RANBP17 Overexpression Restores Nucleocytoplasmic Transport and Ameliorates Neurodevelopment in Induced DYT1 Dystonia Motor Neurons.

DYT1 dystonia is a debilitating neurological movement disorder, and it represents the most frequent and severe form of hereditary primary dystonia. There is currently no cure for this disease due to its unclear pathogenesis. In our previous study utilizing patient-specific motor neurons (MNs), we identified distinct cellular deficits associated with the disease, including a deformed nucleus, disrupted neurodevelopment, and compromised nucleocytoplasmic transport (NCT) functions. However, the precise molecular mechanisms underlying these cellular impairments have remained elusive. In this study, we revealed the genome-wide changes in gene expression in DYT1 MNs through transcriptomic analysis. We found that those dysregulated genes are intricately involved in neurodevelopment and various biological processes. Interestingly, we identified that the expression level of RANBP17, a RAN-binding protein crucial for NCT regulation, exhibited a significant reduction in DYT1 MNs. By manipulating RANBP17 expression, we further demonstrated that RANBP17 plays an important role in facilitating the nuclear transport of both protein and transcript cargos in induced human neurons. Excitingly, the overexpression of RANBP17 emerged as a substantial mitigating factor, effectively restoring impaired NCT activity and rescuing neurodevelopmental deficits observed in DYT1 MNs. These findings shed light on the intricate molecular underpinnings of impaired NCT in DYT1 neurons and provide novel insights into the pathophysiology of DYT1 dystonia, potentially leading to the development of innovative treatment strategies.

Enhanced Interface Charge Carrier Transport of SnO2/CeO2 via Oxygen Vacancy Synergized Heterojunction for Triethylamine Sensing Property.

Efficient charge carrier transport characteristics are critical to achieving the excellent performance of metal-oxide semiconductor gas sensors. Herein, SnO2/CeO2 heterojunction layered nanosheets with abundant oxygen vacancies were successfully synthesized through a simple solvothermal assisted high-temperature calcination method. The synergistic effect of oxygen vacancies and heterojunctions promoting the charge carrier transport properties at the SnO2/CeO2 interface for the enhanced sensing properties of triethylamine (TEA) was highlighted. As a result, the optimized SnO2/CeO2 exhibits improved gas sensing performance at 173 °C to 50 ppm of TEA. These include high response (205), excellent selectivity, low detection limit, and good long-term stability. This enhanced gas sensing property of SnO2/CeO2 is mainly attributed to the fact that the heterojunction and oxygen vacancies act as dual active sites synergistically inducing electron transfer, thereby effectively modulating the transport properties of the interfacial charge carriers, and thus facilitate the surface reactions efficiently. In this work, the dual-engineering strategy of synergistic interaction of heterojunction and oxygen vacancies can provide new perspectives for the design of advanced gas sensing materials.

Lipocalin 2 (LCN2) confers acquired resistance to almonertinib in NSCLC through LCN2-MMP-9 signaling pathway.

Almonertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is highly selective for EGFR-activating mutations as well as the EGFR T790M mutation in patients with advanced non-small cell lung cancer (NSCLC). However, the development of resistance inevitably occurs and poses a major obstacle to the clinical efficacy of almonertinib. Therefore, a clear understanding of the mechanism is of great significance to overcome drug resistance to almonertinib in the future. In this study, NCI-H1975 cell lines resistant to almonertinib (NCI-H1975 AR) were developed by concentration-increasing induction and were employed for clarification of underlying mechanisms of acquired resistance. Through RNA-seq analysis, the HIF-1 and TGF-ß signaling pathways were significantly enriched by gene set enrichment analysis. Lipocalin-2 (LCN2), as the core node in these two signaling pathways, were found to be positively correlated to almonertinib-resistance in NSCLC cells. The function of LCN2 in the drug resistance of almonertinib was investigated through knockdown and overexpression assays in vitro and in vivo. Moreover, matrix metalloproteinases-9 (MMP-9) was further identified as a critical downstream effector of LCN2 signaling, which is regulated via the LCN2-MMP-9 axis. Pharmacological inhibition of MMP-9 could overcome resistance to almonertinib, as evidenced in both in vitro and in vivo models. Our findings suggest that LCN2 was a crucial regulator for conferring almonertinib-resistance in NSCLC and demonstrate the potential utility of targeting the LCN2-MMP-9 axis for clinical treatment of almonertinib-resistant lung adenocarcinoma.

The regulation and its application of the charge decay rate in triboelectric nanogenerator.

