Design, synthesis, and biological evaluation of novel chrysin derivatives as poly(ADP-ribose) polymerase 1 (PARP1) inhibitors for the treatment of breast cancer.

In this study, we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly (ADP-ribose) polymerase 1 (PARP1). Among these derivatives, compound 5d emerged as the most effective chrysin-based inhibitor of PARP1, with an IC50 value of 108 nmol·L-1. This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage. Furthermore, 5d induced apoptosis and caused an extended G1/S-phase in these cell lines. Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1. In vivo, in a xenograft model, 5d effectively reduced tumor growth by downregulating PARP1 expression. Overall, compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.

The risk of free flap revision and subsequent medical costs in patients with hypopharyngeal cancer.

BACKGROUND: Few studies have examined the preoperative risks and healthcare costs related to free flap revision in hypopharyngeal cancer (HPC) patients. METHODS: A 20-year retrospective case-control study was conducted using the Chang Gung Research Database, focusing on HPC patients who underwent tumor excision and free flap reconstruction from January 1, 2001, to December 31, 2019. The impacts of clinical variables on the need for re-exploration due to free flap complications were assessed using logistic regression. The direct and indirect effects of these complications on medical costs were evaluated by causal mediation analysis. RESULTS: Among 348 patients studied, 43 (12.4%) developed complications requiring re-exploration. Lower preoperative albumin levels significantly increased the risk of complications (OR 2.45, 95% CI 1.12-5.35), especially in older and previously irradiated patients. Causal mediation analysis revealed that these complications explained 11.4% of the effect on increased hospitalization costs, after controlling for confounders. CONCLUSIONS: Lower preoperative albumin levels in HPC patients are associated with a higher risk of microvascular free flap complications and elevated healthcare costs, underscoring the need for enhanced nutritional support before surgery in this population.

DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure.

DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Toripalimab plus cetuximab combined with radiotherapy in a locally advanced platinum-based chemotherapy-insensitive nasopharyngeal carcinoma patient: a case report.

Background: Locoregionally advanced nasopharyngeal carcinoma (NPC) is an epithelial malignancy that primarily occurs in East and Southeast Asia, and it is associated with relatively poor overall survival (OS). Currently, there is no reliably effective standard treatment for NPC that progresses after first-line therapy with platinum-based chemotherapy. Case report: A 55-year-old woman diagnosed with stage IVa NPC received two cycles of platinum-based chemotherapy but encountered an increase in the size of cervical lymph nodes and suffered from adverse events. The patient was then switched to toripalimab plus cetuximab combined with radical radiotherapy and had a complete clinical response within 2 months following the completion of radiotherapy without severe treatment-related adverse events. Conclusion: This case report showed that toripalimab plus cetuximab combined with radiotherapy for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma may result in a fast and durable response with a manageable safety profile.

The Effect and Mechanism of Astragalus Polysaccharides on T Cells and Macrophages in Inhibiting Prostate Cancer.

BACKGROUND: The impact and underlying mechanisms of astragalus polysaccharide (APS) on prostate cancer, particularly its role in immunomodulation, remain inadequately elucidated. METHODS: This study employed the XTT assay for assessing proliferation in prostate cancer cells and macrophages. T cell proliferation was determined using the Carboxyfluorescein diacetate succinimidyl ester labeling assay. APS's effect on T cells and macrophages was scrutinized via flow cytometry, Western blot analysis, ELISA, quantitative PCR and cytokine membrane arrays. The effect of APS on interaction between PD-L1 and PD-1 was investigated by the PD-L1/PD-1 homogeneous assay. Additionally, the impact of conditioned medium from T cells and macrophages on PC-3 cell migration was explored through migration assays. RESULTS: It was observed that APS at concentrations of 1 and 5 mg/mL enhanced the proliferation of CD8+ T cells. At a concentration of 5 mg/mL, APS activated both CD4+ and CD8+ T cells, attenuated PD-L1 expression in prostate cancer cells stimulated with interferon gamma (IFN-γ) or oxaliplatin, and moderately decreased the population of PD-1+ CD4+ and PD-1+ CD8+ T cells. Furthermore, APS at this concentration impeded the interaction between PD-L1 and PD-1, inhibited the promotion of prostate cancer migration mediated by RAW 264.7 cells, THP-1 cells, CD4+ T cells, and CD8+ T cells, and initiated apoptosis in prostate cancer cells treated with conditioned medium from APS (5 mg/mL)-treated CD8+ T cells, RAW 264.7 cells, or THP-1 cells. CONCLUSION: The findings indicate a potential role of 5 mg/mL APS in modulating the PD-1/PD-L1 pathway and influencing the immune response, encompassing T cells and macrophages. Consequently, further in vivo research is recommended to assess the efficacy of APS.

