Optimizing Fatigue Performance in Gradient Structural Steels by Manipulating the Grain Size Gradient Rate.

As a new type of high-performance material, gradient structural steel is widely used in engineering fields due to its unique microstructure and excellent mechanical properties. For the prevalent fatigue failure problem, the rate of change in the local grain size gradients along the structure (referred to as the gradient rate) is a key parameter in the design of gradient structures, which significantly affects the fatigue performance of gradient structural steel. In this study, a new method of 'Voronoi primary + secondary modeling' is adopted to successfully establish three typical high-strength steel models corresponding to the convex-, linear-, and concave-type gradient rates for gradient structures, focusing on the stress-strain response and crack propagation in structural steel with different gradient rates under cyclic loading. It was found that the concave gradient rate structural model is dominated by finer grains with larger volume fraction, which is conducive to hindering fatigue crack propagation and has the longest fatigue life, which is 16.16% longer than that of the linear gradient rate structure and 23.66% longer than that of the convex gradient rate structure. The simulation results in this study are consistent with the relevant experimental phenomena. Therefore, when regulating the gradient rate, priority should be given to increasing the volume fraction of fine grains and designing a gradient rate structure dominated by fine grains to improve the fatigue life of the material. This study presents a new strategy for designing engineering materials with better service performance.

A Novel Nomogram to Predict Prognosis of Advanced Hepatocellular Carcinoma Treated with Intensity-Modulated Radiotherapy Plus Anti-PD1.

Purpose: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1. Patients and Methods: The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC). Results: The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3-4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3-4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1-3 years AUROC of 78.7, 78.6, and 93.5, respectively. Conclusion: IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability.

The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti­PD1) showed preliminary efficacy and manageable safety in HCC. We retrospectively evaluated the efficacy and safety of 102 patients with advanced HCC treated with intensity-modulated radiotherapy (IMRT) plus anti-PD1. The study shows that the combination showed promising efficacy with a median PFS and OS of 9.9 months and 14.3 months, respectively. The adverse reactions were controllable. The novel nomogram model established based on independent prognostic factors including albumin, alpha-fetoprotein, neutrophils count 3­4 weeks after IMRT initiation and platelet-to-lymphocyte ratio 3­4 weeks after IMRT initiation demonstrated good reliability.

Progress on the roles of zinc in sperm cryopreservation.

One of the effective methods for the long-term preservation of mammalian genetic resources is the cryopreservation of semen. However, a number of parameters, including diluents, the rate of freezing and thawing, cryoprotectants, etc., can easily alter the survival of frozen-thawed sperm. Numerous studies have documented the addition of a variety of zinc compounds, to the diluents used to cryopreserve sperm. The primary objective of this review is to briefly describe that adding zinc to diluents as an antioxidant significantly enhances frozen-thawed sperm quality. Second, a summary of the present understanding of zinc's molecular mechanism on semen cryopreservation is provided. Thirdly, this study addresses that nanoparticles of zinc can offer suggestions for raising cryopreservation effectiveness.

Radiotherapy plus anti-PD1 versus radiotherapy for hepatic toxicity in patients with hepatocellular carcinoma.

PURPOSE: In this study, we aimed to compare the radiation-induced hepatic toxicity (RIHT) outcomes of radiotherapy (RT) plus antibodies against programmed cell death protein 1 (anti-PD1) versus RT alone in patients with hepatocellular carcinoma (HCC), evaluate prognostic factors of non-classic radiation-induced liver disease (ncRILD), and establish a nomogram for predicting the probability of ncRILD. PATIENTS AND METHODS: Patients with unresectable HCC treated with RT and anti-PD1 (RT + PD1, n = 30) or RT alone (n = 66) were enrolled retrospectively. Patients (n = 30) in each group were placed in a matched cohort using propensity score matching (PSM). Treatment-related hepatotoxicity was evaluated and analyzed before and after PSM. The prognostic factors affecting ncRILD were identified by univariable logistic analysis and Spearman's rank test in the matched cohort to generate a nomogram. RESULTS: There were no differences in RIHT except for increased aspartate aminotransferase (AST) ≥ grade 1 and increased total bilirubin ≥ grade 1 between the two groups before PSM. After PSM, AST ≥ grade 1 occurred more frequently in the RT + PD1 group (p = 0.020), and there were no significant differences in other hepatotoxicity metrics between the two groups. In the matched cohort, V25, tumor number, age, and prothrombin time (PT) were the optimal prognostic factors for ncRILD modeling. A nomogram revealed a good predictive performance (area under the curve = 0.82). CONCLUSIONS: The incidence of RIHT in patients with HCC treated with RT + PD1 was acceptable and similar to that of RT treatment. The nomogram based on V25, tumor number, age, and PT robustly predicted the probability of ncRILD.

