Exploring the metabolic implications of blue light exposure during daytime in rats.

Excessive exposure to light is a global issue. Artificial light pollution has been shown to disrupt the body's natural circadian rhythm. To investigate the impacts of light on metabolism, we studied Sprague-Dawley rats chronically exposed to red or blue light during daytime or nighttime. Rats in the experimental group were exposed to extended light for 4 hours during daytime or nighttime to simulate the effects of excessive light usage. Strikingly, we found systemic metabolic alterations only induced by blue light during daytime. Furthermore, we conducted metabolomic analyses of the cerebrospinal fluid, serum, heart, liver, spleen, adrenal, cerebellum, pituitary, prostate, spermatophore, hypothalamus and kidney from rats in the control and blue light exposure during daytime. Significant changes in metabolites have been observed in cerebrospinal fluid, serum, hypothalamus and kidney of rats exposed to blue light during daytime. Metabolic alterations observed in rats encompassing pyruvate metabolism, glutathione metabolism homocysteine degradation, phosphatidylethanolamine biosynthesis, and phospholipid biosynthesis, exhibit analogous patterns to those inherent in specific physiological processes, notably neurodevelopment, cellular injury, oxidative stress, and autophagic pathways. Our study provides insights into tissue-specific metabolic changes in rats exposed to blue light during the daytime and may help explain potential mechanisms of photopathogenesis.

Genomic epidemiology reveals multiple mechanisms of linezolid resistance in clinical enterococci in China.

BACKGROUND: Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. METHODS: Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. RESULTS: The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. CONCLUSIONS: Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively colleced data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analysed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×103 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group (n=179 patients) and the normalization group (n=73 patients) had better OS and RFS than the non-normalization group (n=65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P<0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P=0.255; RFS, P=0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P=0.025; RFS, P=0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Multi-functional composite dressings with sustained release of MSC-SLP and anti-adhesion property for accelerating wound healing.

Exudate management is of significant clinical value for the treatment of acute wound. Various wound dressings have been developed to restore the function of injured tissues and promote wound healing, but proper exploiting the healing factors inside exudate and achieving anti-adhesion wound care remains a challenge. Herein, we present a novel multi-functional composite dressing (MCD) by coupling supernatant lyophilized powder of mesenchymal stem cells (MSC-SLP) with a sandwich-structured wound dressing (SWD). The developed MCDs demonstrated unique unidirectional drainage capability, stable anti-adhesion characteristics, and improved wound healing performance. The designed SWD with both superhydrophobic inner surface and liquid-absorption ability of mid layer enables the dressings exhibit desired anti-adhesion property to neoformative granulation tissues, favorable shielding effect to exogenous bacteria, as well as appropriate exudate-retaining capability and unidirectional exudate-absorption property. The introduction of MSC-SLP in SWD was demonstrated to further improve wound healing quality. Compared to medical gauze, the synergic effect of SWD and MSC-SLP significantly accelerates wound healing rate by over 30%, avoids tissue avulsion when changing dressings, and produces a flat-smooth closure surface. More importantly, the wound treated with MCDs presents more skin accessory organs and blood vessels in regenerated tissues than other groups. In vivo/vitro biocompatibility evaluations indicated little toxicity, demonstrating the biosecurity of the developed dressings. The proposed method offers great potential in clinical applications particularly for chronic wound treatments.

Serum Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) as a Potential Biomarker for Diagnosis of Hepatocellular Carcinoma.

Objective: To evaluate the diagnostic performance of aldo-keto reductase family 1 member B10 (AKR1B10) in a Beijing cohort with hepatocellular carcinoma (HCC). Methods: This study included 521 subjects who visited Peking Union Medical College Hospital from June 2017 to May 2023, including 109 cases of HCC, 165 cases of healthy controls, 106 cases of benign liver diseases, and 141 cases of other cancers. Serum AKR1B10 levels were measured and compared across various groups. Diagnostic performances of serum AKR1B10 and other tumor markers were assessed using receiver operator characteristic (ROC) curves. In addition, a subset of HCC patients who underwent surgical resection were recruited for clinical follow-up study. Results: We found that serum AKR1B10 expression was higher in patients with HCC relative to other control groups. The association between serum AKR1B10 and clinical features of HCC was not observed. Serum AKR1B10 showed a high diagnostic performance for HCC, and when combined with AFP, the diagnostic effectiveness was significantly improved. Specifically, serum AKR1B10 showed superior diagnostic effectiveness for AFP-negative HCC. The clinical follow-up study indicated a gradual decrease in serum AKR1B10 after surgery. Conclusion: Our study demonstrated that serum AKR1B10 is a promising biomarker for HCC, and when used in combination with AFP can significantly improve the detection rate of HCC.