Seroprevalence of Helicobacter pylori infection among schoolchildren in southern Taiwan-A 20-year longitudinal follow-up.

BACKGROUND: Helicobacter pylori infection is primarily acquired in childhood and can lead to peptic ulcer diseases and gastric cancer. The prevalence of H. pylori infection varies widely in different countries. The aim of this study was to explore the change of pediatric H. pylori seroprevalence in the past two decades and to investigate the risk factors for pediatric H. pylori seropositivity in southern Taiwan. MATERIALS AND METHODS: This study enrolled children aged 7-12 years in Tainan City in 2018 and compared the result with our previous data in 1998, 2005, and 2010. Parents of the participants were invited to fill out questionnaires, including information of personal history, family history of peptic ulcer diseases, annual household income, and source of drinking water. Blood samples were analyzed for anti-H. pylori IgG by enzyme-linked immunosorbent assay. RESULTS: A total of 391, 629, 618, and 488 elementary school students in Tainan City were enrolled in 1998, 2005, 2010, and 2018, respectively. There was a significant decline in H. pylori seroprevalence from 9.2% in 1998, 7.8% in 2005, 6.2% in 2010 to 4.7% in 2018 (p < 0.001). Neither gender difference nor age difference was found in H. pylori seropositivity in each year of enrollment. Low household income was significantly associated with pediatric H. pylori seropositivity. CONCLUSIONS: The seroprevalence of H. pylori infection among elementary schoolchildren has remarkably declined in southern Taiwan in the past two decades. Low household income was a risk factor for pediatric H. pylori seropositivity.

The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis-apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

mTOR signaling promotes rapid m6A mRNA methylation to regulate NK-cell activation and effector functions.

Natural killer (NK) cells can be rapidly activated in response to cytokines during host defense against malignant cells or viral infection. However, it remains unclear what mechanisms precisely and rapidly regulate the expression of the numerous genes involved in activating NK cells. In this study, we discovered that NK-cell N6-methyladenosine (m6A) methylation levels were rapidly upregulated upon short-term NK-cell activation and were repressed in the tumor microenvironment. Deficiency of methyltransferase-like 3 (METTL3) or METTL14 moderately influenced NK-cell homeostasis, while double knockout of METTL3/14 significantly impacted NK-cell homeostasis, maturation, and antitumor immunity. This suggests a cooperative role of METTL3 and METTL14 in regulating NK-cell development and effector functions. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq), we demonstrated that genes involved in NK-cell effector functions, such as Prf1 and Gzmb, were directly modified by m6A methylation. Furthermore, inhibiting mTOR complex 1 (mTORC1) activation prevented m6A methylation levels from increasing when NK cells were activated, and this could be restored by S-adenosylmethionine (SAM) supplementation. Collectively, we have unraveled crucial roles for rapid m6A mRNA methylation downstream of the mTORC1-SAM signal axis in regulating NK-cell activation and effector functions.

Association between urinary phthalates and phthalate metabolites and cancer risk: A systematic review and meta-analysis.

