An all-optical multidirectional mechano-sensor inspired by biologically mechano-sensitive hair sensilla.

Mechano-sensitive hair-like sensilla (MSHS) have an ingenious and compact three-dimensional structure and have evolved widely in living organisms to perceive multidirectional mechanical signals. Nearly all MSHS are iontronic or electronic, including their biomimetic counterparts. Here, an all-optical mechano-sensor mimicking MSHS is prototyped and integrated based on a thin-walled glass microbubble as a flexible whispering-gallery-mode resonator. The minimalist integrated device has a good directionality of 32.31 dB in the radial plane of the micro-hair and can detect multidirectional displacements and forces as small as 70 nm and 0.9 µN, respectively. The device can also detect displacements and forces in the axial direction of the micro-hair as small as 2.29 nm and 3.65 µN, respectively, and perceive different vibrations. This mechano-sensor works well as a real-time, directional mechano-sensory whisker in a quadruped cat-type robot, showing its potential for innovative mechano-transduction, artificial perception, and robotics applications.

Aflatoxin B1-exposed hepatocyte-derived extracellular vesicles: Initiating hepatic stellate cell-mediated liver fibrosis through a p53-Parkin-dependent mitophagy pathway.

Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.

Rebound growth of BRAF mutant pediatric glioma cells after MAPKi withdrawal is associated with MAPK reactivation and secretion of microglia-recruiting cytokines.

INTRODUCTION: Patients with pediatric low-grade gliomas (pLGGs), the most common primary brain tumors in children, can often benefit from MAPK inhibitor (MAPKi) treatment. However, rapid tumor regrowth, also referred to as rebound growth, may occur once treatment is stopped, constituting a significant clinical challenge. METHODS: Four patient-derived pediatric glioma models were investigated to model rebound growth in vitro based on viable cell counts in response to MAPKi treatment and withdrawal. A multi-omics dataset (RNA sequencing and LC-MS/MS based phospho-/proteomics) was generated to investigate possible rebound-driving mechanisms. Following in vitro validation, putative rebound-driving mechanisms were validated in vivo using the BT-40 orthotopic xenograft model. RESULTS: Of the tested models, only a BRAFV600E-driven model (BT-40, with additional CDKN2A/Bdel) showed rebound growth upon MAPKi withdrawal. Using this model, we identified a rapid reactivation of the MAPK pathway upon MAPKi withdrawal in vitro, also confirmed in vivo. Furthermore, transient overactivation of key MAPK molecules at transcriptional (e.g. FOS) and phosphorylation (e.g. pMEK) levels, was observed in vitro. Additionally, we detected increased expression and secretion of cytokines (CCL2, CX3CL1, CXCL10 and CCL7) upon MAPKi treatment, maintained during early withdrawal. While increased cytokine expression did not have tumor cell intrinsic effects, presence of these cytokines in conditioned media led to increased attraction of microglia cells in vitro. CONCLUSION: Taken together, these data indicate rapid MAPK reactivation upon MAPKi withdrawal as a tumor cell intrinsic rebound-driving mechanism. Furthermore, increased secretion of microglia-recruiting cytokines may play a role in treatment response and rebound growth upon withdrawal, warranting further evaluation.

A meta-analysis comparing the efficacy of mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cements in the treatment of vertebral compression fractures.

