Aromatization-driven deconstructive functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis.

Aromatization-driven deconstruction and functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis is developed. The aromatization effect was introduced to synergistically drive unstrained cyclic C-C bond cleavage, with the aim of overcoming the ring-size limitation of nitrogen-centered radical induced deconstruction of carbocycles. Herein, we demonstrate the synergistic photoredox/nickel catalyzed deconstructive cross-coupling of spiro dihydroquinazolinones with organic halides. Remarkably, structurally diverse organic halides including aryl, alkenyl, alkynyl, and alkyl bromides were compatible for the coupling. In addition, this protocol is also characterized by its mild and redox-neutral conditions, excellent functional group compatibility, high atom economy, and easy scalability. A telescoped procedure involving condensation and ring-opening/coupling was found to be accessible. This work provides a complementary strategy to the existing radical-mediated C-C bond cleavage of unstrained carbocycles.

Clinical significance of miR-9-5p in NSCLC and its relationship with smoking.

Purpose: Dysregulated expression of microRNA (miRNAs) in lung cancer has been wildly reported. The clinicopathologic significance of miR-9-5p in non-small-cell lung cancer (NSCLC) patients and its effect on NSCLC progression were explored in this study. Patients and methods: A total of 76 NSCLC patients were included. miR-9-5p expression was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Then, in vitro experiments including cell growth curve assays, colony formation assays, and transwell migration assays were performed. Further clinicopathological and prognostic values were explored using bioinformatics analysis of the TCGA database. Results: miR-9-5p expression was significantly increased in tumor tissues (both P < 0.0001). miR-9-5p expression was relatively higher in larger tumors (P = 0.0327) and in lung squamous carcinoma (LUSC) (P = 0. 0143). In addition, miR-9-5p was significantly upregulated in the normal lung tissues of cigarette smokers (P = 0.0099). In vitro, miR-9-5p was correlated with cell proliferation and migration. After that, bioinformatics analysis of the TCGA database indicated that miR-9-5p was correlated with tumor size (P = 0.0022), lymphatic metastasis (P = 0.0141), LUSC (P < 0.0001), and smoking history (P < 0.0001). Finally, a prognostic study indicated high miR-9-5p expression was correlated with poor prognosis in LUAD (P = 0.0121). Conclusion: Upregulation of miR-9-5p may have an oncogenic effect in NSCLC and may be related to smoking. The conclusion of this study may help find new prognostic and therapeutic targets for NSCLC and the exploration of the relationship between smoking and lung cancer.

[Recording and identification of depolarization-activated current in intercalated cells].

The depolarization-activated current of intercalated cells in the distal nephron was detected for the first time, and the type of ion channel mediating the current was identified based on electrophysiological and pharmacological properties. The whole-cell current of distal nephron in kidney of C57BL/6J mice was recorded by Axon MultiClamp 700B patch-clamp system, and the effects of several K+ channel inhibitors on the depolarization-activated current in intercalated cells were observed. In addition, the immunofluorescence technique was used to investigate the localization of the channel in intercalated cells. The results showed that when K+ concentration of the bath solution was equal to intracellular fluid (140 mmol/L K+), the depolarization-activated current could be recorded in intercalated cells, but this current was not observed in the principal cells. The depolarization-activated current detected in the intercalated cells could be blocked by Kv4.1 inhibitors. The immunofluorescence experiment showed that the fluorescence of Kv4.1 protein was only present in intercalated cells and not observed in principal cells. Kv4.1 protein immunofluorescence was observed in the luminal and basolateral membrane of intercalated cells, but the fluorescence intensity of luminal membrane was higher than that of basolateral membrane. We conclude that the depolarization-activated current detected in intercalated cells is mediated by Kv4.1 and this channel is mainly expressed in the luminal membrane of intercalated cells.

Iron-Catalyzed Cyanide-Free Synthesis of Alkyl Nitriles: Oxidative Deconstruction of Cycloalkanones with Ammonium Salts and Aerobic Oxidation.

