Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

Rational Molecular Design of a Fluorescent Probe for Selectively Sensing Human Cytochrome P450 2D6.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme that mediates the metabolism of various drugs and endogenous substances in humans. However, its biological role in drug-drug interactions especially mechanism-based inactivation (MBI), and various diseases remains poorly understood, owing to the lack of molecular tools suitable for selectively monitoring CYP2D6 in complex biological systems. Herein, using a tailored molecular strategy, we developed a fluorescent probe BDPM for CYP2D6. BDPM exhibits excellent specificity and imaging capability for CYP2D6, making it suitable for the real-time monitoring of endogenous CYP2D6 activity in living bio-samples. Therefore, our tailored strategy proved useful for constructing the highly selective and enzyme-activated fluorescent probes. BDPM as a molecular tool to explore the critical roles of CYP2D6 in the pathogenesis of diseases, high-throughput screening of inhibitors and intensive investigation of CYP2D6-induced MBI in natural systems.

Single-cell sequencing and multiple machine learning algorithms to identify key T-cell differentiation gene for progression of NAFLD cirrhosis to hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC), which is closely associated with chronicinflammation, is the most common liver cancer and primarily involves dysregulated immune responses in the precancerous microenvironment. Currently, most studies have been limited to HCC incidence. However, the immunopathogenic mechanisms underlying precancerous lesions remain unknown. Methods: We obtained single-cell sequencing data (GSE136103) from two nonalcoholic fatty liver disease (NAFLD) cirrhosis samples and five healthy samples. Using pseudo-time analysis, we systematically identified five different T-cell differentiation states. Ten machine-learning algorithms were used in 81 combinations to integrate the frameworks and establish the best T-cell differentiation-related prognostic signature in a multi-cohort bulk transcriptome analysis. Results: LDHA was considered a core gene, and the results were validated using multiple external datasets. In addition, we validated LDHA expression using immunohistochemistry and flow cytometry. Conclusion: LDHA is a crucial marker gene in T cells for the progression of NAFLD cirrhosis to HCC.

Photon-beam-inducing synthesis of a tunable porous graphene/Ti3C2Tx heterostructure for energy conversion-storage system.

Flexible electronic device requires a novel micro supercapacitors (MSCs) energy conversion-storage system based on two-dimensional (2D) materials to solve the problems of stiffness and complexity. Herein, we report a novel catalytic introduction method of graphene with adjustable porosity by high-energy photon beam. The graphene/Ti3C2Tx heterostructure was constructed by electrostatic self-assembly, has a high cycle life (98% after 8,000 cycles), energy density (11.02 mWh cm-3), and demonstrate excellent flexible alternating current line-filtering performance. The phase angle of -79.8° at 120 Hz and a resistance-capacitance constant of 0.068 ms. Furthermore, the porous graphene/Ti3C2Tx structures produced by multiple catalytic inductions allowed ions to deeply penetrate the electrode, thereby increasing the stacking density. The special "pore-layer nesting" graphene structure with adjustable pores effectively increased the specific surface area, and its superior matching with electrolyte solutions greatly improved surface-active site utilization. This work offers an alternative strategy for fabricating a 2D heterostructure for an MSC.

T cell exhaustion and senescence for ovarian cancer immunotherapy.

Ovarian cancer is a common gynecological malignancy, and its treatment remains challenging. Although ovarian cancer may respond to immunotherapy because of endogenous immunity at the molecular or T cell level, immunotherapy has so far not had the desired effect. The functional status of preexisting T cells is an indispensable determinant of powerful antitumor immunity and immunotherapy. T cell exhaustion and senescence are two crucial states of T cell dysfunction, which share some overlapping phenotypic and functional features, but each status possesses unique molecular and developmental signatures. It has been widely accepted that exhaustion and senescence of T cells are important strategies for cancer cells to evade immunosurveillance and maintain the immunosuppressive microenvironment. Herein, this review summarizes the phenotypic and functional features of exhaust and senescent T cells, and describes the key drivers of the two T cell dysfunctional states in the tumor microenvironment and their functional roles in ovarian cancer. Furthermore, we present a summary of the molecular machinery and signaling pathways governing T cell exhaustion and senescence. Possible strategies that can prevent and/or reverse T cell dysfunction are also explored. An in-depth understanding of exhausted and senescent T cells will provide novel strategies to enhance immunotherapy of ovarian cancer through redirecting tumor-specific T cells away from a dysfunctional developmental trajectory.