PURPOSE: Vertebral compression fractures are often treated with vertebroplasty, and filling the injured vertebrae with bone cement is a key part of vertebroplasty. This meta-analysis was performed to compare the clinical efficacy and safety of mineralized collagen-polymethylmethacrylate (MC-PMMA) and polymethylmethacrylate (PMMA) bone cement in the treatment of vertebral compression fractures by vertebroplasty. METHODS: A computerized search of the published literature on mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cement in the treatment of vertebral compression fractures was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Embase, and Cochrane Library. The search was carried out from the time the database was created to March 2023 and 2 researchers independently conducted literature searches to retrieve a total of 884 studies, of which 12 were included in this meta-analysis. Cochrane systematic review methods were used to assess the quality of the literature and a meta-analysis was performed using ReviewManager 5.4 software. RESULTS: The results of the present meta-analysis showed that in postoperative adjacent vertebral fractures [OR = 0.25; 95% CI (0.15, 0.41)], postoperative cement leakage [OR = 0.45; 95% CI (0.30, 0.68)], Oswestry Disability Index (ODI) scores in the first 3 days after surgery [OR = -0.22; 95% CI (-0.42, -0.03)], ODI score at 6-12 months postoperatively [OR = -0.65; 95% CI (-0.97, -0.32)], visual analog scale (VAS) score at 6-12 months postoperatively [OR = -0.21; 95% CI (-0.46, 0.04)], and 1-year postoperative CT values [OR = 5.56; 95% CI (3.06, 8.06)], the MC-PMMA bone cement group was superior to the PMMA bone cement group. However, the differences between the two groups were not statistically different in terms of cement filling time, cement filling volume, operation time, intraoperative bleeding, hospitalization time, postoperative (<1 week, 3-6 months) vertebral body posterior convexity Cobb's angle, postoperative (<1 week, 6-12 months) vertebral body anterior margin relative height, postoperative (≤3 days, 1-3 months) pain VAS score and postoperative (1-3 months) ODI score. CONCLUSIONS: Compared with PMMA bone cement, the application of MC-PMMA bone cement is advantageous in reducing postoperative complications (adjacent vertebral fracture rate, cement leakage rate), pain relief, and functional recovery in the long-term postoperative period (>6 months), but there is still a need for more high-quality randomized controlled studies to provide more adequate evidence.

Potential drug targets for gastroesophageal reflux disease and Barrett's esophagus identified through Mendelian randomization analysis.

Gastroesophageal reflux disease (GERD) is a prevalent chronic ailment, and present therapeutic approaches are not always effective. This study aimed to find new drug targets for GERD and Barrett's esophagus (BE). We obtained genetic instruments for GERD, BE, and 2004 plasma proteins from recently published genome-wide association studies (GWAS), and Mendelian randomization (MR) was employed to explore potential drug targets. We further winnowed down MR-prioritized proteins through replication, reverse causality testing, colocalization analysis, phenotype scanning, and Phenome-wide MR. Furthermore, we constructed a protein-protein interaction network, unveiling potential associations among candidate proteins. Simultaneously, we acquired mRNA expression quantitative trait loci (eQTL) data from another GWAS encompassing four different tissues to identify additional drug targets. Meanwhile, we searched drug databases to evaluate these targets. Under Bonferroni correction (P < 4.8 × 10-5), we identified 11 plasma proteins significantly associated with GERD. Among these, 7 are protective proteins (MSP, GPX1, ERBB3, BT3A3, ANTR2, CCM2, and DECR2), while 4 are detrimental proteins (TMEM106B, DUSP13, C1-INH, and LINGO1). Ultimately, C1-INH and DECR2 successfully passed the screening process and exhibited similar directional causal effects on BE. Further analysis of eQTLs highlighted 4 potential drug targets, including EDEM3, PBX3, MEIS1-AS3, and NME7. The search of drug databases further supported our conclusions. Our study indicated that the plasma proteins C1-INH and DECR2, along with 4 genes (EDEM3, PBX3, MEIS1-AS3, and NME7), may represent potential drug targets for GERD and BE, warranting further investigation.

Correlation between vascular endothelial growth factor A gene polymorphisms and tendon and ligament injury risk: a systematic review and meta-analysis.

BACKGROUND: Relevant evidence suggests that angiogenic factors contribute significantly to fibril matrix reconstruction following physical injuries to tendon ligaments. Vascular endothelial growth factor A (VEGFA), with its potent angiogenic effect, has been studied extensively, and its functional polymorphisms, including rs699947, rs1570360, and rs2010963, have been the focus of numerous investigations. Some scholars have explored the association between gene polymorphisms in the VEGFA and the risk of tendon ligament injury, but the findings are not entirely consistent. OBJECTIVES: The purpose of this study was to investigate the association between rs699947, rs1570360, and rs2010963 gene polymorphisms in VEGFA and the risk of tendon and ligament injuries. METHODS: After including articles about the association of VEGFA rs699947, rs1570360, and rs2010963 polymorphisms with tendon and ligament injuries according to the search strategy, we assessed their quality and conducted meta-analyses to examine the link between these polymorphisms and the risk of tendon and ligament injuries using odds ratios and 95% confidence intervals. RESULTS: Of 86 related articles, six were included in the meta-analysis. Some of these suggest an association between VEGFA rs2010963 and the risk of tendon and ligament injury in the population, with the specific C allele being one of the adverse factors for knee injury. Some studies suggest that VEGFA rs699947 and VEGFA rs1570360 single-nucleotide polymorphisms are associated with anterior cruciate ligament rupture. The risk of non-contact anterior cruciate ligament rupture is nearly doubled in individuals with the rs699947 CC genotype compared to the control group. Our analysis did not find any significant relationship between VEGFA gene polymorphisms (rs699947, rs1570360, and rs2010963) and the chance of tendon and ligament injury without consideration of race. However, the European population reveals that the CC genotype of VEGFA rs699947 can result in a greater risk of tendon and ligament injury, whereas the AG genotype for rs1570360 provides some protection. Additionally, rs2010963 was significantly associated with tendon and ligament injury; individuals with the C allele and the CC genotype had higher risk. False-positive report probability confirmed the high credibility of our results. CONCLUSION: Overall, this study found no significant association between VEGFA rs699947, rs1570360, and rs2010963 polymorphisms and the risk of tendon ligament injury. However, in subgroup analysis, some genotypes of VEGFA rs699947, rs1570360, and rs2010963 were found to increase the risk of tendon ligament injury in European populations.

