Nomogram using intratumoral and peritumoral radiomics for the preoperative prediction of visceral pleural invasion in clinical stage IA lung adenocarcinoma.

BACKGROUND: Accurate prediction of visceral pleural invasion (VPI) in lung adenocarcinoma before operation can provide guidance and help for surgical operation and postoperative treatment. We investigate the value of intratumoral and peritumoral radiomics nomograms for preoperatively predicting the status of VPI in patients diagnosed with clinical stage IA lung adenocarcinoma. METHODS: A total of 404 patients from our hospital were randomly assigned to a training set (n = 283) and an internal validation set (n = 121) using a 7:3 ratio, while 81 patients from two other hospitals constituted the external validation set. We extracted 1218 CT-based radiomics features from the gross tumor volume (GTV) as well as the gross peritumoral tumor volume (GPTV5, 10, 15), respectively, and constructed radiomic models. Additionally, we developed a nomogram based on relevant CT features and the radscore derived from the optimal radiomics model. RESULTS: The GPTV10 radiomics model exhibited superior predictive performance compared to GTV, GPTV5, and GPTV15, with area under the curve (AUC) values of 0.855, 0.842, and 0.842 in the three respective sets. In the clinical model, the solid component size, pleural indentation, solid attachment, and vascular convergence sign were identified as independent risk factors among the CT features. The predictive performance of the nomogram, which incorporated relevant CT features and the GPTV10-radscore, outperformed both the radiomics model and clinical model alone, with AUC values of 0.894, 0.828, and 0.876 in the three respective sets. CONCLUSIONS: The nomogram, integrating radiomics features and CT morphological features, exhibits good performance in predicting VPI status in lung adenocarcinoma.

GluR2 can Drive Neuroinflammation and Cognitive Impairments Following Peripherally Repeated Lipopolysaccharide Exposures.

Neuroinflammation is being increasingly recognized as a vital factor in the development of various neurological and neuropsychiatric diseases. Lipopolysaccharides (LPS), an outer membrane component of gram-negative bacteria, can trigger innate immune responses, resulting in neuroinflammation and subsequent cognitive deficits. The expression of glutamate receptors (GluRs) on glial cells can induce glial activation. Therefore, we hypothesized that repeated LPS exposure can increase GluR levels, promoting microglial activation and ultimately affecting synaptic plasticity and cognitive function. In this study, C57/BL6 mice were repeatedly exposed to LPS to construct a neuroinflammation animal model. The levels of GluRs, inflammatory cytokines, ionized calcium-binding adaptor molecule 1, postsynaptic density protein 95, synaptophysin 38, NMDA receptor 2 A, and NMDA receptor 2B (GluN2B) were measured in the hippocampi. Furthermore, dendritic spine density in the CA1 hippocampal region was determined. Repeated LPS exposure induced cognitive impairments and microglial activation and increased GluR1 and GluR2 levels. This was accompanied by a significant decrease in GluN2B expression and dendritic spine density in the hippocampi. However, CFM-2, an α-amino-3- hydroxy-5-methyl-4-isoxazolepropionate receptor antagonist, reversed these anomalies. Furthermore, minocycline, a microglial inhibitor, reversed these anomalies and downregulated GluR2 but not GluR1 expression. In summary, we demonstrated that GluR2 plays an essential role in microglia-induced neuroinflammation, resulting in synaptic plasticity and cognitive impairment induced by repeated exposure to LPS.

Advances in targeting histone deacetylase for treatment of solid tumors.

Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention. A variety of HDAC inhibitors (HDACis) have been developed to target HDACs. Many preclinical studies have conclusively demonstrated the antitumor effects of HDACis, whether used as monotherapy or in combination treatments. On this basis, researchers have conducted various clinical studies to evaluate the potential of selective and pan-HDACis in clinical settings. In our work, we extensively summarized and organized current clinical trials, providing a comprehensive overview of the current clinical advancements in targeting HDAC therapy. Furthermore, we engaged in discussions about several clinical trials that did not yield positive outcomes, analyzing the factors that led to their lack of anticipated therapeutic effectiveness. Apart from the experimental design factors, issues such as toxicological side effects, tumor heterogeneity, and unexpected off-target effects also contributed to these less-than-expected results. These challenges have naturally become significant barriers to the application of HDACis. Despite these challenges, we believe that advancements in HDACi research and improvements in combination therapies will pave the way or lead to a broad and hopeful future in the treatment of solid tumors.

LINC02257 regulates colorectal cancer liver metastases through JNK pathway.

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of colorectal cancer (CRC) progression, but their roles and underlying mechanisms in colorectal cancer liver metastases (CRLMs) remain poorly understood. Methods: To explore the expression patterns and functions of lncRNAs in CRLMs, we analyzed the expression profiles of lncRNAs in CRC tissues using the TCGA database and examined the expression patterns of lncRNAs in matched normal, CRC, and CRLM tissues using clinical samples. We further investigated the biological roles of LINC02257 in CRLM using in vitro and in vivo assays, and verified its therapeutic potential in a mouse model of CRLM. Results: Our findings showed that LINC02257 was highly expressed in metastatic CRC tissues and its expression was negatively associated with overall survival. Functionally, LINC02257 promoted CRC cell growth, migration, metastasis, and inhibited cell apoptosis in vitro, and enhanced liver metastasis in vivo. Mechanistically, LINC02257 up-regulated phosphorylated c-Jun N-terminal kinase (JNK) to promote CRLM. Conclusions: Our study revealed that LINC02257 played a key role in the proliferation and metastasis of CRC cells through the LINC02257/JNK axis. Targeting this axis may represent a promising therapeutic strategy for the treatment of liver metastases in patients with CRC.

Enhancing Molecular Energy Predictions with Physically Constrained Modifications to the Neural Network Potential.

Exclusively prioritizing the precision of energy prediction frequently proves inadequate in satisfying multifaceted requirements. A heightened focus is warranted on assessing the rationality of potential energy curves predicted by machine learning-based force fields (MLFFs), alongside evaluating the pragmatic utility of these MLFFs. This study introduces SWANI, an optimized neural network potential stemming from the ANI framework. Through the incorporation of supplementary physical constraints, SWANI aligns more cohesively with chemical expectations, yielding rational potential energy profiles. It also exhibits superior predictive precision compared with that of the ANI model. Additionally, a comprehensive comparison is conducted between SWANI and a prominent graph neural network-based model. The findings indicate that SWANI outperforms the latter, particularly for molecules exceeding the dimensions of the training set. This outcome underscores SWANI's exceptional capacity for generalization and its proficiency in handling larger molecular systems.

Serum ASGR2 level: an efficacy biomarker for balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.

Identification and Validation of PKR as a Direct Target for the Novel Sulfonamide-Substituted Tetrahydroquinoline Nonselective Inhibitor of the NLRP3 Inflammasome.

The NLRP3 inflammasome is a critical component of the innate immune system. The persistent abnormal activation of the NLRP3 inflammasome is implicated in numerous human diseases. Herein, sulfonamide-substituted tetrahydroquinoline derivative S-9 was identified as the most promising NLRP3 inhibitor, without obvious cytotoxicity. In vitro, S-9 inhibited the priming and activation stages of the NLRP3 inflammasome. Incidentally, we also observed that S-9 had inhibitory effects on the NLRC4 and AIM2 inflammasomes. To elucidate the multiple anti-inflammatory activities of S-9, photoaffinity probe P-2, which contained a photoaffinity label and a functional handle, was developed for target identification by chemical proteomics. We identified PKR as a novel target of S-9 in addition to NLRP3 by target fishing. Furthermore, S-9 exhibited a significant anti-neuroinflammatory effect in vivo. In summary, our findings show that S-9 is a promising lead compound targeting both PKR and NLRP3 that could emerge as a molecular tool for treating inflammasome-related diseases.