ICDW-YOLO: An Efficient Timber Construction Crack Detection Algorithm.

A robust wood material crack detection algorithm, sensitive to small targets, is indispensable for production and building protection. However, the precise identification and localization of cracks in wooden materials present challenges owing to significant scale variations among cracks and the irregular quality of existing data. In response, we propose a crack detection algorithm tailored to wooden materials, leveraging advancements in the YOLOv8 model, named ICDW-YOLO (improved crack detection for wooden material-YOLO). The ICDW-YOLO model introduces novel designs for the neck network and layer structure, along with an anchor algorithm, which features a dual-layer attention mechanism and dynamic gradient gain characteristics to optimize and enhance the original model. Initially, a new layer structure was crafted using GSConv and GS bottleneck, improving the model's recognition accuracy by maximizing the preservation of hidden channel connections. Subsequently, enhancements to the network are achieved through the gather-distribute mechanism, aimed at augmenting the fusion capability of multi-scale features and introducing a higher-resolution input layer to enhance small target recognition. Empirical results obtained from a customized wooden material crack detection dataset demonstrate the efficacy of the proposed ICDW-YOLO algorithm in effectively detecting targets. Without significant augmentation in model complexity, the mAP50-95 metric attains 79.018%, marking a 1.869% improvement over YOLOv8. Further validation of our algorithm's effectiveness is conducted through experiments on fire and smoke detection datasets, aerial remote sensing image datasets, and the coco128 dataset. The results showcase that ICDW-YOLO achieves a mAP50 of 69.226% and a mAP50-95 of 44.210%, indicating robust generalization and competitiveness vis-à-vis state-of-the-art detectors.

Differences in Clinical Outcomes between One-Stage and Staged Flexible Ureteroscopy for the Treatment of Upper Urinary Tract Stones.

OBJECTIVE: Upper urinary tract stones (UUTSs) are among the most common types of urinary stones, and their incidence rate has been increasing annually in recent years, seriously affecting the daily lives of patients. This study aimed to compare the treatment efficacy of one-stage and staged flexible ureteroscopic lithotripsy (FURL) for UUTSs. METHODS: A total of 142 patients with UUTSs admitted to our hospital between December 2019 and March 2023 were selected for retrospective analysis, including 76 patients who received staged FURL (control group) and 66 patients who received one-stage FURL (observation group). The duration of surgery, length of stay, stone clearance rate, incidence of postoperative complications (from postsurgery to discharge), and total hospitalization cost were analyzed in both groups. The visual analog scale (VAS) score and activities of daily living (ADL) score were assessed before surgery (T0), 3 days after surgery (T1), and 7 days after surgery (T2). Patients were followed up for 1 month after surgery, and their quality of life was assessed using the MOS Item Short Form Health Survey (SF-36). RESULTS: There was no difference in the stone clearance rate or incidence of postoperative complications between the two groups (p > 0.05). The operation time, hospitalization time and hospitalization cost in the observation group were 75.58 ± 15.91 min, 4.20 ± 1.24 days and 14312.62 ± 1078.89 yuan, respectively, which were lower than those in the control group (p < 0.05). In addition, the VAS score at T3 was decreased to 1.49 ± 0.70, while the ADL and SF-36 scores were higher in the observation group (p < 0.05). CONCLUSIONS: One-stage FURL shortens the duration of surgery and length of stay, reduces hospitalization costs, and improves the quality of life of patients with UUTSs.

