Upper Gastrointestinal Involvement in Crohn's Disease as an Independent Predictor of New-Onset Strictures: Insights from an Extensive Retrospective Cohort Analysis.

BACKGROUND/AIMS: Crohn's Disease (CD) can affect the entire gastrointestinal tract, including the upper sections (UGI), which is often overlooked, especially in Asian populations. There's a notable gap in research regarding the impact of UGI involvement on the intricate landscape of ensuing complications. This study aims to address this gap. METHODS: Conducting a retrospective study at Chang Gung Memorial Hospital from January 2001 to September 2023, we compared CD patients with UGI (Montreal L4) involvement against non-L4 counterparts, focusing on baseline characteristics, post-diagnosis complications, and overall outcomes. Routine UGI endoscopy was performed around the time of diagnosis in all patients followed in our inflammatory bowel disease (IBD) center, and all CD patients with adequate follow-up were included in this study. RESULTS: The study included 212 CD patients, 111 in the L4 group and 101 in the non-L4 group, with an average follow-up of 40.8 ± 15.1 months. At baseline, individuals in the L4 category demonstrated elevated smoking rates, increased Crohn's Disease Activity Index scores, a higher prevalence of strictures, and a more prevalent usage of biologics and proton pump inhibitors. Moreover, this group was characterized by reduced albumin levels. Upon concluding the follow-up, those with L4 involvement continued to show escalated CDAI scores and hospitalization frequencies, alongside heightened C-reactive protein levels and diminished albumin concentrations. Additionally, the occurrence of UGI involvement, stricturing disease at the time of diagnosis, and a younger age at the onset of CD were pinpointed as independent predictors for the development of new-onset strictures. CONCLUSIONS: CD patients with UGI involvement exhibit elevated disease activity and serve as independent predictors for the development of intestinal strictures. Thorough UGI evaluations at the time of diagnosis, coupled with assertive treatment strategies, are essential for managing these patients effectively.

Four-Year Treatment Effect of Custom-Made Foot Orthosis on Pediatric Symptomatic Accessory Navicular Bone Combined with Flexible Flatfoot.

Purpose: Congenital accessory navicular bone (ANB) is a common variant in the foot and is prone to cause several clinical symptoms. Wearing custom-made foot orthosis is considered a desirable option; however, there is limited evidence of its effectiveness. This study aims to report the mid-term effect of foot orthosis for symptomatic pediatric ANBs. Methods: School-age children with symptomatic ANBs combined with flexible flatfoot in the authors' institute were recruited and got custom-made foot orthosis treatment. They were followed up over 4 years. The general characteristics of these children were collected before treatment, including age, gender, and body mass index (BMI). The indicators of foot symptoms, including frequency and location of pain, visual analogue scale (VAS), arch index (AI), and hind foot valgus angle (HVA), were measured during pretreatment and at the last follow-up. Results: Twenty-seven children were recruited for this study. After 4 years of custom-made foot orthosis treatment, significant improvements showed in pain frequency, VAS, AI, and HVA (P < 0.001). Type II ANBs showed a higher pain index pretreatment (P < 0.001) and reduced after treatment (P < 0.001). Conclusion: Mid-term effect of custom-made foot orthosis is inspiring in clinical symptoms of pediatric congenital ANBs combined with flexible flatfoot and may be an optional nonoperative treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-024-01210-7.

Age-related dysregulation of CXCL9/10 in monocytes is linked to impaired innate immune responses in a mouse model of Staphylococcus aureus osteomyelitis.

BACKGROUND: Age-associated impairments in innate immunity are believed to be a causative factor responsible for severe pathogenesis of Staphylococcus aureus (S. aureus) infection in the bone tissue. However, the basis for age-associated decline in innate immune response upon S. aureus infection remains poorly understood. RESULTS: Our transcriptional data (GEO: GSE166522) from a mouse model of S. aureus osteomyelitis show up-regulated CXCL9 and CXCL10 (CXCL9/10), which is further confirmed in vitro and in vivo by the present study. Notably, monocytes are a main source for CXCL9/10 production in bone marrow upon S. aureus challenge, but this response declines in middle-aged mice. Interestingly, conditional medium of bone marrow monocytes from middle-aged mice has a strikingly decreased effect on bactericidal functions of neutrophils and macrophages compares with that from young mice. We further show that activation of CXCL9/10-CXCR3 axis between monocytes and macrophages/neutrophils promotes the bactericidal function of the cells, whereas blocking the axis impairs such function. Importantly, treatment with either exogenous CXCL9 or CXCL10 in a middle-aged mice model enhances, while pharmacological inhibition of CXCR3 in young mice model impairs, bacterial clearance and bone marrow structure. CONCLUSIONS: These findings demonstrate that bone marrow monocytes act as a critical promotor of innate immune response via the CXLCL9/10-CXCR3 axis upon S. aureus infection, and that the increased susceptibility to S. aureus infection in skeleton in an aged host may be largely attributable to the declined induction of CXCR9/10 in monocytes.