[Intestinal absorption components and absorption characteristics of Wuwei Qingzhuo San by everted intestinal sac models].

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.

[Research progress on strontium isotope-traced plant remains production areas and implications for traceability of Dao-di herbs in Forbidden City of the Qing Dynasty].

Strontium isotope(~(87)S/~(86)Sr) tracing technology has been widely used in animal remains and origin of modern food origin sources. However, due to the problems of sample contamination and cleaning, this technology has been applied less frequently in the tracing of plant remains. The Palace Museum preserves more than 1 000 relics of medicinal materials from the Forbidden City of the Qing Dynasty, which are rare precious materials for the study of Dao-di herbs. The well-preserved environment of these medicinal materials in the Forbidden City of the Qing Dynasty helps avoid external strontium contamination, making it possible to introduce strontium isotope technology in their tracing research. On this basis, this study discussed the principle of strontium isotope tracing technology and summarized the current research progress on tracing plant remains using strontium isotope. In addition, this study discussed three key problems and their respective solutions encountered when applying strontium isotope technology to the tracing research on medicinal materials from the Forbidden City of the Qing Dynasty: creating strontium isotope ratio maps, dealing with the wide range of traceable results, and addressing the sample contamination and cleaning challenges. The literature and historical materials of the Qing Dynasty are the important basis for understanding the distribution and application of Dao-di herbs in the Qing Dynasty. Based on literature research, the use of strontium isotope to trace the producing area of medicinal materials in the Forbidden City of the Qing Dynasty can provide physical evidence for relevant research. The combined evidence of historical materials and medicinal relics is expected to provide a new perspective for the study of Dao-di herbs in the Qing Dynasty and also provide a reference for the study of the revolution of Dao-di herbs producing areas.

Insights from Japan’s cost-effectiveness analysis policy on pricing for China’s NRDL access / 中国药房

The cost-effectiveness analysis policy for drugs was institutionalized in Japan since 2019， realizing quantitative adjustment of price across varieties. A hierarchical categorization approach was adopted to select medicines with high expected annual sales. For selected medicines， adjustments were made to the premium and profit components within the existing price structure based on a pre-defined incremental cost-effectiveness ratio （ICER） threshold， effectively resolving the issue of inconsistent criteria and magnitudes caused by subjective judgment. Meanwhile， incentive measures like evaluation exemption or threshold enhancement were granted for specific medicines. Besides， a price adjustment mechanism， which was allowed for upward and downward adjustments， involving tiered ICER threshold and quantified formulas， had been established for the premium and profit components of drug price. In China’s National Reimbursement Drug List （NRDL） access， certain issues remained to be addressed： insufficient clarity in the quantitative mechanism of price formation， incomplete price adjustment measures， and lagging in the communication channels. It is recommended that the following measures could be referred to when further improving the scientificity and fairness of drug pricing during China’s NRDL access， such as enhancing the ICER threshold for medicines catering to special populations， quantifying criteria and extents for price adjustment， granting preferential pricing policies to pharmaceutical companies that present high-quality evidence of effectiveness， preceding communication channels with pharmaceutical companies， as well as exploring a price floor mechanism for the drugs with excessive price reduction.