Arula-7 powder improves diarrhea and intestinal epithelial tight junction function associated with its regulation of intestinal flora in calves infected with pathogenic Escherichia coli O1.

BACKGROUND: The effects of Arula-7 powder (ASP) on diarrhea and intestinal barrier function associated with its regulation of intestinal microflora in calves infected with pathogenic Escherichia coli O1 (E. coli O1) were studied. METHOD: Twenty Holstein calves were randomly divided into four treatment groups: normal control (NC), model control (MC), 0.5 mg/kg ciprofloxacin (CIP) and 2.50 g/kg ASP groups. RESULTS: ASP inhibited the relative abundance of Proteobacteria, Selenomonadales, and Enterobacteriales, and increased the relative abundance of Lactobacillus, Faecalibacterium, and Alloprevotella. Moreover, we demonstrated for the first time that the ASP and CIP promoted weight gain, reduced the diarrhea rate (P < 0.05), and enhanced antioxidant capacity (P < 0.05) due to the increase in average daily gain (ADG), total protein (TP), and albumin (ALB). In addition, ASP and CIP increased the expression of Zunola occludens-1 (ZO-1), Occludin, and Claudin-1 in the ileum (P < 0.05), and improved immunity due to increase levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-γ (IFN-γ), immunoglobulin A (IgA), and immunoglobulin G (IgG) in the serum, strengthened CD4+T levels in the ileal mucosa and reducing CD8+T and CD11c+T (P < 0.05). CONCLUSION: Hence, The intestinal microbiota environment formed by early intervention of ASP powder has a protective effect on the intestinal mucosal function of calves infected with pathogenic E. coli. Video Abstract.

Corin Deficiency Diminishes Intestinal Sodium Excretion in Mice.

Sodium excretion, a critical process in sodium homeostasis, occurs in many tissues, including the kidney and intestine. Unlike in the kidney, the hormonal regulation of intestinal sodium excretion remains unclear. Atrial natriuretic peptide (ANP) is a crucial hormone in renal natriuresis. Corin is a protease critical for ANP activation. Corin and ANP are expressed mainly in the heart. In this study, we investigated corin, ANP, and natriuretic peptide receptor A (Npra) expression in mouse intestines. Corin and ANP expression was co-localized in enteroendocrine cells, whereas Npra expression was on the luminal epithelial cells. In Corin knockout (KO) mice, fecal Na+ and Cl- excretion decreased compared with that in wild-type (WT) mice. Such a decrease was not found in conditional Corin KO mice lacking cardiac corin selectively. In kidney conditional Corin KO mice lacking renal corin, fecal Na+ and Cl- excretion increased, compared to that in WT mice. When WT, Corin KO, and the kidney conditional KO mice were treated with aldosterone, the differences in fecal Na+ and Cl- levels disappeared. These results suggest that intestinal corin may promote fecal sodium excretion in a paracrine mechanism independent of the cardiac corin function. The increased fecal sodium excretion in the kidney conditional Corin KO mice likely reflected an intestinal compensatory response to renal corin deficiency. Our results also suggest that intestinal corin activity may antagonize aldosterone action in the promotion of fecal sodium excretion. These findings help us understand the hormonal mechanism controlling sodium excretion the intestinal tract.

The effects of background music on English reading comprehension for English foreign language learners: evidence from an eye movement study.