Lower Risks of New-Onset Hepatocellular Carcinoma in Patients With Type 2 Diabetes Mellitus Treated With SGLT2 Inhibitors Versus DPP4 Inhibitors.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for development of hepatocellular carcinoma (HCC). The association between risk of developing HCC and treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP4i) is currently unknown. This study aimed to compare the risk of new-onset HCC in patients treated with SGLT2i versus DPP4i. METHODS: This was a retrospective cohort study of patients with T2DM in Hong Kong receiving either SGLT2i or DPP4i between January 1, 2015, and December 31, 2020. Patients with concurrent DPP4i and SGLT2i use were excluded. Propensity score matching (1:1 ratio) was performed by using the nearest neighbor search. Multivariable Cox regression was applied to identify significant predictors. RESULTS: A total of 62,699 patients were included (SGLT2i, n=22,154; DPP4i, n=40,545). After matching (n=44,308), 166 patients (0.37%) developed HCC: 36 in the SGLT2i group and 130 in the DPP4i group over 240,269 person-years. Overall, SGLT2i use was associated with lower risks of HCC (hazard ratio [HR], 0.42; 95% CI, 0.28-0.79) compared with DPP4i after adjustments. The association between SGLT2i and HCC development remained significant in patients with cirrhosis or advanced fibrosis (HR, 0.12; 95% CI, 0.04-0.41), hepatitis B virus (HBV) infection (HR, 0.32; 95% CI, 0.17-0.59), or hepatitis C virus (HCV) infection (HR, 0.41; 95% CI, 0.22-0.80). The results were consistent in different risk models, propensity score approaches, and sensitivity analyses. CONCLUSIONS: SGLT2i use was associated with a lower risk of HCC compared with DPP4i use after adjustments, and in the context of cirrhosis, advanced fibrosis, HBV infection, and HCV infection.

Optimization of immunosuppression strategies for the establishment of chronic hepatitis E virus infection in rabbits.

Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of chronic hepatitis E virus (HEV) infection is linked to the type of immunosuppressant used. Animal models are crucial for the study of pathogenesis of chronic hepatitis E. We previously established a stable chronic HEV infection rabbit model using cyclosporine A (CsA), a calcineurin inhibitor (CNI)-based immunosuppressant. However, the immunosuppression strategy and timing may be optimized, and how different types of immunosuppressants affect the establishment of chronic HEV infection in this model is still unknown. Here, we showed that chronic HEV infection can be established in 100% of rabbits when CsA treatment was started at HEV challenge or even 4 weeks after. Tacrolimus or prednisolone treatment alone also contributed to chronic HEV infection, resulting in 100% and 77.8% chronicity rates, respectively, while mycophenolate mofetil (MMF) only led to a 28.6% chronicity rate. Chronic HEV infection was accompanied with a persistent activation of innate immune response evidenced by transcriptome analysis. The suppressed adaptive immune response evidenced by low expression of genes related to cytotoxicity (like perforin and FasL) and low anti-HEV seroconversion rates may play important roles in causing chronic HEV infection. By analyzing HEV antigen concentrations with different infection outcomes, we also found that HEV antigen levels could indicate chronic HEV infection development. This study optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits and highlighted the potential association between the development of chronic HEV infection and immunosuppressants.IMPORTANCEOrgan transplant recipients are at high risk of chronic hepatitis E and generally receive a CNI-based immunosuppression regimen containing CNI (tacrolimus or CsA), MMF, and/or corticosteroids. Previously, we established stable chronic HEV infection in a rabbit model by using CsA before HEV challenge. In this study, we further optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits. Chronic HEV infection can also be established when CsA treatment was started at the same time or even 4 weeks after HEV challenge, clearly indicating the risk of progression to chronic infection under these circumstances and the necessity of HEV screening for both the recipient and the donor preoperatively. CsA, tacrolimus, or prednisolone instead of MMF significantly contributed to chronic HEV infection. HEV antigen in acute infection phase indicates the development of chronic infection. Our results have important implications for understanding the potential association between chronic HEV infection and immunosuppressants.