Phthalates, widely utilized in industrial products, are classified as endocrine-disrupting chemicals (EDCs). Although certain phthalate and their metabolites have been implicated in cancer development, the reported findings have exhibited inconsistencies. Therefore, we conducted the comprehensive literature search to assess the association between phthalate and their metabolites and cancer risk by identifying original studies measuring phthalates or their metabolites and reporting their correlation with cancer until July 4, 2023. The Odds Ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted and analyzed to estimate the risk. Pooled data from eleven studies, including 3101 cancer patients and 6858 controls, were analyzed using a fixed- or random-effects model based on heterogeneity tests. When comparing extreme categories of different phthalates and their metabolites, we observed a significant association between urinary phthalates and phthalate metabolites (MEHHP, MECPP, DBP and MBzP) and cancer risk. The findings of our meta-analysis reinforce the existing evidence that urinary phthalates and phthalate metabolites is strongly associated with cancer development. Further investigations are warranted to elucidate the underlying mechanisms of this association. These results may offer novel insights into cancer development.

Microbial Analysis in Chronic Rhinosinusitis Patients with Chronic Kidney Disease and End-Stage Renal Disease.

INTRODUCTION: This study aimed to elucidate the bacterial profile of chronic rhinosinusitis (CRS) in patients with end-stage renal disease (ESRD) and chronic kidney disease (CKD) compared with nonrenal patients, guiding antibiotic selection for clinicians. METHODS: We retrospectively analyzed 13,906 inpatients from the Chang Gung Research Database who underwent sinus surgery (2004-2018). Patients were categorized into ESRD-CRS, CKD-CRS, and non-CKD-CRS based on the estimated glomerular filtration rate. Bacterial cultures from surgical samples were classified as facultative anaerobes or aerobes (e.g., Klebsiella pneumoniae [KP], Pseudomonas aeruginosa [Ps.a]), anaerobes, and fungi and ranked by prevalence. RESULTS: Data from 47 ESRD-CRS, 230 CKD-CRS, and 13,123 non-CKD-CRS patients were analyzed. In ESRD-CRS, the predominant species were KP (31.6%), Ps.a (21.1%), and Coagulase-negative Staphylococcus (CoNS, 15.8%). CKD-CRS showed Staphylococcus epidermidis (27.7%), CoNS (20.5%), and Ps.a (20.5%). Non-CKD-CRS had Staphylococcus epidermidis (29.8%), CoNS (25.0%), and Staphylococcus aureus (15.5%). For anaerobes, ESRD-CRS was dominated by Fusobacterium nucleatum (10.5%) and Peptostreptococcus micros (10.5%), whereas CKD-CRS and non-CKD-CRS showed Propionibacterium acnes as a primary strain (14.5% and 28.7%, respectively). CONCLUSION: For CRS in ESRD, antibiotics targeting KP and Fusobacterium nucleatum are recommended. In CKD-CRS, a focus on Staphylococcus epidermidis and Propionibacterium acnes is suggested. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

The Value of the Nutritional Indicators in Predicting Free Flap Failure From a Multicentre Database.

OBJECTIVE: Nutritional and inflammatory statuses have been associated with complications in microvascular-free flaps during head and neck surgeries. This study aimed to evaluate the potential of nutritional indicators in predicting postoperative free flap complications. STUDY DESIGN: We conducted a 20-year retrospective, case-control study within a defined cohort. SETTING: The study involved head and neck cancer patients from the Chang Gung Research Database who underwent simultaneous tumor ablation and free flap wound reconstruction between January 1, 2001, and December 31, 2019. METHODS: We employed logistic regression and stratified analysis to assess the risk of free flap complications and the subsequent need for flap revision or redo in relation to nutritional indicators and other clinical variables. RESULTS: Of the 8066 patients analyzed, 687 (8.5%) experienced free flap complications. Among these, 197 (2.4%) had free flap failures necessitating a redo of either a free flap or a pedicled flap. Beyond comorbidities such as chronic obstructive pulmonary disease, end-stage renal disease, and a history of prior radiotherapy, every 10-unit decrease in the preoperative prognostic nutritional index (PNI) was consistently associated with an increased risk of both free flap complications and failure. The covariate-adjusted odds ratios were 1.90 (95% confidence interval [CI]: 1.42-2.54) and 1.89 (95% CI: 1.13-3.17), respectively. CONCLUSION: A lower preoperative PNI suggests a higher likelihood of microvascular free flap complications in head and neck surgeries. Further randomized controlled trial designs are required to establish causality.