The severity of preoperative bone marrow oedema negatively influences short-term clinical outcomes following arthroscopic bone marrow stimulation for osteochondral lesions of the talus.

PURPOSE: The purpose of this study was to study the effects of the severity of preoperative bone marrow oedema (BME) on the postoperative short-term outcomes following bone marrow stimulation (BMS) for osteochondral lesions of the talus (OLTs) and to propose a new metric that combines volume and signal density to evaluate BME. METHODS: Sixty-five patients with symptomatic OLTs (<100 mm2) and preoperative BME, who received BMS in our institution from April 2017 to July 2021 with follow-ups of 3, 6 and 12 months, were analysed retrospectively. The area, volume and signal value of the BME were collected on preoperative magnetic resonance imaging. The enroled patients were divided into two groups according to the BME index (BMEI), which was defined as the product of oedema relative signal intensity and the relation of oedema volume to total talar volume. Visual analogue scale, American Orthopedic Foot and Ankle Society (AOFAS), Tegner, Foot and Ankle Ability Measure (FAAM)-activities of daily living (ADL) and Sports scores were assessed before surgery and at each follow-up. The relationship between the scores and the volume, relative signal intensity and BMEI was explored. RESULTS: Sixty-five patients with preoperative BME were divided into the mild (n = 33) and severe (n = 32) groups based on the BMEI. A significant difference was found for each score with the general linear model for repeated measures through all follow-up time points (p < 0.001). For the preoperative and 12-month postoperative changes of the enroled patients, 53 patients (81.5%) exceeded the minimal clinically important difference of AOFAS and 26 (40.0%) exceeded that of FAAM-sports in this study. The mild group showed significantly more improvement in AOFAS scores at 12 months (89.6 ± 7.0 vs. 86.2 ± 6.2) and FAAM-ADL scores at 6 months (83.6 ± 7.6 vs. 79.7 ± 7.7) and 12 months (88.5 ± 8.5 vs. 84.4 ± 7.7) than the severe group (p < 0.05). No significant difference of all the scores between the groups was found at 3 months. No significant correlation was found in each group between BMEI and clinical outcomes. CONCLUSION: The severity of the preoperative BME negatively affected short-term clinical outcomes following arthroscopic BMS for OLTs. Worse clinical outcomes were shown at postoperative 6 and 12 months in patients with a high preoperative BMEI, which could be a favourable parameter for assessing the severity of BME and assist in developing personalised rehabilitation plans and determining the approach and timing of surgery. LEVEL OF EVIDENCE: Level III.

Recapitulation of HIV-1 Neutralization Breadth in Plasma by the Combination of Two Broadly Neutralizing Antibodies from Different Lineages in the Same SHIV-Infected Rhesus Macaque.

Viral infection generally induces polyclonal neutralizing antibody responses. However, how many lineages of antibody responses can fully represent the neutralization activities in sera has not been well studied. Using the newly designed stable HIV-1 Env trimer as hook, we isolated two distinct broadly neutralizing antibodies (bnAbs) from Chinese rhesus macaques infected with SHIV1157ipd3N4 for 5 years. One lineage of neutralizing antibodies (JT15 and JT16) targeted the V2-apex in the Env trimers, similar to the J038 lineage bnAbs identified in our previous study. The other lineage neutralizing antibody (JT18) targeted the V3 crown region in the Env, which strongly competed with human 447-52D. Each lineage antibody neutralized a different set of viruses. Interestingly, when the two neutralizing antibodies from different lineages isolated from the same macaque were combined, the mixture had a neutralization breath very similar to that from the cognate sera. Our study demonstrated that a minimum of two different neutralizing antibodies can fully recapitulate the serum neutralization breadth. This observation can have important implications in AIDS vaccine design.

A novel causative factor of injury: Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles.

Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles have not been reported to date. We retrospectively studied 419 patients admitted to our burn intensive care unit from January 2016 to December 2021. Of these 419 patients, 26 (22 male, 4 female; median age, 42 years) had burns related to lithium-ion battery fires and explosions, and all of their injury characteristics were similar to those of traditional flame burns. Lithium-ion battery-related burns were the eighth most common cause of burn injuries among all hospitalized patients. The 26 patients comprised 10 unemployed and 16 employed individuals. Twenty-three patients were injured at home during the battery charging process, and three were injured outdoors (one by a fire while the electric motorcycle was stationary and the others two by a fire while riding the motorcycle). The burn sites were distributed over the whole body; the burn area ranged from 10 % to 100 % of the total body surface area, and the burn depth ranged from superficial second-degree burns to third-degree burns. Twenty-three patients had inhalation injuries, and ten underwent prophylactic tracheostomy and intubation. Multiple operations were required for wound repair. Although convenient, lithium-ion electric motorcycles can also cause severe burns. To prevent these injuries, we must increase public safety awareness and education, develop new battery energy storage systems and battery management systems, and ensure the safety of batteries. Consumers should be aware of the potential dangers of lithium-ion batteries and comply with related security measures.

Comparative Efficacy of Fecal Microbiota Transplantation in Treating Refractory or Recurrent Clostridioides difficile Infection among Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study.

Clostridioides difficile infection (CDI) worsens inflammatory bowel disease (IBD) prognosis. While fecal microbiota transplantation (FMT) is effective for refractory or recurrent CDI (rrCDI), comparative success rates between IBD and non-IBD patients are scarce. This study addresses this gap. A retrospective cohort study was conducted at Chang Gung Memorial Hospital from April 2019 to October 2023. Patients receiving FMT for rrCDI were categorized into IBD and non-IBD groups. Baseline characteristics and outcomes were compared at one month and one year, with successful FMT defined as the resolution of diarrhea without CDI recurrence. The study included 88 patients: 30 with IBD and 58 without IBD. The IBD group was younger, with fewer comorbidities. Success rates at one month were similar between groups (IBD: 80.0% vs. non-IBD: 78.9%, p = 0.908), as were negative toxin tests (IBD: 83.3% vs. non-IBD: 63.8%, p = 0.174). One-year success rates (IBD: 70.0% vs. non-IBD: 67.6%, p = 0.857) and eradication rates (IBD: 94.4% vs. non-IBD: 73.9%, p = 0.112) were also similar. Poor bowel preparation predicted FMT failure at one month (OR = 0.23, p = 0.019). No safety issues were reported. FMT is a safe, effective treatment for rrCDI, demonstrating similar success rates in patients with and without IBD.

Insight into the Catalytic Oxidation Mechanism of Hydrogen Isotopes by Pt Clusters Confined by Silicalite-1.

Highly efficient removal of low concentrations of hydrogen isotope gas in air is crucial for the safe operation of nuclear energy plants. Herein, silicalite-1-confined Pt cluster catalysts were used for the catalytic oxidation of hydrogen isotopes, and the related catalytic mechanism was revealed. Increased temperature in direct hydrogen reduction treatment slightly increased the size of Pt clusters from 1.6 nm at 400 °C to 1.8 nm at 600 °C. The catalyst reduced at 600 °C exhibited excellent performance (99%) in hydrogen isotope oxidation at 75 °C, as well as high stability and catalytic efficiency in continuous and intermittent operation for 7200 min. X-ray absorbance spectroscopy confirmed the existence of Pt clusters in the catalysts, and the theoretical results showed that the total net charge was -0.07 e, indicating a slight charge transfer from the zeolite to the Pt atoms. The metal-support interaction thermally stabilized Pt clusters and altered the metal electronic structure, which enhanced the catalytic activity following a hydroperoxyl (OOH)-mediated route. Based on the low reaction temperature, efficient hydrogen conversion rate, and high stability, the silicalite-1-confined Pt cluster catalyst is expected to be used in hydrogen isotope oxidation treatment to achieve nuclear safety.

Imbalance of mitochondrial quality control regulated by STING and PINK1 affects cyfluthrin-induced neuroinflammation.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.

[Huaier triggering mitochondria apoptosis in colorectal cancer cells through oxidative stress].