Kinase modulators approved by FDA in 2022 / 药学学报

The FDA approved a total of 37 new drugs in 2022, including 22 new molecular entities and 15 new biological products. This is the year with the lowest number of new drugs approved by the FDA since 2017. Among these approved drugs, 21 new drugs belong to the "first-in-class" category, accounting for 56% of the total approved drugs, which is the highest ratio in the past 10 years. Among the drugs approved in 2022, there are 5 small molecule kinase modulators, including the tyrosine kinase 2 (TYK2) allosteric inhibitor deucravacitinib, the first oral pyruvate kinase (PK) activator mitapivat, the Janus kinase 1 (JAK1) selective inhibitor abcrocitinib, the JAK2 selective inhibitor pacritinib and the broad-spectrum fibroblast growth factor receptor (FGFR) inhibitor futibatinib. This review briefly describes the discovery background, research and development process, synthesis routes and clinical efficacy and safety of small molecule kinase modulators approved by the FDA in 2022, hoping to provide ideas and methods for further research on kinase modulators.

The Efficacy, Safety, and Economic Outcomes of Using Ferric Derisomaltose for the Management of Iron Deficiency in China: A Rapid Health Technology Assessment.

Intravenous (IV) iron supplementation is the preferred treatment option for managing severe iron deficiency (ID) and ID anemia (IDA). Three of the available IV iron preparations are ferric derisomaltose (FDI), ferric carboxymaltose (FCM), and iron sucrose (IS). The objective of the present work was to review the published literature about the efficacy, safety, quality of life (QoL), and economic outcomes of using FDI, FCM, and IS for the treatment of ID. A systematic literature search was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies were assessed for quality using appropriate tools, and data were extracted and analyzed for key outcomes. The evidence synthesis was based on published systematic literature reviews (SLRs), meta-analyses (MAs), indirect treatment comparisons (ITCs), and health technology assessments (HTAs); we also included economic evaluations performed from a Chinese perspective. Out of 337 initial hits, the review included 12 studies. The findings indicated that FDI, FCM, and IS had comparable efficacy in terms of hemoglobin (Hb) improvement. FDI showed a better safety profile with a lower risk of hypophosphatemia, hypersensitivity reactions, and cardiovascular adverse events (AEs) compared to IS and FCM. FDI also demonstrated better cost-effectiveness compared to IS, with potential cost savings attributed to fewer infusions and improved compliance. None of the included studies evaluated QoL after IV iron administration for ID. FDI offers a safe, efficacious, and cost-effective treatment option for ID. It exhibits comparable efficacy to FCM and IS but presents a better safety profile and economic advantage. FDI fulfills the criteria of efficacy, safety, economy, innovation, suitability, and accessibility, making it a promising choice for ID management in China.

Protein phosphatase 2A-B55ß mediated mitochondrial p-GPX4 dephosphorylation promoted sorafenib-induced ferroptosis in hepatocellular carcinoma via regulating p53 retrograde signaling.

Rationale: As a key endogenous negative regulator of ferroptosis, glutathione peroxidase 4 (GPX4) can regulate its antioxidant function through multiple post-translational modification pathways. However, the effects of the phosphorylation/dephosphorylation status of GPX4 on the regulation of inducible ferroptosis in hepatocellular carcinoma (HCC) remain unclear. Methods: To investigate the effects and molecular mechanism of GPX4 phosphorylation/dephosphorylation modification on ferroptosis in HCC cells. Sorafenib (Sora) was used to establish the ferroptosis model in HCC cells in vitro. Using the site-directed mutagenesis method, we generated the mimic GPX4 phosphorylation or dephosphorylation HCC cell lines at specific serine sites of GPX4. The effects of GPX4 phosphorylation/dephosphorylation modification on ferroptosis in HCC cells were examined. The interrelationships among GPX4, p53, and protein phosphatase 2A-B55ß subunit (PP2A-B55ß) were also explored. To explore the synergistic anti-tumor effects of PP2A activation on Sora-administered HCC, we established PP2A-B55ß overexpression xenograft tumors in a nude mice model in vivo. Results: In the Sora-induced ferroptosis model of HCC in vitro, decreased levels of cytoplasmic and mitochondrial GPX4, mitochondrial dysfunction, and enhanced p53 retrograde signaling occurred under Sora treatment. Further, we found that mitochondrial p53 retrograded remarkably into the nucleus and aggravated Sora-induced ferroptosis. The phosphorylation status of GPX4 at the serine 2 site (GPX4Ser2) revealed that mitochondrial p-GPX4Ser2 dephosphorylation was positively associated with ferroptosis, and the mechanism might be related to mitochondrial p53 retrograding into the nucleus. In HCC cells overexpressing PP2A-B55ß, it was found that PP2A-B55ß directly interacted with mitochondrial GPX4 and promoted Sora-induced ferroptosis in HCC. Further, PP2A-B55ß reduced the interaction between mitochondrial GPX4 and p53, leading to mitochondrial p53 retrograding into the nucleus. Moreover, it was confirmed that PP2A-B55ß enhanced the ferroptosis-mediated tumor growth inhibition and mitochondrial p53 retrograde signaling in the Sora-treated HCC xenograft tumors. Conclusion: Our data uncovered that the PP2A-B55ß/p-GPX4Ser2/p53 axis was a novel regulatory pathway of Sora-induced ferroptosis. Mitochondrial p-GPX4Ser2 dephosphorylation triggered ferroptosis via inducing mitochondrial p53 retrograding into the nucleus, and PP2A-B55ß was an upstream signal modulator responsible for mitochondrial p-GPX4Ser2 dephosphorylation. Our findings might serve as a potential theranostic strategy to enhance the efficacy of Sora in HCC treatment through the targeted intervention of p-GPX4 dephosphorylation via PP2A-B55ß activation.

