and computed tomography (CT) and magnetic resonance imaging (MRI) confirmed complete fracture and dislocation of C7. Before operation, the halo frame was fixed traction, but the reduction was not successful. Finally, the fracture reduction and internal fixation were successfully performed by surgery. The postoperative pain of the patient was significantly relieved, and the sensory movement of the limbs was the same as before. Two years after surgery, the patient's left little finger and ulnar forearm shallow sensation recovered, and the right flexion muscle strength basically returned to normal., Conclusion: This case suggests that when patients with trauma are encountered in the clinic, they should be carefully examined, and the presence of cervical fracture and dislocation should not be ignored because of the absence of neurological symptoms or mild symptoms. In addition, positioning during handling and surgery should be particularly avoided to increase the risk of paralysis., (© 2024. The Author(s).)

Background: Pulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables., Methods: This retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001-2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools., Results: Minimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p < 0.001; DFS p < 0.001) also correlated with poorer prognosis. In the SCLC subgroup, elevated preoperative CEA independently predicted worse OS (p = 0.012) and DFS (p = 0.004). T4 disease (OS p < 0.001; DFS p = 0.002) and advanced TNM staging (stage III OS p = 0.043; DFS p = 0.045; stage IV OS p < 0.001, DFS p < 0.001) were associated with worse outcomes. In LCNEC patients, VATS resection improved OS (p = 0.048) and DFS (p = 0.027) despite conversion. Prior malignancy predicted worse OS (p < 0.001). Advanced TNM disease (stage III OS p = 0.047; stage IV OS p = 0.003, DFS p = 0.005) were also negative prognostic factors. The prognostic nomogram incorporating above variables effectively stratified risk. Calibration plots revealed good correlation between predicted and actual survival., Conclusions: We identified minimally invasive surgery, early TNM stage, younger age, and normal preoperative CEA as positive prognostic factors following pHGNEC resection. Our study provides an applicable prognostic nomogram to facilitate personalized pHGNEC management., (© 2024. The Author(s).)

Background: In the context of increasing exposure to silica nanoparticles (SiNPs) and ensuing respiratory health risks, emerging evidence has suggested that SiNPs can cause a series of pathological lung injuries, including fibrotic lesions. However, the underlying mediators in the lung fibrogenesis caused by SiNPs have not yet been elucidated., Results: The in vivo investigation verified that long-term inhalation exposure to SiNPs induced fibroblast activation and collagen deposition in the rat lungs. In vitro, the uptake of exosomes derived from SiNPs-stimulated lung epithelial cells (BEAS-2B) by fibroblasts (MRC-5) enhanced its proliferation, adhesion, and activation. In particular, the mechanistic investigation revealed SiNPs stimulated an increase of epithelium-secreted exosomal miR-494-3p and thereby disrupted the TGF-β/BMPR2/Smad pathway in fibroblasts via targeting bone morphogenetic protein receptor 2 (BMPR2), ultimately resulting in fibroblast activation and collagen deposition. Conversely, the inhibitor of exosomes, GW4869, can abolish the induction of upregulated miR-494-3p and fibroblast activation in MRC-5 cells by the SiNPs-treated supernatants of BEAS-2B. Besides, inhibiting miR-494-3p or overexpression of BMPR2 could ameliorate fibroblast activation by interfering with the TGF-β/BMPR2/Smad pathway., Conclusions: Our data suggested pulmonary epithelium-derived exosomes serve an essential role in fibroblast activation and collagen deposition in the lungs upon SiNPs stimuli, in particular, attributing to exosomal miR-494-3p targeting BMPR2 to modulate TGF-β/BMPR2/Smad pathway. Hence, strategies targeting exosomes could be a new avenue in developing therapeutics against lung injury elicited by SiNPs., (© 2024. The Author(s).)

Background: Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years., Case Presentation: A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND., Conclusion: The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities., (© 2024. The Author(s).)

Anabasis aphylla (A. aphylla), a species of the Amaranthaceae family, is widely distributed in northwestern China and has high pharmacological value and ecological functions. However, the growth characteristics are poorly understood, impeding its industrial development for biopesticide development. Here, we explored the regenerative capacity of A. aphylla. To this end, different lengths of the secondary branches of perennial branches were mowed at the end of March before sprouting. The four treatments were no mowing (M0) and mowing 1/3, 2/3, and the entire length of the secondary branches of perennial branches (M1-M3, respectively). Next, to evaluate the compensatory growth after mowing, new assimilate branches' related traits were recorded every 30 days, and the final biomass was recorded. The mowed plants showed a greater growth rate of assimilation branches than un-mowed plants. Additionally, with the increasing mowing degree, the growth rate and the final biomass of assimilation branches showed a decreasing trend, with the greatest growth rate and final biomass in response to M1. To evaluate the mechanism of the compensatory growth after mowing, a combination of dynamic (0, 1, 5, and 8 days after mowing) plant hormone-targeted metabolomics and transcriptomics was performed for the M0 and M1 treatment. Overall, 26 plant hormone metabolites were detected, 6 of which significantly increased after mowing compared with control: Indole-3-acetyl-L-valine methyl ester, Indole-3-carboxylic acid, Indole-3-carboxaldehyde, Gibberellin A24, Gibberellin A4, and cis (+)-12-oxo-phytodienoic acid. Additionally, 2,402 differentially expressed genes were detected between the mowed plants and controls. By combining clustering analysis based on expression trends after mowing and gene ontology analysis of each cluster, 18 genes related to auxin metabolism were identified, 6 of which were significantly related to auxin synthesis. Our findings suggest that appropriate mowing can promote A. aphylla growth, regulated by the auxin metabolic pathway, and lays the foundation for the development of the industrial value of A. aphylla., (© 2024. The Author(s).)