This study investigates the specific mechanisms of Huaier-induced mitochondrial apoptosis in colorectal cancer. HCT116 and SW480 cells were subjected to Huaier treatment. Cell proliferation and migration capabilities were examined through CCK-8 and scratch experiments, respectively. Apoptotic cells were clarified with Annexin-PE staining. DCFH-DA staining, malondialdehyde(MDA), and glutathione(GSH) were used to evaluate the oxidative stress damage level of cells. MitoSOX and JC-1 probes were used to selectively target mitochondria reactive oxygen species(mtROS) and mitochondria membrane potential(MMP) for the evaluation of mitochondria damage. Western blot(WB) experiment was performed to determine apoptosis proteins and PINK1/Parkin pathway. Experiments reveal that in different concentrations of Huaier treatment, the proliferation and migration capabilities of HCT116 and SW480 cells were both restrained. Additionally, mitochondrial apoptosis was activated. Compared with the control group, excessive ROS in colorectal cancer cells was generated in the Huaier group, while MDA increased, and GSH decreased, indicating oxidative stress damage. mtROS increased, and MMP decreased in colorectal cancer cells treated with Huaier, indicating mitochondrial damage. WB result revealed that Huaier suppressed the PINK1/Parkin pathway, hindered the clearance of impaired mitochondria, and subsequently facilitated apoptosis. In conclusion, Huaier impairs colorectal cancer cells through oxidative stress and mitochondria damage. Furthermore, it suppressed the PINK1/Parkin pathway, promoting mitochondria apoptosis in colorectal cancer cells.

Human papillomavirus prevalence, genotype distribution, and prognostic factors of vaginal cancer.

We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I-Lan, Taiwan) and E6 type-specific-PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non-SCC. The median follow-up time was 134.3 months (range 0.9-273.4). Among nine initially HPV-negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole-genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non-SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5-year cancer-specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16- and HPV-positivity, LN metastasis and stage), were included in models 2-5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64-4.56) and LN metastasis (HR = 2.81-3.44) were significant negative predictors of CSS, whereas p16-positivity (HR = 0.29-0.32) and HPV-positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV-positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16- and HPV-positivity were significantly associated with better prognosis.

Mechanism analysis of essential oil from Radix Bupleuri for the treatment of asthma through regulation of ectopic olfactory receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Bupleuri is the root of Bupleurum chinense DC. (BC) and a classic aromatic traditional Chinese medicine. The traditional pharmacological effects of Radix Bupleuri are alleviating bronchial spasms, dilating airways, and promoting the resolution of respiratory inflammation, thereby reducing asthma symptoms. AIM OF THE STUDY: Studies have demonstrated the efficacy of water extracts from BC in asthma treatment. However, the potential role of volatile oil, another active constituent in BC, remains unexplored with asthma. Notably, volatile oil is renowned for its ease of absorption and direct targeting of affected areas, offering distinct advantages in alleviating airway inflammation. This study aims to explain the anti-asthmatic mechanism of BC-oil through in vivo and in vitro pharmacological experiments. MATERIALS AND METHODS: Firstly, the OVA-induced SD rat asthma model was utilized to evaluate the pharmacological effect of BC-oil by lung function monitoring, HE staining, flow cytometry, ELISA, and RT-qPCR. The anti-asthmatic mechanism was further analyzed by combining transcriptomic analysis of lung tissue from rat model and airway smooth muscle tissue from public database. Initially, GC-MS was used to analyze the components of BC-oil. The anti-asthmatic activity was evaluated in 16-HBE, RBL-2H3, and ASMC cells using CAMKII inhibitors to explore of the critical signal transduction regulated by BC-oil. Furthermore, molecular docking and calcium flow assay were utilized to screen and identify the active components from BC-oil. RESULTS: Oral administration of BC-oil significantly enhanced pulmonary function in asthmatic SD rats by reducing airway resistance and elastic resistance. Additionally, BC-oil inhibited inflammatory cytokines, including serum IL-2, pulmonary Il1b, Tnf, and Cxcl13, demonstrating potent anti-inflammatory and immunomodulatory effects. In this study, we analyzed the significant role of OR2W3 in asthma using public transcriptomic data. Furthermore, we indicated that BC-oil regulated the expression of Olr1433 and GNAL in rat lung tissue. BC-oil reduced degranulation and inhibited gene expression of Il3 and Tnf in RBL-2H3 cells and suppressed gene expression of IL8 and TNF in 16-HBE cells. BC-oil also attenuated airway smooth muscle cell proliferation and expression of Acta2 and Ccnd1. Furthermore, BC-oil regulates asthma-related cellular processes by activating CAMKII. GC-MS analysis identified 11 components of BC-oil, and n-hexadecanoic acid, linoleic acid and oleic acid from BC-oil were identified to interact with OR2W3 by molecular docking. The calcium flow assay revealed linoleic acid as a significant activator of OR2W3 and indicated that BC-oil alleviated asthma through the ectopic olfactory signaling pathway. CONCLUSIONS: The mechanism of BC-oil in treating asthma through signal transduction of OR2W3 is revealed at the molecular and cellular levels.