A sustainable, cyanide-free synthesis of alkyl nitriles via the aerobic oxidative deconstruction of unstrained cycloalkanones with ammonium salts has been developed. Using inexpensive and stable ammonium salts as the nitrogen source, a variety of alkyl nitriles containing a distal carbonyl group were obtained in good yields under visible-light-promoted iron catalysis. This protocol is characterized by mild conditions, abundant and environmentally benign materials, and high atom and step economy with minimal waste generation. The primary mechanism study revealed that 1O2 is likely to be involved in this reaction.

Multi-omics integration with weighted affinity and self-diffusion applied for cancer subtypes identification.

BACKGROUND: Characterizing cancer molecular subtypes is crucial for improving prognosis and individualized treatment. Integrative analysis of multi-omics data has become an important approach for disease subtyping, yielding better understanding of the complex biology. Current multi-omics integration tools and methods for cancer subtyping often suffer challenges of high computational efficiency as well as the problem of weight assignment on data types. RESULTS: Here, we present an efficient multi-omics integration via weighted affinity and self-diffusion (MOSD) to dissect cancer heterogeneity. MOSD first construct local scaling affinity on each data type and then integrate all affinities by weighted linear combination, followed by the self-diffusion to further improve the patients' similarities for the downstream clustering analysis. To demonstrate the effectiveness and usefulness for cancer subtyping, we apply MOSD across ten cancer types with three measurements (Gene expression, DNA methylation, miRNA). CONCLUSIONS: Our approach exhibits more significant differences in patient survival and computationally efficient benchmarking against several state-of-art integration methods and the identified molecular subtypes reveal strongly biological interpretability. The code as well as its implementation are available in GitHub: https://github.com/DXCODEE/MOSD .

Vulture: cloud-enabled scalable mining of microbial reads in public scRNA-seq data.

The rapidly growing collection of public single-cell sequencing data has become a valuable resource for molecular, cellular, and microbial discovery. Previous studies mostly overlooked detecting pathogens in human single-cell sequencing data. Moreover, existing bioinformatics tools lack the scalability to deal with big public data. We introduce Vulture, a scalable cloud-based pipeline that performs microbial calling for single-cell RNA sequencing (scRNA-seq) data, enabling meta-analysis of host-microbial studies from the public domain. In our benchmarking experiments, Vulture is 66% to 88% faster than local tools (PathogenTrack and Venus) and 41% faster than the state-of-the-art cloud-based tool Cumulus, while achieving comparable microbial read identification. In terms of the cost on cloud computing systems, Vulture also shows a cost reduction of 83% ($12 vs. ${\$}$70). We applied Vulture to 2 coronavirus disease 2019, 3 hepatocellular carcinoma (HCC), and 2 gastric cancer human patient cohorts with public sequencing reads data from scRNA-seq experiments and discovered cell type-specific enrichment of severe acute respiratory syndrome coronavirus 2, hepatitis B virus (HBV), and Helicobacter pylori-positive cells, respectively. In the HCC analysis, all cohorts showed hepatocyte-only enrichment of HBV, with cell subtype-associated HBV enrichment based on inferred copy number variations. In summary, Vulture presents a scalable and economical framework to mine unknown host-microbial interactions from large-scale public scRNA-seq data. Vulture is available via an open-source license at https://github.com/holab-hku/Vulture.

Recent progress in bone-repair strategies in diabetic conditions.

Bone regeneration following trauma, tumor resection, infection, or congenital disease is challenging. Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia. It can result in complications affecting multiple systems including the musculoskeletal system. The increased number of diabetes-related fractures poses a great challenge to clinical specialties, particularly orthopedics and dentistry. Various pathological factors underlying DM may directly impair the process of bone regeneration, leading to delayed or even non-union of fractures. This review summarizes the mechanisms by which DM hampers bone regeneration, including immune abnormalities, inflammation, reactive oxygen species (ROS) accumulation, vascular system damage, insulin/insulin-like growth factor (IGF) deficiency, hyperglycemia, and the production of advanced glycation end products (AGEs). Based on published data, it also summarizes bone repair strategies in diabetic conditions, which include immune regulation, inhibition of inflammation, reduction of oxidative stress, promotion of angiogenesis, restoration of stem cell mobilization, and promotion of osteogenic differentiation, in addition to the challenges and future prospects of such approaches.

Improve the prediction of liver transplant mortality based on pre-transplant factors: A multi-center study from China: Mortality prediction of LT.