Background: Intussusception presents a significant emergency that often necessitates bowel resection, leading to severe complications and management challenges. This study aims to investigate and establish a scoring system to enhance the prediction of bowel resection necessity in pediatric intussusception patients., Methods: This retrospective study analyzed 660 hospitalized patients with intussusception who underwent surgical management at a pediatric hospital in Southwest China from April 2008 to December 2020. The necessity of bowel resection was assessed and categorized in this cohort. Variables associated with bowel resection were examined using univariate and multivariate logistic regression analyses. Based on these analyses, a scoring system was developed, grounded on the summation of the coefficients (β)., Results: Among the 660 patients meeting the inclusion criteria, 218 required bowel resection during surgery. Bowel resection occurrence was linked to an extended duration of symptoms (Odds Ratio [OR] = 2.14; 95% Confidence Interval [CI], 1.03-5.23; P = 0.0015), the presence of gross bloody stool (OR = 8.98; 95% CI, 1.76-48.75, P < 0.001), elevated C-reactive protein levels (OR = 4.79; 95% CI, 1.12-28.31, P = 0.0072), lactate clearance rate (LCR) (OR = 17.25; 95% CI, 2.36-80.35; P < 0.001), and the intussusception location (OR = 12.65; 95% CI, 1.46-62.67, P < 0.001), as determined by multivariate logistic regression analysis. A scoring system (totaling 14.02 points) was developed from the cumulative β coefficients, with a threshold of 5.22 effectively differentiating infants requiring surgical intervention from others with necrotizing enterocolitis (NEC), exhibiting a sensitivity of 78.3% and a specificity of 71.9%., Conclusions: This study successfully identified multiple risk factors for bowel resection and effectively used a scoring system to identify patients for optimal clinical management., (© 2024. Crown.)

Background: Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation., Methods: To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis., Conclusions: This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis., (© 2024. The Author(s).)

Background: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors., Methods: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance., Results: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative., Conclusions: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings., (© 2024. The Author(s).)

Background: This study was designed to investigate the mechanism by which miR-30a-5p mediates cardiomyocyte apoptosis after acute myocardial infarction (AMI) induced by hypoxia/reoxygenation (H/R)., Methods: Differentially expressed miRNAs were analyzed by RNA high-throughput sequencing in acute myocardial infarction (ST-elevation myocardial infarction) patients versus healthy individuals (controls). The H/R model was used to assess the regulatory mechanism of miRNAs in AMI. Lentivirus-associated vectors were used to overexpress or knock down miR-30a-5p in cellular models. The pathological mechanisms of miR-30a-5p regulating the development of acute myocardial infarction were serially explored by qPCR, bioinformatics, target gene prediction, dual luciferase, enzyme-linked immunosorbent assays (ELISAs) and Western blotting., Results: The results showed that the expression of miR-30a-5p was significantly increased in AMI patients and H9C2 cells. Hypoxia decreased cardiomyocyte survival over time, and reoxygenation further reduced cell survival. Bax and Phosphatase and tensin homolog (PTEN)were suppressed, while Bcl-2 was upregulated. Additionally, miR-30a-5p specifically targeted the PTEN gene. According to the GO and KEGG analyses, miR-30a-5p may participate in apoptosis by interacting with PTEN. The miR-30a-5p mimic decreased the expression of apoptosis-related proteins and the levels of the proinflammatory markers IL-1β, IL-6, and TNF-α by activating the PTEN/PI3K/Akt signaling pathway. Conversely, anti-miR-30a-5p treatment attenuated these effects. Additionally, silencing PTEN and anti-miR-30a-5p had opposite effects on H/R-induced cell apoptosis., Conclusions: miR-30a-5p plays a crucial role in cardiomyocyte apoptosis after hypoxia-induced acute myocardial infarction. Our findings provide translational evidence that miR-30a-5p is a novel potential therapeutic target for AMI., (© 2024. The Author(s).)