Association between physical frailty and cortical structure in middle-aged and elderly people: a Mendelian randomization study.

Introduction: Physical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures. Methods: The Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran's Q test, and weighted median were employed. Results: At the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable. Discussion: The results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.

Topological phases, local magnetic moments, and spin polarization triggered by C558-line defects in armchair graphene nanoribbons.

The topological and magnetic properties induced by topological defects in graphene have attracted attention. Here, we study a novel topological defect structure for graphene nanoribbons interspersed with C558-line defects along the armchair boundary, which possesses topological properties and is tritopic. Using strain engineering to regulate the magnitude of hopping at defects, the position of the energy level can be easily changed to achieve a topological phase transition. We also discuss the local magnetic moment and the ferromagnetic ground state in the context of line defects. This leads to spin polarization of the whole system. Finally, when C558 graphene nanoribbons are controlled by a nonlocal exchange magnetic field, spin-polarized quantum conductivity occurs near the Fermi level. Consequently, spin filtering can be achieved by varying the incident energy of the electrons. Our results provide new insights into realizing topological and spin electronics in low-dimensional quantum devices.

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation.

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.

A genomic compendium of cultivated human gut fungi characterizes the gut mycobiome and its relevance to common diseases.

The gut fungal community represents an essential element of human health, yet its functional and metabolic potential remains insufficiently elucidated, largely due to the limited availability of reference genomes. To address this gap, we presented the cultivated gut fungi (CGF) catalog, encompassing 760 fungal genomes derived from the feces of healthy individuals. This catalog comprises 206 species spanning 48 families, including 69 species previously unidentified. We explored the functional and metabolic attributes of the CGF species and utilized this catalog to construct a phylogenetic representation of the gut mycobiome by analyzing over 11,000 fecal metagenomes from Chinese and non-Chinese populations. Moreover, we identified significant common disease-related variations in gut mycobiome composition and corroborated the associations between fungal signatures and inflammatory bowel disease (IBD) through animal experimentation. These resources and findings substantially enrich our understanding of the biological diversity and disease relevance of the human gut mycobiome.

In Situ Ions Induced Formation of KxF-Rich SEI Layers toward Ultrastable Life of Potassium-Ion Batteries.

Engineering F-rich solid electrolyte interphase (SEI) layers is regarded as an effective strategy to enable the long-term cycling stability of potassium-ion batteries (KIBs). However, in the conventional KPF6 carbonate electrolytes, it is challenging to form F-containing SEI layers due to the inability of KPF6 to decompose into KxF. Herein, AlCl3 is employed as a novel additive to change the chemical environment of the KPF6 carbonate electrolyte. First, due to the large charge-to-radius ratio of Al3+, the Al-containing groups in the electrolyte can easily capture F from PF6 - and accelerate the formation of KxF in SEI layer. In addition, AlCl3 also reacts with trace H2O or solvents in the electrolytes to form Al2O3, which can further act as a HF scavenger. Upon incorporating AlCl3 into conventional KPF6 carbonate electrolyte, the hard carbon (HC) anode exhibits an ultra-long lifespan of 10000 cycles with a high coulombic efficiency of ≈100%. When coupled with perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA), the full cell exhibits a high capacity retention of 81% after 360 cycles-significantly outperforming cells using conventional electrolytes. This research paves new avenues for advancing electrolyte engineering towards developing durable batteries tailored for large-scale energy storage applications.

Does income matter for the policy effect of public long-term care insurance on informal care use in China? A quasi-experimental study.