Based on previous literature, the present study examines the effects of background music on English reading comprehension using eye tracking techniques. All the participants, whose first language was Chinese, were selected from a foreign language college and all of them were sophomores who majored in English. The experiment in this study was a 2 (music tempo: fast and slow) × 2 (text difficulty: difficult and easy) × 2 (background music preference: high and low) mixed design. Both musical tempo and English reading passage were within-subjects factors, and the level of music listening preference was a between-subjects factor. The results showed that the main effect of the music tempo was statistically significant, which indicated that participants read texts more quickly in the fast-tempo music condition than in the slow-tempo music condition. Furthermore, the main effect of the text difficulty was statistically significant. Additionally, the interaction between the text difficulty and music tempo was statistically significant. The music tempo had a greater effect on easy texts than on difficult texts. The results of this study reveal that it is beneficial for people who have a stronger preference for music listening to conduct English reading tasks with fast-tempo music. It is detrimental for people who have little preference for background music listening to complete difficult English reading tasks with slow-tempo music.

Establishment and validation of a prognostic pomogram in unresectable hepatocellular carcinoma treated with intensity modulated radiotherapy: a real world study.

BACKGROUND: To establish a prognostic model to predict the overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC) treated with intensity modulated radiotherapy (IMRT). METHODS: The unresectable HCC patients treated with IMRT were retrospectively analyzed and randomized into development cohort (n = 237) and validation cohort (n = 103) in a 7:3 ratio. We developed a prognosis model with the multivariate Cox regression analysis in the development cohort to derive the predictive nomogram, which was then validated in the validation cohort. Model performance was evaluated by the c-index, the area under curve(AUC) and the calibration plot. RESULTS: A total of 340 patients were enrolled. Tumor numbers > 3 (HR = 1.69, 95% CI = 1.21-2.37), AFP ≥ 400 ng/ml (HR = 1.52, 95% CI = 1.10-2.10), PLT < 100 × 10^9(HR = 1.7495% CI = 1.11-2.73), ALP > 150U/L (HR = 1.65, 95% CI = 1.15-2.37) and prior surgery (HR = 0.63, 95% CI = 0.43-0.93) were independent prognostic factors. The nomogram based on independent factors was constructed. The c-index for OS prediction was 0.658 (95% CI, 0.647-0.804) and 0.683 (95% CI, 0.580-0.785) in the development and validation cohort, respectively. The nomogram demonstrated good discriminative ability with AUC rates of 0.726, 0.739 and 0.753 at 1-year, 2-year and 3-year models in the development cohort, and 0.715, 0.756 and 0.780 in the validation cohort, respectively. Additionally, good prognostic discrimination of the nomogram is also reflected in stratifying patients into two subgroups with distinct prognosis. CONCLUSIONS: We constructed a prognostic nomogram for predicting the survival of patients with unresectable HCC treated with IMRT.

Non-classic radiation-induced liver disease after intensity-modulated radiotherapy for Child-Pugh grade B patients with locally advanced hepatocellular carcinoma.

BACKGROUND: The incidence of classic radiation-induced liver disease (cRILD) has been significantly reduced. However, non-classic radiation-induced liver disease (ncRILD) remains a major concern following radiotherapy in patients with hepatocellular carcinoma (HCC). This study evaluated the incidence of ncRILD following intensity-modulated radiotherapy (IMRT) for Child-Pugh grade B (CP-B) patients with locally advanced HCC and established a nomogram for predicting ncRILD probability. METHODS: Seventy-five CP-B patients with locally advanced HCC treated with IMRT between September 2014 and July 2021 were included. The max tumor size was 8.39 cm ± 5.06, and the median prescribed dose was 53.24 Gy ± 7.26. Treatment-related hepatotoxicity was evaluated within three months of completing IMRT. A nomogram model was formulated to predict the probability of ncRILD, using univariate and multivariate analysis. RESULTS: Among CP-B patients with locally advanced HCC, ncRILD occurred in 17 (22.7%) patients. Two patients (2.7%) exhibited a transaminase elevation of ≥ G3, fourteen (18.7%) exhibited a Child-Pugh score increase of ≥ 2, and one (1.3%) demonstrated both a transaminase elevation of ≥ G3 and a Child-Pugh score increase of ≥ 2. No cRILD cases were observed. A mean dose to the normal liver of ≥ 15.1 Gy was used as the cutoff for ncRILD. Multivariate analysis revealed that the prothrombin time before IMRT, tumour number, and mean dose to the normal liver were independent risk factors for ncRILD. The nomogram established on the basis of these risk factors displayed exceptional predictive performance (AUC = 0.800, 95% CI 0.674-0.926). CONCLUSIONS: The incidence of ncRILD following IMRT for CP-B patients with locally advanced HCC was acceptable. A nomogram based on prothrombin time before IMRT, tumour number, and mean dose to the normal liver accurately predicted the probability of ncRILD in these patients.

