Precise Acetabular Prosthesis Positioning Using a Novel Robot-Assisted Total Hip Arthroplasty System: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: Total hip arthroplasty (THA) is currently one of the most effective treatment methods for end-stage hip joint disease, and its long-term effectiveness largely depends on the accurate placement of the acetabular prosthesis. In conventional surgery, the placement of the acetabular prosthesis mainly relies on the surgeon's clinical experience and surgical techniques. To further improve the accuracy of prosthesis placement, a new robotic system for THA is designed. The purpose of this study is to verify the effectiveness and safety of THA assisted by this robotic system. METHOD: A multicenter, prospective, randomized controlled, superiority study design was adopted with statistical methods of t test and Chi-squared test. Participants undergoing primary THA have been enrolled in three centers of joint surgery in China since July 17, 2023. Robotic THA was operated in the experimental group, and conventional instruments were used in the control group. The primary outcome is the proportion of anteversion and inclination angles in the safe zone. The secondary outcomes include operation time, WOMAC score, Harris score, SF-36 health questionnaire, dislocation rate of hip joint, and rates of adverse events and serious adverse events. RESULTS: A total of 138 patients were included in this study. The proportion of both anteversion and inclination angles in the safe zone was 92.2% in the experimental group and 50.8% in the control group, with significant difference (p < 0.01). The average operation time in the experimental group and control group was 116.4 and 80.5 min respectively, with significant difference (p < 0.01). There was no significant difference in WOMAC score, Harris score, and SF-36 between the two groups (6 ± 2) weeks after operation (p > 0.05). The dislocation rate of hip joint in the experimental group and control group were 3.0% and 1.5%, respectively, without significant difference (p > 0.05). The rate of adverse events and severe adverse events in the experimental group and control group also showed no significant difference (p > 0.05). No adverse events or serious adverse events were judged to be "definitely related" to the experimental instruments. CONCLUSION: Robotic THA could prolong the operation time within an acceptable range, but more precise acetabular prosthesis positioning could be obtained when compared with conventional surgery. Besides, no significant difference was found in function scores, dislocation rate or other adverse events, which indicates that this new robot system shows both good effectiveness and safety in THA. TRIAL REGISTRATION: Clinical Trials: NCT05947734.

Effects of Wab-WPPEP on post-intensive care syndrome-family in family caregivers of heart valve replacement patients: A randomized controlled trial.

OBJECTIVES: To evaluate the effects of a WeChat applet-based whole process psychological empowerment program (Wab-WPPEP) on post-intensive care syndrome-family in family caregivers of heart valve replacement patients. DESIGN: Two-arm, parallel, randomized controlled clinical trial. SETTINGS: A tertiary general hospital in Fuzhou, China. METHODS: Participants were randomly assigned to two groups. The intervention group received Wab-WPPEP, while the control group received routine care. The intervention was implemented from ICU admission to one month post-discharge. The primary outcome was anxiety, while secondary outcomes included depression, post-traumatic stress disorder (PTSD), and quality of life. Outcomes were assessed at baseline (T0), before ICU transfer (T1), pre-discharge (T2), and one month post-discharge (T3) using standardized questionnaires. Generalized estimating equations were used to analyze the repeated-measures data. RESULTS: The intervention group exhibited greater improvements in anxiety (T1: ß = -1.92, 95 % CI: -2.35 to -1.49, P < 0.001; T2: ß = -1.66, 95 % CI: -2.03 to -1.29, P < 0.001; T3: ß = -3.98, 95 % CI: -4.34 to -3.62, P < 0.001), depression (T1: ß = -1.32, 95 % CI: -1.79 to -0.85, P < 0.001; T2: ß = -1.70, 95 % CI: -2.08 to -1.32, P < 0.001), and quality of life (T2: ß = 31.16, 95 % CI: 21.35 to 40.98, P < 0.001) compared to the routine-care group. PTSD scores were also significantly lower in the intervention group (t = -6.454, P < 0.001). CONCLUSIONS: Wab-WPPEP significantly reduced anxiety and depression, improved quality of life, and alleviated PTSD symptoms in family caregivers of heart valve replacement patients. IMPLICATIONS FOR CLINICAL PRACTICE: Comprehensive psychological interventions should be implemented throughout the ICU stay and recovery period to improve family caregiver well-being.