OBJECTIVE: Since 2016, the Chinese government has been piloting a public long-term care insurance (LTCI) scheme. This study examined whether the LTCI scheme reduced the use of informal care and how this has varied across income groups. METHOD: We used data from the 2011, 2014, and 2018 waves of Chinese Longitudinal Healthy Longevity Survey, focusing on community-dwelling older adults aged 65 years and older. We used staggered difference-in-differences analyses with propensity score matching to examine the effects of the policy. RESULTS: The LTCI scheme reduced the probability and intensity of informal care use by 5.7% (p < .05) and 17.4% (p < .05), respectively. The policy impact was limited to older people in the middle-income group, reducing the probability and intensity of informal care use by 15.6% (p < .001) and 43.1% (p < .05), respectively. We did not find a statistically significant policy effect for older adults with high or low incomes. CONCLUSIONS: The LTCI scheme had different effects on reducing the informal care burden for family caregivers by income level. We suggest that the scheme should entitle people with low incomes to a preferential co-payment rate, thereby enhancing their access to formal care.

Identifying optimal surgical approach among T1N2-3M0 non-small cell lung cancer patients: a population-based analysis.

Background: Whether stage T1N2-3M0 non-small cell lung cancer (NSCLC) patients could benefit from surgery and the optimal surgical procedure have remained controversial and unclear. This study aimed to investigate whether stage T1N2-3M0 NSCLC can benefit from different surgery types and develop a tool for survival prediction. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with stage T1N2-3M0 NSCLC between 2000 and 2015. A 1:1 propensity score-matched (PSM) analysis was used to balance the distribution of clinical characteristics. Survival analyses were performed by using the Kaplan-Meier (KM) curves and Cox proportional hazards regression. All patients were randomly split at a ratio of 7:3 into training and validation cohorts. The nomogram was constructed by integrating all independent predictors for overall survival (OS) and cancer-specific survival (CSS). The model's performance was evaluated by discrimination, calibration ability, and risk stratification ability. Results: A total of 4,671 patients were enrolled. After 1:1 PSM, the distribution proportions of clinical characteristics in 1,146 patients were balanced (all P>0.05). The non-surgical approach was associated with worse survival compared with sublobectomy and lobectomy in the unmatched and matched cohorts. The multivariate Cox analysis showed that sublobectomy and lobectomy were both related to better OS and CSS rates compared with no surgery (P<0.001). Moreover, the results of subgroup analyses based on age, N stage, and radiotherapy or chemotherapy strategy were consistent. A total of 801 patients were included in the training cohort and 345 cases constituted the validation cohort. The nomogram constructed for the 1-, 3-, and 5-year OS and CSS prediction showed good discrimination, performance, and calibration both in the training and validation sets. Significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed (all P<0.001). Conclusions: Stage T1N2-3M0 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provides better survival benefits. We developed and validated nomograms, which could offer clinicians instructions for strategy making.

Clinical Observation on the Therapeutic Effect of Port-Wine Stains with Intravenous Injection of Hematoporphyrin Monomethyl Ether (HMME).

Background: Hematoporphyrin monomethyl ether (HMME) is a promising photosensitizer for photodynamic therapy (PDT) and has found wide application in the treatment of port-wine stains (PWS). Objective: This study aims to observe and analyze the clinical efficacy and safety of HMME-PDT in the treatment of PWS patients. It also aims to evaluate the usefulness of color Doppler flow imaging (CDFI), an ultrasound technique for detecting blood flow in skin lesions, in assessing clinical efficacy. Methods: Thirty-three patients with PWS underwent HMME-PDT at our dermatology outpatient clinic between January 2019 and March 2020. Data on patient demographics, lesion location, lesion type (pink, purple, nodular thickening), treatment frequency, and pre- and post-treatment images were collected and retrospectively analyzed. CDFI was performed on three patients. Results: All patients received intravenous HMME and underwent irradiation with 532 nm green LED light. Of these, 5 patients received 1 session of HMME-PDT, 14 received 2 sessions, 9 received 3 sessions and the remaining 5 patients received more than 3 sessions. Of the 33 patients, 9 were cured (27.27%), 10 showed improvement (30.30%), 11 experienced a reduction in symptoms (33.33%), and 3 showed no significant improvement (9.09%). Most patients reported local pain and oedema, and no systemic adverse effects were observed. Clinical efficacy correlated with lesion type and total number of treatment sessions. CDFI appears to be an excellent technique for assessing clinical efficacy. Conclusion: HMME-PDT is a safe and effective method for the treatment of PWS. CDFI examination appears to be a promising assessment tool. However, further validation with larger sample sizes is warranted.