Highly sensitive, modification-free, and dynamic real-time stereo-optical immuno-sensor.

Modification-free biosensing with high specificity and sensitivity is essential for miniaturized, online, integrated, and rapid, or even real-time molecular analyses. However, most optical biosensors are based on surface pre-modification or fluorescent labeling, and have either low sensitivity or low quality factor (Q). To address these difficulties, in this study, an optical sensor prototype was developed with a microbubble optofluidic channel integrated inside a Fabry-Pérot cavity to three-dimensionally tailor the intra-cavity light field via the intra-cavity lensing (microbubble) configuration. A high Q-factor (∼105), small mode volume, and high light energy density were experimentally achieved with this "stereo-sensor" while maintaining an ultrahigh refractive index (RI) sensitivity (679 nm/RIU) and ultra-small RI resolution (∼10-7 RIU at 950 nm). Moreover, specific detection of very low concentration of biomolecules (5 fg/mL for human IgG and 0.5 pg/mL for human serum albumin (HSA)) and wide range of protein concentrations (e.g., fg/mL-ng/mL for human IgG and pg/mL-ng/mL for HSA) without probe pre-modification were achieved owing to the RI change specifically associated with the probe-target binding and the corresponding bio-macromolecular conformation change. This modification-free stereosensing scenario is applicable to continuous, real-time, and multiplexed operations, thus showing potential for online, integrated, dynamic, biomolecular analyses in vitro or in vivo, such as the dynamic metabolic analysis of single cells or organoids and point-of-care tests.

Flexural properties of porcupine quill-inspired sandwich panels.

This paper presents the bending behaviour of the porcupine quill and bioinspired Voronoi sandwich panels, aiming to explore the effect of geometrical design on the bending performance of the inspired structures. Through the x-ray micro-computed tomography, the internal morphology of the quill is explored. The longitudinal cross-section of the porcupine quill revealed a functionally graded design in the foam structure. Based on this observation, Voronoi sandwich panels are designed by incorporating the Voronoi seed distribution strategy and gradient transition design configurations. Porcupine-inspired sandwich panels with various core designs are fabricated via material jetting technique and tested under three-point bending condition. Results show that the sample failed at the bottom face panels for uniform sandwich panels, whereas graded samples failed in the core panel. The bending behaviour developed via simulation software shows a good agreement with the experimental results. The parametric study provides insights into structural designs for engineering applications, particularly in the aerospace and automobile industries.

A Novel Radiomics Model Integrating Luminal and Mesenteric Features to Predict Mucosal Activity and Surgery Risk in Crohn's Disease Patients: A Multicenter Study.