Overlapping large facial nevus spilus and nevus of Ota: A case report diagnosed with dermoscopy and reflectance confocal microscopy.

We report a rare case of large facial hyperpigmentation in a 25-year-old female. Starting one month after birth, the patient developed a blue-brown patch on the right side of her face, interspersed with black macules and papules. As she aged, the lesion progressively enlarged and darkened, eventually covering the entire right side of her face. Dermoscopic and reflectance confocal microscopy examinations indicated nevus spilus in some areas and nevus of Ota in others, leading to a definitive diagnosis of overlapping nevus spilus and nevus of Ota. With no signs of malignant transformation on clinical or imaging examination, successful treatment was achieved using Q-switched alexandrite laser without any adverse effects. Our case underscores the critical value of dermoscopy and reflectance confocal microscopy in diagnosing rare facial pigmentary conditions, as we compare the imaging characteristics of nevus spilus, nevus of Ota, and similar conditions, alongside their clinical and histopathological correlations. Furthermore, our findings highlight the significant role of imaging examinations in monitoring malignancy and guiding treatment decisions.

RGS22 maintains the physiological function of ependymal cells to prevent hydrocephalus.

Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid (CSF) flow by beating their motile cilia coordinately. The ependymal denudation or ciliary dysfunction causes hydrocephalus. Here, we report that the deficiency of regulator of G-protein signaling 22 (RGS22) results in severe congenital hydrocephalus in both mice and rats. Interestingly, RGS22 is specifically expressed in ependymal cells within the brain. Using conditional knock-out mice, we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce hydrocephalus. Mechanistically, we show that Rgs22 deficiency leads to the ependymal denudation and impaired ciliogenesis. This phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor (LPAR) signaling under Rgs22-/- condition, as the LPAR blockade effectively alleviates hydrocephalus in Rgs22-/- rats. Therefore, our findings unveil a previously unrecognized role of RGS22 in the central nervous system, and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus.

Factors affecting the syncopal episodes in pediatric vasovagal syncope.

OBJECTIVE: To investigate factors that influence the syncopal episodes in pediatric vasovagal syncope (VVS). METHODS: A retrospective analysis was performed on the clinical data of 2908 children who were diagnosed with VVS for the first time between January 2001 and February 2023. The study examined the linear relationships among age, sex, height, weight, heart rate (HR), blood pressure, hemodynamic type, and head-up tilt test (HUTT) mode in relation to the onset of syncope. RESULTS: (1) Comparative analysis of intergroup differences revealed statistically significant variations in sex, age, height, weight, HR, systolic blood pressure, hemodynamic classification, and HUTT mode among syncopal episodes groups (P < 0.05); (2) Univariate analysis identified age, female, height, weight, VVS-cardioinhibited type (VVS-CI), VVS-mixed type (VVS-M) as potential risk factors for syncope episodes. Conversely, HR and sublingual nitroglycerin HUTT (SNHUT) emerged as potential protective factors against syncope episodes. (3) Multivariate analysis indicated that the frequency of syncope episodes increased by 0.27/0.02 for each unit increase in age/weight. When females compared to males and VVS-CI and VVS-M compared to VVS-vasoinhibited type (VVS-VI), the frequency of syncope episodes increased by 1.36, 0.53, and 0.66 respectively. Furthermore, SNHUT was associated with a reduction in the number of syncope episodes by 0.34 relative to basic HUTT. CONCLUSION: Female, age, weight, VVS-CI, and VVS-M were identified as independent risk factors for syncopal episodes, while SNHUT was recognized as an independent protective factor against syncopal episodes.

Transjugular intrahepatic portosystemic shunt for esophagogastric variceal bleeding in patients with hepatocellular carcinoma and portal vein tumor thrombus.