Outcomes associated to the time to treatment with intravenous tenecteplase for acute ischaemic stroke: subgroup analysis of the TRACE-2 randomised controlled clinical trial.

BACKGROUND: The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks. METHODS: This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0-1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0-90 min, 91-180 min and 181-270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment. RESULTS: Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0-90 min, 1.23 (95% CI 0.88 to 1.71) for 91-180 min and 1.21 (95% CI 0.88 to 1.65) for 181-270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI -0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI -2.66 to 6.20; p=0.58) for 0-180 min. CONCLUSIONS: In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.

Theoretical Investigation on Indirect Tensile Strength of Concrete with Rectangular Cross-Section under Locally Distributed Load.

The indirect tensile test plays a crucial role in experimental investigations of brittle material properties. In this study, a mechanical analysis model of the rectangular test block is established based on the theory of elastic mechanics for the characteristics of the indirect tensile test. The theoretical solution of the triangular series is derived for the rectangular test block under the locally distributed load. The finite element simulation results and splitting test results were compared with the theoretical results. The results of the study verify the accuracy of the theoretical solutions. Based on the proposed analytical solution, the effects of loading width and length-to-height ratio (h/l) of local loading on the measured tensile strength of test block are discussed. The results demonstrate that the tensile strength of the test block increases as the loading width expands, and the rate of growth in the recorded tensile strength gradually stabilizes. The variation in loading width affects the location of crack initiation points during the concrete test block splitting tests. When the loading width exceeds 6% of the side length of test block, the cracking point is positioned at the center of test block, ensuring the effectiveness of the splitting test. As the length-to-height ratio of the test block increases, there is a general upward trend in the measured tensile strength. When h/l < 0.6, the measured tensile strength initially increases before decreasing. However, when h/l > 0.6, the measured tensile strength consistently increases, with the rate of increase gradually diminishing until it stabilizes. The length-to-height ratio also significantly influences the location of the cracking point in the test block. As the length-to-height ratio increases, the cracking point initially shifts from around the center to the central point and then further from the center toward the edge. To ensure that the location of the crack initiation point is in the center of the specimen and that the tensile strength is close to the measured result, the length to height ratio can be chosen at around 0.85.

Prevalence of Ureaplasma species among patients at a tertiary hospital in China: a 10-year retrospective study from 2013 to 2022.

BACKGROUND: Ureaplasma species are common pathogens of the urogenital tract and can cause a range of diseases. Unfortunately, there is still a scarcity of large-scale and cross-sectional studies on the prevalence of Ureaplasma species in China to clarify their epidemic patterns. METHODS: This study retrospectively analyzed the data of 18667 patients who visited Peking Union Medical College Hospital for showing various symptoms of (suspected) Ureaplasma species infection during the period 2013-2022. The overall prevalence of Ureaplasma species was calculated, and subgroup analyses were conducted in view of gender, age, specimen types, and diagnosis in every year within the period studied. Furthermore, previous literature that reported on the prevalence of Ureaplasma species in various regions of China was searched and summarized. RESULTS: The overall positive rate of Ureaplasma species in this study reached 42.1% (7861/18667). Specifically, the prevalence of Ureaplasma species was significantly higher in female patients, while the highest detection rate was found in the 21-50 age group. From 2013 to 2022, there were no significant differences in positive rates of Ureaplasma species among years. However, the detection rate of Ureaplasma species was decreased in COVID-19 period (2020-2022) compared to pre-COVID-19 period (2017-2019). In view of the distribution of patients, outpatients predominated, but the detection rate was lower than inpatients. Urine was the most common specimen type, while cervical swabs had the highest detection rate of Ureaplasma species. When grouped by diagnosis, the highest positive rate of Ureaplasma species was seen in patients with adverse pregnancy outcomes and the lowest rate in patients with prostate disease. The previous literature, although heterogeneous, collectively suggested a high prevalence of Ureaplasma species in China. CONCLUSIONS: Our study has shown that Ureaplasma species have reached a significant prevalence in China and demands adequate attention.