The decay rate of charge in the friction layer is one of the key factors affecting the output performance of triboelectric nanogenerators (TENG). Reducing the decay rate of the triboelectric charge can increase the charge-carrying capacity of the friction layer and improve the output current and voltage of the TENG. This makes a friction generator more suitable for discontinuous driving environments. In contrast, increasing the decay rate of the charge in the friction layer can greatly improve the recovery time of the device, although it reduces the output performance of the generator. This is conducive to the application of friction generator in the field of sensors. In this study, polystyrene (PS) and carbon nanotubes (CNTs) were added to polyvinylidene fluoride (PVDF) nanofibers to adjust the charge decay time in the friction layer, thereby regulating the output performance of the friction generator and sensor. When the amount of added PS in the PVDF nanofiber reached 20%, the charge density on the friction surface increased by 1.9 times, and the charge decay time decreased by 64 times; when 0.1 wt% CNTs were added in the PVDF nanofiber, the charge decay time increased by more than 10 times. The former is more conducive to improving the power generation performance of the TENG, and the latter significantly improves the stability and repeatability of TENG-based sensors.

Pigment Diversity in Leaves of Caladium × hortulanum Birdsey and Transcriptomic and Metabolic Comparisons between Red and White Leaves.

Leaf color is a key ornamental characteristic of cultivated caladium (Caladium × hortulanum Birdsey), a plant with diverse leaf colors. However, the genetic improvement of leaf color in cultivated caladium is hindered by the limited understanding of leaf color diversity and regulation. In this study, the chlorophyll and anthocyanin content of 137 germplasm resources were measured to explore the diversity and mechanism of leaf color formation in cultivated caladium. Association analysis of EST-SSR markers and pigment traits was performed, as well as metabolomics and transcriptomics analysis of a red leaf variety and its white leaf mutant. We found significant differences in chlorophyll and anthocyanin content among different color groups of cultivated caladium, and identified three, eight, three, and seven EST-SSR loci significantly associated with chlorophyll-a, chlorophyll-b, total chlorophyll and total anthocyanins content, respectively. The results further revealed that the white leaf mutation was caused by the down-regulation of various anthocyanins (such as cyanidin-3-O-rutinoside, quercetin-3-O-glucoside, and others). This change in concentration is likely due to the down-regulation of key genes (four PAL, four CHS, six CHI, eight F3H, one F3'H, one FLS, one LAR, four DFR, one ANS and two UFGT) involved in anthocyanin biosynthesis. Concurrently, the up-regulation of certain genes (one FLS and one LAR) that divert the anthocyanin precursors to other pathways was noted. Additionally, a significant change in the expression of numerous transcription factors (12 NAC, 12 bZIP, 23 ERF, 23 bHLH, 19 MYB_related, etc.) was observed. These results revealed the genetic and metabolic basis of leaf color diversity and change in cultivated caladium, and provided valuable information for molecular marker-assisted selection and breeding of leaf color in this ornamental plant.

cPKCγ Inhibits Caspase-9-Initiated Neuronal Apoptosis in an Ischemia Reperfusion Model In Vitro Through p38 MAPK-p90RSK-Bad Pathway.

Strokes are one of the leading causes of death and disability in the world. Previously we have found that conventional protein kinase Cγ (cPKCγ) plays neuroprotective role in ischemic strokes. Further, we found that cPKCγ knockdown increased the level of cleaved (cl)-Caspase-3. However, the precise mechanisms underlying cPKCγ-mediated neuronal death remain unclear. To this end, a model incorporating 1 h oxygen-glucose deprivation/24 h reoxygenation (1 h OGD/24 h R) was established in cortical neurons. We found that cPKCγ knockdown remarkably increased neuronal death after OGD. We also found that cPKCγ knockdown increased the level of cl-Caspase-3 through the upstream initiators Capsases-9 (not Caspase-8/12) in OGD-treated neurons. Overexpression of cPKCγ could decrease neuronal death and cl-Caspase-3 and -9 levels. Moreover, cPKCγ knockdown further reduced the phosphorylation levels of p38 MAPK, p90RSK, and Bad. In addition, the protein levels of Bcl-2 and Bcl-xl were decreased after cPKCγ knockdown, whereas that of Bax was increased. In conclusion, our results suggest that cPKCγ partly alleviates ischemic injury through activating the p38 MAPK-p90RSK-Bad pathway and inhibiting Caspase-9 initiated apoptosis. This may have potential as a therapeutic target for ischemic stroke.

