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The traditional square spot of street lamp is not suitable for the lighting requirements of the annular road lighting. In this paper, a lens design method for producing annular spot of high mast lamp is proposed. The method mainly contains three optical surfaces, in which the inner surface collimates the energy of the centre part of the light source, the total internal reflection surface collimates the light with large angle and low energy and the outer surface refracts all the collimated light to realise the annular illumination distribution on the target surface. In this design, we can change the diameter of the lighting spot through the variation of the inclination angle of the outer surface from 14° to 19° and the diameter of the spot changes from 10.2 m to 12.3 m at the distance of 30 m. The lighting requirements of high mast lighting are realised based on the TIR lens array, in which the average illuminance is more than 20 lx, the illuminance uniformity is more than 0.7 and the light optical utilisation factor is more than 90%. [ABSTRACT FROM AUTHOR]

Objectives: Vaccine hesitancy persists as a significant global health concern, especially during public health crises. This study aimed to explore factors influencing vaccination acceptance during a major public health crisis and establish a model of influencing factors., Design: A cross-sectional study., Methods: An anonymous cross-sectional survey was conducted online, encompassing sociodemographic characteristics, anxiety levels, personal risk perception and attitudes towards vaccination acceptance. Data analysis was performed using t-tests, one-way analysis of variance and multiple linear regression techniques in IBM SPSS Statistics V.25.0 (IBM Corp., Armonk, NY, USA)., Results: A total of 3921 participants participated in the survey. The mean acceptance attitudes were above the moderate level (M=4.02, SD=0.51), the mean risk perception score was below the moderate level (M=2.66, SD=0.58), and the mean score on the Self-Rating Anxiety Scale was also below the moderate level (M=2.05, SD=0.53). The results showed that internal variables (gender, age, marital status, professional background, region) and external variables (average family income, distance from home to vaccination site, family medical background) were statistically significant (p<0.05). Gender, region, distance from home to the vaccination site, anxiety, family medical background, risk coping, emotional perception and psychological representation of unusual severity were identified as significant predictors of vaccination acceptance attitudes, with the model explaining 35% of the variance (R²= 0.35, adjusted R²= 0.33). Based on these results, we constructed a theoretical model of influencing factors for vaccine acceptance attitudes., Conclusions: Despite increased acceptance of vaccination during major public health events, factors that both support and hinder acceptance remain. Identifying these factors allows for effective disease control and informs the development of public health strategies and crisis response measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Calcium oxalate urolithiasis, commonly referred to as kidney stones, is a prevalent condition marked by the development of solid crystals within the urinary system. Currently, there is no established treatment to cure calcium oxalate urolithiasis. The underlying processes of calcium oxalate urolithiasis remain unclear, and the aim of this study was to clarify the correlation and prediction of IL-10Ra and DKK-4 plasma levels in patients with calcium oxalate urolithiasis., Methods: In this study, we explored the role of body mass index, eating habits score, levels of IL-10Ra and DKK-4, C-reactive protein, white blood cell count, blood urea nitrogen, and blood uric acid in HCC. In total, 85 patients with COU, attending our hospitals between January 2022 and June 2023, were enrolled in this study as experimental group (n = 85), and 85 healthy individuals, who underwent physical examinations during the same period, were collected as control group (n = 85). The obtained blood samples were collected for further testing. Numerous assays, including ELISA assay, western blot, and qRT-PCR, were employed to investigate the role of IL-10Ra and DKK-4 in calcium oxalate urolithiasis., Results: The results indicate that the upregulation of IL-10Ra and DKK-4 may accelerate the progression of calcium oxalate urolithiasis. The logistic regression analysis indicates that the levels of IL-10Ra and DKK-4 positively correlated with calcium oxalate urolithiasis., Conclusions: In summary, the expression levels of IL-10Ra and DKK-4 positively correlated with the progression of calcium oxalate urolithiasis, suggesting that IL-10Ra and DKK-4 could serve as potential predictive factors and risk factors for calcium oxalate urolithiasis.

Ovarian cancer (OC) remains the primary cause of mortality among gynecological malignancies, and the identification of reliable molecular biomarkers to prognosticate OC outcomes is yet to be achieved. The gene palmitoyl protein thioesterase 2 (PPT2), which has been sparsely studied in OC, was closely associated with metabolism. This study aimed to determine the association between PPT2 expression, prognosis, immune infiltration, and potential molecular mechanisms in OC. We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases, then Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to assess and verify the role of PPT2. Gene set enrichment analysis (GSEA) was used to figure out the closely correlated pathways with PPT2. Overexpression experiment was performed to explore the function of PPT2. Our findings showed that PPT2 mRNA expression was apparent down-regulation in OC tissue compared to normal ovarian tissues in TCGA, GTEx datasets, and GEO datasets. This differential expression was also confirmed in our in-house datasets at both the mRNA and protein levels. Decreased PPT2 expression correlated with lower survival rates in TCGA, several GEO datasets, and our in-house datasets. Multivariate analysis revealed that PPT2 was an independent factor in predicting better outcomes for OC patients in TCGA and GEO. A negative correlation was revealed between immune infiltration and PPT2 expression through Single-sample GSEA (ssGSEA). Additionally, PPT2 was negatively correlated with an up-regulated immune score, stromal score, and estimate score, suggesting that patients with low PPT2 expression might benefit more from immunotherapy. Numerous chemical agents showed lower IC50 in patients with high PPT2 expression. In single-cell RNA sequencing (scRNA-seq) analysis of several OC datasets, we found PPT2 was mainly expressed in endothelial cells. Furthermore, we found that PPT2 inhibited OC cell proliferation in vitro. Our results demonstrated that PPT2 was considered a favorable prognostic biomarker for OC and may be vital in predicting response to immunotherapy and chemotherapy. Further research was needed to fully understand the relationship between PPT2 and immunotherapy efficacy in OC patients., (© 2024. The Author(s).)