BACKGROUND: To investigate the feasibility of integrating radiomics and morphological features based on computed tomography enterography (CTE) for developing a noninvasive grading model for mucosal activity and surgery risk of Crohn's disease (CD) patients. METHODS: A total of 167 patients from three centers were enrolled. Radiomics and image morphological features were extracted to quantify segmental and global simple endoscopic score for Crohn's disease (SES-CD). An image-fusion-based support vector machine (SVM) classifier was used for grading SES-CD and identifying moderate-to-severe SES-CD. The performance of the predictive model was assessed using the area under the receiver operating characteristic curve (AUC). A multiparametric model was developed to predict surgical progression in CD patients by combining sum-image scores and clinical data. RESULTS: The AUC values of the multicategorical segmental SES-CD fusion radiomic model based on a combination of luminal and mesenteric radiomics were 0.828 and 0.709 in training and validation cohorts. The image fusion model integrating the fusion radiomics and morphological features could accurately distinguish bowel segments with moderate-to-severe SES-CD in both the training cohort (AUC = 0.847, 95% confidence interval (CI): 0.784-0.902) and the validation cohort (AUC = 0.896, 95% CI: 0.812-0.960). A predictive nomogram for interval surgery was developed based on multivariable cox analysis. CONCLUSIONS: This study demonstrated the feasibility of integrating lumen and mesentery radiomic features to develop a promising noninvasive grading model for mucosal activity of CD. In combination with clinical data, the fusion-image score may yield an accurate prognostic model for time to surgery.

Enhance the Accuracy of Landslide Detection in UAV Images Using an Improved Mask R-CNN Model: A Case Study of Sanming, China.

Extracting high-accuracy landslide areas using deep learning methods from high spatial resolution remote sensing images is a hot topic in current research. However, the existing deep learning algorithms are affected by background noise and landslide scale effects during the extraction process, leading to poor feature extraction effects. To address this issue, this paper proposes an improved mask regions-based convolutional neural network (Mask R-CNN) model to identify the landslide distribution in unmanned aerial vehicles (UAV) images. The improvement of the model mainly includes three aspects: (1) an attention mechanism of the convolutional block attention module (CBAM) is added to the backbone residual neural network (ResNet). (2) A bottom-up channel is added to the feature pyramidal network (FPN) module. (3) The region proposal network (RPN) is replaced by guided anchoring (GA-RPN). Sanming City, China was selected as the study area for the experiments. The experimental results show that the improved model has a recall of 91.4% and an accuracy of 92.6%, which is 12.9% and 10.9% higher than the original Mask R-CNN model, respectively, indicating that the improved model is more effective in landslide extraction.

Efficacy of oblique lumbar interbody fusion versus transforaminal lumbar interbody fusion in the treatment of lumbar degenerative diseases: a systematic review and meta-analysis.

INTRODUCTION: This meta-analysis aimed to compare the differences in postoperative efficacy between oblique lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of lumbar degenerative diseases. MATERIALS AND METHODS: Strictly based on the search strategy, we searched the published papers on OLIF and TLIF for the treatment of lumbar degenerative diseases in PubMed, Embase, CINAHL, and Cochrane Library. A total of 607 related papers were retrieved, and 15 articles were finally included. The quality of the papers was evaluated according to the Cochrane systematic review methodology, and the data were extracted and meta-analyzed using Review manager 5.4 software. RESULTS: Through comparison, it was found that in the treatment of lumbar degenerative diseases, the OLIF group had certain advantages over the TLIF group in terms of intraoperative blood loss, hospital stay, visual analog scale (VAS) for leg pain (VAS-LP), Oswestry disability index (ODI), disc height (DH), foraminal height (FH), fused segmental lordosis (FSL), and cage height, and the differences were statistically significant. The results were similar in terms of surgery time, complications, fusion rate, VAS for back pain (VAS-BP) and various sagittal imaging indicators, and there was no significant difference. CONCLUSIONS: OLIF and TLIF can relieve low back pain symptoms in the treatment of lumbar degenerative diseases, but OLIF has certain advantages in terms of ODI and VAS-LP. In addition, OLIF has the advantages of minor intraoperative trauma and quick postoperative recovery.

Oblique lumbar interbody fusion versus minimally invasive transforaminal lumbar interbody fusion for the treatment of degenerative disease of the lumbar spine: a systematic review and meta-analysis.