BACKGROUND: Whether hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and acute esophagogastric variceal bleeding (EGVB) can improve the success rate of endoscopic hemostasis and overall survival (OS) from transjugular intrahepatic portosystemic shunt (TIPS) remains controversial. AIM: To compare the clinical outcomes between TIPS and standard treatment for such HCC patients. METHODS: This monocenter, retrospective cohort study included patients diagnosed as HCC with PVTT and upper gastrointestinal bleeding. Patients were grouped by the treatment (TIPS or standard conservative treatment). The success rate of endoscopic hemostasis, OS, rebleeding rates, and main causes of death were analyzed. RESULTS: Between July 2015 and September 2021, a total of 77 patients (29 with TIPS and 48 with standard treatment) were included. The success rate of endoscopic hemostasis was 96.6% in the TIPS group and 95.8% in the standard treatment group. All the 29 patients in TIPS group successful underwent TIPS procedure and had a better OS compared with standard treatment within the first 160 days after treatment (68 days vs 43 days, P = 0.022), but shorter OS after 160 days (298 days vs 472 days, P = 0.022). Cheng's Classification of PVTT, total bilirubin and Child-Pugh class were independently negative associated with OS (all P < 0.05). The main causes of death were liver failure or hepatic encephalopathy (75.9%) in the TIPS group and rebleeding (68.8%) in the standard treatment. CONCLUSION: TIPS could reduce the risk of early death due to rebleeding and prolong short-term survival in HCC patients with PVTT and acute EGVB, which deserves further investigation.

Pain and immune function in patients undergoing gastric cancer surgery following stellate ganglion block with total intravenous anesthesia.

BACKGROUND: Stellate ganglion block is a commonly used sympathetic nerve block technique that restores the balance of the sympathetic and vagal nervous systems of the body and inhibits sympathetic nerve activity. AIM: To analyze the effect of a stellate ganglion block combined with total diploma intravenous anesthesia on postoperative pain and immune function in patients undergoing laparoscopic radical gastric cancer (GC) surgery to provide a reference basis for the formulation of anesthesia protocols for radical GC surgery. METHODS: This study included 112 patients who underwent laparoscopic radical surgery for GC between January 2022 and March 2024. There was no restriction on sex. The patient grouping method used was a digital random table method, and the number of cases in each group was 56. The control group was administered total intravenous anesthesia, and the observation group compounded the stellate ganglion block according to the total intravenous anesthesia protocol. Postoperative hemodynamics, pain levels, and immune indices were compared between the groups. RESULTS: The heart rate and mean arterial pressure in the observation group after intubation were lower than those in the control group (P < 0.05). Pain levels were compared between the two groups at 2 hours, 12 hours, 24 hours, and 48 hours after surgery (P > 0.05). The number of CD3+, CD4+, and CD4+/CD8+ cells at the end of surgery was higher in the observation group than in the control group, and the number of CD8+ cells was lower in the observation group than in the control group (P < 0.05). There were no significant differences between the two groups in terms of propofol dosage, awakening time, extubation time, or postoperative adverse reactions (P > 0.05). CONCLUSION: The application of a stellate ganglion block combined with total intravenous anesthesia had no significant effect on postoperative pain levels in patients undergoing laparoscopic radical GC surgery. However, it can safely reduce the effect of surgery on the immune function of patients and is worth applying in clinical practice.

Protein Nanospheres and Nanofibers Prepared by Ice-Templating for the Controlled Release of Hydrophobic Drugs.