This study investigated the anti-gastric cancer activity and mechanism of Panacis Quinquefolii Radix(Panax quinquefolium L.), and preliminarily compared the in vivo anti-gastric cancer efficacy of American-imported(JK-AG) and domestically produced(Shandong) Panacis Quinquefolii Radix decoctions(SD-AG). Based on network pharmacology predictions, a LUC-MGC803 cell ectopic gastric cancer nude mouse model was established. Mice were administered JK-AG and SD-AG at 1 g·kg~(-1) via gavage for 21 consecutive days. The positive control group received intraperitoneal injections of 5-fluorouracil(5-FU) at 20 mg·kg~(-1) every other day. Tumor volume was measured during the experiment. At the end of the experiment, high-resolution ultrasound imaging was used to measure tumor size, and an in vivo imaging system was used to observe tumor fluorescence expression. Tumor tissues were excised, weighed, and subjected to pathological histological examination. The terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL) assay and TUNEL+caspase-1 fluorescence double staining were used to detect tissue apoptosis and caspase-1 expression. Immunohistochemistry(IHC), Western blot(WB), and quantitative real-time PCR(RT-qPCR) techniques were used to detect the expression of predicted key proteins and genes involved in apoptosis and pyroptosis in tumor tissues. Network pharmacology predictions indicated that Panacis Quinquefolii Radix had anti-gastric cancer activity, primarily due to its ginsenoside components. Apoptosis induced by tumor necrosis factor(TNF)-α activation and caspase-1 may be key molecular mechanisms of its anti-cancer effects. In in vivo anti-tumor studies, compared to the model group, JK-AG and SD-AG did not affect the body weight or organ indices of the mice, whereas 5-FU significantly reduced body weight(P&lt;0.05) and increased lung and liver indices(P&lt;0.05). The tumor inhibition rates of JK-AG and SD-AG were 29.76% and 27.97%, respectively, which were lower than that of 5-FU. However, both JK-AG and SD-AG significantly reduced tumor tissue fluorescence intensity and three-dimensional tumor volume(P&lt;0.05 or P&lt;0.01). HE staining results showed that the drug groups had larger areas of tumor tissue necrosis. TUNEL and TUNEL+caspase-1 fluorescence staining indicated that both groups induced tumor cell apoptosis and increased caspase-1 expression. Both JK-AG and SD-AG significantly increased the expression of cleaved-caspase-8 and cleaved-caspase-3 proteins in tumor tissues detected by IHC and WB, as well as the mRNA expression of TNF-α, caspase-8, and caspase-9 detected by PCR, while reducing B-cell lymphoma 2(Bcl-2) protein expression. IHC showed that SD-AG increased the expression of TNF-α, caspase-9, cleaved-caspase-9, and tumor necrosis factor receptor 1(TNFR1) proteins more significantly than JK-AG, and also increased the Bax/Bcl-2 ratio, whereas JK-AG increased Bax mRNA expression more significantly than SD-AG. Additionally, JK-AG and SD-AG significantly increased the expression of NLRP3, caspase-1, cleaved-caspase-1, Gasdermin D(GSDMD), cleaved-GSDMD, IL-18, Gasdermin E(GSDME), and GSDME-NT proteins and the mRNA expression of caspase-1 and GSDME. JK-AG increased cleaved-caspase-1 protein expression more significantly than SD-AG in WB analysis. At the same time, JK-AG increased the expression of GSDMD mRNA, which was significantly higher than that of SD-AG group. For GSDME-NT protein expression, SD-AG increased it more significantly than JK-AG. The above studies indicate that Panacis Quinquefolii Radix has anti-gastric cancer effects, and the efficacy of American and Shandong ginsengs is comparable. Their mechanisms are related to TNF-α-mediated extrinsic apoptosis pathways and the induction of pyroptosis. The sensitivity of their action targets varies between American and Shandong ginsengs.