Background: Adult neurogenesis occurs in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. The neuronal stem cells in these two neurogenic niches respond differently to various physiological and pathological stimuli. Recently, we have found that the decrement of carboxypeptidase E (CPE) with aging impairs the maturation of brain-derived neurotrophic factor (BDNF) and neurogenesis in the SVZ. However, it remains unknown whether these events occur in the hippocampus, and what the role of CPE is in the adult hippocampal neurogenesis in the context of Alzheimer's disease (AD)., Methods: In vivo screening was performed to search for miRNA mimics capable of upregulating CPE expression and promoting neurogenesis in both neurogenic niches. Among these, two agomirs were further assessed for their effects on hippocampal neurogenesis in the context of AD. We also explored whether these two agomirs could ameliorate behavioral symptoms and AD pathology in mice, using direct intracerebroventricular injection or by non-invasive intranasal instillation., Results: Restoration of CPE expression in the hippocampus improved BDNF maturation and boosted adult hippocampal neurogenesis. By screening the miRNA mimics targeting the 5'UTR region of Cpe gene, we developed two agomirs that were capable of upregulating CPE expression. The two agomirs significantly rescued adult neurogenesis and cognition, showing multiple beneficial effects against the AD-associated pathologies in APP/PS1 mice. Of note, noninvasive approach via intranasal delivery of these agomirs improved the behavioral and neurocognitive functions of APP/PS1 mice., Conclusions: CPE may regulate adult hippocampal neurogenesis via the CPE-BDNF-TrkB signaling pathway. This study supports the prospect of developing miRNA agomirs targeting CPE as biopharmaceuticals to counteract aging- and disease-related neurological decline in human brains., (© 2024. The Author(s).)

Background: The gibberellic acid (GA) inhibitor, uniconazole, is a plant growth regulator commonly used in banana cultivation to promote dwarfing but also enhances the cold resistance in plants. However, the mechanism of this induced cold resistance remains unclear., Results: We confirmed that uniconazole induced cold tolerance in bananas and that the activities of Superoxide dismutase and Peroxidase were increased in the uniconazole-treated bananas under cold stress when compared with the control groups. The transcriptome and metabolome of bananas treated with or without uniconazole were analyzed at different time points under cold stress. Compared to the control group, differentially expressed genes (DEGs) between adjacent time points in each uniconazole-treated group were enriched in plant-pathogen interactions, MAPK signaling pathway, and plant hormone signal transduction, which were closely related to stimulus-functional responses. Furthermore, the differentially abundant metabolites (DAMs) between adjacent time points were enriched in flavone and flavonol biosynthesis and linoleic acid metabolism pathways in the uniconazole-treated group than those in the control group. Temporal analysis of DEGs and DAMs in uniconazole-treated and control groups during cold stress showed that the different expression patterns in the two groups were enriched in the linoleic acid metabolism pathway. In addition to strengthening the antioxidant system and complex hormonal changes caused by GA inhibition, an enhanced linoleic acid metabolism can protect cell membrane stability, which may also be an important part of the cold resistance mechanism of uniconazole treatment in banana plants., Conclusions: This study provides information for understanding the mechanisms underlying inducible cold resistance in banana, which will benefit the production of this economically important crop., (© 2024. The Author(s).)

Background: Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear., Methods: RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein., Results: We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5'-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma., Conclusions: These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma., (© 2024. The Author(s).)

Background: Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described., Results: We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum. Meanwhile, the activation of myocardial ferroptosis by SiNPs was certified by the extensive iron overload, declined FTH1 and FTL, and lipid peroxidation. The correlation analysis among detected indexes hinted ferroptosis was responsible for the SiNPs-aroused myocardial injury. Further, in vitro tests, SiNPs triggered iron overload and lipid peroxidation in cardiomyocytes. Concomitantly, altered expressions of TfR, DMT1, FTH1, and FTL indicated dysregulated iron metabolism of cardiomyocytes upon SiNP stimuli. Also, shrinking mitochondria with ridge fracture and ruptured outer membrane were noticed. To note, the ferroptosis inhibitor Ferrostatin-1 could effectively alleviate SiNPs-induced iron overload, lipid peroxidation, and myocardial cytotoxicity. More importantly, the mechanistic investigations revealed miR-125b-2-3p-targeted HO-1 as a key player in the induction of ferroptosis by SiNPs, probably through regulating the intracellular iron metabolism to mediate iron overload and ensuing lipid peroxidation., Conclusions: Our findings firstly underscored the fact that ferroptosis mediated by miR-125b-2-3p/HO-1 signaling was a contributor to SiNPs-induced myocardial injury, which could be of importance to elucidate the toxicity and provide new insights into the future safety applications of SiNPs-related nano products., (© 2024. The Author(s).)

Objective: To compare neuronavigation-assisted intracerebral hematoma puncture and drainage with neuroendoscopic hematoma removal for treatment of hypertensive cerebral hemorrhage., Method: Ninety-one patients with hypertensive cerebral hemorrhage admitted to our neurosurgery department from June 2022 to May 2023 were selected: 47 patients who underwent endoscopic hematoma removal with the aid of neuronavigation in observation Group A and 44 who underwent intracerebral hematoma puncture and drainage in control Group B. The duration of surgery, intraoperative bleeding, hematoma clearance rate, pre- and postoperative GCS score, National Institutes of Health Stroke Scale (NIHSS) score, mRS score and postoperative complications were compared between the two groups., Results: The duration of surgery, intraoperative bleeding and hematoma clearance were significantly lower in Group B than in Group A (p < 0.05). Conversely, no significant differences in the preoperative, 7-day postoperative, 14-day postoperative or 1-month postoperative GCS or NIHSS scores or the posthealing mRS score were observed between Groups A and B. However, the incidence of postoperative complications was significantly greater in Group B than in Group A (p < 0.05), with the most significant difference in incidence of intracranial infection (p < 0.05)., Conclusion: Both neuronavigation-assisted intracerebral hematoma puncture and drainage and neuroendoscopic hematoma removal are effective at improving the outcome of patients with hypertensive cerebral hemorrhage. The disadvantage of neuronavigation is that the incidence of complications is significantly greater than that of other methods; postoperative care and prevention of complications should be strengthened in clinical practice., (© 2024. The Author(s).)

