Comparative postoperative prognosis of ceramic-on-ceramic and ceramic-on-polyethylene for total hip arthroplasty: an updated systematic review and meta-analysis.

Objective: To compare the clinical outcomes between ceramic-on-ceramic (CoC) and ceramic-on-polyethylene (CoP) bearing surfaces in patients undergoing total hip arthroplasty (THA) through a pooled analysis and evidence update. Methods: We performed a systematic literature search using PubMed, Embase, Cochrane Library and Web of Science up to March 2023 for studies that compared the bearing surfaces of CoC and CoP in patients undergoing THA. The primary outcomes were the incidence of common postoperative complications and the rate of postoperative revision. The secondary outcome was the Harris Hip Score. Results: A total of 10 eligible studies involving 1,946 patients (1.192 CoC-THA versus 906 CoP-THA) were included in the evidence synthesis. Pooled analysis showed no significant difference in the rates of common postoperative complications (dislocation, deep vein thrombosis, infection, wear debris or osteolysis) and of revision. After eliminating heterogeneity, the postoperative Harris Hip Score was higher in the CoC group than in the CoP group. However, the strength of evidence was moderate for the Harris Hip Score. Conclusion: CoC articulations are more commonly used in younger, healthier, and more active patients. While the performance of conventional polyethylene is indeed inferior to highly cross-linked polyethylene, there is currently a lack of sufficient research comparing the outcomes between highly cross-linked polyethylene and CoC bearing surfaces. This area should be a focal point for future research, and it is hoped that more relevant articles will emerge. Given the limited number of studies included, the heterogeneity and potential bias of those included in the analysis, orthopaedic surgeons should select a THA material based on their experience and patient-specific factors, and large multicentre clinical trials with >15 years of follow-up are needed to provide more evidence on the optimal bearing surface for initial THA.

Identification and validation of endoplasmic reticulum stress-related genes in patients with steroid-induced osteonecrosis of the femoral head.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a debilitating condition caused by long-term corticosteroid use, leading to impaired blood flow and bone cell death. The disruption of cellular processes and promotion of apoptosis by endoplasmic reticulum stress (ERS) is implicated in the pathogenesis of SONFH. We identified ERS-associated genes in SONFH and investigated their potential as therapeutic targets. We analysed the GSE123568 GEO dataset to identify differentially expressed genes (DEGs) related to ERS in SONFH. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, identified hub genes by protein-protein interaction (PPI) analyses, and evaluated their functions by gene set enrichment analysis (GSEA). We constructed mRNA-miRNA networks, identified potential therapeutics, and assessed immune cell infiltration. We performed cross-validation using the GEO dataset GSE74089, qRT-PCR on clinical samples from patients with SONFH and controls, and a receiver operating characteristic (ROC) curve analysis to assess the diagnostic performance of the hub genes. We identified 195 ERS-related genes in SONFH, which were primarily involved in oxidative stress, immune responses, and metabolic pathways. The PPI network suggested CXCL8, STAT3, IL1B, TLR4, PTGS2, TLR2, CASP1, CYBB, CAT, and HOMX1 to be key hub genes, which were shown by GSEA to be involved in biological pathways related to metabolism, immune modulation, and cellular integrity. We also identified 261 microRNAs (miRNAs) as well as drugs such as dibenziodolium and N-acetyl-L-cysteine that modulated inflammatory responses in SONFH. Twenty-two immune cell subtypes showed significant correlations, such as a positive correlation between activated mast cells and Tregs, and patients with SONFH had fewer dendritic cells than controls. The hub genes CYBB and TLR4 showed significant correlations with M1 macrophages and CD8 T cells, respectively. Cross-validation and qRT-PCR confirmed the upregulation of STAT3, IL1B, TLR2, and CASP1 in patients with SONFH, validating the bioinformatics findings. An ROC curve analysis confirmed the diagnostic potential of the hub genes. The top 10 hub genes show promise as ERS-related diagnostic biomarkers for SONFH. We discovered that 261 miRNAs, including hsa-miR-23, influence these genes and identified potential therapeutics such as dibenziodolium and simvastatin. Immune profiling indicated altered immune functions in SONFH, with significant correlations among immune cell types. Validation confirmed the upregulation of STAT3, IL1B, TLR2 and CASP1, which had diagnostic potential. The findings suggest potential diagnostic markers and therapeutic targets for SONFH.

A fast and genotype-independent in planta Agrobacterium-mediated transformation method for soybean.