Association Between Red Blood Cell Distribution Width in Late Pregnancy and the Incidence of Adverse Perinatal Outcomes: A Retrospective Cohort Study.

BACKGROUND AND AIMS: This study aimed to quantify adverse perinatal outcomes (APO), including small/large for gestational age (SGA/LGA) and preterm birth (PTB), in pregnant women with abnormal red cell distribution width (RDW) and explore the related mechanisms. METHODS: This study included 11,659 pregnant women who delivered in a specialized hospital. At the time of admission, the lipid profiles and whole blood cell counts were assessed, and APO was analyzed. RESULTS: Women with high RDW (>18.5% [the 97.5th percentile]) in late pregnancy had a higher risk of LGA compared with those with low RDW (<12.3% [the 2.5th percentile]), whereas women with low RDW had a higher risk of SGA and PTB, compared with those with high RDW. A 1% increase in RDW was associated with an increased risk of LGA and a decreased risk of SGA and PTB. Consistent associations were observed in sensitivity analysis among pregnant women of non-advanced age, non-obesity, non-pregnancy complications, and non-PTB (for SGA/LGA only). Increased RDW was significantly associated with increased triglycerides and decreased high-density lipoprotein cholesterol (HDL-C). Triglycerides and HDL-C significantly mediated 10.63 and 15.8% of RDW-associated LGA, 9.51% and 9.40 of RDW-associated SGA, and 8.44 and -8.25% of RDW-associated PTB, respectively. CONCLUSION: Abnormal RDW was associated with an increased risk of APO, and the RDW-associated APO risk could be partially mediated by triglycerides and HDL-C, suggesting that RDW may be a promising APO predictor.

All-2D-Materials Subthreshold-Free Field-Effect Transistor with Near-Ideal Switching Slope.

The Boltzmann Tyranny, set by thermionic statistics, dictates the lower limit of switching slope (SS) of a MOSFET to be 60 mV/dec, the fundamental barrier for low-dissipative electronics. The large SS leads to nonscalable voltage, significant leakage, and power consumption, particularly at short channels, making transistor scaling an intimidating challenge. In recent decades, an array of steep-slope transistors has been proposed; none is close to an ideal switch with ultimately abrupt switching (SS ∼ 0 mV/dec) between the binary logic states. We demonstrated an all-2D-materials van-der-Waals-heterostructure (vdW)-based FET that exhibits ultrasteep switching (0.33 mV/dec), a large on/off current ratio (∼107), and an ultralow off current (∼0.1 pA). The "Subthreshold-Free" operation achieved by the collective behavior of functional materials enables FET switching directly from the OFF-state to the ON-state with entirely eliminated subthreshold region, behaving as the ideal logic switch. Two-inch wafer-scale device fabrication is demonstrated. Boosted by device innovation and emerging materials, the research presents an advancement in achieving the "beyond-Boltzmann" transistors, overcoming one of the CMOS electronics' most infamous technology barriers that have plagued the research community for decades.

Highly Efficient Phosphazene-Derivative-Based Flame Retardant with Comprehensive and Enhanced Fire Safety and Mechanical Performance for Polycarbonate.

Polycarbonate (PC) as a widely used engineering plastic that shows disadvantages of flammability and large smoke production during combustion. Although many flame-retardant PCs have been developed, most of them show enhanced flame retardancy but poor smoke suppression or worsened mechanical performance. In this work, a novel nitrogen-phosphorus-sulfur synergistic flame retardant (Pc-FR) was synthesized and incorporated into PC with polytetrafluoroethylene (PTFE). The extremely low content of PC-FR (0.1-0.5 wt%) contributes significantly to the flame retardancy, smoke suppression and mechanical performance of PC. PC/0.3 wt% Pc-FR/0.3 wt% PTFE (PC-P0.3) shows the UL-94 V-0 and LOI of 33.5%. The PHRR, THR, PSPR, PCO and TCO of PC-P0.3 decreased by 39.44%, 14.38%, 17.45%, 54.75% and 30.61%, respectively. The impact strength and storage modulus of PC-P0.1 increased by 7.7 kJ/m2 and 26 MPa, respectively. The pyrolysis mechanism of PC-P0.3 is also revealed. The pyrolysis mechanism of PC-P0.3 is stochastic nucleation and subsequent growth and satisfies the Aevrami-Erofeev equation. The reaction order of PC-P0.3 is 1/2. The activation energy of PC-P0.3 is larger than PC-0, which proves that the Pc-FR can suppress the pyrolysis of the PC. This work offers a direction on how to design high-performance PC.