Free-range domestic chickens can distinguish between different alarm calls of Japanese tits.

Heterospecific eavesdropping of alarm information is an anti-predator adaptation in the wild as it improves the monitoring of shared predators and hence provides opportunities to avoid predators. Our current understanding of heterospecific eavesdropping information is based primarily on studies of bird, primate, or ungulate populations in the wild, whereas little is known regarding the ability of domesticated species to respond to alarm signals from wild individuals. Using sound playback experiments, we assessed the behavioral responses of free-range domestic chickens (Gallus gallus domesticus) in Hainan to alarm calls (test playback) and songs (control playback) of wild Japanese tits (Parus minor). The results revealed that free-range domestic chickens showed greater vigilance to the alarm calls of Japanese tits than to the songs of Japanese tits, especially their alarm calls for Siberian chipmunks (Tamias sibiricus). Furthermore, individual-foraging single chickens were significantly more vigilant than those foraging collectively in groups. Our findings suggest that free-range domestic chickens are as capable as wild birds in responding to heterospecific alarm calls and are likely to be able to distinguish between different types of heterospecific alarm calls.

Diversity, classification, and EST-SSR-based association analysis of caladium ornamental traits.

Caladium (Caladium × Hortulanum Birdsey) is a popular ornamental plant with a wide range of vibrant leaf color among Araceae. Even after years of breeding, creating new caladium leaf color variations is extremely difficult. Molecular marker-assisted selection is an effective approach for accelerating breeding, but few studies on the molecular markers associated with caladium traits have been performed. In the current study, 144 caladium accessions were used to examine 12 phenotypic characteristics. The coefficient of variation for four numerical characters ranged from 23.94% to 43.22%, and the Shannon-Wiener indexes for eight descriptive characters ranged from 0.13 to 1.52. Based on L*, a*, b*, C, h° values determined by a colorimeter and hierarchical cluster analysis, the leaf color can be divided into four groups: pale green, green, light pink, and red. Furthermore, 7708 new SSR loci were identified by transcriptome sequencing, and 26 SSR markers with high polymorphism and reproducibility were screened. Genetic structure, NJ clustering, and PCoA analysis revealed that 144 accessions could be divided into three clusters, with genetic structure being closely related to germplasm origin. An association analysis revealed that the SSR markers 2, 1, 1, 1, 1, and 1 were mainly associated with petiole color, main vein color, blade upperside glossiness, and C, b*, and L* of leaf color (p < 0.01). These findings will serve as a valuable reference for evaluating germplasm resources and caladium molecular marker-assisted breeding.

Development and validation of a nomogram for predicting dysphagia in long-term care facility residents.

BACKGROUND: Dysphagia is a common problem that can seriously affect the health of elderly residents in long-term care facilities. Early identification and targeted measures can significantly reduce the incidence of dysphagia. AIM: This study aims to establish a nomogram to evaluate the risk of dysphagia for elderly residents in long-term care facilities. METHODS: A total of 409 older adults were included in the development set, and 109 were included in the validation set. Least absolute shrinkage selection operator (LASSO) regression analysis was used to select the predictor variables, and logistic regression was used to establish the prediction model. The nomogram was constructed based on the results of logistic regression. The performance of the nomogram was evaluated by receiver operating characteristic (ROC) curve, calibration, and decision curve analysis (DCA). Internal validation was performed using tenfold cross-validation with 1000 iterations. RESULTS: The predictive nomogram included the following variables: stroke, sputum suction history (within one year), Barthel Index (BI), nutrition status, and texture-modified food. The area under the curve (AUC) for the model was 0.800; the AUC value for the internal validation set was 0.791, and the AUC value for the external validation set was 0.824. The nomogram showed good calibration in both the development set and validation set. Decision curve analysis (DCA) demonstrated that the nomogram was clinically valuable. DISCUSSION: This predictive nomogram provides a practical tool for predicting dysphagia. The variables included in this nomogram were easy to assess. CONCLUSIONS: The nomogram may help long-term care facility staff identify older adults at high risk for dysphagia.

Fine-Scale Structuring of Planktonic Vibrio spp. in the Chinese Marginal Seas.