Efficient genotype-independent transformation and genome editing are highly desirable for plant biotechnology research and product development efforts. We have developed a novel approach to enable fast, high-throughput, and genotype-flexible Agrobacterium-mediated transformation using the important crop soybean as a test system. This new method is called GiFT (genotype-independent fast transformation) and involves only a few simple steps. The method uses germinated seeds as explants, and DNA delivery is achieved through Agrobacterium infection of wounded explants as in conventional in vitro-based methods. Following infection, the wounded explants are incubated in liquid medium with a sublethal level of selection and then transplanted directly into soil. The transplanted seedlings are then selected with herbicide spray for 3 weeks. The time required from initiation to fully established healthy T0 transgenic events is about 35 days. The GiFT method requires minimal in vitro manipulation or use of tissue culture media. Because the regeneration occurs in planta, the GiFT method is highly flexible with respect to genotype, which we demonstrate via successful transformation of elite germplasms from diverse genetic backgrounds. We also show that the soybean GiFT method can be applied to both conventional binary vectors and CRISPR-Cas12a vectors for genome editing applications. Analyses of T1 progeny demonstrate that the events have a high inheritance rate and can be used for genome engineering applications. By minimizing the need for tissue culture, the novel approach described here significantly improves operational efficiency while greatly reducing personnel and supply costs. It is the first industry-scale transformation method to utilize in planta selection in a major field crop.

Effect of Fe2+-activated persulfate combined with biodegradation in removing gasoline BTX from karst groundwater: A box-column experimental study.

In-situ chemical oxidation with persulfate (PS-ISCO) is a preferred approach for the remediation of fuel-contaminated groundwater. Persulfate (PS) can be activated by various methods to produce stronger sulfate radicals for more efficient ISCO. Despite karst aquifers being widespread, there are few reports on PS-ISCO combined with Fe2+-activated PS. To better understand the effects of Fe2+-activated PS for the remediation of gasoline-contaminated aquifers in karst areas, a box-column experiment was conducted under flow conditions, using karst groundwater and limestone particles to simulate an aquifer. Gasoline was used as the source of hydrocarbon contaminants. Dissolved oxygen and nitrate were added to enhance bioremediation (EBR) and ferrous sulfate was used to activate PS. The effect of Fe2+-activated PS combined with biodegradation was compared during the periods of EBR + ISCO and ISCO alone, using the mass flow method for data analysis. The results showed that the initial dissolution of benzene, toluene, and xylene (BTX) from gasoline injection was rapid and variable, with a decaying trend at an average pseudo-first-order degradation rate constant of 0.032 d-1. Enhanced aerobic biodegradation and denitrification played a significant role in limestone-filled environments, with dissolved oxygen and nitrate utilization ratios of 59 ~ 72% and 12-70%, respectively. The efficiency of EBR + ISCO was the best method for BTX removal, compared with EBR or ISCO alone. The pseudo-first-order degradation rate constants of BTX reached 0.022-0.039, 0.034-0.070, and 0.027-0.036 d-1, during the periods of EBR alone, EBR + ISCO, and ISCO alone, respectively. The EBR + ISCO had a higher BTX removal ratio range of 71.0 ~ 84.3% than the ISCO alone with 30.1 ~ 45.1%. The presence of Fe2+-activated PS could increase the degradation rate of BTX with a range of 0.060 ~ 0.070 d-1, otherwise, with a range of 0.034-0.052 d-1. However, Fe2+-activated PS also consumed about 3 times the mass of PS, caused a further decrease in pH with a range of 6.8-7.6, increased 3-4 times the Ca2+ and 1.6-1.8 times the HCO3- levels, and decreased the BTX removal ratio of ISCO + EBR, compared to the case without Fe2+ activation. In addition, the accumulation of ferric hydroxides within a short distance indicated that the range of PS activated by Fe2+ may be limited. Based on this study, it is suggested that the effect of Fe2+-activated PS should be evaluated in the remediation of non-carbonate rock aquifers.

Melatonin alleviates high-fat-diet-induced dry eye by regulating macrophage polarization via IFT27 and lowering ERK/JNK phosphorylation.