AIMS: To designed a new model using pre-transplant data to predict post-transplant mortality for Chinese population and compared its performance to that of existing models. METHODS: In this multicenter study, 544 recipients of liver transplants for non-tumor indications were enrolled in the training group and 276 patients in the validation group. The new Simplified Mortality Prediction Scores (SMOPS) model was compared to the MELD and four existing models using the C-statistic. RESULTS: SMOPS model used 6 independent pre-transplantation risk factors screened from the training group (chronic liver failure/organ failure scores, fever > 37.6 â„ƒ, ABO blood-type compatibility, arterial lactate level, leukocyte count and re-transplantation). The SMOPS accurately predicted patients' 30-day, 90-day and 365-day mortality following liver transplantation, and its' scores were more accurate than those of the other models. The SMOPS generated four levels of risk: low risk (<10 points), moderate risk (11-20 points), high risk (21-25 points) and futile risk (≥26 points). The survival within all risk levels was not different between MELD=40 and MELD<40. The survival within moderate-, high- or extreme-risk ALF was not different between ALF and non-ALF. CONCLUSION: The SMOPS model uses pre-transplant risk factors to stratify post-transplant survival and is superior to current models for Chinese population, and has the potential to contribute to improvements in organ-allocation policies.

Comparison of the two surgery methods combined with accelerated rehabilitation in the treatment of lateral compression type 1 pelvic fractures in the elderly.

BACKGROUND: Treating lateral compression type 1 (LC1) pelvic ring injuries in older patients is controversial. This study evaluated surgical treatments combined with ERAS for treating LC1 pelvic fractures in the elderly. METHODS: In this retrospective study, patients who underwent surgery with INFIX (supra-acetabular spinal pedicle screws, and a subcutaneous connecting rod; the experimental group) or superior pubic ramus cannulated screw (the control group) fixation of LC1 pelvic fracture from January 2019 to January 2022 were reviewed. Injury radiography and computed tomography were performed to determine the Young-Burgess classification. All patients performed standardized early rehabilitation exercises after surgery and were followed up for > 12 months. After surgery, the Matta score and the visual analog scale (VAS) were evaluated, and the postoperative weight-bearing time and the length of stay (LOS) were recorded. The Barthel index and the Majeed score were evaluated at 4 months after surgery and at the last follow-up. RESULTS: Fifty-three patients were included. Thirty-two patients included in the experimental group had a mean age of 75.0 ± 6.2 (range, 66-86) years, and the other 21 patients in the control group had a mean age of 74.6 ± 4.6 (range, 68-83) years. The mean follow-up time was 13.1 ± 1.6 (range, 12-18) months in the experimental group and 13.4 ± 1.3 (range, 12-16) months in the control group. There were no significant differences in follow-up time between the groups (P > 0.05). The mean VAS score, time to weight-bearing, and LOS were 2.0 ± 0.7 (range, 1-3), 1.1 ± 0.3 (range, 1-2) d, and 5.8 ± 0.9 (range, 4-7) d in the experimental group and 2.3 ± 1.2 (range, 1-5), 2.5 ± 1.6 (range, 1-7) d, and 6.1 ± 1.6 (range, 5-11) d in the control group, respectively. Between the two groups, there was a significant difference in the postoperative time to weight-bearing (P < 0.05), while there was no significant difference in the LOS (P > 0.05). No bedrest-related complications occurred in either group. The Matta score was 90.6% in the experimental group and 90.4% in the control group (P > 0.05). At the 4-months follow-up, the experimental group had a better Barthel index and Majeed score compared with the control group, which were 86.1 ± 6.2 (range, 70-95) vs. 81.2 ± 4.1 (range, 75-90) and 86.3 ± 3.3 (range, 78-91) vs. 80.3 ± 3.9 (range, 76-86), respectively. The experimental group had better early rehabilitation effect than the control group. There was no significant difference in Barthel index and Majeed score between the two groups at the last follow-up (P > 0.05). CONCLUSION: Both INFIX and intramedullary superior pubic ramus cannulated screws can successfully treat LC1 pelvic fractures and reduce bed rest complications among older patients.

Risk factors and prediction model of nomogram for preoperative calf muscle vein thrombosis in geriatric hip fracture patients.