Vibrio is ubiquitous in marine environments with high metabolism flexibility and genome plasticity. Studies have investigated the ecological distribution of Vibrio spp. in several narrow zones, but a broad scale pattern of distribution and community assembly is still lacking. Here, we elucidated the distribution of Vibrio spp. in seawater along the Chinese marginal seas with a high spatial range. Comparison of Vibrio abundance between 3- and 0.2-µm-pore-size membranes showed distinction in preferential lifestyle. Vibrio spp. in the Yellow Sea (YS) was low in abundance and adopted a particle-associated lifestyle, whereas that in the East China Sea (ECS) and South China Sea (SCS) was more abundant and was likely in a temporary free-living state as a strategy to cope with nutrient limitation. Vibrio community compositions were also separated by sampling area, with different dominant groups in YS (Vibrio chagasii and Vibrio harveyi), ECS and SCS (Vibrio japonicus and V. chagasii). The community niche breadth was significantly wider in ECS and SCS than that of YS. Among species, V. chagasii and V. harveyi had the largest niche breadths likely reflecting strong competitive positions. Stochastic processes played important roles in shaping the geographical pattern of the vibrionic community. Environmental selection (e.g., temperature, salinity, and dissolved oxygen) had a much greater impact on the community in surface than in bottom water. The large proportions of unexplained variations (78.9%) imply complex mechanisms in their community assembly. Our study provides insights into the spatial distribution patterns and underlying assembly mechanisms of Vibrio at a broad spatial scale. IMPORTANCE Vibrio spp. may exert large impacts on biogeochemical cycling in coastal habitats, and their ecological importance has drawn increasing attention. Here, we investigated the spatial distribution pattern and community assembly of Vibrio populations along the Chinese marginal seas, spanning a wide spatial scale. Our results showed that the abundances of the Vibrio population increased with decreasing latitude and their preferential lifestyle differed among adjacent coastal areas. The compositions of Vibrio spp. were also separated by geographical location, which was mainly attributable to stochastic processes. Overall, this work contributes to the understanding of the ecological distribution patterns and the community assembly mechanisms of marine vibrios at a high spatial range. The large proportion of unexplained variations indicates the existence of complex mechanisms in the assembly of vibrionic community which should be considered comprehensively in future.

Evaluation of pharmacist interventions as part of a multidisciplinary cancer pain management team in a Chinese academic medical center.

OBJECTIVE: The objective of this study was to evaluate pharmacist interventions in the cancer pain management of hospitalized patients, focusing on a clinically meaningful change in drug-related problems and pain score. METHODS: A retrospective data analysis was performed at a single academic comprehensive cancer center. Hospitalized patients with moderate to severe pain who had already received analgesic medication for at least 3 consecutive days were included. For patients who met the criteria for admission, a pharmacist followed up daily during hospitalization and evaluated the patient during pre- (first) and postintervention (second, third, and fourth) visits. Medication problems, medication changes, and changes in pain scores were assessed. RESULTS: A total of 195 patients were included in the study. The pharmacist identified 12 types of pharmacotherapeutic drug-related problems. The top 3 problems were nonadherence or missed doses (27.69%), inappropriate opioid selection (22.56%), and inappropriate dosage (16.41%). After the intervention of pharmacists, these drug-related problems decreased by 74.54% on average. Across all visits, the changes in pain scores (mean ± SD: 2.80 ± 1.92 vs. 1.90 ± 1.58, P < 0.05) and the number of patients with mild (172 vs. 128, P < 0.05), moderate (58 vs. 21, P < 0.05), and severe pain (9 vs. 2, P < 0.05) indicated a marked decrease in patients' pain levels after the inclusion of pharmacist in the cancer pain multidisciplinary management team (CPMMT). CONCLUSION: Participation by the pharmacist in the CPMMT led to a marked reduction in most of the drug-related problems and a statistically significant change in pain score during the 4 visits, indicating that pharmacists play an active role in CPMMT.

Moxibustion treatment for diarrhea-predominant irritable bowel syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a worldwide disease with high morbidity. The effect of current treatment with Western medicine is not satisfactory. Although moxibustion treatment is widely used for gastrointestinal diseases, randomized controlled trials on the use of this treatment for IBS are limited. This study aims to evaluate the clinical efficacy and safety of moxibustion treatment in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS/DESIGN: A multi-center, randomized, single-blind and placebo-controlled trial is employed. 104 cases will be divided into two groups: (1) a mild-warm moxibustion group in which moxa stick is 3-5 cm away from acupuncture points and the skin temperature is maintained at 43 ± 1 °C; and (2) a placebo moxibustion group in which moxa stick is 8-10 cm away from acupuncture points and the skin temperature is maintained at 37 ± 1 °C. Moxibustion is performed on bilateral ST25 and ST36 in the two groups for 30 min each time, three times a week for 6 weeks. The patients are followed up at the 12th and 18th weeks. Adequate relief is used as a primary outcome measure; IBS symptom severity score, Bristol stool form scale, IBS quality-of-life questionnaire, and hospital anxiety and depression scale are used as secondary outcome measures. DISCUSSION: This study aims to demonstrate the safety and efficacy of moxibustion treatment for IBS-D, which may validate moxibustion as an effective therapy for treating IBS-D. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02421627 (8 April 2015).