Dry eye disease is the most common ocular surface disease globally, requiring a more effective treatment. We observed that a high-fat diet induced macrophage polarization to M1 and further induced inflammation in the meibomian and lacrimal glands. A four-week treatment with melatonin (MLT) eye drops can regulate macrophage polarization and alleviate dry eye signs. To investigate the therapeutic effects and mechanisms of action of MLT on high-fat-diet-induced dry eye disease in mice, RAW 264.7 cells pretreated with LPS and/or MLT underwent digital RNA with the perturbation of genes sequencing (DRUG-seq). Results showed that IFT27 was up-regulated, and MAPK pathways were suppressed after MLT pre-treatment. ERK/JNK phosphorylation was reduced in meibomian glands of MLT-treated dry eye mice and increased in IFT27 knockdown RAW 264.7 cells. In summary, MLT regulated macrophage polarization via IFT27 and reduced ERK/JNK phosphorylation. These results support that MLT is a promising medication for dry eye disease.

Down-Regulation of AKT Proteins Slows the Growth of Mutant-KRAS Pancreatic Tumors.

Serine/threonine kinase AKT isoforms play a well-established role in cell metabolism and growth. Most pancreatic adenocarcinomas (PDACs) harbor activation mutations of KRAS, which activates the PI3K/AKT signaling pathway. However, AKT inhibitors are not effective in the treatment of pancreatic cancer. To better understand the role of AKT signaling in mutant-KRAS pancreatic tumors, this study utilized proteolysis-targeting chimeras (PROTACs) and CRISPR-Cas9-genome editing to investigate AKT proteins. The PROTAC down-regulation of AKT proteins markedly slowed the growth of three pancreatic tumor cell lines harboring mutant KRAS. In contrast, the inhibition of AKT kinase activity alone had very little effect on the growth of these cell lines. The concurrent genetic deletion of all AKT isoforms (AKT1, AKT2, and AKT3) in the KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cell line also dramatically slowed its growth in vitro and when orthotopically implanted in syngeneic mice. Surprisingly, insulin-like growth factor-1 (IGF-1), but not epidermal growth factor (EGF), restored KPC cell growth in serum-deprived conditions, and the IGF-1 growth stimulation effect was AKT-dependent. The RNA-seq analysis of AKT1/2/3-deficient KPC cells suggested that reduced cholesterol synthesis may be responsible for the decreased response to IGF-1 stimulation. These results indicate that the presence of all three AKT isoforms supports pancreatic tumor cell growth, and the pharmacological degradation of AKT proteins may be more effective than AKT catalytic inhibitors for treating pancreatic cancer.

Down-regulation of AKT proteins slows the growth of mutant-KRAS pancreatic tumors.

Serine/threonine kinase AKT isoforms play a well-established role in cell metabolism and growth. Most pancreatic adenocarcinoma (PDAC) harbors activation mutations of KRAS, which activates the PI3K/AKT signaling pathway. However, AKT inhibitors are not effective in the treatment of pancreatic cancer. To better understand the role of AKT signaling in mutant-KRAS pancreatic tumors, this study utilizes proteolysis-targeting chimeras (PROTACs) and CRISPR-Cas9-genome editing to investigate AKT proteins. PROTAC down-regulation of AKT proteins markedly slowed the growth of three pancreatic tumor cell lines harboring mutant KRAS. In contrast, inhibition of AKT kinase activity alone had very little effect on the growth of these cell lines. Concurrent genetic deletion of all AKT isoforms (AKT1, AKT2, and AKT3) in the KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cell line also dramatically slowed its growth in vitro and when orthotopically implanted in syngeneic mice. Surprisingly, insulin-like growth factor-1 (IGF-1), but not epidermal growth factor (EGF), restored KPC cell growth in serum-deprived conditions and the IGF-1 growth stimulation effect was AKT dependent. RNA-seq analysis of AKT1/2/3-deficient KPC cells suggested that reduced cholesterol synthesis may be responsible for the decreased response to IGF-1 stimulation. These results indicate that the presence of all three AKT isoforms supports pancreatic tumor cell growth and pharmacological degradation of AKT proteins may be more effective than AKT catalytic inhibitors for treating pancreatic cancer.

A Two-Decade Bibliometric Analysis of Laser in Ophthalmology: From Past to Present.

Background: Laser therapy has been proven as an effective technique for managing ophthalmological disorders. To guide future research, we conducted a bibliometric analysis of laser applications in eye diseases from 1990 to 2022, aiming to identify key themes and trends. Methods: We retrieved 3027 publications from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks. Results: From a co-citation reference network, we identified 52 distinct clusters. Our analysis uncovered three main research trends. The first trend revolves around the potential evolution of corneal laser surgery techniques, shifting from the treatment of refractive errors to broader applications in biomedical optics. The second trend illustrates the advancement of laser applications in treating a range of disorders, from retinal and ocular surface diseases to glaucoma. The third trend focuses on the innovative uses of established technologies. Conclusion: This study offers significant insights into the evolution of laser applications in ophthalmology over the past 30 years, which will undoubtedly assist scientists in directing further research in this promising field.