Outcomes of FETD versus UBE in the treatment of L5S1 foraminal stenosis: A comparative study.

Background: The L5S1 level exhibits unique anatomical features compared with other levels. This makes minimally invasive surgery for L5S1 foraminal stenosis (FS) challenging. This study compared the surgical outcomes of full endoscopic transforaminal decompression (FETD) and unilateral biportal endoscopy with the far-lateral approach (UBEFLA) in patients with L5S1FS. Methods: In this retrospective study, 49 patients with L5S1FS were divided into two groups. Of these, 24 patients underwent FETD, 25 patients underwent UBEFLA. The study assessed demographic data, leg pain visual analog scale (VAS) score, back pain VAS score, Oswestry Disability Index (ODI), modified MacNab outcome scale, and radiographic parameters including postoperative lateral facet preservation (POLFP). Results: The Mann-Whitney U test revealed that the UBEFLA group exhibited a higher VAS score for back pain at one week after the operation, whereas the FETD group exhibited a higher leg pain VAS score 6 weeks after the operation. All four undesired MacNab outcomes in the FETD group were attributed to residual leg pain, whereas all five undesired MacNab outcomes in the UBEFLA group were due to recurrent symptoms. Radiographically, the FETD group exhibited greater POLFP. Conclusions: When L5S1FS is performed, there may be challenges in adequately clearing the foraminal space in FETD. On the other hand, UBEFLA allowed for a more comprehensive clearance. However, this advantage of UBEFLA was associated with spinal instability as a future outcome.

A Joint Model Based on Post-Treatment Longitudinal Prognostic Nutritional Index to Predict Survival in Nasopharyngeal Carcinoma.

BACKGROUND: a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. METHODS: In this retrospective study using data from the Chang Gung Research Database (2007-2019), we enrolled patients with NPC undergoing curative treatment. We analyzed the correlation between patient characteristics, including the PNI, and overall survival. A joint model combining a longitudinal sub-model with a time-to-event sub-model was used to further evaluate the prognostic value of longitudinal PNI. RESULTS: A total of 2332 patient were enrolled for the analysis. Separate survival analyses showed that longitudinal PNI was an independent indicator of a reduced mortality risk (adjusted HR 0.813; 95% CI, 0.805 to 0.821). Joint modeling confirmed longitudinal PNI as a consistent predictor of survival (HR 0.864; 95% CI, 0.850 to 0.879). An ROC analysis revealed that a PNI below 38.1 significantly increased the risk of 90-day mortality, with 90.0% sensitivity and 89.6% specificity. CONCLUSIONS: Longitudinal PNI data independently predicted the overall survival in patients with NPC, significantly forecasting 90-day survival outcomes. We recommend routine PNI assessments during each clinic visit for these patients.

The impact of SARS-Cov-2 Omicron infection on short-term outcomes after elective surgery in patients with gastrointestinal cancer.

With the emergence of novel variants, Omicron variant caused a different clinical picture than the previous variants and little evidence was reported regarding perioperative outcomes after Omicron variants. The aim of the study was to evaluate the postoperative outcomes of gastrointestinal cancer patients following Omicron variants infection and also to determine the timing of surgery after infection recovery. A total of 124 patients who underwent gastrointestinal cancer surgery with prior SARS-CoV-2 infection between December 2022 and February 2023 were retrospectively reviewed. 174 cases underwent the same operation during December 2018 and February 2019 as control group. SARS-CoV-2-infected patients were further categorized into three groups based on infected time (1-3 weeks; 4-6 weeks; and ≥ 7 weeks). 90.3% of SARS-CoV-2-infected patients had mild symptoms. The COVID-19 vaccination rate was 71.0%, with a full vaccination rate of 48.4%. There were no significant differences in 30-day morbidity and mortality. There was also no significant difference in pulmonary complications, cardiovascular complications, and surgical complications between the three different diagnosis time groups. In conclusion, reducing waiting time for elective surgery was safe for gastrointestinal cancer patients in the context of an increased transmissibility and milder illness severity with Omicron variant.

Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients.

BACKGROUND AND AIMS: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. APPROACH AND RESULTS: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). CONCLUSIONS: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

Garlic-Derived Exosome-like Nanovesicles-Based Wound Dressing for Staphylococcus aureus Infection Visualization and Treatment.

Garlic-derived exosome-like nanovesicles (GELNs) could function in interspecies communication and may serve as natural therapeutics to regulate the inflammatory response or as nanocarriers to efficiently deliver specific drugs. Staphylococcus aureus (S. aureus) is able to hide within host cells to evade immune clearance and antibiotics, leading to life-threatening infections. On-site detection and efficient treatment of intracellular S. aureus infection in wounds remain challenging. Herein, we report a thermosensitive, injectable, visible GELNs-based wound dressing, Van@GELNs/F127 hydrogel (gel Van@GELNs), which is H2O2-responsive and can slowly release vancomycin into host cells forS. aureus infection visualization and treatment in wounds. GELNs show inherent antibacterial activity, which is significantly enhanced after loading vancomycin. Both GELNs and Van@GELNs have the ability to be internalized by cells, so Van@GELNs are more effective than free vancomycin in killing S. aureus in RAW 264.7 macrophages. When applied to an S. aureus-infected wound on a mouse, the colorless HRP&ABTS/Van@GELNs/F127 solution immediately changes to a green hydrogel and shows better therapeutic effect than vancomycin. Thus, direct visualization by the naked eye and effective treatment of S. aureus infection in wounds are achieved by gel Van@GELNs. We anticipate gel Van@GELNs be applied for the theranostics of S. aureus infection diseases in the clinic in the near future.

An investigation of neutron shielding and activation performances of four types of concrete for carbon ion therapy facility.

Carbon ions have unique physical and biological properties that allow for precise targeting of tumors while minimizing damage to surrounding healthy tissues. The emitted neutrons dominate the radiation field in the treatment room and pose challenges for radiological shielding. Concrete is extensively utilized in the construction of radiotherapy facilities due to its good shielding characteristics, and it can be easily poured into the desired shapes and thickness. The difference in composition of concrete affects the characteristics of neutron attenuation and activation performance. Therefore, the purpose of this study is to clarify the shielding properties and activation performances of four types of concrete for carbon ion therapy facilities. The Monte Carlo method is used to analyze the neutron spectra from thick targets upon carbon ion bombardment. Furthermore, the deep attenuation efficiency of the secondary neutron in different compositions of concrete is discussed. The shielding design is developed to ensure compliance with the prescribed dose limit outside the shielding during operation. Finally, the induced radioactivity in concrete is estimated for both short-term and long-term operation. The produced radionuclides inventories and depth profiling are determined. This study reveals the shielding and radioactivity issue of carbon ion therapy facilities and is expected to aid in the design or construction of similar facilities.

Ir-Doped CuPd Single-Crystalline Mesoporous Nanotetrahedrons for Ethylene Glycol Oxidation Electrocatalysis: Enhanced Selective Cleavage of C-C Bond.

The development of highly efficient electrocatalysts for complete oxidation of ethylene glycol (EG) in direct EG fuel cells is of decisive importance to hold higher energy efficiency. Despite some achievements, their progress, especially electrocatalytic selectivity to complete oxidated C1 products, is remarkably slower than expected. In this work, we developed a facile aqueous synthesis of Ir-doped CuPd single-crystalline mesoporous nanotetrahedrons (Ir-CuPd SMTs) as high-performance electrocatalyst for promoting oxidation cleavage of C-C bond in alkaline EG oxidation reaction (EGOR) electrocatalysis. The synthesis relied on precise reduction/co-nucleation and epitaxial growth of Ir, Cu and Pd precursors with cetyltrimethylammonium chloride as the mesopore-forming surfactant and extra Br- as the facet-selective agent under ambient conditions. The products featured concave nanotetrahedron morphology enclosed by well-defined (111) facets, single-crystalline and mesoporous structure radiated from the center, and uniform elemental composition without any phase separation. Ir-CuPd SMTs disclosed remarkably enhanced electrocatalytic activity and excellent stability as well as superior selectivity of C1 products for alkaline EGOR electrocatalysis. Detailed mechanism studies demonstrated that performance improvement came from structural and compositional synergies, which kinetically accelerated transports of electrons/reactants within active sites of penetrated mesopores and facilitated oxidation cleavage of high-energy-barrier C-C bond of EG for desired C1 products. More interestingly, Ir-CuPd SMTs performed well in coupled electrocatalysis of anode EGOR and cathode nitrate reduction, highlighting its high potential as bifunctional electrocatalyst in various applications.