Mechanism of lncRNA SNHG16 on kidney clear cell carcinoma cells by targeting miR-506-3p/ETS1/RAS/ERK molecular axis.

Objective: This study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future. Methods: Thirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior. Results: SNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P < 0.05). After SNHG16 silence, KIRC cells showed decreased proliferation, invasion and migration capabilities and increased apoptosis rate; correspondingly, increase in SNHG16 expression achieved opposite results (P < 0.05). Finally, in the rescue experiment, the effects of elevated SNHG16 on KIRC cells were reversed by simultaneous increase in miR-506-3p, and the effects of miR-506-3p were reversed by ETS1. Activation of the RAS/ERK pathway had the same effect as increase in ETS1, which further worsened the malignancy of KIRC. After miR-506-3p increase and ETS1 silence, the RAS/ERK signaling pathway was inhibited (P < 0.05). At last, the rescue experiment (co-transfection) confirmed that the effect of SNHG16 on KIRC cells is achieved via the miR-506-3p/ETS1/RAS/ERK molecular axis. Conclusion: SNHG16 regulates the biological behavior of KIRC cells by targeting the miR-506-3p/ETS1/RAS/ERK molecular axis.

Both arthroscopic one-step Broström-Gould and Lasso-loop stitch techniques achieved favourable clinical outcomes for chronic lateral ankle instability.

PURPOSE: Both the arthroscopic Broström-Gould and Lasso-loop stitch techniques are commonly used to treat chronic lateral ankle instability (CLAI). The purpose of this study is to introduce an arthroscopic one-step outside-in Broström-Gould (AOBG) technique and compare the mid-term outcomes of the AOBG technique and Lasso-loop stitch technique. METHODS: All CLAI patients who underwent arthroscopic lateral ankle stabilization surgery in our department from 2018 to 2019 were retrospectively enrolled. The patients were divided into two groups according to the surgical methods employed: the AOBG technique (Group A) and the Lasso-loop technique (Group B). The visual analogue scale pain score, American Orthopaedic Foot and Ankle Society ankle hindfoot score, Tegner activity score and Karlsson-Peterson score were evaluated preoperatively and during the follow-up from June to December 2022. The surgical duration, return to sports, sprain recurrence and surgical complications were also recorded and compared. RESULTS: A total of 74 patients (Group A, n = 42; Group B, n = 32) were included in this study with a mean follow-up of 39 months. No statistically significant differences were observed in demographic parameters or follow-up time between the two groups. Postoperative clinical scores indicated a significant improvement (all with p < 0.001) with no significant difference between the two groups (not significant [n.s.]). There was no significant difference in the surgical duration (46.1 vs. 49.7 min, n.s.), return to sports (92.9% vs. 93.8%, n.s.), or sprain recurrence (4.8% vs. 6.3%, n.s.). Only two cases in Group A reported knot irritation (4.8% vs. 0, n.s.), and one case in Group A experienced local skin numbness (0 vs. 3.1%, n.s.), with no significant difference. CONCLUSION: Both the AOBG and Lasso-loop stitch techniques yielded comparable favourable mid-term outcomes and return to sports with a low rate of surgical complications. Both procedures could be feasible strategies for CLAI patients. LEVEL OF EVIDENCE: Level III.