Protein scaffolds play a vital role in drug delivery systems. However, few research studies have been focused on loading hydrophobic drugs on protein scaffolds in biomedical fields. Here, we report on the development of protein microspheres and nanofibers by a simple ice-templating approach and their use as scaffolds for the controlled release of hydrophobic drugs, with bovine serum albumin (BSA) as the model protein and curcumin as the model hydrophobic drug. The BSA scaffolds display the unique nanofibrous and microspherical structures. This is a surprising discovery because there has been no report on the formation of microspheres via simple ice-templating of solutions or suspensions. To further understand the formation of microspheres by this approach, lysozyme, papain, and their composites with BSA are also studied. It is speculated that nanoparticles are first formed in aqueous BSA solution, attributed to the overlapping of hydration layers and autoassembly of inner hydrophobic cores of BSA globular molecules. Nanoprecipitation and soaking evaporation approaches are then used to load curcumin into the BSA scaffolds, followed by cross-linking with glutaraldehyde vapor to improve stability in an aqueous medium. The controlled release of curcumin is demonstrated, paving the way for various hydrophobic drugs loaded into this biodegradable and nonimmunogenic protein scaffold for potential treatments of diverse diseases.

Decoding Long-Chain Fatty Acid Ethyl Esters during the Distillation of Strong Aroma-Type Baijiu and Exploring the Adsorption Mechanism with Magnetic Nanoparticles.

Simultaneous detection of the dynamic distribution of long-chain fatty acid ethyl esters (LCFAEEs) during Baijiu distillation is crucial for optimizing its flavor and health attributes. In this study, we synthesized a simple, cost-effective Fe3O4@NH2 adsorbent to simultaneously extract eight LCFAEEs from Baijiu. Through density functional theory and adsorption experiments, we elucidated 1,6-hexanediamine as a surface modifier, with the -NH2 groups providing adsorption sites for the LCFAEEs via hydrogen-bonding interactions and van der Waals forces. Additionally, we established the magnetic solid-phase extraction-GC-MS extraction technique combined with stable isotope dilution analysis to analyze LCFAEEs. This method revealed the dynamic distribution patterns of LCFAEEs during strong aroma-type Baijiu (SAB) distillation. We observed that the concentrations of the eight LCFAEEs gradually decreased with prolonged distillation and were significantly correlated with ethanol concentration. To ensure optimal flavor and clarity in SAB, it is recommended to select the heart-stage base Baijiu with an alcohol content of 58%-63%.

Delayed simvastatin treatment improves neurological recovery after cryogenic traumatic brain injury through downregulation of ELOVL1 by inhibiting mTOR signaling.

Statins are well-tolerated and widely available lipid-lowering medications with neuroprotective effects against traumatic brain injury (TBI). However, whether delayed statin therapy starting in the subacute phase promotes recovery after TBI is unknown. Elongation of the very long-chain fatty acid protein 1 (ELOVL1) is involved in astrocyte-mediated neurotoxicity, but its role in TBI and the relationship between ELOVL1 and statins are unclear. We hypothesized that delayed simvastatin treatment promotes neurological functional recovery after TBI by regulating the ELOVL1-mediated production of very long-chain fatty acids (VLCFAs). ICR male mice received daily intragastric administration of 1, 2 or 5 mg/kg simvastatin on Days 1-14, 3-14, 5-14, or 7-14 after cryogenic TBI (cTBI). The results showed that simvastatin promoted motor functional recovery in a dose-dependent manner, with a wide therapeutic window of at least 7 days postinjury. Meanwhile, simvastatin inhibited astrocyte and microglial overactivation and glial scar formation, and increased total dendritic length, neuronal complexity and spine density on day 14 after cTBI. The up-regulation of ELOVL1 expression and saturated VLCFAs concentrations in the cortex surrounding the lesion caused by cTBI was inhibited by simvastatin, which was related to the inhibition of the mTOR signaling. Overexpression of ELOVL1 in astrocytes surrounding the lesion using HBAAV2/9-GFAP-m-ELOVL1-3xFlag-EGFP partially attenuated the benefits of simvastatin. These results showed that delayed simvastatin treatment promoted functional recovery and brain tissue repair after TBI through the downregulation of ELOVL1 expression by inhibiting mTOR signaling. Astrocytic ELOVL1 may be a potential target for rehabilitation after TBI.

Nomogram predicting the prognosis of primary liver cancer after radiofrequency ablation combined with transcatheter arterial chemoembolization.