Ultrasound manifestations of primary intestinal non-Hodgkin lymphoma with liver metastasis in a child.

Non-Hodgkin lymphoma (NHL) is a highly aggressive malignant tumor arising in lymph nodes or extra-nodal lymphoid tissues, with an incidence of 8.3 per million. It accounts for approximately 7% of childhood and adolescent malignancies, second only to leukemia and brain tumors. Despite the gastrointestinal tract being the most common extra-nodal site involved by lymphoma, primary intestinal lymphoma (PIL) is rare and typically affects middle-aged men without specific clinical symptoms. Here, we present the case of a 2-year-old child indicative of PIL with the informed consent of the parents.

Advances in research on factors affecting chimeric antigen receptor T-cell efficacy.

Chimeric antigen receptor T-cell (CAR-T) therapy is becoming an effective technique for the treatment of patients with relapsed/refractory hematologic malignancies. After analyzing patients with tumor progression and sustained remission after CAR-T cell therapy, many factors were found to be associated with the efficacy of CAR-T therapy. This paper reviews the factors affecting the effect of CAR-T such as tumor characteristics, tumor microenvironment and immune function of patients, CAR-T cell structure, construction method and in vivo expansion values, lymphodepletion chemotherapy, and previous treatment, and provides a preliminary outlook on the corresponding therapeutic strategies.

The improvement of inflammatory infiltration and pregnancy outcome in mice with recurrent spontaneous abortion by human amniotic mesenchymal stem cells.

Recurrent spontaneous abortion (RSA) is thought to be mostly triggered by immune-related causes. Mesenchymal stem cells (MSCs), which exhibit the traits of multi-directional differentiation capacity and low immunogenicity, have recently been recommended as a viable treatment for spontaneous abortion-prone mice to increase the success of pregnancy. Amniotic membrane tissue is a byproduct of pregnancy and delivery that has a wide range of potential uses due to its easy access to raw materials and little ethical constraints. To construct an abortion-prone mouse model for this investigation, CBA/J female mice were coupled with male DBA/2 mice, while CBA/J female mice were paired with male BALB/c mice as a control. The identical volume of hAMSCs or PBS was injected intraperitoneally on the 4.5th day of pregnancy. CBA/J female mice were sacrificed by cervical dislocation on the 13.5th day of pregnancy, the embryo absorption rate was calculated, and the uterus, decidua tissues and placenta were gathered for examination. Through detection, it was discovered that hAMSCs significantly increased the expression of interleukin 10 (IL-10) and transforming growth factor beta (TGF-ß), while significantly decreased the expression of interleukin 1 beta (IL-1ß) and interleukin 6 (IL-6), improved vascular formation and angiogenesis, minimized the embryo absorption rate and inflammatory cell infiltration in the RSA + hAMSCs group. In any case, hAMSCs regulate inflammatory factors and cell balance at the maternal-fetal interface, which result in a reduction in the rate of embryo absorption and inflammatory infiltration and provide an innovative perspective to the clinical therapy of RSA.

AudioGest: Gesture-based Interaction for Virtual Reality using Audio Devices.

Current virtual reality (VR) system takes gesture interaction based on camera, handle and touch screen as one of the mainstream interaction methods, which can provide accurate gesture input for it. However, limited by application forms and the volume of devices, these methods cannot extend the interaction area to such surfaces as walls and tables. To address the above challenge, we propose AudioGest, a portable, plug-and-play system that detects the audio signal generated by finger tapping and sliding on the surface through a set of microphone devices without extensive calibration. First, an audio synthesis-recognition pipeline based on micro-contact dynamics simulation is constructed to generate modal audio synthesis from different materials and physical properties. Then the accuracy and effectiveness of the synthetic audio are verified by mixing the synthetic audio with real audio proportionally as the training sets. Finally, a series of desktop office applications are developed to demonstrate the application potential of AudioGest's scalability and versatility in VR scenarios.