Pathological Features and Genetic Polymorphism Analysis of Tomato Spotted Wilt Virus in Infected Tomato Fruit.

An in-house tomato inbred line, YNAU335, was planted in a greenhouse in spring from 2014 to 2017, and showed immunity to tomato spotted wilt virus (TSWV). YNAU335 was infected with TSWV in the spring from 2018 to 2020, and disease was observed on the leaves, sepals, and fruits. In 2021 and 2022, YNAU335 was planted in spring in the same greenhouse, which was suspected of being infected with TSWV, and visible disease symptoms were observed on the fruits. Transmission electron microscopy, deep sequencing of small RNAs, and molecular mutation diagnosis were used to analyze the pathological features and genetic polymorphism of TSWV infecting tomato fruit. Typical TSWV virions were observed in the infected fruits, but not leaves from YNAU335 grown between 2021 and 2022, and cross-infection was very rarely observed. The number of mitochondria and chloroplasts increased, but the damage to the mitochondria was greater than that seen in the chloroplasts. Small RNA deep sequencing revealed the presence of multiple viral species in TSWV-infected and non-infected tomato samples grown between 2014-2022. Many virus species, including TSWV, which accounted for the largest proportion, were detected in the TSWV-infected tomato leaves and fruit. However, a variety of viruses other than TSWV were also detected in the non-infected tissues. The amino acids of TSWV nucleocapsid proteins (NPs) and movement proteins (MPs) from diseased fruits of YNAU335 picked in 2021-2022 were found to be very diverse. Compared with previously identified NPs and MPs from TSWV isolates, those found in this study could be divided into three types: non-resistance-breaking, resistance-breaking, and other isolates. The number of positive clones and a comparison with previously identified amino acid mutations suggested that mutation F at AA118 of the MP (GenBank OL310707) is likely the key to breaking the resistance to TSWV, and this mutation developed only in the infected fruit of YNAU335 grown in 2021 and 2022.

Effect of domestic COVID-19 vaccine on the plasma D-dimer levels of early pregnant women in China.

Objective: To investigate the effect of COVID-19 vaccination on plasma D-dimer levels in early pregnant women. Methods: A total of 834 early pregnant women(gestational age ≤ 13 weeks), who visited Northwest Women and Children's Hospital between December 2020 and April 2022, were selected. There were 696 women in the healthy group (group A) and 138 in the group with a history of adverse pregnancy and childbirth (group B). The plasma D-dimer levels of all participants were tested, and the COVID-19 vaccine history of all participants was collected using a survey questionnaire. Results: The plasma D-dimer levels did not differ between group A and the group B (p = 0.1327). In the group A, 470 were vaccinated and 226 were unvaccinated. The D-dimer levels of vaccinated individuals were lower than those of unvaccinated individuals (p = 0.0047). In the group B, 84 were vaccinated and 54 were unvaccinated; no difference in D-dimer levels was found between the vaccinated and unvaccinated individuals (p = 0.0542). In the group A, the D-dimer levels of the unvaccinated group were not different from those of women vaccinated with one dose (p = 0.208), but they were higher than those who received two doses (p = 0.019) or three doses (p = 0.003). And, no significant difference in D-dimer levels was found among women who received different vaccine brands and with different vaccination times. Conclusion: This study preliminarily indicates that COVID-19 vaccination does not increase D-dimer levels in early pregnant women.

The Microscopic Mechanism and Rheological Properties of SBS-Modified Asphalt with Warm Mixing Fast-Melting.

To overcome the shortcomings of traditional wet styrene-butadiene-styrene (SBS) modification technology, such as its high energy consumption and thermal decomposition, a warm mix and fast-melting SBS modifier was developed. Based on the theory of rheology, a dynamic shear rheometer (DSR) was applied to investigate the viscoelastic properties of the warm mix and fast-melting SBS-modified asphalt using a frequency scanning test. Atomic force microscopy (AFM) was used to reveal the modification mechanism of the SBS-modified asphalt. An investigation of the thermal stability of the asphalt binder was conducted using a thermogravimetric test (TG). The results exhibited that the SBS-modified asphalt had good viscoelastic properties, as well as thermal stability. The "bee structure" of the SBS-modified asphalt was finer and more stable. In addition, the adhesion and the Derjaguin-Muller-Toporov (DMT) modulus of the SBS-modified asphalt at a warm mixing speed was higher than that of regular SBS-modified asphalt.