Genetic correlation between circulating cytokines and risk of three ophthalmic diseases: a bidirectional two-sample Mendelian randomization study.

PURPOSE: Pathogenesis and the associated risk factors of cataracts, glaucoma, and age-related macular degeneration (AMD) remain unclear. We aimed to investigate causal relationships between circulating cytokine levels and the development of these diseases. PATIENTS AND METHODS: Genetic instrumental variables for circulating cytokines were derived from a genome-wide association study of 8293 European participants. Summary-level data for AMD, glaucoma, and senile cataract were obtained from the FinnGen database. The inverse variance weighted (IVW) was the main Mendelian randomization (MR) analysis method. The Cochran's Q, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used for sensitivity analysis. RESULTS: Based on the IVW method, MR analysis demonstrated five circulating cytokines suggestively associated with AMD (SCGF-ß, 1.099 [95%CI, 1.037-1.166], P = 0.002; SCF, 1.155 [95%CI, 1.015-1.315], P = 0.029; MCP-1, 1.103 [95%CI, 1.012-1.202], P = 0.026; IL-10, 1.102 [95%CI, 1.012-1.200], P = 0.025; eotaxin, 1.086 [95%CI, 1.002-1.176], P = 0.044), five suggestively linked with glaucoma (MCP-1, 0.945 [95%CI, 0.894-0.999], P = 0.047; IL1ra, 0.886 [95%CI, 0.809-0.969], P = 0.008; IL-1ß, 0.866 [95%CI, 0.762-0.983], P = 0.027; IL-9, 0.908 [95%CI, 0.841-0.980], P = 0.014; IL2ra, 1.065 [95%CI, 1.004-1.130], P = 0.035), and four suggestively associated with senile cataract (TRAIL, 1.043 [95%CI, 1.009-1.077], P = 0.011; IL-16, 1.032 [95%CI, 1.001-1.064], P = 0.046; IL1ra, 0.942 [95%CI, 0.887-0.999], P = 0.047; FGF-basic, 1.144 [95%CI, 1.052-1.244], P = 0.002). Furthermore, sensitivity analysis results supported the above associations. CONCLUSION: This study highlights the involvement of several circulating cytokines in the development ophthalmic diseases and holds potential as viable pharmacological targets for these diseases.

Performance Evaluation of Newly-Developed Tumor Markers Assay Kit Based on Flow Fluorescence Assay.

BACKGROUND: The purpose of this study is to evaluate the performance of recently developed tumor marker clinical kits in China, with the aim of encouraging local medical technology innovation and thus narrowing the research and development gap with foreign kits. METHODS: The newly established reagent kits were analyzed on the TESMI F3999-Luminex200 flow lattice instrument to verify precision, sensitivity (blank limit), linearity, anti-interference ability, carry-over contamination rate, hook effect, and reference interval verification. Additionally, the newly established reagent kits were compared to other commercially available detection kits (reference reagent kits) to analyze the correlation between the two types of kits. RESULTS: The intra-assay and inter-assay precision had coefficients of variations (CVs) less than 3.50% and 6.91%, respectively. The tumor marker blank limits were lower than the manufacturer's statement. The newly established reagent kits demonstrated excellent linearity (r > 0.99). Rheumatoid factor, triglycerides, bilirubin, and hemoglobin did not have significant interference with the determination of tumor markers. The carry-over contamination rates were all much lower than 3%. At extremely high concentrations of AFP (277,335 ng/mL and 1,031,424 ng/mL), the measured tumor marker values were higher than the upper limit of the linear range and no hook effect occurred. The reference interval was suitable for use in clinical laboratory settings. Correlation analysis indicated a satisfactory relevance and consistency between the newly developed reagent kits and reference reagent kits, with correlation coefficients of r > 0.967 among 654 patients and healthy individuals. CONCLUSIONS: The newly developed reagent kits for tumor markers performed well in all evaluated parameters, having the potential for clinical promotion and application.

An pair of an atypical NLR encoding genes confer Asian soybean rust resistance in soybean.