Effects of sericin and egg white on the inflammation of damaged skin in mice.

Sericin and egg white (EW) have shown the ability to promote wound healing. However, there have been insufficient studies regarding the effects of sericin and EW mixtures on wound healing. This study aimed to investigate the effects of a hybrid sericin and EW solution on wound repair and inflammation-related indicators in mouse skin. In this work, sericin with a low molecular weight was first mixed with homogeneous EW to prepare a hybrid wound dressing. Histology evaluation, the expression of C-reactive protein (CRP) and inflammatory cytokines in mice were tested to determine the effects of this dressing on skin injuries in mice. The results showed that sericin and the hybrid solution of sericin and EW effectively promoted wound healing in mouse skin. The wound recovery rates of mice 12 days after treatment with a medium dose of sericin (0.2 g ml-1) and the same dosage of sericin with added EW were 1.32 and 1.65 times that of mice treated with phosphate buffer saline as a control, respectively. In addition, the mixture solution was more effective in wound healing than sericin alone. Sericin with EW significantly reduced the expression of CRP and inflammatory cytokines in mice during wound healing. A sericin and EW hybrid solution can effectively shorten the time needed for wound healing and reduce inflammation-related indicators in mice, making it a promising candidate for wound dressing.

Combination treatment of acupoint therapy and conventional medication for motor function of Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Combination treatment with acupoint therapy and conventional medication (CM) has been proposed as a strategy that could improve motor dysfunction in Parkinson's disease (PD). We performed this systematic review and meta-analysis to assess the effects of this combination treatment on motor function in patients with PD. METHODS: We searched randomized controlled trials (RCTs) from eight databases, comparing combined acupoint therapy and CM and CM (alone or with sham interventions). The quality of the trials was evaluated according to the Cochrane risk of bias. Subgroup and sensitivity analyses were performed on different types of acupoint interventions. RESULTS: Forty-seven trials of 2929 participants were included, with 45 studies used for the meta-analyses. Combination treatment yielded an improved reduction in United Parkinson's disease rating scale (UPDRS) III of -3.85 [95% CI, -4.83 to -2.86] and Webster scale score of -3.17 [95% CI, -4.07 to -2.27]. Further analyses demonstrated that real (compared with sham) intervention was linked to a decreased UPDRS III of -2.02 ([95% CI, -3.60 to -0.44], I2 = 40%), and beneficial effects were observed when combination intervention was used for patients with Hoehn-Yahr (H-Y) stages >3 with mild to moderate stimulation for 4-12-week treatment. CONCLUSIONS: Acupoint therapy and CM treatment may improve motor function of patients with PD. Patients with H-Y stage >3 could tolerate real acupoint intervention with mild to moderate stimulation for 4-12-week treatment and showed improvement. However, this was demonstrated with low to moderate levels of evidence in statistical description.

Prognostic value of a nomogram based on peripheral blood immune parameters in unresectable hepatocellular carcinoma after intensity-modulated radiotherapy.