Temporal manipulation of light propagation via cross-intensity modulation in unbalanced fiber Mach-Zehnder interferometers.

We theoretically propose and experimentally demonstrate an approach to achieve temporal manipulation of light propagation via cross-intensity modulation (XIM) effect in an unbalanced fiber Mach-Zehnder interferometer (MZI). By changing the optical loss indices (which can also be gain indices theoretically) discrepantly in the two branches of the MZI, we can obtain the largest time shifts at the minima of the transmission frequency spectrum, while there shows no time shifts at the maxima. This scheme provides a flexibility of ultra-wide bandwidth operation both on optical wavelength and modulation frequency.

Fast-light-assisted four-wave mixing in the photonic bandgap.

In this Letter, the enhanced four-wave mixing (FWM) in the photonic bandgap of fiber Bragg grating (FBG) has been achieved with an extra phase introduced by fast-light effect in the bandgap. The experiment for phase-matched FWM generation in the bandgap in a special-designed FBG was carried out, as well as simulations. The enhanced energy conversion with such a FWM in the bandgap has been demonstrated but the transmissivity has not. The experimental results show agreement with the simulations.

Efficient soybean regeneration and Agrobacterium-mediated transformation using a whole cotyledonary node as an explant.

An optimized regeneration and Agrobacterium-mediated transformation protocol based on whole cotyledonary node explants was developed in soybean (Glycine max) cultivar Zhong Huang 13. Adding 6-benzylaminopurine (BAP) in a germinating medium could significantly increase regeneration efficiency; the optimal BAP concentration for shoot formation was 0.5 mg/L. The concentrations of plant growth regulators in a shoot induction medium were optimized by the orthogonal test [L9 (3(3))]. The best combination for shoot regeneration was a medium of Murashige & Skoog salts with B5 vitamins (MSB) supplemented with 3.5 mg/L BAP, 0.2 mg/L indole-3-butyric acid (IBA), and 0.2 mg/L kinetin (KT). Under this favorable condition, one node could regenerate 28-30 shoots. Soybean whole cotyledonary nodes were transformed by inoculation with A. tumefaciens strain EHA105 harboring a vector pBI121 containing a ß-glucuronidase gene (gus). GUS assay, polymerase chain reaction, and Southern blot analysis indicated that the gus gene was transformed into soybean plants with 23.1% transformation efficiency. Transgenic plants could be obtained within 5-6 weeks, which was about 4 weeks less than that of a traditional single cotyledonary node method.

Flexible fiber nanogenerator with 209 V output voltage directly powers a light-emitting diode.

On the basis of a vertically aligned ultralong Pb(Zr(0.52)Ti(0.48))O(3) (PZT) nanowire array fabricated using electrospinning nanofibers, we developed a new type of integrated nanogenerator (NG) with ultrahigh output voltage of 209 V and current density of 23.5 µA/cm(2), which are 3.6 times and 2.9 times of the previous record values, respectively. The output electricity can be directly used to stimulate the frog's sciatic nerve and to induce a contraction of a frog's gastrocnemius. The NG can instantaneously power a commercial light-emitting diode (LED) without the energy storage process.

The prevalence of antinuclear antibodies in the general population of china: a cross-sectional study.

BACKGROUND: The incidence of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis has increased significantly in China. Information about the susceptibility or potential of autoimmune diseases in the general population is lacking. OBJECTIVE: To explore the prevalence of antinuclear antibody (ANA) and its specificities in the general population in China. METHODS: Twenty thousand nine hundred seventy sera samples were taken from the physical examination center in Baoding, China. Indirect immunofluorescence and line immunoassays were used to detect ANA and its specificities, respectively. RESULTS: Samples from females had a higher prevalence of ANA than samples from males (χ(2) = 278.55; P < 0.01). For both sexes, the prevalence of ANA positively correlated with age and there were significant differences among different age groups at 10-year intervals, except the 80 years group (P < 0.05). One thousand two hundred forty-three ANA-positive samples were further analyzed with line immunoassays. There was a significant difference among age groups and between sex groups in terms of the specific autoantibodies (P < 0.01). The autoantibodies with the top-3 positive frequencies were anti-Ro-52, anti-M2, and anti-SSA. CONCLUSIONS: There was a high prevalence of ANA positivity in the general Chinese population that seemed to be influenced by sex and age and correlated with specific autoantibodies.