Asian soybean rust (ASR), caused by Phakopsora pachyrhizi, is a devastating disease that is present in all major soybean-producing regions. The limited availability of resistant germplasm has resulted in a scarcity of commercial soybean cultivars that are resistant to the disease. To date, only the Chinese soybean landrace SX6907 has demonstrated an immune response to ASR. In this study, we present the isolation and characterization of Rpp6907-7 and Rpp6907-4, a gene pair that confer broad-spectrum resistance to ASR. Rpp6907-7 and Rpp6907-4 encode atypic nucleotide-binding leucine-rich repeat (NLR) proteins that are found to be required for NLR-mediated immunity. Genetic analysis shows that only Rpp6907-7 confers resistance, while Rpp6907-4 regulates Rpp6907-7 signaling activity by acting as a repressor in the absence of recognized effectors. Our work highlights the potential value of using Rpp6907 in developing resistant soybean cultivars.

Genetic correlation between circulating metabolites and chalazion: a two-sample Mendelian randomization study.

Background: Lipid metabolism disorders were observationally associated with chalazion, but the causality of the related circulating metabolites on chalazion remained unknown. Here, we investigated the potential causal relationship between circulating metabolites and chalazion using two-sample Mendelian randomization (MR) analysis. Methods: For the primary analysis, 249 metabolic biomarkers were obtained from the UK Biobank, and 123 circulating metabolites were obtained from the publication by Kuttunen et al. for the secondary analysis. Chalazion summary data were obtained from the FinnGen database. Inverse variance weighted (IVW) is the main MR analysis method, and the MR assumptions were evaluated in sensitivity and colocalization analyses. Results: Two MR analyses results showed that the common metabolite, alanine, exhibited a genetic protective effect against chalazion (primary analysis: odds ratio [OR] = 0.680; 95% confidence interval [CI], 0.507-0.912; p = 0.010; secondary analysis: OR = 0.578; 95% CI, 0.439-0.759; p = 0.00008). The robustness of the findings was supported by heterogeneity and horizontal pleiotropy analysis. Two colocalization analyses showed that alanine did not share a region of genetic variation with chalazion (primary analysis: PPH4 = 1.95%; secondary analysis: PPH4 = 25.3%). Moreover, previous studies have suggested that an increase in the degree of unsaturation is associated with an elevated risk of chalazion (OR = 1.216; 95% CI, 1.055-1.401; p = 0.007), with omega-3 fatty acids (OR = 1.204; 95% CI, 1.054-1.377; p = 0.006) appearing to be the major contributing factor, as opposed to omega-6 fatty acids (OR = 0.850; 95% CI, 0.735-0.982; p = 0.027). Conclusion: This study suggests that alanine and several unsaturated fatty acids are candidate molecules for mechanistic exploration and drug target selection in chalazion.

The effects of live streamer's expertise and entertainment on the viewers' purchase and follow intentions.

This study explores the impact of two characteristics of streamers-expertise and entertainment-on viewers' purchase intention and follow intention in live-streaming e-commerce, with a specific focus on viewers' trust and flow experience as two mediators and viewers' optimal stimulation level as a moderator. We implemented a methodological approach where participants were randomly directed to enter a live broadcast room and watch a 10-min live session before engaging in a structured questionnaire. 399 valid questionnaires were collected from the participants. These 399 valid questionnaires were subsequently utilized to validate the research model using structural equation modeling (SEM). The results suggest that streamer expertise and entertainment enhance viewers' trust and flow experience, which then leads to an increase in their intention to make a purchase and continue following the streamer. Furthermore, the viewers' optimal stimulation level acts as a moderator in the connections between streamer characteristics and viewers' trust and flow experience, suggesting that individual differences among consumers affect how they respond to streamer characteristics. From the dual perspectives of the streamer and the viewer, this study provides a more comprehensive theoretical perspective on customer behavior in live streaming commerce by not only focusing on consumers' short-term, transactional behavior inclinations but also long-term, relational behavior intentions.

Ceramic fragmentation after total hip arthroplasty: two case reports and literature review.