Macular hole following scleral buckling for rhegmatogenous retinal detachment: a case series.

BACKGROUND: Macular hole (MH) development following scleral buckling (SB) surgery for rhegmatogenous retinal detachment (RRD) repair is rare. This study presents both full-thickness MH (FTMH) and lamellar MH (LMH) cases following SB for the treatment of RRD. METHODS: Clinical records of patients undergoing SB surgery for treatment of RRD at the Xi'an People's Hospital (Xi'an Fourth Hospital) from January 2016 to December 2021 were reviewed, and cases with postoperative MH were selected. Clinical features and follow-up data were summarised, and possible causes were analysed. RESULTS: Among 483 identified cases (483 eyes), four eyes (three male patients, one female patient) had postoperative MH, with prevalence, mean age, and mean axial length of 0.83%, 43.5 ± 10.66 years, and 29.13 ± 3.80 mm, respectively. All patients did not undergo subretinal fluid (SRF) drainage. The mean time for detecting MH was 26 ± 15.5 days postoperatively. Macula-off RRD with high myopia and FTMH combined with retinal re-detachment were diagnosed in three patients. One patient had macula-on RRD with outer LMH. The average follow-up duration was 7.25 ± 1.5 months. The FTMH closed successfully after reoperation, while the outer LMH closed without intervention. Visual acuity insignificantly improved or slightly decreased in all patients. CONCLUSIONS: Patients with high myopia combined with macula-off RRD might be more susceptible to FTMH, causing MH related retinal detachment. Additionally, LMH following SB was noted in patients with macula-on RRD. Therefore, we should raise awareness of MH following SB for RRD repair.

Cohort profile: the China surgery and anesthesia cohort (CSAC).

The China Surgery and Anaesthesia Cohort (CSAC) study was launched in July 2020 and is an ongoing prospective cohort study recruiting patients aged 40-65 years who underwent elective surgeries with general anaesthesia across four medical centres in China. The general objective of the CSAC study is to improve our understanding of the complex interaction between environmental and genetic components as well as to determine their effects on a wide range of interested surgery/anaesthesia-related outcomes. To achieve this goal, we collected enriched phenotypic data, e.g., sociodemographic characteristics, lifestyle factors, perioperative neuropsychological changes, anaesthesia- and surgery-related complications, and medical conditions, at recruitment, as well as through both active (at 1, 3, 7 days and 1, 3, 6, 12 months after surgery) and passive (for more than 1 year after surgery) follow-up assessments. We also obtained omics data from blood samples. In addition, COVID-19-related information was collected from all participants since January 2023, immediately after COVID-19 restrictions were eased in China. As of July 18, 2023, 12,766 participants (mean age = 52.40 years, 57.93% were female) completed baseline data collection (response rate = 94.68%), among which approximately 70% donated blood and hair samples. The follow-up rates within 12 months after surgery were > 92%. Our initial analyses have demonstrated the incidence of and risk factors for chronic postsurgical pain (CPSP) and postoperative cognitive dysfunction (POCD) among middle-aged Chinese individuals, which may prompt further mechanistic exploration and facilitate the development of effective interventions for preventing those conditions. Additional studies, such as genome-wide association analyses for identifying the genetic determinants of CPSP and POCD, are ongoing, and their findings will be released in the future.