Background: Schistosomiasis, a neglected tropical disease, remains an important public health problem. Although there are various methods for diagnosing schistosomiasis, many limitations still exist. Early diagnosis and treatment of schistosomiasis can significantly improve survival and prognosis of patients., Methodology: Circulating cell-free (cf)DNA has been widely used in the diagnosis of various diseases. In our study, we evaluated the diagnostic value of circulating cfDNA for schistosomiasis caused by Schistosoma japonicum. We focused on the tandem sequences and mitochondrial genes of S. japonicum to identify highly sensitive and specific targets for diagnosis of Schistosomiasis japonica., Results: Through data screening and analysis, we ultimately identified four specific tandem sequences (TD-1, TD-2, TD-3. and TD-4) and six mitochondrial genes (COX1(1), COX1(2), CYTB, ATP6, COX3, and ND5). We designed specific primers to detect the amount of circulating cfDNA in S. japonicum-infected mouse and chronic schistosomiasis patients. Our results showed that the number of tandem sequences was significantly higher than that of the mitochondrial genes. A S. japonicum infection model in mice suggested that infection of S. japonicum can be diagnosed by detecting circulating cfDNA as early as the first week. We measured the expression levels of circulating cfDNA (TD-1, TD-2, and TD-3) at different time points and found that TD-3 expression was significantly higher than that of TD-1 or TD-2. We also infected mice with different quantities of cercariae (20 s and 80 s). The level of cfDNA (TD-3) in the 80 s infection group was significantly higher than in the 20 s infection group. Additionally, cfDNA (TD-3) levels increased after egg deposition. Meanwhile, we tested 42 patients with chronic Schistosomiasis japonica and circulating cfDNA (TD-3) was detected in nine patients., Conclusions: We have screened highly sensitive targets for the diagnosis of Schistosomiasis japonica, and the detection of circulating cfDNA is a rapid and effective method for the diagnosis of Schistosomiasis japonica. The levels of cfDNA is correlated with cercariae infection severity. Early detection and diagnosis of schistosomiasis is crucial for patient treatment and improving prognosis., (© 2024. The Author(s).)

Background: Root system architecture (RSA) exhibits significant genetic variability and is closely associated with drought tolerance. However, the evaluation of drought-tolerant cotton cultivars based on RSA in the field conditions is still underexplored., Results: So, this study conducted a comprehensive analysis of drought tolerance based on physiological and morphological traits (i.e., aboveground and RSA, and yield) within a rain-out shelter, with two water treatments: well-watered (75 ± 5% soil relative water content) and drought stress (50 ± 5% soil relative water content). The results showed that principal component analysis identified six principal components, including highlighting the importance of root traits and canopy parameters in influencing drought tolerance. Moreover, the systematic cluster analysis was used to classify 80 cultivars into 5 categories, including drought-tolerant cultivars, relatively drought-tolerant cultivars, intermediate cultivars, relatively drought-sensitive cultivars, and drought-sensitive cultivars. Further validation of the drought tolerance index showed that the yield drought tolerance index and biomass drought tolerance index of the drought-tolerant cultivars were 8.97 and 5.05 times higher than those of the drought-sensitive cultivars, respectively., Conclusions: The RSA of drought-tolerant cultivars was characterised by a significant increase in average length-all lateral roots, a significant decrease in average lateral root emergence angle and a moderate root/shoot ratio. In contrast, the drought-sensitive cultivars showed a significant decrease in average length-all lateral roots and a significant increase in both average lateral root emergence angle and root/shoot ratio. It is therefore more comprehensive and accurate to assess field crop drought tolerance by considering root performance., (© 2024. The Author(s).)