Background: Ceramic fragmentation is a rare but serious complication after total hip arthroplasty (THA). We reviewed the PubMed literature from 1990 to 2023 and found only 31 case reports of ceramic fragmentation after THA. Our case reports help to expand understanding of this rare complication. We shared our surgical experience and identified an ideal material for revision surgery, which can serve as a useful reference for other orthopedic surgeons to perform ceramic fragmentation revision surgery in the future. We also analyzed the possible causes, diagnosis, and treatment opinions of ceramic fragmentation. Case presentation: This study presents two cases of ceramic fragmentation after THA. One patient had ceramic head fragmentation 10 years after the primary THA, and one patient had ceramic liner fragmentation 5 years after the primary THA. Both patients presented with pain, and one patient also reported a clicking sound in the hip. The two patients described here had BMIs of 23.7 and 23.1, respectively. Both patients' ceramic fragmentation were due to aseptic loosening, not periprosthetic joint infections, as confirmed by negative microbiological cultures. Radiographic examinations of both patients revealed radio-opaque wear debris around the hip joint prostheses and we describe the surgical protocols and intraoperative findings in both cases in detail. Conclusion: Our cases and the literature suggest that ceramic fragmentation can occur at any time after THA. The most immediate symptoms are pain and noise, but some patients may be asymptomatic. Ceramic on polyethylene bearings is recommended for revision surgery whenever possible; metal bearings should be avoided.

Preoperative serum level of CA153 and a new model to predict the sub-optimal primary debulking surgery in patients with advanced epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to establish a preoperative model to predict the outcome of primary debulking surgery (PDS) for advanced ovarian cancer (AOC) patients by combing Suidan predictive model with HE4, CA125, CA153 and ROMA index. METHODS: 76 AOC Patients in revised 2014 International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent PDS between 2017 and 2019 from Yunnan Cancer Hospital were included. Clinical data including the levels of preoperative serum HE4, CA125, CA153 and mid-lower abdominal CT-enhanced scan results were collected. The logistics regression analysis was performed to find factors associated with sub-optimal debulking surgery (SDS). The receiver operating characteristic curve was used to evaluate the predictive performances of selected variables in the outcome of primary debulking surgery. The predictive index value (PIV) model was constructed to predict the outcome of SDS. RESULTS: Optimal surgical cytoreduction was achieved in 61.84% (47/76) patients. The value for CA125, HE4, CA153, ROMA index and Suidan score was lower in optimal debulking surgery (ODS) group than SDS group. Based on the Youden index, which is widely used for evaluating the performance of predictive models, the best cutoff point for the preoperative serum HE4, CA125, CA153, ROMA index and Suidan score to distinguish SDS were 431.55 pmol/l, 2277 KU/L, 57.19 KU/L, 97.525% and 2.5, respectively. Patients with PIV≥5 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing SDS were 73.7%, 82.9%, 62.9% and 72.3%, respectively. In the constructed model, the AUC of the SDS prediction was 0.770 (95% confidence interval: 0.654-0.887), P<0.001. CONCLUSION: Preoperative serum CA153 level is an important non-invasive predictor of primary SDS in advanced AOC, which has not been reported before. The constructed PIV model based on Suidan's predictive model plus HE4, CA125, CA153 and ROMA index can noninvasively predict SDS in AOC patients, the accuracy of this prediction model still needs to be validated in future studies.

Advancements in drug-loaded hydrogel systems for bone defect repair.

Bone defects are primarily the result of high-energy trauma, pathological fractures, bone tumor resection, or infection debridement. The treatment of bone defects remains a huge clinical challenge. The current treatment options for bone defects include bone traction, autologous/allogeneic bone transplantation, gene therapy, and bone tissue engineering amongst others. With recent developments in the field, composite scaffolds prepared using tissue engineering techniques to repair bone defects are used more often. Among the various composite scaffolds, hydrogel exhibits the advantages of good biocompatibility, high water content, and degradability. Its three-dimensional structure is similar to that of the extracellular matrix, and as such it is possible to load stem cells, growth factors, metal ions, and small molecule drugs upon these scaffolds. Therefore, the hydrogel-loaded drug system has great potential in bone defect repair. This review summarizes the various natural and synthetic materials used in the preparation of hydrogels, in addition to the latest research status of hydrogel-loaded drug systems.