[Evaluation of markers associated with primary biliary cirrhosis in a population of anti-mitochondrial antibody-M2-positive individuals].

OBJECTIVE: To explore the distribution of the main clinical symptoms and signs of primary biliary cirrhosis (PBC) in a population of individuals with positivity for anti-mitochondrial antibody-M2 (AMA-M2). METHODS: A total of 20 970 persons who participated in routine health examinations at our hospital were tested for presence and level of antinuclear antibodies (ANAs) using an indirect immunofluorescence (IIF) assay and of AMA-M2 by western blotting. The chi-square test was used for statistical analysis. RESULTS: Titers of ANAs more than 1:320 were detected in 1 243 of all the study participants, with 156 of those individuals having detectable AMA-M2.The overall rate ofAMA-M2 positivity was 0.74%, with a significantly higher rate among female subjects (males:0.3% (32/10 550) vs.females:1.2% (124/10 420); x2=55.85, P less than 0.05). Among the AMA-M2-positive population there were 66 cases of abnormal liver function, 58 cases of increased alkaline phosphatase, 72 cases of abnormal findings for routine blood testing, 47 cases of gallbladder disease history, 49 cases of diabetes history, 22 cases of allergy, 75 cases of abdominal discomfort, 38 cases of weakness, 3 cases of jaundice, and 11 cases of pruritus. There were significant differences between the AMA-M2-negative individuals and the AMA-M2-positive individuals. CONCLUSION: Among the general population, individuals with substandard states of health, such as those with abnormal findings in routine blood tests and abnormal liver function, should be screened for AMA-M2. This screening will facilitate early diagnosis of PBC and timely initiation of disease management, improving the patient's life quality of life and prolonging their life.

Laparoscopic continuous seromuscular circumsuture for myomectomy: a real-world, retrospective, East-Asian cohort study.

OBJECTIVE: This study aimed to introduce a novel laparoscopic haemostasis for myomectomy and investigate the independent risk factors for uterine fibroid recurrence. DESIGN: A retrospective cohort study. SETTING: Following strengthening the reporting of observational studies in epidemiology (STROBE) criteria, a retrospective study of prospectively collected available data of the consecutive patients who underwent the myomectomy in the department of obstetrics and gynaecology of the single centre between February 2018 and December 2020. PARTICIPANTS: 177 patients who underwent laparoscopic myomectomy resection were enrolled in the present cohort study. MATERIALS AND METHODS: Patients were classified into two groups according to their different methods of haemostasis in laparoscopic surgery. Recurrence-free survival was compared between the groups during an average follow-up of nearly 2 years. RESULTS: Of the 177 patients from 672 consecutive patients in the retrospective cohort, laparoscopic circular suture and baseball suture were carried out in 102 (57.6%) and 75 (42.4%) patients, respectively. The total amount of blood lost during surgery varied significantly (37.6 vs 99.5 mL) (p<0.001). Univariable analyses identified that age ≥40 years, position at intramural myoma, multiple fibroids and largest fibroid volume ≥50 mm3 (HR 2.222, 95% CI 1.376 to 3.977, p=0.039; HR 3.625, 95% CI 1.526 to 6.985, p=0.003; HR 3.139, 95% CI 1.651 to 5.968, p<0.001; HR 2.328, 95% CI 0.869 to 3.244, p=0.040, respectively) are independent risk factor of the recurrence of uterine fibroids. The formula of the nomogram prediction model was established as the practical clinical tool. CONCLUSION: The laparoscopic continuous seromuscular circumsuture for myomectomy can effectively reduce the amount of surgical bleeding and accelerate the perioperative recovery for surgical safety. The main factors affecting the recurrence of uterine fibroids were age, location, number and volume of uterine fibroids. The nomogram can more straightforwardly assist clinicians to determine the risk of recurrence after laparoscopic myomectomy.

Hepatitis-related adverse events associated with immune checkpoint inhibitors in cancer patients: an observational, retrospective, pharmacovigilance study using the FAERS database.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data. Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs. Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80-21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95-248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65-5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8-72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78-6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy. Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.