The impact of maternal smoking during pregnancy and the age of smoking initiation on incident dementia: A prospective cohort study.

INTRODUCTION: The impact of early-life tobacco exposure on dementia has remained unknown. METHODS: Using the UK Biobank, the associations of maternal smoking during pregnancy (MSDP) and age of smoking initiation (ASI) with the onset time of all-cause dementia were estimated with accelerated failure time models. The effects of MSDP and ASI on brain structure and their genetic correlation to Alzheimer's disease (AD) were analyzed. A Mendelian randomization (MR) analysis was conducted. RESULTS: The time ratios for smokers starting in childhood, adolescence, and adulthood (vs never smokers) were 0.87 (0.76 to 0.99), 0.92 (0.88 to 0.96), and 0.95 (0.89 to 1.01). MSDP and smoking in adolescence altered many brain regions, including the hippocampus. In genetic analysis, MSDP was genetically and causally linked to AD, and a younger ASI was genetically correlated to a higher AD risk. DISCUSSION: Early-life smoking accelerated dementia onset and was genetically correlated to AD. MSDP demonstrated genetic and causal linkage to AD risks. HIGHLIGHTS: Unlike the commonly used Cox proportional hazards model, this article uses a parametric survival analysis method - the accelerated failure model - to explore the relationship between exposure to onset time. It can be used as an alternative method when the proportional hazards assumption is not met. Genetic analyses including genetic correlation study and MR analysis and brain structure analyses were conducted to support our findings and explore the potential mechanisms. The study reveals the relationship between different smoking initiation periods and the onset time of dementia and shows that earlier smoking exposure has a more significant impact on dementia. It emphasizes the importance of preventing early smoking. In the future, more research focusing on the relationship between early exposure and dementia is called for to provide more detailed prevention measures for dementia that cover all age groups.

Experimental Generation of Spin-Photon Entanglement in Silicon Carbide.

A solid-state approach for quantum networks is advantageous, as it allows the integration of nanophotonics to enhance the photon emission and the utilization of weakly coupled nuclear spins for long-lived storage. Silicon carbide, specifically point defects within it, shows great promise in this regard due to the easy of availability and well-established nanofabrication techniques. Despite of remarkable progresses made, achieving spin-photon entanglement remains a crucial aspect to be realized. In this Letter, we experimentally generate entanglement between a silicon vacancy defect in silicon carbide and a scattered single photon in the zero-phonon line. The spin state is measured by detecting photons scattered in the phonon sideband. The photonic qubit is encoded in the time-bin degree of freedom and measured using an unbalanced Mach-Zehnder interferometer. Photonic correlations not only reveal the quality of the entanglement but also verify the deterministic nature of the entanglement creation process. By harnessing two pairs of such spin-photon entanglement, it becomes straightforward to entangle remote quantum nodes at long distance.

Stimulus-Induced Dynamic Behavior Regulation of Flexible Crystals through the Tuning of Module Rigidity.

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

Mitochondrial GPX4 acetylation is involved in cadmium-induced renal cell ferroptosis.

Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD+-dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3-/- mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.

Risk Factors for Postoperative Complications of Laparoscopic Right Colectomy: A Post Hoc Analysis of RELARC Trial.