Performance evaluation of QuantStudio 1 plus real-time PCR instrument for clinical laboratory analysis: A proof-of-concept study.

Objective: The real-time PCR system is one of the most powerful research tools available in the life sciences field. The aim of this study was to preliminarily evaluate the analytical performance of QuantStudio 1 Plus real-time PCR system (QS 1 plus) for clinical procedures. Methods: The consistency of QS 1 plus with the reference system in terms of various clinical procedures was evaluated. For qualitative data, the Kappa test was used to analyze the agreement of the results. For the quantitative data, Passing-Bablok regression analysis and Bland-Altman plot analysis were used to assess the concordance between QS 1 plus and the reference instrument. Results: Passing-Bablok regression showed an excellent agreement between the QS 1 plus and LC 480 systems for HBV DNA quantification (y = 0.928 + 0.970x), whereas Bland-Altman plot analysis showed very small mean deviations between the two systems. The QS 1 plus yielded perfectly consistent results with the reference instrument for methylenetetrahydrofolate reductase (MTHFR) C677T melting curve genotyping analysis, MTHFR C677T genotyping analysis, Norovirus RNA negative/positive analysis, influenza B virus (Flu B) RNA negative/positive analysis, Mycobacterium tuberculosis (MTB) DNA negative/positive analysis, Human Papillomavirus (HPV) genotyping analysis, epidermal growth factor receptor (EGFR) gene mutation analysis. Both the relative quantitative analysis and the relative quantitative analysis (standard curve) confirmed the satisfactory concordance between the QS 1 plus instrument and the ABI 7500 instrument by Passing-Bablok regression analysis (y = 0.180 + 0.817x and y = 0.012 + 1.000x, respectively) and Bland-Altman plot analysis. Conclusions: Our research has proven that QS 1 plus is adaptable to most test procedures in the clinical laboratory. This may provide the basis for its further application.

ACCURACY OF NEW INTRAOCULAR LENS CALCULATION FORMULAE IN EYES UNDERGOING SILICONE OIL REMOVAL/PARS PLANA VITRECTOMY-CATARACT SURGERY.

PURPOSE: To investigate the performance of novel intraocular lens calculation formulae (Barrett Universal II, Emmetropia Verifying Optical, and Kane) and conventional formulae (Haigis, Hoffer Q, Holladay 1, and Sanders-Retzlaff-Kraff/T [SRK/T]) in patients who underwent pars plana vitrectomy or silicone oil removal combined with cataract surgery. METHODS: In total, 301 eyes from 301 patients who underwent pars plana vitrectomy/silicone oil removal with concomitant cataract surgery were enrolled and divided into the following four groups according to preoperative diagnosis: silicone oil-filled eyes after pars plana vitrectomy, epiretinal membrane, primary retinal detachment, and macular hole. RESULTS: Barrett Universal II exhibited the smallest mean absolute error (0.65 diopters [D]) and median absolute error (0.39 D) in total. In patients with primary retinal detachment, each formula exhibited the worst refractive outcomes in diverse vitreoretinal pathologies ( P < 0.01), and no difference in accuracy between the seven formulas was observed ( P = 0.075). For long eyes, the second linear (Wang-Koch 2) version of the Wang-Koch adjustment significantly reduced the median absolute error for Holladay 1 and SRK/T ( P < 0.001 and P = 0.019). CONCLUSION: In combined surgery, both new and conventional formulas using the second linear version of the Wang-Koch 2 adjustment demonstrated satisfactory performance, with Barrett Universal II exhibiting the best overall performance. However, in patients with primary retinal detachment, all seven formulas showed less favorable performance.

Amentoflavone mitigates doxorubicin-induced cardiotoxicity by suppressing cardiomyocyte pyroptosis and inflammation through inhibition of the STING/NLRP3 signalling pathway.