Background: Proximal tubular cells (PTCs) play a critical role in the progression of diabetic kidney disease (DKD). As one of important progenitor markers, CD133 was reported to indicate the regeneration of dedifferentiated PTCs in acute kidney disease. However, its role in chronic DKD is unclear. Therefore, we aimed to investigate the expression patterns and elucidate its functional significance of CD133 in DKD., Methods: Data mining was employed to illustrate the expression and molecular function of CD133 in PTCs in human DKD. Subsequently, rat models representing various stages of DKD progression were established. The expression of CD133 was confirmed in DKD rats, as well as in human PTCs (HK-2 cells) and rat PTCs (NRK-52E cells) exposed to high glucose. The immunofluorescence and flow cytometry techniques were utilized to determine the expression patterns of CD133, utilizing proliferative and injury indicators. After overexpression or knockdown of CD133 in HK-2 cells, the cell proliferation and apoptosis were detected by EdU assay, real-time cell analysis and flow analysis. Additionally, the evaluation of epithelial, progenitor cell, and apoptotic indices was performed through western blot and quantitative RT-PCR analyses., Results: The expression of CD133 was notably elevated in both human and rat PTCs in DKD, and this expression increased as DKD progressed. CD133 was found to be co-expressed with CD24, KIM-1, SOX9, and PCNA, suggesting that CD133+ cells were damaged and associated with proliferation. In terms of functionality, the knockdown of CD133 resulted in a significant reduction in proliferation and an increase in apoptosis in HK-2 cells compared to the high glucose stimulus group. Conversely, the overexpression of CD133 significantly mitigated high glucose-induced cell apoptosis, but had no impact on cellular proliferation. Furthermore, the Nephroseq database provided additional evidence to support the correlation between CD133 expression and the progression of DKD. Analysis of single-cell RNA-sequencing data revealed that CD133+ PTCs potentially play a role in the advancement of DKD through multiple mechanisms, including heat damage, cell microtubule stabilization, cell growth inhibition and tumor necrosis factor-mediated signaling pathway., Conclusion: Our study demonstrates that the upregulation of CD133 is linked to cellular proliferation and protects PTC from apoptosis in DKD and high glucose induced PTC injury. We propose that heightened CD133 expression may facilitate cellular self-protective responses during the initial stages of high glucose exposure. However, its sustained increase is associated with the pathological progression of DKD. In conclusion, CD133 exhibits dual roles in the advancement of DKD, necessitating further investigation., (© 2024. The Author(s).)

Background: Studies on the factors affecting vault after posterior chamber phakic Implantable Collamer Lens (ICL) have been carried out, but most of them are single-centered and subjective selections of parameters. The present study aimed to systematically analyze the factors for vault., Methods: A systematic review of case series, case-control, and cohort studies derived from the articles published in PubMed, the Cochrane Library, Embase, Web of Science, CNKI, CBM, Wanfang and VIP, as well as ClinicalTrials, which were conducted to search for studies on factors of vault using four core terms: phakic intraocular lenses, vault, risk factor and observational study, from January 01, 1997, to February 20, 2023. The included studies were meta-analyzed quantitatively and described qualitatively. Subsequently, meta-regression and subgroup analysis were used., Results: We identified 13 studies (1,607 subjects), and 14 factors were considered. Meta-analysis showed that anterior chamber depth (ACD), horizontal corneal white-to-white (hWTW), ICL-size, and age are dual effects of the abnormal vaults; anterior chamber volume (ACV) and lens thickness (LT) are a one-way effect; while axial length (AL), ICL- spherical equivalent (ICL-SE) and Km are insignificant. In addition, descriptive analysis of anterior chamber angle (ACA), horizontal sulcus to sulcus (hSTS), ciliary processes height (T value), crystalline lens rise (CLR), and gender showed that all factors except gender tend to have significant effects on vault. Sensitivity analysis showed stable combined results. Country and design respectively affect the heterogeneity in ACD and ICL-size at low vault, while design affects the heterogeneity in ACD at high vault. No publication bias exists., Conclusions: Vault after ICL is related to multiple factors, especially anterior segmental biologic parameters, and they are weighted differently. We hope to provide a reference for the selection and adjustment of ICL., (© 2024. The Author(s).)

Purpose: Previous reports argue that preoperative sleep conditions of patients can influence the dosage of general anaesthesia drugs. Therefore, we aimed to investigate the dose-effect relationship of preoperative sleep disorders on the induction of general anaesthesia with remimazolam tosilate and calculate the Median effective (ED50) and 95% effective (ED95) dosages., Methods: Included in our study were 56 patients who underwent laparoscopic cholecystectomy at our hospital. A separate group of 27 patients with sleep disorders (SD group) and 29 patients without sleep disorders (NSD group) using the Pittsburgh Sleep Quality Index (PSQI) were also included. According to the Dixon 'up-and-down' design, patients received remimazolam at preselected concentrations starting at 0.2 mg/kg. After the administration of remimazolam, loss of consciousness was observed. By observing whether consciousness disappeared within a minute, we adjusted the dose of remimazolam by 0.1 mg/kg (up and down) in the following patient. The Median effective dose (ED50), 95% effective dose (ED95), and 95% confidence interval (CI) of remimazolam for effective sedation were calculated., Results: The ED50 of remimazolam was 0.226 mg/kg (95%CI 0.221-0.232 mg/kg) in the SD group and 0.191 mg/kg (95%CI, 0.183-0.199 mg/kg) in the NSD group. The ED95 of remimazolam was 0.237 mg/kg (95%CI 0.231-0.262 mg/kg) in the SD group and 0.209 mg/kg (95%CI 0.200-0.254 mg/kg) in the NSD group., Conclusions: In the SD group, the ED50 and ED95 of remimazolam during anaesthesia induction were 0.226 and 0.237 mg/kg, respectively. The induction dose of remimazolam in the SD group was significantly higher than that in the NSD group., (© 2024. The Author(s).)