The role of Ginkgo Folium on antitumor: Bioactive constituents and the potential mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. is a well-known and highly regarded resource in Chinese traditional medicine due to its effectiveness and safety. Ginkgo Folium, the leaf of Ginkgo biloba L., contains biologically active constituents with diverse pharmacological activities. Recent studies have shown promising antitumor effects of the bioactive constituents found in Ginkgo Folium against various types of cancer cells, highlighting its potential as a natural source of antitumor agents. Further research is needed to elucidate the underlying mechanisms and optimize its therapeutic potential. AIM OF THE REVIEW: To provide a detailed understanding of the pharmacological activities of Ginkgo Folium and its potential therapeutic benefits for cancer patients. MATERIALS AND METHODS: In this study, we conducted a thorough and systematic search of multiple online databases, including PubMed, Web of Science, Medline, using relevant keywords such as "Ginkgo Folium," "flavonoids," "terpenoids," "Ginkgo Folium extracts," and "antitumor" to cover a broad range of studies that could inform our review. Additionally, we followed a rigorous selection process to ensure that the studies included in our review met the predetermined inclusion criteria. RESULTS: The active constituents of Ginkgo Folium primarily consist of flavonoids and terpenoids, with quercetin, kaempferol, isorhamnetin, ginkgolides, and bilobalide being the major compounds. These active constituents exert their antitumor effects through crucial biological events such as apoptosis, cell cycle arrest, autophagy, and inhibition of invasion and metastasis via modulating diverse signaling pathways. During the process of apoptosis, active constituents primarily exert their effects by modulating the caspase-8 mediated death receptor pathway and caspase-9 mediated mitochondrial pathway via regulating specific signaling pathways. Furthermore, by modulating multiple signaling pathways, active constituents effectively induce G1, G0/G1, G2, and G2/M phase arrest. Among these, the pathways associated with G2/M phase arrest are particularly extensive, with the cyclin-dependent kinases (CDKs) being most involved. Moreover, active constituents primarily mediate autophagy by modulating certain inflammatory factors and stressors, facilitating the fusion stage between autophagosomes and lysosomes. Additionally, through the modulation of specific chemokines and matrix metalloproteinases, active constituents effectively inhibit the processes of epithelial-mesenchymal transition (EMT) and angiogenesis, exerting a significant impact on cellular invasion and migration. Synergistic effects are observed among the active constituents, particularly quercetin and kaempferol. CONCLUSION: Active components derived from Ginkgo Folium demonstrate a comprehensive antitumor effect across various levels and pathways, presenting compelling evidence for their potential in new drug development. However, in order to facilitate their broad and adaptable clinical application, further extensive experimental investigations are required to thoroughly explore their efficacy, safety, and underlying mechanisms of action.

Propionyl-CoA carboxylase subunit B regulates anti-tumor T cells in a pancreatic cancer mouse model.

Most human pancreatic ductal adenocarcinoma (PDAC) are not infiltrated with cytotoxic T cells and are highly resistant to immunotherapy. Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. Our previous study demonstrated that ablation of Pik3ca in KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cells induced host T cells to infiltrate and completely eliminate the tumors in a syngeneic orthotopic implantation mouse model. Now, we show that implantation of Pik3ca-/- KPC (named αKO) cancer cells induces clonal expansion of cytotoxic T cells infiltrating the pancreatic tumors. To identify potential molecules that can regulate the activity of these anti-tumor T cells, we conducted an in vivo genome-wide gene-deletion screen using αKO cells implanted in the mouse pancreas. The result shows that deletion of propionyl-CoA carboxylase subunit B gene (Pccb) in αKO cells (named p-αKO) leads to immune evasion, tumor progression and death of host mice. Surprisingly, p-αKO tumors are still infiltrated with clonally expanded CD8+ T cells but they are inactive against tumor cells. However, blockade of PD-L1/PD1 interaction reactivated these clonally expanded T cells infiltrating p-αKO tumors, leading to slower tumor progression and improve survival of host mice. These results indicate that Pccb can modulate the activity of cytotoxic T cells infiltrating some pancreatic cancers and this understanding may lead to improvement in immunotherapy for this difficult-to-treat cancer.

Systematic analysis of hip-preserving treatment for early osteonecrosis of the femoral head from the perspective of bibliometrics (2010-2023).

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a serious condition that causes bone tissue death, femoral head collapse, and hip joint destruction. Early intervention through hip-preserving treatment is crucial to slow down disease progression, preserve hip joint function, and improve the quality of life of patients. We analyzed the knowledge map, research gaps, and future research directions in the field of hip-preserving treatment for early ONFH. METHODS: All publications related to hip-preserving treatment for early ONFH published between 2010 and 2023 were identified from the Web of Science Core Collection and analyzed using VOSviewer 1.6.19, CiteSpace 6.2.R2, and Scimago Graphica 1.0.35. RESULTS: In total, 234 articles were analyzed. The results showed an exponential growth trend in the number of publications related to hip-preserving treatment for early ONFH in the past decade. China and the USA were the main contributors. International Orthopaedics published the most papers in this field, whereas Bone and Joint Surgery-American Volume had the highest average citation count per article. Several stable research topics were noted in this field, including core decompression (CD), osteotomy, bone transplantation in hip-preserving surgery, and cell therapy, which have become research hotspots in hip-preserving treatment. CONCLUSIONS: Hip-preserving treatment for early ONFH has received increasing attention, and research in this field is expected to grow. Stable research topics include core decompression (CD), osteotomy, bone transplantation, and cell therapy. Future research is predicted to focus on cell therapy and combination therapy, resulting in an increasing number of publications on hip-preserving treatment for early ONFH.