BACKGROUND: There is concern regarding the possibility of postoperative complications for laparoscopic right colectomy. OBJECTIVE: To evaluate the risk factors of postoperative complications for patients undergoing laparoscopic right colectomy. DESIGN: This was an observational study. SETTINGS: This was a post-hoc analysis of a prospective, multicenter, randomized controlled trial (RELARC trial, NCT02619942). PATIENTS: Patients included in the modified intention-to-treat analysis in RELARC trial were all enrolled in this study. MAIN OUTCOME MEASURES: Risk factors for postoperative complications were identified using univariate and multivariable logistic regression analysis. RESULTS: Of 995 patients, 206 (20.7%) had postoperative complications. Comorbidity (p = 0.02, OR: 1.544, 95% CI: 1.077-2.212) and operative time >180 min (p = 0.03, OR: 1.453, 95% CI: 1.032-2.044) were independent risk factors for postoperative complications. While female (p = 0.04, OR: 0.704, 95% CI: 0.506-0.980) and extracorporeal anastomosis (p < 0.001, OR: 0.251, 95% CI: 0.166-0.378) were protective factors. Eighty (8.0%) had overall surgical site infection, 53 (5.3%) had incisional SSI, and 33 (3.3%) had organ/space SSI. Side-to-side anastomosis was a risk factor for overall surgical site infection (p < 0.001, OR: 1.912, 95% CI: 1.118-3.268) and organ/space surgical site infection (p = 0.005, OR: 3.579, 95% CI: 1.455-8.805). Extracorporeal anastomosis was associated with a reduced risk of overall surgical site infection (p < 0.001, OR: 0.239, 95% CI: 0.138-0.413), organ/space surgical site infection (p = 0.002 OR: 0.296, 95% CI: 0.136-0.646), and incisional surgical site infection (p < 0.001, OR: 0.179, 95% CI: 0.099-0.322). Diabetes (p = 0.039 OR: 2.090, 95% CI: 1.039-4.205) and conversion to open surgery (p = 0.013 OR: 5.403, 95% CI: 1.437-20.319) were risk factors for incisional surgical site infection. LIMITATIONS: Due to the retrospective nature, the key limitation is the lack of prospective documentation and standardization about perioperative management of these patients such as preoperative optimization, bowel prep regimes and antibiotic regimes, which may be confounder factors of complications. All surgeries were done by experienced surgeons and the patients enrolled were relatively young, generally healthy, and non-obese. It is unclear whether the results will be generalizable to obese and other populations worldwide. CONCLUSIONS: Male, comorbidity, prolonged operative time, and intracorporeal anastomosis were independent risk factors of postoperative complications of laparoscopic right colectomy. Side-to-side anastomosis was associated with an increased risk of organ/space surgical site infection. Extracorporeal anastomosis could reduce the incidence of overall surgical site infection. Diabetes and conversion to open surgery were associated with an increased risk of incisional surgical site infection. See Video Abstract.

Hypoxic indices for obstructive sleep apnoea severity and cardiovascular disease risk prediction: A comparison and application in a community population.

BACKGROUND AND OBJECTIVE: The apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) encounter challenges in capturing the intricate relationship between obstructive sleep apnoea (OSA) and cardiovascular disease (CVD) risks. Although novel hypoxic indices have been proposed to tackle these limitations, there remains a gap in comprehensive validation and comparisons across a unified dataset. METHODS: Samples were derived from the Sleep Heart Health Study (SHHS), involving 4485 participants aged over 40 years after data quality screening. The study compared several key indices, including AHI, ODI, the reconstructed hypoxic burden (rHB), the percentage of sleep time with the duration of respiratory events causing desaturation (pRED_3p) and the sleep breathing impairment index (SBII), in relation to CVD mortality and morbidity risks. Adjusted Cox proportional models were employed to calculate hazard ratios (HRs) for each index, and comparisons were performed. RESULTS: SBII and pRED_3p exhibited significant correlations with both CVD mortality and morbidity, with SBII showing the highest adjusted HR (95% confidence interval) for mortality (2.04 [1.25, 3.34]) and pRED_3p for morbidity (1.43 [1.09-1.88]). In contrast, rHB was only significant in predicting CVD mortality (1.63 [1.05-2.53]), while AHI and ODI did not show significant correlations with CVD outcomes. The adjusted models based on SBII and pRED_3p exhibited optimal performance in the CVD mortality and morbidity datasets, respectively. CONCLUSION: This study identified the optimal indices for OSA-related CVD risks prediction, SBII for mortality and pRED_3p for morbidity. The open-source online platform provides the computation of the indices.