BACKGROUND: For patients with unresectable hepatocellular carcinoma (uHCC), intensity-modulated radiotherapy (IMRT) has become one of the options for clinical local treatment. Immune parameters, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammatory (SII), predict survival in various cancers. This study aimed to determine whether peripheral immune parameters can predict survival in patients with uHCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction. METHODS: The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training (n = 216) and validation (n = 93) cohorts. PLR, NLR and SII were collected before and after IMRT. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival, which were used to generate a nomogram. RESULTS: The median survival was 16.3 months, and significant increases in PLR, NLR, and SII were observed after IMRT (P < 0.001). High levels of immune parameters were associated with poor prognosis (P < 0.001); enlarged spleen, Barcelona clinic liver cancer stage (B and C), post-SII, and delta-NLR were independent risk factors for survival and were included in the nomogram, which accurately predicted 3- and 5-year survival. The nomogram was well verified in the validation cohort. CONCLUSIONS: High levels of immune parameters are associated with poor prognosis in uHCC patients receiving IMRT. Our nomogram accurately predicts the survival of patients with uHCC receiving IMRT.

The efficacy of a transdiagnostic group cognitive behavioral intervention for Chinese elderly with emotional disorders: A one-year follow-up randomized clinical trial.

Background: With the global aging, geriatric emotional disorders have received more and more attention. Psychotherapy is an effective approach for alleviating the symptoms associated with emotional disorder, but the number of experienced therapists is low. Studies should be conducted to explore a low-cost and efficient treatment method. Previous findings indicate that transdiagnostic cognitive behavior therapy is an effective approach for treatment of emotional disorders. Group therapy is appropriate for the elderly as they are characterized by high levels of loneliness. In this study, we compared and explored the effects of a transdiagnostic group cognitive behavioral intervention (TD-GCBT), a transdiagnostic individual cognitive behavioral intervention (TD-CBT), and treatment as usual (TAU) on treatment of emotional disorders among the elderly. Method: A total of 120 elderly patients diagnosed with emotional disorders were randomly assigned to the TD-GCBT group (40), TD-CBT group (40), and TAU group (40). Changes in symptoms were assessed using HAMD, PHQ-9, HAMA, and GAD-7 scales at baseline, post-treatment (three months), six-month and twelve-months follow-up. The efficacies of the three intervention strategies were compared using linear mixed-effects models. Post-hoc and simple effect analyses were conducted to determine the differences among the three groups. Results: The HAMD, PHQ-9, HAMA, and GAD-7 scores revealed a significant effect from baseline to 12 months for time (p < 0.001), group (p < 0.001) and time × group interaction (p < 0.001) in TD-GCBT group compared with the TD-CBT group and TAU group. The effect of TD-GCBT (HAMD: Cohen's d (3th month, 6th month, 12th month) = 2.69, 3.98, 4.51; HAMA: Cohen's d = 2.84, 4.13, 5.20) and TD-CBT (HAMD: Cohen's d = 2.55, 2.87, 2.63; HAMA: Cohen's d = 2.43, 2.83, 2.78) group was better relative to that of the TAU group (HAMD: Cohen's d = 0.41, 1.13, 1.46; HAMA: Cohen's d = 0.64, 1.22, 1.57) (p < 0.001). The scores of the TD-GCBT group showed the most significant decrease compared with the other two groups. Conclusion: The findings indicate that TD-GCBT method is effective for treatment of emotional disorders among the elderly. TD-GCBT is effective for alleviating depression and anxiety symptoms up to at least nine months after treatment. The results indicate that TD-GCBT is a cost-effective and resource-effective strategy and can be used an alternative therapy for treatment of mental disorders. Clinical trial registration: [https://www.chictr.org.cn], identifier [ChiCTR1900021806].

Does green credit promote green sustainable development in regional economies?-Empirical evidence from 280 cities in China.