Background: This study aimed to validate the availability of superimposing full-color mandibular digital models (DMs) by the morphological characteristics of vessels in extraction adult patients., Methods: Twenty-eight adult patients were included, and their DMs were superimposed with pre- and posttreatment cone beam computed tomography (CBCT) and the morphological characteristics of lingual vessels. The measurements of each tooth were compared under the same coordinate system., Results: The ICC results displayed exceptional agreement in intra- and interrater assessments, with scores exceeding 0.891 in the crown for intrarater agreement and scores surpassing 0.888 in the crown for interrater agreement. Furthermore, no statistically significant differences were found in the 2 superimposition methods (P > 0.05)., Conclusion: The morphological characteristics of vessels under the mucogingival junction in the lingual side of mandible of are stable enough for the superimposition of mandibular DMs in the adult patients undergo orthodontic treatment with premolars extraction., (© 2024. The Author(s).)

Objective: To explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model., Methods: A single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression., Results: A total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1-128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p < 0.001). No benefits of postoperative radiotherapy (PORT) were observed in patients with advanced stage and non-R0 resection (p = 0.114 and 0.284, respectively)., Conclusion: The best treatment strategy for type B thymoma is the detection and achievement of R0 resection as early as possible. Long-term follow-up is necessary, especially for patients with advanced Masaoka stage and who have not achieved R0 resection. No prognostic benefits were observed for PORT., (© 2024. The Author(s).)

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in adults. Various C. difficile strains circulate currently, associated with different outcomes and antibiotic resistance profiles. However, most studies still focus on the reference strain 630 that does not circulate anymore, partly due to the lack of immunological tools to study current clinically important C. difficile PCR ribotypes. The goal of this study was to generate monoclonal antibodies recognizing various epidemic ribotypes of C. difficile. To do so, we immunized mice expressing human variable antibody genes with the Low Molecular Weight (LMW) subunit of the surface layer protein SlpA from various C. difficile strains. Monoclonal antibodies purified from hybridomas bound LMW with high-affinity and whole bacteria from current C. difficile ribotypes with different cross-specificities. This first collection of anti-C. difficile mAbs represent valuable tools for basic and clinical research., (© 2024. The Author(s).)

Background: The role of pyroptosis in kidney disease is limited and incomplete. Quercetin, a flavonoid compound present in a variety of fruits, vegetables, and plants, has shown antioxidant and anti-inflammatory properties. This study was designed to validate the importance of pyroptosis in an experimental model of folic acid nephropathy and to explore the effect of quercetin in protecting against pyroptosis., Methods: Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were used to establish the correlation between pyroptosis and folic acid nephropathy. Immune cell infiltration, network pharmacology and single-cell RNA sequencing analysis were utilized to ascertain the specific target of quercetin in relation to pyroptosis. Finally, quercetin's role was verified in vivo and in vitro., Results: The GSEA analysis revealed a significant correlation between pyroptosis and folic acid nephropathy (NES = 1.764, P = 0.004). The hub genes identified through WGCNA were closely associated with inflammation. Molecular docking demonstrated a strong binding affinity between quercetin and caspase-1, a protein known to be involved in macrophage function, as confirmed by immune cell infiltration and single-cell analysis. Quercetin demonstrated a significant amelioration of kidney injury and reduction in macrophage infiltration in the animal model. Furthermore, quercetin exhibited a significant inhibition of caspase-1 expression, subsequently leading to the inhibition of pro-inflammatory cytokines expression, such as IL-1β, IL-18, TNF-α, and IL-6. The inhibitory effect of quercetin on macrophage pyroptosis was also confirmed in RAW264.7 cells., Conclusion: This study contributes substantial evidence to support the significant role of pyroptosis in the development of folic acid nephropathy, and highlights the ability of quercetin to downregulate caspase-1 in macrophages as a protective mechanism against pyroptosis., (© 2024. The Author(s).)

Background: Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT)., Methods: We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage., Results: Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12-0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18-0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16-0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18-0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year., Conclusions: Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients., Trial Registration: Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013)., (© 2024. The Author(s).)

Background: The benefits of first-line, cisplatin-based chemotherapy for muscle-invasive bladder cancer are limited due to intrinsic or acquired resistance to cisplatin. Increasing evidence has revealed the implication of cancer stem cells in the development of chemoresistance. However, the underlying molecular mechanisms remain to be elucidated. This study investigates the role of LASS2, a ceramide synthase, in regulating Wnt/β-catenin signaling in a subset of stem-like bladder cancer cells and explores strategies to sensitize bladder cancer to cisplatin treatment., Methods: Data from cohorts of our center and published datasets were used to evaluate the clinical characteristics of LASS2. Flow cytometry was used to sort and analyze bladder cancer stem cells (BCSCs). Tumor sphere formation, soft agar colony formation assay, EdU assay, apoptosis analysis, cell viability, and cisplatin sensitivity assay were used to investigate the functional roles of LASS2. Immunofluorescence, immunoblotting, coimmunoprecipitation, LC-MS, PCR array, luciferase reporter assays, pathway reporter array, chromatin immunoprecipitation, gain-of-function, and loss-of-function approaches were used to investigate the underlying mechanisms. Cell- and patient-derived xenograft models were used to investigate the effect of LASS2 overexpression and a combination of XAV939 on cisplatin sensitization and tumor growth., Results: Patients with low expression of LASS2 have a poorer response to cisplatin-based chemotherapy. Loss of LASS2 confers a stem-like phenotype and contributes to cisplatin resistance. Overexpression of LASS2 results in inhibition of self-renewal ability of BCSCs and increased their sensitivity to cisplatin. Mechanistically, LASS2 inhibits PP2A activity and dissociates PP2A from β-catenin, preventing the dephosphorylation of β-catenin and leading to the accumulation of cytosolic phospho-β-catenin, which decreases the transcription of the downstream genes ABCC2 and CD44 in BCSCs. Overexpression of LASS2 combined with a tankyrase inhibitor (XAV939) synergistically inhibits tumor growth and restores cisplatin sensitivity., Conclusions: Targeting the LASS2 and β-catenin pathways may be an effective strategy to overcome cisplatin resistance and inhibit tumor growth in bladder cancer patients., (© 2024. The Author(s).)