Introduction: Calf muscular vein thrombosis (CMVT) is a common complication in geriatric hip fracture patients. Despite its high incidence, prior research on the topic is limited. The occurrence of CMVT in patients will prolong the preoperative waiting time and even lead to serious thromboembolic events, which can be detrimental to the patient's prognosis. Therefore, this study aimed to identify the risk factors for preoperative CMVT in geriatric hip fracture patients and construct a nomogram model to predict the risk of preoperative CMVT in patients. Materials and methods: Geriatric hip fracture patients who underwent surgery between January 2019 and January 2022 were included. The patients were categorized into two groups depending on whether they had preoperative CMVT, confirmed through Color Doppler ultrasound or venography examination. Univariate and multivariate logistic regression analyses were used to analyze demographic characteristics, medical history, comorbidities, and laboratory tests. A nomogram was constructed to predict preoperative CMVT in geriatric hip fracture patients based on the results of the multivariate logistic regression. Results: Three hundred and eighty-eight geriatric hip fracture patients, including one hundred and thirty-four patients with CMVT and two hundred and fifty-four patients without CMVT, were ultimately included in our study. After multivariable logistic regression analysis, the time from injury to admission, smoking history, serum albumin levels, and D-dimer levels was identified as independent risk factors and was entered into a nomogram model. The nomogram showed robust discrimination, with an area under the receiver operating characteristic curve of 0.805. The calibration curve showed strong agreement between the CMVT probabilities predicted by the nomogram and the actual probabilities. The decision curve analysis illustrates the excellent clinical utility of the model. Conclusion: We have constructed a new nomogram prediction model that can effectively predict the risk of preoperative CMVT in geriatric hip fracture patients based on their medical history and blood test results. This model can help clinicians make individualized predictions of CMVT that are tailored to each patient's unique circumstances.

Iron-catalyzed alkoxyl radical-mediated C-C bond cleavage/phosphorothiolation: a new approach to functionalized S-alkyl phosphorothioates.

An efficient iron-catalyzed alkoxyl radical-mediated C-C bond cleavage/phosphorothiolation cascade is presented. This protocol features mild and redox neutral conditions, wide substrate scope and easy scalability, allowing straightforward access to functionalized S-alkyl organophosphorus compounds in moderate to good yields.

Comparison on greenhouse gas footprint of three types of oriented strand board manufacturing process in China.

The greenhouse gas (GHG) footprints of oriented strand boards (OSB) have been gaining growing concern. China is one of the largest manufacturers and traders of OSB in the world. However, little data are available concerning the GHG footprint of Chinese OSB production. The purpose of this study is to quantify and compare the GHG footprints of three types of OSB produced in China. Cradle-to-gate GHG footprints assessment models were built for OSB according to PAS 2050 guidelines. The results showed that the cradle-to-gate GHG footprints of OSB/2, OSB/3, and OSB/4 were 142.7 kg CO2 e/m3, 173.2 kg CO2 e/m3, and 374.2 kg CO2 e/m3, respectively. Raw material acquisition was the largest contributor to GHG footprint for three types of OSB (52.6~57.6%), followed by the production process of OSB (25.6~27.3%) and transportation (15.3~20.1%). The consumption of wood, MDI, electricity, and the transportation of wood were main emission hotspots in Chinese OSB production. Ultimately, four feasible GHG emission reduction measures were put forward from the perspective of reducing the usage of wood and MDI adhesive, decreasing the electricity consumption, and shortening the transport distance of wood.

Iron-Catalyzed Alkoxyl Radical-Induced C-C Bond Cleavage/gem-Difluoroalkylation Cascade.

An inexpensive iron-catalyzed alkoxyl radical-induced C-C bond cleavage/gem-difluoroalkylation cascade is presented. Regulated by the structure of alkoxyl radical precursors, fluorinated distal diketones were synthesized through a ring-opening strategy and difluoroalkylated medium-sized lactones and macrolactones were constructed via a ring-expansion strategy. Both protocols proceeded under mild and redox neutral conditions with a broad substrate scope and good functional group compatibility.

Surgical treatment and functional outcome of bilateral symmetrical hip dislocation and Pipkin type II femoral head fracture: a 5-year follow-up case report and literature review.