BACKGROUND: The incidence and mortality rates of primary hepatocellular carcinoma (HCC) are high, and the conventional treatment is radiofrequency ablation (RFA) with transcatheter arterial chemoembolization (TACE); however, the 3-year survival rate is still low. Further, there are no visual methods to effectively predict their prognosis. AIM: To explore the factors influencing the prognosis of HCC after RFA and TACE and develop a nomogram prediction model. METHODS: Clinical and follow-up information of 150 patients with HCC treated using RFA and TACE in the Hangzhou Linping Hospital of Traditional Chinese Medicine from May 2020 to December 2022 was retrospectively collected and recorded. We examined their prognostic factors using multivariate logistic regression and created a nomogram prognosis prediction model using the R software (version 4.1.2). Internal verification was performed using the bootstrapping technique. The prognostic efficacy of the nomogram prediction model was evaluated using the concordance index (CI), calibration curve, and receiver operating characteristic curve. RESULTS: Of the 150 patients treated with RFA and TACE, 92 (61.33%) developed recurrence and metastasis. Logistic regression analysis identified six variables, and a predictive model was created. The internal validation results of the model showed a CI of 0.882. The correction curve trend of the prognosis prediction model was always near the diagonal, and the mean absolute error before and after internal validation was 0.021. The area under the curve of the prediction model after internal verification was 0.882 [95% confidence interval (95%CI): 0.820-0.945], with a specificity of 0.828 and sensitivity of 0.656. According to the Hosmer-Lemeshow test, χ 2 = 3.552 and P = 0.895. The predictive model demonstrated a satisfactory calibration, and the decision curve analysis demonstrated its clinical applicability. CONCLUSION: The prognosis of patients with HCC after RFA and TACE is affected by several factors. The developed prediction model based on the influencing parameters shows a good prognosis predictive efficacy.

Emerging trends and research hotspots in the relationship between mast cells and atopic dermatitis based on the literature from 2001 to 2024: A bibliometric and visualized analysis.

BACKGROUND: Atopic dermatitis (AD) is a prevalent chronic inflammatory and highly pruritic skin condition characterized by the infiltration of immune cells, notably eosinophils and mast cells. Mast cells (MCs) critically participate in the complex pathogenesis of AD through multiple pathways and have recently garnered growing attention in research. Despite the abundance of related studies published over the years, a comprehensive bibliometric analysis on this topic remains lacking. OBJECTIVE: Our objective was to perform an up-to-date bibliometric analysis of the literature focusing on the relationship between MCs and AD. This analysis would provide valuable insights through a thorough bibliometric review, enabling a clearer understanding of the current research landscape, pinpointing key studies, and detecting emerging trends within this field. METHODS: We searched the Web of Science Core Collection (WoSCC) database on 15 July 2024. The data retrieval strategy was structured as follows: #1: TS = ("mast cells") OR TS = ("mast cell") OR TS = ("mastocyte"); #2: TS = ("atopic dermatitis") OR TS = ("atopic eczema") Final data: (#1 AND #2). A total of 2272 items published between 2001 and 2024 were included. Several scientometric visualization tools, including VOSviewer, R-bibliometrix, CiteSpace and an online analytical platform, were utilized to conduct text mining and to visualize the bibliometric data, facilitating a comprehensive analysis of research trends and patterns. RESULTS: Out of the initial 2272 articles retrieved, 2168 were selected for analysis after applying inclusion and exclusion criteria based on publication type. The findings indicate a steady and substantial exponential growth in the annual number of publications focused on the relationship between over the years. The South Korea (547/2168), USA (465/2168) and Japan (436/2168) were the major contributors within this field, collectively constituting more than half of the total publications. To clarify the underlying mechanisms and role of MCs in the pathogenesis of AD and to make MCs prime targets for therapeutic intervention have garnered the most attention in this field. According to references analysis, the research emphasis has shifted to developing MC-related therapeutics and intervention and regulating the immune system of AD patients through modulating the activity of various immune cells. On the basis of keywords analysis, we outlined the following research frontiers and hotpots in the future: the role of oxidative stress in the pathogenesis; imbalance in the different types of T helper (Th) cells during immune response; skin barrier and barrier dysfunction; improving quality of life; sensory neurons; biological agents and small-molecule drugs. Furthermore, IL-13, IL-4, NFKB1, BCGF-1 and CD4 ranked as the top five genes that have received the most investigative attention in the intersection of MCs and AD. CONCLUSION: In a word, this analysis would greatly benefit from a thorough bibliometric review to gain a deeper understanding of the current research landscape, identify pivotal studies and pinpoint emerging trends in the field of MCs and AD. Meanwhile, our findings offered researchers a holistic perspective of ongoing developments, serving as a valuable resource for guiding future research and informing decision-making for both researchers and policymakers in this area.