Background: Self-harm, a severe mental health concern among children and adolescents, has varying global prevalence rates. Previous studies have suggested potential associations between specific behavioral aspects of biological rhythm and self-harm risk in these populations., Objective: Our study aimed to elucidate the relationship between biological rhythm patterns and the propensity of self-harm among Chinese children and adolescents using the Baoxing Youth Mental Health (BYMH) cohort., Methods: We included 1883 Chinese children and adolescents from the BYMH cohort. The self-report questions used to assess biological rhythm and self-harm. We applied Principal Component Analysis (PCA) to distinguish patterns of biological rhythms. Logistic regression models were conducted to estimate the associations between biological rhythm, as well as biological rhythm patterns and risk of self-harm., Results: Of the participants, 35.0% reported experiencing lifetime self-harm. PCA revealed six significantly predominant biological rhythm patterns. Elevated risks of self-harm were linked with unhealthy eating practices, daytime tiredness, and unhealthy bedtime snacking. Conversely, patterns emphasizing physical exercise, family meals for breakfast, and nutritious diet exhibited decreased self-harm propensities. These trends persisted across varied self-harm attributes, including type, recency, and frequency of self-harm., Conclusions: This study underscores the critical impact of biological rhythms on self-harm risks among Chinese youth. Targeted lifestyle interventions, focusing on improved sleep and dietary habits, could serve as potent preventive measures. Our findings lay the groundwork for future longitudinal studies to further probe these associations, fostering the creation of tailored interventions to curb self-harm and enhance mental well-being in younger populations., (© 2023. The Author(s).)

Aim: Pathologists are currently supposed to be aware of both domestic and international guidelines for breast cancer diagnosis, but it is unclear how successfully these guidelines have been integrated into routine clinical practice in China. Thus, this national proficiency testing (PT) scheme for breast pathology was set up to conduct a baseline assessment of the diagnostic capability of pathologists in China., Methods: This national PT plan is designed and implemented according to the "Conformity assessment-General requirements for proficiency testing" (GB/T27043-2012/ISO/IEC 17043:2010). Five cases of breast cancer with six key items, including histologic type, grade, ER, PR, HER2, and Ki67, were selected for testing among 96 participants. The final PT results were published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927/cn/col22/362 )., Results: Our study demonstrated that the median PT score was 89.5 (54-100). Two institutions with scores < 67 were deemed unacceptable. The accuracy of histologic type, ER, PR, HER2, and Ki67 was satisfactory (all > 86%). However, the histologic grade showed low accuracy (74.0%). The unacceptable results mainly included incorrect evaluation of histologic grade (36.7%), inaccurate evaluation of ER/PR/HER2/Ki67 (28.2%), incorrect identification of C-AD as IBC-NST (15.7%), inappropriate use of 1+/2+/3+ rather than staining percentage for ER/PR (6.1%), misclassification of ER/PR < 1% weak expression as positive staining (1.4%), and no evaluation of histologic grade in ILC, MC, and IMC (5.8%)., Conclusions: our nationwide PT program exhibited a satisfactory baseline assessment of the diagnostic capability of pathologists in China. More importantly, we identify some areas for further improvement., (© 2023. The Author(s).)

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Riboflavin, one of water soluble vitamins, plays a role in lipid metabolism and antioxidant function. However, the effects of riboflavin deficiency on NAFLD development have not yet to be fully explored., Methods: In the present study, an animal model of NAFLD was induced by high fat diet feeding in mice and a cellular model of NAFLD was developed in HepG2 cells by palmitic acid (PA) exposure. The effects of riboflavin deficiency on lipid metabolism and antioxidant function were investigated both in vivo and in vitro. In addition, the possible role of peroxisome proliferator-activated receptor gamma (PPARγ) was studied in HepG2 cells using gene silencing technique., Results: The results showed that riboflavin deficiency led to hepatic lipid accumulation in mice fed high fat diet. The expressions of fatty acid synthase (FAS) and carnitine palmitoyltransferase 1 (CPT1) were up-regulated, whereas that of adipose triglyceride lipase (ATGL) down-regulated. Similar changes in response to riboflavin deficiency were demonstrated in HepG2 cells treated with PA. Factorial analysis revealed a significant interaction between riboflavin deficiency and high dietary fat or PA load in the development of NAFLD. Hepatic PPARγ expression was significantly upregulated in mice fed riboflavin deficient and high fat diet or in HepG2 cells treated with riboflavin deficiency and PA load. Knockdown of PPARγ gene resulted in a significant reduction of lipid accumulation in HepG2 cells exposed to riboflavin deficiency and PA load., Conclusions: There is a synergetic action between riboflavin deficiency and high dietary fat on the development of NAFLD, in which PPARγ may play an important role., (© 2023. The Author(s).)