BACKGROUND: China has been exploring a sustainable development path that harmonizes economic growth and environmental protection, targeting to build a beautiful China. The role of green finance in adjusting the misallocation of financial resources and leading the green sustainable development of the real economy is receiving increasingly more attention. Currently, green credit accounts for more than 90% of the total green finance funding in China and constitutes the most significant component of the green finance matrix. Whether green credit effectively promotes the green and sustainable development of the regional economy largely determines the success of China's economic green transformation. OBJECTIVE: Existing studies of green credit mainly focus on its influences on financing, investment, and emission reduction of environmental pollution industries or companies. Extending the literature by exploring whether green credit is effective in promoting green sustainable development and what impact green credit exerts on the upstream (energy inputs), midstream (technological innovation), and downstream (pollution outputs) stages of the green sustainable development value chain, is the leading research objective of this paper. METHODS: This paper discusses the impact of green credit on green sustainable development based on city panel data from 2012 to 2019. The level of green sustainable development is calculated by the GML index based on SBM directional distance function. The city-level green credit scale is calculated from the green credit issued by banks, weighted by the density of bank branches in a city. Synthetic control methods are employed in the robustness analysis to reduce the impact of endogeneity issues. RESULTS AND CONCLUSION: The results of this paper indicate that green credit can promote green sustainable development and the impact gradually strengthens over time as the incremental implementations of complementary policies with substantial constraints and incentives, through which pollution control and economic growth achieve a "win-win" situation. Furthermore, the results indicate that green credit reduces the overall amount of energy inputs while optimizing the energy input structure. However, green credit does not boost the green technological level and even crowds out high technical value green innovations. Besides, the pollution reduction effects of green credit are associated with the strength of green credit constraints and the importance of pollution industries in the local economy, which means green credit performs better pollution reduction effects in regions with relatively strong green credit binding effects or in regions where pollution industries are not local economic pillars. The empirical results are further validated through robustness tests, including changing scope and measurement variables and applying the synthetic control method. LIMITATIONS: Although this paper provides valuable contributions to the research area of green credit and green sustainable development, specific limitations exist in the current study. Firstly, as the official information disclosure of green credit in China is not sufficient, existing studies, including ours, could only use estimation methods through different perspectives to measure green credit, which is overall logical and reasonable but may lose some accuracy. Secondly, since there might be a certain degree of lag in the effect of green credit on the economy, the dynamic impact and long-term effects of green credit deserve further study. Thirdly, considering the characteristics of the Chinese administrative systems, introducing the behavior of local governments and local officials into the analysis of green credit and green sustainable development could be valuable.

Combining stereotactic body radiotherapy with camrelizumab for unresectable hepatocellular carcinoma: a single-arm trial.

PURPOSE: Stereotactic body radiotherapy (SBRT) may have significant immunomodulatory effects that enhance tumor response to immune checkpoint inhibitors. This phase 2 clinical trial was conducted to evaluate the safety and efficacy of combining palliative SBRT with camrelizumab (an anti-PD1 monoclonal antibody) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Patients with uHCC, Child-Pugh A/B liver function, and at least one measurable lesion were enrolled between April 2020 and August 2022. Patients were administered 200 mg camrelizumab intravenously from the first day of palliative SBRT and then every 3 weeks. Palliative SBRT was delivered daily over five fractions per week, with a dose range of 30-50 Gy. The primary endpoints were objective response rate (ORR) and safety. This trial was registered at ClinicalTrials.gov (NCT04193696). RESULTS: Twenty-one patients were enrolled; the median radiation dose was 40 Gy, and the median number of cycles of camrelizumab was five. The ORR was 52.4%. After a median follow-up of 19.7 months, the median progression-free and overall survival were 5.8 and 14.2 months, respectively. The overall survival probability was 85.7% at 6 months, 76.2% at 9 months, and 59.9% at 12 months. All grade 3 treatment-related adverse events (TRAEs) occurred in five patients (23.8%) and were manageable. No grade 4/5 TRAEs were observed. CONCLUSION: Palliative SBRT plus camrelizumab showed promising antitumor activity against uHCC. Toxicities were manageable with no unexpected safety issues. This study provides evidence of a new therapeutic method for the treatment of uHCC.

Prevalence and Antimicrobial Resistance of Ureaplasma urealyticum and Mycoplasma hominis in Patients with Genital Tract Infection in Jiangsu, China.