Background: Bilateral posterior hip dislocation and femoral head fracture are rare injuries, which may be the earliest case report that focuses on treatment with open reduction via the direct anterior approach (DAA) for bilateral symmetrical Pipkin type II fracture within 5 years of the follow-up period. Case report: We present a case of bilateral posterior dislocation with a femoral head fracture (Pipkin II) of the hip in 47-year-old woman caused by a high-velocity accident. The dislocation was successfully reduced under general anesthesia at a local hospital and transferred to a tertiary center for surgical management. She was surgically treated with internal fixation using three Herbert screws on the bilateral hips. The DAA was used during surgery. Follow-up for 5 years was performed, and functional outcomes were evaluated using the D'Aubigné range of motion and modified Harris hip score. The range of motion in the bilateral hip was satisfactory, with no signs of post-traumatic arthritis, heterotopic ossification, or avascular necrosis of the femoral head. Conclusion: Surgical management of bilateral Pipkin type II fractures was performed successfully with open reduction and internal fixation using a safe and reliable direct anterior approach, with good functional outcomes at 5-year follow-up.

TRPM2 regulates cell cycle through the Ca2+-CaM-CaMKII signaling pathway to promote HCC.

BACKGROUND: HCC is one of the most common causes of cancer-related deaths. Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable cation channel, was reported to be involved in carcinogenesis and tumor growth recently. However, whether TRPM2 is involved in the pathogenesis and progression of HCC remains unclear. Herein, we systematically elucidated the functional role of TRPM2 in HCC cell cycle regulation and proliferation. APPROACH AND RESULTS: We determine TRPM2 expression to be strongly upregulated in the tumor tissues of HCC patients and associated with a negative prognosis. TRPM2 is highly expressed in HCC cell lines Huh-7 and HepG2 cells, rather than in normal hepatocytes. Inhibition or silencing of TRPM2, or inhibition of the downstream Ca2+-CaM-CaMKII signaling pathway, significantly suppressed the proliferation of Huh-7 and HepG2 cells by arresting the cell cycle at the G1/S phase, accompanied with reduced expression of G1/S checkpoint proteins. Importantly, inhibition or depletion of TRPM2 remarkably slowed down the growth of patient-derived xenografts and Huh-7 xenografts in mice. CONCLUSION: Our results indicate that TRPM2 promotes HCC cell proliferation via activating the Ca2+-CaM-CaMKII signaling pathway to induce the expression of the key G1/S regulatory proteins and accelerate the cell cycle. This study provides compelling evidence of TRPM2 involvement in a previously unrecognized mechanism that drives HCC progression and demonstrates that TRPM2 is a potential target for HCC treatment.

[Preparation and properties of a new artificial bone composite material].

Objective: To study the preparation and properties of the hyaluronic acid (HA)/α-calcium sulfate hemihydrate (α-CSH)/ß-tricalcium phosphate (ß-TCP) material (hereinafter referred to as composite material). Methods: Firstly, the α-CSH was prepared from calcium sulfate dihydrate by hydrothermal method, and the ß-TCP was prepared by wet reaction of soluble calcium salt and phosphate. Secondly, the α-CSH and ß-TCP were mixed in different proportions (10∶0, 9∶1, 8∶2, 7∶3, 5∶5, and 3∶7), and then mixed with HA solutions with concentrations of 0.1%, 0.25%, 0.5%, 1.0%, and 2.0%, respectively, at a liquid-solid ratio of 0.30 and 0.35 respectively to prepare HA/α-CSH/ ß-TCP composite material. The α-CSH/ß-TCP composite material prepared with α-CSH, ß-TCP, and deionized water was used as the control. The composite material was analyzed by scanning electron microscope, X-ray diffraction analysis, initial/final setting time, degradation, compressive strength, dispersion, injectability, and cytotoxicity. Results: The HA/α-CSH/ß-TCP composite material was prepared successfully. The composite material has rough surface, densely packed irregular block particles and strip particles, and microporous structures, with the pore size mainly between 5 and 15 µm. When the content of ß-TCP increased, the initial/final setting time of composite material increased, the degradation rate decreased, and the compressive strength showed a trend of first increasing and then weakening; there were significant differences between the composite materials with different α-CSH/ß-TCP proportion ( P<0.05). Adding HA improved the injectable property of the composite material, and it showed an increasing trend with the increase of concentration ( P<0.05), but it has no obvious effect on the setting time of composite material ( P>0.05). The cytotoxicity level of HA/α-CSH/ß-TCP composite material ranged from 0 to 1, without cytotoxicity. Conclusion: The HA/α-CSH/ß-TCP composite materials have good biocompatibility. Theoretically, it can meet the clinical needs of bone defect repairing, and may be a new artificial bone material with potential clinical application prospect.