The Elabela-APJ axis attenuates sepsis-induced myocardial dysfunction by reducing pyroptosis by balancing the formation and degradation of autophagosomes.

BACKGROUND: Sepsis is a life-threatening severe inflammatory reaction caused by the host's dysregulated response to infection. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to occur in 50 % of patients with septic shock. Currently, the pathophysiological mechanism of SIMD is complex, and there is no targeted treatment. Elabela is another endogenous ligand of Aplnr (APJ). The protective effect of APJ on the heart has been proven. Elabela (Ela) has been shown to have a variety of cardiovascular protective effects. However, there are no studies demonstrating the protective effect of Ela-APJ axis on SIMD. MATERIALS AND METHODS: In vivo, C57BL/J mice were injected subcutaneously with 1 mg/kg/d Ela for 2 weeks, and in vitro, AC16 cells were treated with 1 µM Ela for 24 h. A 7-0 thread was used to ligate the distal end of the cecum, followed by puncture with a 20-gauge needle. Once a small amount of fluid leaks out, release the cecum back into the abdominal cavity. We measured the survival rates of the mice, performed ultrasound on their hearts, and evaluated the effects of the treatments. The serum and cell supernatant were extracted to detect myocardial injury markers and pyroptosis-related indicators. Western blotting was used to detect autophagy and pyroptosis-related protein. Molecular docking and other experiments were also used to detect changes in related proteins. RESULTS: In vivo, Ela significantly improved the survival rate of septic mice, improved cardiac function, and reduced the production of myocardial injury markers, oxidative stress and pyroptosis. In vitro, Ela unblocked autophagy flow by affecting TFEB transcription. Autophagy reduces inflammation and oxidative stress by selectively degrading inflammatory bodies and ultimately alleviates pyroptosis. CONCLUSION: We had demonstrated for the first time that in sepsis, Ela promoted the degradation of inflammasomes, reduced oxidative stress, and inhibited the occurrence of pyroptosis by unblocking autophagy flow.

Psychometric validation of the Chinese version of the dry eye-related quality-of-life score questionnaire.

AIM: To psychometrically validate the Chinese version of the dry eye-related quality-of-life score questionnaire (DEQS-CHN) among Chinese patients with dry eye. METHODS: This study involved 231 participants, including 191 with dry eye disease (DED) comprising the dry eye disease group, and 40 healthy participants forming the control group. Participants were required to complete the DEQS-CHN, and Chinese dry eye questionnaire and undergo clinical tests including the fluorescein breakup time (FBUT), corneal fluorescein staining (CFS), and Schirmer I test. To assess the internal consistency and retest reliability, Cronbach's α and the intraclass correlation coefficient (ICC) were employed. Content validity was assessed by item-level content validity index (ICV) and an average scale-level content validity index (S-CVI/Ave). Construct validity was assessed by confirmatory factor analysis. The concurrent validity was assessed by calculating correlations between DEQS-CHN and Chinese dry eye questionnaire. Discriminative validity was evaluated through non-parametric tests, with receiver operating characteristic (ROC) curve serving as conclusive indicators of the questionnaire's distinguishing capability. RESULTS: The Cronbach's α coefficients for frequency and degree of ocular symptoms, impact on daily life, and summary score were 0.736, 0.704, 0.811, 0.818, 0.861, and 0.860, respectively, and the ICC were 0.611, 0.677, 0.715, 0.769, 0.711, and 0.779, respectively. All I-CVI scores ranged from 0.833 to 1.000, with an S-CVI/Ave of 0.956. Confirmatory factor analysis results exhibited a well-fitting model consistent with the original questionnaire [χ 2/df=2.653, incremental fit index (IFI)=0.924, comparative fit index (CFI)=0.924, Tucker-Lewis index (TLI)=0.909, and root mean square error of approximation (RMSEA)=0.065]. There was a moderate positive correlation between the DEQS-CHN and the Chinese dry eye questionnaire (r 2=0.588). The dry eye group demonstrated significantly higher scores compared to the control group, and the area under the curve (AUC) value was 0.8092. CONCLUSION: The DEQS-CHN has been demonstrated as a valid and reliable instrument for assessing the impact of dry eye disease on the quality of life among Chinese individuals with DED.