Cumulative live birth rate and neonatal outcomes after early rescue ICSI: a propensity score matching analysis.

STUDY QUESTION: Is early rescue ICSI (E-RICSI) an effective and safe technique compared to conventional ICSI? SUMMARY ANSWER: Despite the higher multi-pronucleus (PN) rate compared to conventional ICSI, E-RICSI did not add extra risks to clinical and neonatal outcomes. WHAT IS KNOWN ALREADY: Based on the finding that the second polar body was released in 80% of fertilized oocytes by 4 h after exposure to spermatozoa and in ∼90% of fertilized oocytes by 6 h, E-RICSI brings forward the timing of rescue ICSI to 6 h after initial insemination, and effectively prevents oocyte aging and embryo-uterus asynchrony. However, some researchers still voice concerns about the efficacy and safety of E-RICSI, and comparative studies are limited. STUDY DESIGN SIZE DURATION: A retrospective cohort study was conducted on patients who underwent conventional ICSI or E-RICSI treatment between January 2015 and December 2020 at a university-affiliated hospital. Using 1:1 propensity score matching, 1496 cases entered each group. PARTICIPANTS/MATERIALS SETTING METHODS: In total, 1496 couples undergoing conventional ICSI oocyte retrieval cycles and 1496 undergoing E-RICSI oocyte retrieval cycles were enrolled in this study, and basic clinical characteristics, embryologic data, clinical outcomes and neonatal data were compared between groups. The embryos in the E-RICSI group were divided into two subgroups: those fertilized by iIVF (IVF subgroup) and those fertilized by E-RICSI (E-RICSI subgroup); the embryologic data, clinical outcomes, and neonatal data for these subgroups were also compared with the conventional ICSI group. Logistic regression was used for statistical analysis with potential confounder adjustment. MAIN RESULTS AND THE ROLE OF CHANCE: The 2PN rate, blastocyst formation rate, and viable blastocyst formation rate of the E-RICSI group were significantly lower compared to the conventional ICSI group (2PN rate: P < 0.001; blastocyst formation rate: P < 0.001; viable blastocyst formation rate: P = 0.004), and the multi-PN rate in the E-RICSI group was significantly higher than the conventional ICSI group (P < 0.001). However, the number of 2PN embryos, normal cleavage embryo rate, Day 3 high-quality cleavage embryo rate, and high-quality blastocyst rate were similar between groups. When considering the IVF embryos and E-RCSI embryos in the E-RICSI group independently, the 2PN rate of the conventional ICSI group was significantly lower than E-RICSI subgroup but higher than the IVF subgroup, whereas the blastocyst formation rate and viable blastocyst formation rate were higher than E-RICSI embryos but comparable to IVF embryos. As for the clinical and neonatal outcomes, the implantation rate of the E-RICSI subgroup was significantly lower than the IVF subgroup but comparable to the conventional ICSI group, while the low birthweight (LBW) rate was significantly lower compared with the conventional ICSI group but similar with the IVF subgroup. No other differences were observed among the three groups for cumulative clinical pregnancy rate, cumulative live birth rate, and the pregnancy outcomes per transfer including clinical pregnancy, ectopic pregnancy, miscarriage, and live birth, either in fresh or frozen embryo transfer cycles. Furthermore, neonatal outcomes, including cesarean section, sex ratio, LBW, preterm birth, and macrosomia, were similar among groups. LIMITATIONS REASONS FOR CAUTION: This study is limited by the retrospective design, limited sample size, and short follow-up period. However, our study underlies the need for large-scale, multi-center randomized controlled trials with long-term follow-up. WIDER IMPLICATIONS OF THE FINDINGS: Short-term insemination (3 h) combined with E-RICSI may be a safe and effective method to prevent the occurrence of total fertilization failure, and patients with normal or borderline sperm could be encouraged to try IVF first. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from the National Key & Development Program of China (No. 2021YFC2700603) and the National Natural Science Foundation of China (No. 81801443). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.