Potassium Activates mTORC2-dependent SGK1 Phosphorylation to Stimulate Epithelial Sodium Channel: Role in Rapid Renal Responses to Dietary Potassium.

SIGNIFICANCE STATEMENT: Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular K + concentration in kidney tissue is increasingly recognized as an important regulator of K + secretion, the underlying mechanisms that are relevant in vivo remain controversial. To assess the role of the signaling kinase mTOR complex-2 (mTORC2), the authors compared the effects of K + administered by gavage in wild-type mice and knockout mice with kidney tubule-specific inactivation of mTORC2. They found that mTORC2 is rapidly activated to trigger K + secretion and maintain electrolyte homeostasis. Downstream targets of mTORC2 implicated in epithelial sodium channel regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. These findings offer insight into electrolyte physiologic and regulatory mechanisms. BACKGROUND: Increasing evidence implicates the signaling kinase mTOR complex-2 (mTORC2) in rapid renal responses to changes in plasma potassium concentration [K + ]. However, the underlying cellular and molecular mechanisms that are relevant in vivo for these responses remain controversial. METHODS: We used Cre-Lox-mediated knockout of rapamycin-insensitive companion of TOR (Rictor) to inactivate mTORC2 in kidney tubule cells of mice. In a series of time-course experiments in wild-type and knockout mice, we assessed urinary and blood parameters and renal expression and activity of signaling molecules and transport proteins after a K + load by gavage. RESULTS: A K + load rapidly stimulated epithelial sodium channel (ENaC) processing, plasma membrane localization, and activity in wild-type, but not in knockout, mice. Downstream targets of mTORC2 implicated in ENaC regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. We observed differences in urine electrolytes within 60 minutes, and plasma [K + ] was greater in knockout mice within 3 hours of gavage. Renal outer medullary potassium (ROMK) channels were not acutely stimulated in wild-type or knockout mice, nor were phosphorylation of other mTORC2 substrates (PKC and Akt). CONCLUSIONS: The mTORC2-SGK1-Nedd4-2-ENaC signaling axis is a key mediator of rapid tubule cell responses to increased plasma [K + ] in vivo . The effects of K + on this signaling module are specific, in that other downstream mTORC2 targets, such as PKC and Akt, are not acutely affected, and ROMK and Large-conductance K + (BK) channels are not activated. These findings provide new insight into the signaling network and ion transport systems that underlie renal responses to K +in vivo .

Association of Types of Sleep Apnea and Nocturnal Hypoxemia with Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy.

BACKGROUND: Data regarding the association between sleep apnea (SA) and atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) are still limited. We aim to investigate the association of both types of SA, obstructive sleep apnea (OSA) and central sleep apnea (CSA), and nocturnal hypoxemia with AF in HCM. METHODS: A total of 606 patients with HCM who underwent sleep evaluations were included. Logistic regression was used to assess the association between sleep disorder and AF. RESULTS: SA was presented in 363 (59.9%) patients, of whom 337 (55.6%) had OSA and 26 (4.3%) had CSA. Patients with SA were older, more often male, had a higher body mass index, and more clinical comorbidities. Prevalence of AF was higher in patients with CSA than patients with OSA and without SA (50.0% versus 24.9% and 12.8%, p < 0.001). After adjustment for age, sex, body mass index, hypertension, diabetes mellitus, cigarette use, New York Heart Association class and severity of mitral regurgitation, SA (OR, 1.79; 95% CI, 1.09-2.94) and nocturnal hypoxemia (higher tertile of percentage of total sleep time with oxygen saturation < 90% [OR, 1.81; 95% CI, 1.05-3.12] compared with lower tertile) were significantly associated with AF. The association was much stronger in the CSA group (OR, 3.98; 95% CI, 1.56-10.13) than in OSA group (OR, 1.66; 95% CI, 1.01-2.76). Similar associations were observed when analyses were restricted to persistent/permanent AF. CONCLUSION: Both types of SA and nocturnal hypoxemia were independently associated with AF. Attention should be paid to the screening of both types of SA in the management of AF in HCM.