Identification of novel drug targets for osteoarthritis by integrating genetics and proteomes from blood.

BACKGROUND: Osteoarthritis (OA) is a degenerative osteoarticular disease, involving genetic predisposition. How the risk variants confer the risk of OA through their effects on proteins remains largely unknown. Therefore, we aimed to discover new and effective drug targets for OA and its subtypes. METHODS: A proteome-wide association study (PWAS) was performed based on OA and its subtypes genome-wide association studies (GWAS) summary datasets and the protein quantitative trait loci (pQTL) data. Subsequently, Mendelian randomization (MR) and colocalization analysis was conducted to estimate the associations between protein and OA risk. The replication analysis was performed in an independent dataset of human plasma pQTL data. RESULTS: The abundance of seven proteins was causally related to OA, two proteins to knee OA and six proteins to hip OA, respectively. We replicated 2 of these proteins using an independent pQTL dataset. With the further support of colocalization, and higher ECM1 level was causally associated with a higher risk of OA and hip OA. Higher PCSK1 level was causally associated with a lower risk of OA. And higher levels of ITIH1, EFEMP1, and ERLEC1 were associated with decreased risk of hip OA. CONCLUSION: Our study provides new insights into the genetic component of protein abundance in OA and a promising therapeutic target for future drug development.

Au/Ag@polyoxometalate core-shell structures: from nanoparticles to atomically precise nanoclusters.

This review summarizes the progress in the research on polyoxometalate (POM)-decorated gold (Au) and silver (Ag) core-shell structures (Au/Ag@POMs), emphasizing their substantial application potential in catalysis, medicine, and biology. It outlines the central strategies for fabricating Au/Ag@POMs with diverse morphologies and dimensions, leveraging POMs as protective ligands and reducing agents as well as for ligand exchange. Of particular note is the focus on the analysis of the nanoparticle size, shape, and intricate architecture of POM shells using cryo-electron microscopy techniques. By integrating recent findings on atomically precise POM-stabilized nanoclusters, this review delves deeper into understanding surface interface structures, intrinsic atomic architectures, and electronic interactions between POM shells and metallic cores. Collectively, advancements in this field underscore significant strides in the controllable synthesis and precise structural manipulation of Au/Ag@POM architectures, thus paving the way for engineering high-performance metal catalysts.

Persistence of Lugol-unstaining is Associated With an Increased Risk of Progression to Malignancy in the Esophagus.