BACKGROUND: Doxorubicin (DOX) is a potent anticancer chemotherapeutic agent whose clinical application is substantially constrained by its cardiotoxicity. The pathophysiology of DOX-induced cardiotoxicity manifests as cardiomyocyte pyroptosis and inflammation. Amentoflavone (AMF) is a naturally occurring biflavone possessing anti-pyroptotic and anti-inflammatory properties. However, the mechanism through which AMF alleviates DOX-induced cardiotoxicity remains undetermined. PURPOSE: This study aimed at investigating the role of AMF in alleviating DOX-induced cardiotoxicity. STUDY DESIGN AND METHODS: To assess the in vivo effect of AMF, DOX was intraperitoneally administered into a mouse model to induce cardiotoxicity. To elucidate the underlying mechanisms, the activities of STING/NLRP3 were quantified using the NLRP3 agonist nigericin and the STING agonist amidobenzimidazole (ABZI). Primary cardiomyocytes isolated from neonatal Sprague-Dawley rats were treated with saline (vehicle) or DOX with or without AMF and/or ABZI. The echocardiogram, haemodynamics, cardiac injury markers, heart/body weight ratio, and pathological alterations were monitored; the STING/NLRP3 pathway-associated proteins were detected by western blot and cardiomyocyte pyroptosis was analysed by immunofluorescence staining of cleaved N-terminal GSDMD and scanning electron microscopy. Furthermore, we evaluated the potential of AMF in compromising the anticancer effects of DOX in human breast cancer cell lines. RESULTS: AMF substantially alleviated cardiac dysfunction and reduced heart/body weight ratio and myocardial damage in mice models of DOX-induced cardiotoxicity. AMF effectively suppressed DOX-mediated upregulation of IL-1ß, IL-18, TNF-α, and pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and cleaved N-terminal GSDMD. The levels of apoptosis-related proteins, namely Bax, cleaved caspase-3, and BCL-2 were not affected. In addition, AMF inhibited STING phosphorylation in DOX-affected hearts. Intriguingly, the administration of nigericin or ABZI dampened the cardioprotective effects of AMF. The in vitro anti-pyroptotic effect of AMF was demonstrated in attenuating the DOX-induced reduction in cardiomyocyte cell viability, upregulation of cleaved N-terminal GSDMD, and pyroptotic morphology alteration at the microstructural level. AMF exhibited a synergistic effect with DOX to reduce the viability of human breast cancer cells. CONCLUSION: AMF alleviates DOX-induced cardiotoxicity by suppressing cardiomyocyte pyroptosis and inflammation via inhibition of the STING/NLRP3 signalling pathway, thereby validating its efficacy as a cardioprotective agent.

Development of a model based on the age-adjusted Charlson comorbidity index to predict survival for resected perihilar cholangiocarcinoma.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) has a poor prognosis and urgently needs a better predictive method. The predictive value of the age-adjusted Charlson comorbidity index (ACCI) for the long-term prognosis of patients with multiple malignancies was recently reported. However, pCCA is one of the most surgically difficult gastrointestinal tumors with the poorest prognosis, and the value of the ACCI for the prognosis of pCCA patients after curative resection is unclear. AIM: To evaluate the prognostic value of the ACCI and to design an online clinical model for pCCA patients. METHODS: Consecutive pCCA patients after curative resection between 2010 and 2019 were enrolled from a multicenter database. The patients were randomly assigned 3:1 to training and validation cohorts. In the training and validation cohorts, all patients were divided into low-, moderate-, and high-ACCI groups. Kaplan-Meier curves were used to determine the impact of the ACCI on overall survival (OS) for pCCA patients, and multivariate Cox regression analysis was used to determine the independent risk factors affecting OS. An online clinical model based on the ACCI was developed and validated. The concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve were used to evaluate the predictive performance and fit of this model. RESULTS: A total of 325 patients were included. There were 244 patients in the training cohort and 81 patients in the validation cohort. In the training cohort, 116, 91 and 37 patients were classified into the low-, moderate- and high-ACCI groups. The Kaplan-Meier curves showed that patients in the moderate- and high-ACCI groups had worse survival rates than those in the low-ACCI group. Multivariable analysis revealed that moderate and high ACCI scores were independently associated with OS in pCCA patients after curative resection. In addition, an online clinical model was developed that had ideal C-indexes of 0.725 and 0.675 for predicting OS in the training and validation cohorts. The calibration curve and ROC curve indicated that the model had a good fit and prediction performance. CONCLUSION: A high ACCI score may predict poor long-term survival in pCCA patients after curative resection. High-risk patients screened by the ACCI-based model should be given more clinical attention in terms of the management of comorbidities and postoperative follow-up.