Short-term OS as a surrogate endpoint for 5-year OS in nasopharyngeal carcinoma in non-endemic area.

PURPOSE: To address this evidence gap and validate short-term OS at less than 5 years as a reliable surrogate endpoint for 5-year OS. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on non-metastatic NPC patients diagnosed between 2010 and 2015. Patients were categorized into radiotherapy and chemoradiotherapy groups. RESULTS: This retrospective study examined 2,047 non-metastatic NPC patients. Among them, 217 received radiotherapy, and 1,830 received chemoradiotherapy. Our analysis results indicated that the 4-year OS may serve as a reliable surrogate endpoint for patients with AJCC clinical stage I (80 vs. 78%, P = 0.250), regardless of the treatment received. Specifically, in the radiotherapy group, patients with stage I, T0-T1, and N0 NPC showed similar OS rates at 4 and 5 years (83 vs. 82%, P = 1.000; 78 vs. 76%, P = 0.250; 78 vs. 77%, P = 0.500, respectively). Similarly, patients with stage II-IV, T2-T4, and N1-3 NPC showed no significant difference in OS rates between 3 and 5 years (57 vs. 51%, P = 0.063; 52 vs. 46%, P = 0.250; 54 vs. 46%, P = 0.125, respectively) in the radiotherapy group. In the chemoradiotherapy group, only the 3-year OS rate did not significantly differ from that at 5 years in stage I patients (79vs. 72%, P = 0.063). CONCLUSIONS: Our study suggests that short-term surrogate endpoints may be valuable for evaluating 5-year OS outcomes in NPC patients in non-endemic areas.

The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

The roles of circular RNAs in nerve injury and repair.

Nerve injuries significantly impact the quality of life for patients, with severe cases posing life-threatening risks. A comprehensive understanding of the pathophysiological mechanisms underlying nerve injury is crucial to the development of effective strategies to promote nerve regeneration. Circular RNAs (circRNAs), a recently characterized class of RNAs distinguished by their covalently closed-loop structures, have been shown to play an important role in various biological processes. Numerous studies have highlighted the pivotal role of circRNAs in nerve regeneration, identifying them as potential therapeutic targets. This review aims to succinctly outline the latest advances in the role of circRNAs related to nerve injury repair and the underlying mechanisms, including peripheral nerve injury, traumatic brain injury, spinal cord injury, and neuropathic pain. Finally, we discuss the potential applications of circRNAs in drug development and consider the potential directions for future research in this field to provide insights into circRNAs in nerve injury repair.

Demographic and lifestyle factors associated with dry eye disease in China: A cross-sectional multi-center study.

PURPOSE: Associations were assessed between demographic/lifestyle factors and tear film breakup time (TBUT) defined dry eye disease (DED) in China. METHODS: The cross-sectional study involved 50,280 subjects (54 ± 17 y) in 217 clinics (25 provinces). Data included sleep disorders; digital screen exposure; and use of cosmetics, contact lenses, and eye drops (for asthenopia). Clinical examinations included TBUT; Schirmer I test; meibomian gland plug status. TBUT-defined DED was TBUT <10 seconds, with TBUT ≤5 seconds also considered (i.e., short TBUT-type DED), either unilateral or bilateral. RESULTS: TBUT-defined DED was present in 81.6% overall. The highest rates were in those 71 years or older, living in the north, with chronic daily sleep disorder, or daily cosmetic application; or daily digital screen exposure for 5 years, contact lenses 4 hours, or 3 months eye drops. Compared with those without TBUT-defined DED, those with TBUT-defined DED showed lower Schirmer I results and more severe meibomian gland plug status (each, P <0.001). Independent risk factors of DED were: aging; living in the southwest; daily digital screen exposure ≥3 hours; and occasional cosmetic use. Risk factors of DED TBUT ≤ 5 s were: living in the southwest; wearing contact lenses (>3 y); and using eye drops. Rates of unilateral and bilateral DED were comparable. CONCLUSIONS: DED in China is more likely in the aged and those in the north/southwest. DED rates increase with digital screen exposure, and use of cosmetics, contact lenses, or eye drops for asthenopia. Unilateral DED should be treated as promptly as bilateral.