Accelerated rehabilitation in treating neer type V distal clavicle fractures using anatomical locking plates with coracoclavicular ligament augmentation.

Background: There is still no gold standard treatment for Neer type V distal clavicle fractures. This study was designed to evaluate the therapeutic effects of accelerated rehabilitation in treating Neer type V fractures using anatomical locking plate (ALP) fixation with additional coracoclavicular (CC) ligament augmentation. Methods: In this retrospective study, patients who underwent ALP fixation with additional suture anchor fixation of acute Neer type V distal clavicle fracture from January 2016 to January 2021 were reviewed. Injury radiography and computed tomography (CT) were performed to determine the Neer classification. All patients performed standardized early rehabilitation exercises after surgery and were followed up for more than 12 months. The Constant-Murley score (CMS); the disabilities of the arm, shoulder, and hand (DASH) questionnaire; visual analog scale (VAS); and the percentage of modified CC distance (MCCD%) were evaluated at the last follow-up. Results: Thirty-two patients were included in this study. The mean follow-up time was 31.1 ± 10.4 months. All patients achieved bone union 6-8 weeks (7.2 ± 0.7 weeks) after surgery and were allowed to return to normal daily life. No surgery-related complications occurred in any case. The MCCD% value at the last follow-up (104.7% ± 8.5%) significantly decreased compared with preoperative MCCD% value (162.8% ± 7.2%) (p < 0.001), indicating that all patients achieved ideal fracture reduction. And all patients obtained satisfactory shoulder joint function with a mean CMS of 97.1 ± 2.6, a mean DASH score of 1.6 ± 1.3, and a mean VAS score of 0.4 ± 0.6. Conclusion: This study has demonstrated that ALP fixation with additional suture anchor fixation is a promising strategy for accelerated rehabilitation in treating patients with Neer type V fracture.

An immune, stroma, and epithelial-mesenchymal transition-related signature for predicting recurrence and chemotherapy benefit in stage II-III colorectal cancer.

BACKGROUND: Debates exist on the treatment decision of the stage II/III colorectal cancer (CRC) due to the insufficiency of the current TNM stage-based risk stratification system. Epithelial-mesenchymal transition (EMT) and tumor microenvironment (TME) have both been linked to CRC progression in recent studies. We propose to improve the prognosis prediction of CRC by integrating TME and EMT. METHODS: In total, 2382 CRC patients from seven datasets and one in-house cohort were collected, and 1640 stage II/III CRC patients with complete survival information and gene expression profiles were retained and divided into a training cohort and three independent validation cohorts. Integrated analysis of 398 immune, stroma, and epithelial-mesenchymal transition (ISE)-related genes identified an ISE signature independently associated with the recurrence of CRC. The underlying biological mechanism of the ISE signature and its influence on adjuvant chemotherapy was further explored. RESULTS: We constructed a 26-gene signature which was significantly associated with poor outcome in Training cohort (p < 0.001, HR [95%CI] = 4.42 [3.25-6.01]) and three independent validation cohorts (Validation cohort-1: p < 0.01, HR [95%CI] = 1.70 [1.15-2.51]; Validation cohort-2: p < 0.001, HR [95% CI] = 2.30 [1.67-3.16]; Validation cohort-3: p < 0.01, HR [95% CI] = 2.42 [1.25-4.70]). After adjusting for known clinicopathological factors, multivariate cox analysis confirmed the ISE signature's independent prognostic value. Subgroup analysis found that stage III patients with low ISE score might benefit from adjuvant chemotherapy (p < 0.001, HR [95%CI] = 0.15 [0.04-0.55]). Hypergeometric test and enrichment analysis revealed that low-risk group was enriched in thr immune pathway while high-risk group was associated with the EMT pathway and CMS4 subtype. CONCLUSION: We proposed an ISE signature for robustly predicting the recurrence of stage II/III CRC and help treatment decision by identifying patients who will not benefit from current standard treatment.