BACKGROUND: The aim of this study was to investigate the infection and antimicrobial resistance of Ureaplasma urealyticum (U. urealyticum) and Mycoplasma hominis (M. hominis) in patients with genital tract diseases in Jiangsu, China. METHODS: A total of 3,321 patients suspected with genital tract infectious diseases were enrolled in this study from September 2017 to September 2020. The Mycoplasma detection and antimicrobial susceptibility were tested using the commercially available Mycoplasma kit. RESULTS: Among the 3,321 specimens tested, 1,503 (45.3%) were positive for Mycoplasmas, and the proportion of mono-infection of U. urealyticum is highest (79.5%). The overall infection rate has been increasing in the past 3 years. The positive rate in females (68.7%) was higher than in males (25.0%), and the main infection age group was 20 - 39 (81.2%). Besides, U. urealyticum and M. hominis displayed relative lower resistance rates to gatifloxacin, josamycin, minocycline, and doxycycline (6.0%, 6.5%, 3.1%, and 3.2%, respectively). However, the antimicrobial resistance rates to azithromycin, clindamycin, roxithromycin, sparfloxacin, and ofloxacin were relatively high (45.4%, 42.1%, 34.9, 36.0, and 65.5%, respectively). Antimicrobial resistance of U. urealyticum and M. hominis to these 14 drugs have been changing in the past 3 years. CONCLUSIONS: In total, these preliminary data showed the prevalence and antimicrobial resistance status of U. urealyticum and M. hominis in patients suspected with genital tract infectious diseases, which has use for reference on both prevention and treatment of diseases caused by them.

Identification and Validation of a Novel Six-Gene Expression Signature for Predicting Hepatocellular Carcinoma Prognosis.

Background: Hepatocellular carcinoma (HCC) is a highly lethal disease. Effective prognostic tools to guide clinical decision-making for HCC patients are lacking. Objective: We aimed to establish a robust prognostic model based on differentially expressed genes (DEGs) in HCC. Methods: Using datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Genome Consortium (ICGC), DEGs between HCC tissues and adjacent normal tissues were identified. Using TCGA dataset as the training cohort, we applied the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analyses to identify a multi-gene expression signature. Proportional hazard assumptions and multicollinearity among covariates were evaluated while building the model. The ICGC cohort was used for validation. The Pearson test was used to evaluate the correlation between tumor mutational burden and risk score. Through single-sample gene set enrichment analysis, we investigated the role of signature genes in the HCC microenvironment. Results: A total of 274 DEGs were identified, and a six-DEG prognostic model was developed. Patients were stratified into low- or high-risk groups based on risk scoring by the model. Kaplan-Meier analysis revealed significant differences in overall survival and progression-free interval. Through univariate and multivariate Cox analyses, the model proved to be an independent prognostic factor compared to other clinic-pathological parameters. Time-dependent receiver operating characteristic curve analysis revealed satisfactory prediction of overall survival, but not progression-free interval. Functional enrichment analysis showed that cancer-related pathways were enriched, while immune infiltration analyses differed between the two risk groups. The risk score did not correlate with levels of PD-1, PD-L1, CTLA4, or tumor mutational burden. Conclusions: We propose a six-gene expression signature that could help to determine HCC patient prognosis. These genes may serve as biomarkers in HCC and support personalized disease management.

Treatment Effect of Regional Sodium Citrate Anticoagulation in Elderly Patients With High-Risk Bleeding Receiving Continuous Renal Replacement Therapy.

OBJECTIVE: To investigate the safety and efficacy of regional citrate anticoagulation (RCA) on elderly patients at high risk of bleeding after continuous renal replacement therapy (CRRT). METHODS: A total of 31 patients at high risk of bleeding who received CRRT in the intensive care unit were collected. The patients were divided into RCA group (n = 17) and no anticoagulation group (NA, n = 14) according to whether RCA was used or not. The levels of creatinine (Cr), blood urea nitrogen (BUN), prothrombin time (PT), activated partial thromboplastin time (APTT), total calcium (tCa), ionized calcium ion (iCa2+), sodium ion (Na+), bicarbonate ion (HCO3-), tCa/iCa2+ ratio, and pH were observed after treatment. The filter use time, number of filters used, filter obstruction events, clinical outcomes, and safety evaluation indexes were compared post-treatment. RESULTS: After treatment, serum Cr and BUN levels, APTT and PT levels in the RCA group were significantly lower than the NA group. The tCa, iCa2+, HCO3-, tCa/iCa2+, and pH were within the normal range after RCA treatment while Na+ levels saw a significant increase. In the RCA group, the filter using time was significantly longer, with significantly reduced numbers of filter use within 72 h and filter disorder events. Additionally, patients in the RCA group showed significant recovery of renal function and a significant reduction in bleeding events and in-hospital mortality. CONCLUSION: RCA treatment significantly improves clinical outcome of patients at high risk of bleeding after CRRT, safely and effectively prolongs the filter life and avoids coagulation incidences.