Neurological involvement in hematopoietic stem cell transplantation-associated thrombotic microangiopathy.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a well-recognized serious complication of hematopoietic stem cell transplantation (HSCT). The understanding of TA-TMA pathophysiology has expanded in recent years. Dysregulation of the complement system is thought to cause endothelial injury and, consequently, microvascular thrombosis and tissue damage. TA-TMA can affect multiple organs, and each organ exhibits specific features of injury. Central nervous system (CNS) manifestations of TA-TMA include posterior reversible encephalopathy syndrome, seizures, and encephalopathy. The development of neurological dysfunction is associated with a significantly lower overall survival in patients with TA-TMA. However, there are currently no established histopathological or radiological criteria for the diagnosis of CNS TMA. Patients who receive total body irradiation (TBI), calcineurin inhibitors (CNI), and severe acute and chronic graft-versus-host disease (GVHD) are at a high risk of experiencing neurological complications related to TA-TMA and should be considered for directed TA-TMA therapy. However, the incidence and clinical manifestations of TA-TMA neurotoxicity remain unclear. Studies specifically examining the involvement of CNS in TMA syndromes are limited. In this review, we discuss clinical manifestations and imaging abnormalities in patients with nervous system involvement in TA-TMA. We summarize the mechanisms underlying TA-TMA and its neurological complications, including endothelial injury, evidence of complement activation, and treatment options for TA-TMA.

Anterior Shoulder Stabilization Using Single Needle-Assisted Outside-In Remplissage Technique and Bankart Repair.

Arthroscopic repair of Bankart injury is the first choice for the treatment of anterior shoulder instability. How to avoid recurring shoulder joint dislocation is a challenge, especially when combined with Hill-Sachs lesions. The arthroscopy technology allows for broader vision and less surgical trauma but is limited by a smaller operating space. At present, extensive descriptions about the surgical procedure of arthroscopic Bankart repair have been published. In this Technical Note, we describe the use of remplissage filling with Hill-Sachs lesion combined with Bankart repair to further improve the surgical accuracy and clinical efficacy. In particular, the application of single needle-assisted outside-in remplissage technique and Bankart repair is introduced in detail.

Exploring the casual association between gut microbiome, circulating inflammatory cytokines and chronic pancreatitis: A Mendelian randomization analysis.

It has been established that gut dysbiosis contributed to the pathogenesis of digestive disorders. We aimed to explore the causal relationships between intestinal microbiota, circulating inflammatory cytokines and chronic pancreatitis (CP). Summary statistics of genome-wide association studies (GWAS) of intestinal microbiome was retrieved from the MiBioGen study and the GWAS data of 91 circulating inflammatory cytokines and CP were obtained from the GWAS catalog. The 2-sample bidirectional Mendelian randomization (MR) analysis was performed between gut microbiota, circulating inflammatory cytokines and CP, in which the inverse variance weighted (IVW) method was regarded as the primary analysis approach. To prove the reliability of the causal estimations, multiple sensitivity analyses were utilized. IVW results revealed that genetically predicted 2 genera, including Sellimonas and Eubacteriumventriosumgroup, and plasm C-C motif chemokine 23 (CCL23) level were positively associated with CP risk, while genus Escherichia Shigella, Eubacteriumruminantiumgroup and Prevotella9, and plasma Caspase 8, Adenosine Deaminase (ADA), and SIR2-like protein 2 (SIRT2) level, demonstrated an ameliorative effect on CP. Leave-one-out analysis confirmed the robustness of the aforementioned causal effects and no significant horizontal pleiotropy or heterogeneity of the instrumental variables was detected. However, no association was found from the identified genera to the CP-related circulating inflammatory cytokines. Besides, the reverse MR analysis demonstrated no causal relationship from CP to the identified genera and circulating inflammatory cytokines. Taken together, our comprehensive analyses offer evidence in favor of the estimated causal connections from the 5 genus-level microbial taxa and 4 circulating inflammatory cytokines to CP risk, which may help to reveal the underlying pathogenesis of CP.