[Study on the evaluation of glenoid bone defects by MRI three-dimensional reconstruction].

Objective: To investigate the feasibility of MRI three-dimensional (3D) reconstruction model in quantifying glenoid bone defect by comparing with CT 3D reconstruction model measurement. Methods: Forty patients with shoulder anterior dislocation who met the selection criteria between December 2021 and December 2022 were admitted as study participants. There were 34 males and 6 females with an average age of 24.8 years (range, 19-32 years). The injury caused by sports injury in 29 cases and collision injury in 6 cases, and 5 cases had no obvious inducement. The time from injury to admission ranged from 4 to 72 months (mean, 28.5 months). CT and MRI were performed on the patients' shoulder joints, and a semi-automatic segmentation of the images was done with 3D slicer software to construct a glenoid model. The length of the glenoid bone defect was measured on the models by 2 physicians. The intra-group correlation coefficient ( ICC) was used to evaluate the consistency between the 2 physicians, and Bland-Altman plots were constructed to evaluate the consistency between the 2 methods. Results: The length of the glenoid bone defects measured on MRI 3D reconstruction model was (3.83±1.36) mm/4.00 (0.58, 6.13) mm for physician 1 and (3.91±1.20) mm/3.86 (1.39, 5.96) mm for physician 2. The length of the glenoid bone defects measured on CT 3D reconstruction model was (3.81±1.38) mm/3.80 (0.60, 6.02) mm for physician 1 and (3.99±1.19) mm/4.00 (1.68, 6.38) mm for physician 2. ICC and Bland-Altman plot analysis showed good consistency. The ICC between the 2 physicians based on MRI and CT 3D reconstruction model measurements were 0.73 [95% CI (0.54, 0.85)] and 0.80 [95% CI (0.65, 0.89)], respectively. The 95% CI of the difference between the two measurements of physicians 1 and 2 were (-0.46, 0.49) and (-0.68, 0.53), respectively. Conclusion: The measurement of glenoid bone defect based on MRI 3D reconstruction model is consistent with that based on CT 3D reconstruction model. MRI can be used instead of CT to measure glenoid bone defects in clinic, and the soft tissue of shoulder joint can be observed comprehensively while reducing radiation.

Plasminogen Activator Inhibitor-1 4G/5G (rs1799889) Polymorphism in Chinese Patients with Diabetes Mellitus and Hypertension.

Objective: To determine the plasminogen activator inhibitor-1 (PAI-1) 4G/5G (rs1799889) genotype of the subjects in a robust detection method and to explore the association of the PAI-1 4G/5G polymorphism with susceptibility to diabetes mellitus (DM) and hypertension (HTN) as well as clinical characteristics. Methods: This study recruited 208 patients (68 patients were diagnosed with DM, 70 patients with HTN and 70 patients with DM combined with HTN) and 132 healthy controls (HC). A subset of the population was selected to evaluate the accuracy of the Real-time PCR (RT-PCR) method for detecting PAI-1 4G/5G polymorphism by using the sequencing method as the gold standard. Furthermore, the association of the PAI-1 4G/5G polymorphism with genetic susceptibility to DM and HTN was explored. Moreover, variations in clinical characteristics among individuals with various PAI-1 genotypes were also analyzed in the DM group, the HTN group and the DM+HTN group. Results: There was a high concordance between the RT-PCR method and the sequencing method in determining the PAI-1 4G/5G polymorphism. No association was observed between the PAI-1 4G/5G polymorphism and susceptibility to DM, HTN and DM+HTN, respectively. There were no statistical differences in all study indicators among individuals that carrying various genotypes in the HC group. There were several variations in clinical characteristics among individuals harboring different PAI-1 4G/5G genotypes in the DM group, the HTN group and the DM+HTN group. Conclusion: The RT-PCR method can accurately identify the PAI-1 4G/5G genotype in different individuals. The PAI-1 4G/5G polymorphism may not be associated with genetic susceptibility to DM, HTN and DM+HTN, but differences in clinical characteristics among individuals with various genotypes may provide a reference for disease assessment and personalized treatment of patients.

Elasto-Plastic Design of Ultrathin Interlayer for Enhancing Strain Tolerance of Flexible Electronics.