3D-Printing Biodegradable PU/PAAM/Gel Hydrogel Scaffold with High Flexibility and Self-Adaptibility to Irregular Defects for Nonload-Bearing Bone Regeneration.

A three-dimensional (3D) printed biodegradable hydrogel scaffold with a strong self-expanding ability to conform to the contour of irregular bone defects and be closely adjacent to host tissues is reported herein. The scaffold has a triple cross-linked network structure consisting of photo-cross-linked polyacrylamide (PAAM) and polyurethane (PU) as the primary IPN network and chemical cross-linked gelatin (Gel) as the secondary network, which confers the scaffold with good mechanical properties. The addition of PU in the polymerization process of acrylamide (AAM) can improve the ultraviolet (UV) photocuring efficiency of the hydrogel and incorporate abundant hydrogen bonds between the PAAM copolymer chain and the PU chain. The results show that the hydrogel scaffold contains regular structures with smooth morphology, excellent dimensional stability, and uniform aperture. The degradation rate of the hydrogel scaffold is controllable through adjusting cross-linking agents and can be up to about 60% after degradation for 28 days. More importantly, the rapid self-inflating characteristic of the scaffold in water, that is, the volume of hydrogel scaffold can increase to about 8 times that of their own in an hour and can generate a slight compressive stress on the surrounding host tissue, thus stimulating the reconstruction and growth of new bone tissues. The in vitro experiment indicates that the scaffold is nontoxic and biocompatible. The in vivo experiment shows that the PU/PAAM/Gel chemically cross-linked scaffold displays the desirable osteogenic capability. This UV-curable 3D printed self-adaptive and degradable hydrogel scaffold holds great potential for nonload-bearing bone repair.

TNFAIP3 Interacting Protein 3 Is an Activator of Hippo-YAP Signaling Protecting Against Hepatic Ischemia/Reperfusion Injury.

BACKGROUND AND AIMS: Hepatic ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver surgical procedures, causes a large proportion of early graft failure and organ rejection cases. The identification of key regulators of hepatic I/R injury may provide potential strategies to clinically improve the prognosis of liver surgery. Here, we aimed to identify the role of tumor necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in hepatic I/R injury and further reveal its immanent mechanisms. APPROACH AND RESULTS: In the present study, we found that hepatocyte TNIP3 was markedly up-regulated in livers of both persons and mice subjected to I/R surgery. Hepatocyte-specific Tnip3 overexpression effectively attenuated I/R-induced liver necrosis and inflammation, but improved cell proliferation in mice, whereas TNIP3 ablation largely aggravated liver injury. This inhibitory effect of TNIP3 on hepatic I/R injury was found to be dependent on significant activation of the Hippo-YAP signaling pathway. Mechanistically, TNIP3 was found to directly interact with large tumor suppressor 2 (LATS2) and promote neuronal precursor cell-expressed developmentally down-regulated 4-mediated LATS2 ubiquitination, leading to decreased Yes-associated protein (YAP) phosphorylation at serine 112 and the activated transcription of factors downstream of YAP. Notably, adeno-associated virus delivered TNIP3 expression in the liver substantially blocked I/R injury in mice. CONCLUSIONS: TNIP3 is a regulator of hepatic I/R injury that alleviates cell death and inflammation by assisting ubiquitination and degradation of LATS2 and the resultant YAP activation.TNIP3 represents a promising therapeutic target for hepatic I/R injury to improve the prognosis of liver surgery.