This meta-analysis compared the efficacy of oblique lumbar interbody fusion (OLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of lumbar degenerative diseases. A computer search for the published literature on OLIF and MIS-TLIF for the treatment of lumbar degenerative diseases in the PubMed, Web of Science, Embase, CINAHL, MEDLINE, Cochrane Library, and other databases was performed, from which 522 related articles were retrieved and 13 were finally included. Two reviewers independently extracted data from the included studies and analyzed them using RevMan 5.4. The quality of the studies was assessed using the Cochrane systematic analysis and the Newcastle-Ottawa scale. Meta-analysis showed that the blood loss [95% confidence intervals (CI) (- 121.01, - 54.56), [Formula: see text]], hospital stay [95% CI (- 1.98, - 0.85), [Formula: see text]], postoperative fusion rate [95%CI (1.04, 3.60), [Formula: see text]], postoperative disc height [95% CI (0.50, 3.63), [Formula: see text]], and postoperative foraminal height [95% CI (0.96, 4.13), [Formula: see text]] were all better in the OLIF group; however, the complication rates were significantly lower in the MIS-TLIF group [95% CI (1.01, 2.06), [Formula: see text]]. However, there were no significant differences between the two in terms of surgery time, patient satisfaction, or postoperative functional scores. The OLIF group had the advantages of lower blood loss, a shorter hospital stay, a higher postoperative fusion rate, and better recovery of the disc and foraminal heights, whereas MIS-TLIF had a relatively lower complication rate.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy.

BACKGROUND: A high prevalence of diabetes mellitus (DM) coexisting with autoimmune pancreatitis (AIP) is observed. However, evidence on the circumstances under which corticosteroid therapy (CST) for AIP improves or worsens DM is scarce. This study aimed to demonstrate and identify predictors of DM control under the influence of CST. METHODS: Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed: pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as 'improvement' and 'non-improvement' (including 'no change' and 'exacerbation'). RESULTS: Among 101 patients with type 1 AIP, 52 (51.5%) patients were complicated with DM at the time of AIP diagnosis, with 36 patients in the cDM group and 16 patients in the pDM group. The incidences of diffuse pancreatic swelling (72.2%) and pancreatic body/tail involvement (91.7%) were significantly higher in the cDM group than in both the pDM and nDM groups. Of the 52 patients with DM, CST was administered in 48 cases. Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase (GGT) level at AIP diagnosis [odds ratio (OR) = 0.032, 95% confidence interval (CI): 0.003-0.412, P = 0.008] and pancreatic atrophy after CST (OR = 0.027, 95% CI: 0.003-0.295, P = 0.003) were negatively associated with DM control improvement. CONCLUSIONS: Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis. CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis, particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

[Analysis of molecular genetics and clinical characteristics of 3 children with Waardenburg syndrome].

Objective:To analyze the molecular genetics and clinical characteristics of 3 children with syndromic deafness were analyzed to clarify their causative genes and genetic characteristics. Methods:The medical records of 3 children and their parents were collected and analyzed, including physical examination, hearing evaluation, temporal bone CT, and cranial MRI. Whole-exome sequencing（WES） was used to screen for pathogenic gene variants, and Sanger sequencing was used to verify the candidate positive variants in the probands and their parents. Results:All 3 patients were female with normal intelligence. Patient 1 and 3 had a family history of deafness, which conformed to the pattern of autosomal dominant inheritance. All three patients had bilateral profound sensorineural hearing impairment with bright-blue sclera. Other phenotypes included hypertelorism（patient 1）, multiple dyschromatosis（patient 2）, and yellowish hair（patient 2）, blepharoptosis（patient 3）. Patient 3 had bilateral vestibular enlargement, internal auditory canal enlargement, and bilateral inner ear malformations. Mother of patient 1 had only left mild hearing impairment; mother of patient 3 had bilateral hearing impairment with unilateral bright-blue sclera and yellowish hair. WES detected heterozygous variants, PAX3 c.811C>T, MITF c.632T>C, and SOX10 c.1359_1360 insGCCCCACA, in patient 1, 2, and 3, respectively. The variants in patient 1 and 3 were inherited from their mothers who had hearing impairment, and MITFvariant in patient 2 may be a spontaneous variation. The final diagnoses were that patient 1 with Waardenburg syndrome type 1（WS1）, and the mother of patient 1, patient 2, patient 3, and the mother of patient 3 with WS2. Conclusion:WS is a syndromic deafness, and the main clinical features include autosomal dominant inheritance and scleral pigment abnormalities. However, the findings of this study show that there is still phenotypic heterogeneity in WS even caused by the same gene variant, so it depends on genetic tests to confirm the diagnosis; The gene variant of patient 1 and 2 was never been reported in other patients, which expands the pathogenic variant spectrum of WS.