The ability to tolerate large strains during various degrees of deformation is a core issue in the development of flexible electronics. Commonly used strategies nowadays to enhance the strain tolerance of thin film devices focus on the optimization of the device architecture and the increase of bonding at the materials interface. In this paper, we propose a strategy, namely elasto-plastic design of an ultrathin interlayer, to boost the strain tolerance of flexible electronics. We demonstrate that insertion of an ultrathin, stiff (high Young's modulus) and elastic (high yield strain) interlayer between an upper rigid film/device and a soft substrate, regardless of the substrate thickness or the interfacial bonding, can significantly reduce the actual strain applied on the film/device when the substrate is bent. Being independent of existing strategies, the elasto-plastic design strategy offers an effective method to enhance the device flexibility without redesigning the device structure or altering the material interface.

A Nomogram Based on Atelectasis/Obstructive Pneumonitis Could Predict the Metastasis of Lymph Nodes and Postoperative Survival of Pathological N0 Classification in Non-small Cell Lung Cancer Patients.

The eighth TNM staging system proposal classifies lung cancer with partial or complete atelectasis/obstructive pneumonia into the T2 category. We aimed to develop nomograms to predict the possibility of lymph node metastasis (LNM) and the prognosis for NSCLC based on atelectasis and obstructive pneumonitis. METHODS: NSCLC patients over 20 years old diagnosed between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The nomograms were based on risk factors that were identified by Logistic regression. The area under the receiver operating characteristic (ROC) curve (AUC) was performed to confirm the predictive values of our nomograms. Cox proportional hazards analysis and Kaplan-Meier survival analysis were also used in this study. RESULTS: A total of 470,283 patients were enrolled. Atelectasis/obstructive pneumonitis, age, gender, race, histologic types, grade, and tumor size were defined as independent predictive factors; then, these seven factors were integrated to establish nomograms of LNM. The AUC is 0.70 (95% CI: 0.694-0.704). Moreover, the Cox proportional hazards analysis and Kaplan-Meier survival analysis showed that the scores derived from the nomograms were significantly correlated with the survival of pathological N0 classification. CONCLUSION: Nomograms based on atelectasis/obstructive pneumonitis were developed and validated to predict LNM and the postoperative prognosis of NSCLC.

Clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a life-threatening cardiovascular syndrome that characterized by the imbalance of hemostasis and thrombosis and the formation of thrombi in the blood vessels. The aim of this study was to elucidate the clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with VTE. METHODS: A total of 169 subjects (89 VTE, 10 hyperbilirubinemia, 10 hyperlipidemia and 60 healthy controls) were recruited at Peking Union Medical College Hospital. The accuracy of the TaqMan-MGB RT-PCR method for detecting F5 G1691A (FVL) and PAI-1 4G/5G polymorphisms was evaluated by using sequencing method as the gold standard. Besides, the association of the PAI-1 4G/5G polymorphism with susceptibility, treatment efficacy and recurrence status of VTE in Chinese population were explored. Eventually, the plasma PAI-1 antigen levels and PAI-1 4G/5G polymorphisms were determined on additional 64 subjects (32 VTE and 32 healthy controls) simultaneously. RESULTS: The TaqMan-MGB RT-PCR method was proven to be highly accurate in determining the FVL and PAI-1 4G/5G polymorphisms without interference from bilirubin and lipids in the samples. No obvious correlation of the PAI-1 4G/5G polymorphism with VTE was observed in our study by using five genetic models (allele, genotype, dominant, recessive and additive). Additionally, we also observed that individuals with the 4G/5G genotype had lower neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) than the 5G/5G genotype. Furthermore, we found that the patients with the 5G/5G genotype were more likely to achieve complete recanalization compared to the 4G/4G genotype. In addition, individuals carrying the 5G/5G genotype were more likely to develop a recurrence-free status as compared to individuals with the 4G/4G or 4G/5G genotypes. PAI-1 antigen levels in the VTE group were significantly higher than those in the HC group. However, there was no significant difference in the antigen levels of PAI-1 among subjects carrying various genotypes in the VTE group or HC group. CONCLUSION: The PAI-1 4G/5G polymorphism has potential value in assessing the prognosis of Chinese patients with VTE. Our study has laid the foundation for the application of PAI-1 4G/5G polymorphism in the personalized management and monitoring of patients with VTE.