BACKGROUND & AIMS: The aim of this study was to investigate the persistence of Lugol-unstained lesions (LULs) in the esophagus detected by chromoendoscopy and explore their association with progression to malignancy. METHODS: We enrolled 647 participants from a population-based screening trial who had biopsied LULs at the baseline chromoendoscopy and underwent a chromoendoscopy re-examination after a median of 4.39 years. Cases of persistent LUL were defined as those in whom a visible LUL was observed during re-examination at the documented location (±2 cm) where a LUL was detected at baseline chromoendoscopy. Logistic regression was applied to explore risk factors for the persistence of LULs. The primary outcome was clinical-stage esophageal squamous cell carcinoma identified over 6.78 years of follow-up, and the secondary outcome was re-examination-detected severe dysplasia and above lesions. The cumulative incidence was calculated to assess the progression risk associated with the persistence of LULs. RESULTS: The proportion of participants with persistent LULs was 81.92%. Dysplasia (adjusted odds ratio [OR], 6.16; 95% confidence interval [CI], 2.70-17.80), large LULs (adjusted OR, 1.90; 95% CI, 1.18-3.15), and irregularly shaped LULs (adjusted OR, 1.63; 95% CI, 1.03-2.56) at baseline were associated with an increased risk of LUL persistence. Eleven clinical-stage esophageal squamous cell carcinoma cases and 31 severe dysplasia and above lesions detected during reexamination were identified, all of which originated from patients with persistent LULs (Pclinical-stage ESCC = .136; Pre-examination-detected SDA = .015). CONCLUSION: The persistence of LULs is associated with progression to malignancy in the esophagus, even in individuals without dysplastic lesions. Based on this, a more efficient post-screening surveillance strategy could be established.

Resting-State Alpha Activity in the Frontal and Occipital Lobes and Assessment of Cognitive Impairment in Depression Patients.

Background: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals. Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated. Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05). Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction.

A new isoprenyl-phenol-type meroterpenoid from mangrove endophytic fungus Aspergillus sp. GXNU-Y65.

Asperphenol A (1), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds (2-6). All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC50 values of 26.71 and 43.50 µM, respectively.

[The Relationship Between Serum CysC, ß2-MG and the Efficacy of Demethylation Therapy in Patients with Acute Myeloid leukemia].

OBJECTIVE: To analyze the relationship between serum cystatin C (CysC), ß2-microglobulin (ß2-MG) and the efficacy of demethylation therapy in patients with acute myeloid leukemia (AML). METHODS: A prospective cohort study was conducted on 98 AML patients admitted to the Affiliated Hospital of Inner Mongolia Medical University from February 2019 to January 2022. All patients were treated with decitabine (DAC) + HAG regimen, 28 days as a course and treated for 3-4 courses. At the end of each course of treatment, the treatment effect of the patients was evaluated, and the patients who achieved complete remission (CR) transferred to consolidation therapy, while the patients who did not reach CR at the end of the course of treatment were considered as treatment failure. The examination items before treatment include routine blood parameters, serum CysC, and ß2-MG, and general clinical data of the patients were collected. According to the statistical results, logistic regression model was used to analyze the relationship between serum CysC, ß2-MG and the efficacy of demethylation therapy in AML patients. The ROC curves were drawn, and the predictive efficacy of serum CysC, ß2-MG on demethylation therapy in AML patients was evaluated by the area under the curve (AUC). RESULTS: Of the 98 AML patients enrolled in the study, 5 cases were excluded during the treatment period, and 93 cases finally completed the chemotherapy courses. Among them, 23 patients achieved CR after the initial induction chemotherapy (course 1-2), and 11 patients achieved CR after the re-induction chemotherapy (course 3-4). The success rate of demethylation therapy was 36.56 % (34/93). Compared with the patients in treatment success group, patients in treatment failure group had a higher proportion of intermediate- and adverse-risk, lower levels of platelet (PLT) and hemoglobin (Hb), and higher expression levels of serum CysC and ß2-MG, all of which were statistically significant (P < 0.05). Logistic regression analysis showed that high expression of serum CysC, ß2-MG and adverse-risk were independent risk factors for failure of demethylation treatment in AML patients (OR >1, P < 0.05). The ROC curves showed that the AUC values of serum CysC, ß2-MG alone and combined in predicting the efficacy of demethylation therapy in AML patients were 0.788, 0.785 and 0.834, respectively. CONCLUSION: The failure of demethylation therapy in AML patients is related to the high expression of serum CysC and ß2-MG, and detection of serum CysC and ß2-MG before treatment can predict the risk of demethylation therapy failure in AML patients.