Background: Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients., Methods: From August 2005 to April 2019, 315 patients with decompensated cirrhosis receiving autologous peripheral blood stem cell (PBSC) transplantation were enrolled in this study. They were randomly classified into training (2/3) and validation (1/3) groups. A predictive model was developed using Cox proportional hazard models and subsequently validated. The predictive performance of the model was evaluated and also compared with other prognostic models., Results: Age, creatinine, neutrophil-to-lymphocyte ratio, and Child-Turcotte-Pugh class were included in the nomogram as prognostic variables. The nomogram showed high discrimination power concerning the area under receiver operating characteristic curves (3/5-year AUC: 0.742/0.698) and good consistency suggested by calibration plots. Patients could be accurately stratified into poor- and good-outcome groups regarding liver-transplantation free survival after receiving PBSC therapy (P < 0.001). Compared with poor-outcome group, the liver function of patients listed for liver transplantation in the good-outcome group was significantly improved (P < 0.001). Besides, our nomogram achieved a higher C-index (0.685, 95% CI 0.633-0.738) and better clinical utility compared with other conventional prognostic models., Conclusions: The proposed nomogram facilitated an accurate prognostic prediction for patients with decompensated cirrhosis receiving PBSC transplantation. Moreover, it also held the promise to stratify patients in clinical trials or practice to implement optimal treatment regimens for individuals., (© 2023. The Author(s).)

Background: Depression is being increasingly acknowledged as a global public health concern, and following this trend, attention towards eating disorders (EDs) has surged within China's national consciousness. EDs symptoms frequently coexist with various mental health conditions, including depression. However, research focusing on EDs symptoms and depressive symptoms among Tibetan students in China remains scant. This study employs network analysis to estimate the relational network between EDs and depressive symptoms., Methods: Tibetan (n = 2,582) and Han (n = 1,743) students from two universities in the Xizang Autonomous Region, China, completed the Eating Attitude Test-26 (EAT-26) and the Patient Health Questionnaire-9 (PHQ-9). We estimated the network structure of EDs symptoms and depressive symptoms, identified central and bridge symptoms, and examined whether network characteristics differed by gender and ethnic., Results: The core symptoms identified within this study were Calorie&#95;awareness, Desire&#95;to&#95;thin and Fatigue. Conversely, bridge symptoms included Appetite, Suicide, Anhedonia, Guilty, Body&#95;fat&#95;awareness, and Food&#95;preoccupation. The study also revealed no significant gender differences within the network model. However, disparities among ethnic groups were observed within the network structure., Conclusions: Our study examined the correlation between EDs symptoms and depressive symptoms in Tibetan college students. Focusing on the individual's quest for the perfect body shape and some Tibetan students' appetite problems - potentially stemming from transitioning to a new university environment, adapting to the school canteen's diet, or being away from their hometown - could aid in the prevention and management of EDs and depression symptoms. It could reduce the incidence of complications by helping students maintain good physical and mental health. Concurrently, our research provides insights into the relatively higher levels of depression triggered by the unique plateau environment., (© 2023. The Author(s).)

Objectives: In response to the controversy surrounding observational studies of the association between lipid profiles and the risk of insomnia, the aim of this study was to analyze lipid profiles, including triglycerides (TG), apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB) and lipoprotein A (LPA), in a European population to further assess the causal relationship between these lipid types and insomnia., Materials and Methods: This study explores the causal effect of lipid profiles on insomnia based on a genome-wide association study (GWAS)-derived public dataset using two-sample and multivariate Mendelian randomization (MVMR) analysis. The main MR analyses used inverse variance weighting (IVW) odds ratio (OR), and the sensitivity analyses included weighted median (WM) and MR‒Egger., Results: Both MR and MVMR showed that lowering ApoA-1 and LPA levels had causal effects on the risk of insomnia [MR: per 10 units, ApoA-1: OR: 0.7546, 95% CI: 0.6075-0.9372, P = 0.011; LPA: OR: 0.8392, 95% CI: 0.7202-0.9778, P = 0.025; MVMR: per 10 units, ApoA-1: OR: 0.7600, 95% CI: 0.6362-0.9079, P = 0.002; LPA, OR: 0.903, 95% CI: 0.8283-0.9845, P = 0.021]. There were no causal effects of TG or ApoB on insomnia (all P > 0.05). The MR‒Egger intercept test, funnel plot, and IVW methods all suggested an absence of strong directional pleiotropy, and leave-one-out permutation analysis did not detect any single single-nucleotide polymorphism that had a strong influence on the results., Conclusion: Elevated levels of ApoA-1 and LPA were independently and causally associated with the risk of insomnia, suggesting that elevated ApoA-1 and LPA levels may contribute to a reduced risk of insomnia., (© 2023. The Author(s).)