In gynecological oncology, ovarian cancer (OC) remains the most lethal, highlighting its significance in public health. Our research focused on the role of long non-coding RNA (lncRNA) in OC, particularly senescence-related lncRNAs (SnRlncRNAs), crucial for OC prognosis. Utilizing data from the genotype-tissue expression (GTEx) and cancer genome Atlas (TCGA), SnRlncRNAs were discerned and subsequently, a risk signature was sculpted using co-expression and differential expression analyses, Cox regression, and least absolute shrinkage and selection operator (LASSO). This signature's robustness was validated through time-dependent receiver operating characteristics (ROC), and multivariate Cox regression, with further validation in the international cancer genome consortium (ICGC). Gene set enrichment analyses (GSEA) unveiled pathways intertwined with risk groups. The ROC, alongside the nomogram and calibration outcomes, attested to the model's robust predictive accuracy. Of particular significance, our model has demonstrated superiority over several commonly utilized clinical indicators, such as stage and grade. Patients in the low-risk group demonstrated greater immune infiltration and varied drug sensitivities compared to other groups. Moreover, consensus clustering classified OC patients into four distinct groups based on the expression of 17 SnRlncRNAs, showing diverse survival rates. In conclusion, these findings underscored the robustness and reliability of our model and highlighted its potential for facilitating improved decision-making in the context of risk assessment, and demonstrated that these markers potentially served as robust, efficacious biomarkers and prognostic tools, offering insights into predicting OC response to anticancer therapeutics., Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-024-00163-z., Competing Interests: Conflict of InterestAll authors declare no conflicts of interest., (© International Human Phenome Institutes (Shanghai) 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear., Methods: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE., Results: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models., Conclusions: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Ethnopharmacological Relevance: Perioperative or postoperative adjuvant chemotherapy based on 5-fluorouracil (5-FU) is a common first-line adjuvant therapy for gastric cancer (GC). However, drug resistance and the side effects of 5-FU have reduced its efficacy. Among these side effects, gastrointestinal (GI) toxicity is one of the most common. Xianglian Pill (XLP) is a Chinese patent medicine that is commonly used for the treatment of diarrhoea. It can reduce inflammation and has a protective effect on the intestinal mucosa. Recent studies have shown that many components of XLP can inhibite tumor cell growth. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear., Aim of the Study: To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity., Materials and Methods: XLP was administered orally during intraperitoneal injection of 5-FU in GC mice model. Mice were continuously monitored for diarrhea and xenograft tumor growth. After 2 weeks, the mice were sacrificed and serum was collected to determine interleukin-6 levels. Pathological changes, the expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) in GI tissue were determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined., Results: The results showed that XLP could alleviate GI mucosal injury caused by 5-FU, alleviated diarrhea, and inhibited the expression of nuclear factor (NF)-κB and myeloid differentiation primary response-88. Besides, XLP could promote the 5-FU-induced apoptosis of GC cells and enhance the inhibitory effect of 5-FU on tumor xenografts. Further study showed that XLP administration could regulate the expression of p38 MAPK., Conclusions: XLP in combination with 5-FU could alleviate its GI side effects and enhance its inhibitory effect on xenograft tumor. Moreover, these effects were found to be related to the regulation of the p38 MAPK/NF-κB pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of optical optics for low-location road lighting is a challenging problem in providing high luminance and uniformity of illumination and meeting many other specific requirements. This study proposes an optical design method of low-location illumination based on an asymmetric double freeform surface lens. The ray emitted from the light source is refracted and reflected through the different surface types to the corresponding area of the receiving surface. In the design example, the road has dual-side mounted luminaires and a width of 6 m, and a height of 0.8 m. Simulation results indicate that, compared with conventional high-pole streetlights, the luminance uniformity had increased from 0.60 to 0.66, the illuminance uniformity had improved from 0.75 to 0.86, and the glare had been reduced., (© 2024 John Wiley & Sons Ltd.)

Population growth and climate change pose challenges to the sustainability of poultry farming. The emphasis on high-yield traits in commercialized breeds has led to a decline in their adaptability. Chicken varieties adapted to the local environment, possessing traits that facilitate adaptation to climate change, such as disease resistance and tolerance to extreme weather conditions, can improve hybridization outcomes. In this study, we conducted an analysis of the population structure and genetic diversity of 110 chickens representing indigenous breeds from southern China and two different commercial breeds. Further, we performed comparative population genomics, utilizing nucleotide diversity and fixation statistics, to characterize genomic features of natural selection and to identify unique genetic traits and potential selection markers developed by indigenous breeds after adapting to the local environment. Results based on genetic diversity and population structure analyses showed that indigenous varieties exhibited high levels of genetic diversity. Commercial breeds that have been indigenously bred demonstrated higher levels of genetic diversity than those that have not, and breeds with different selection practices displayed significant differences in genetic structure. Additionally, we further searched for potential genomic regions in native chicken ecotypes, uncovering several candidate genes related to ecological adaptations affecting local breeds, such as IKBKB, S1PR1, TSHR, IL1RAPL1 and AMY2A, which are involved in disease resistance, heat tolerance, immune regulation and behavioral traits. This work provides important insights into the genomic characterization of ecotypes of native chicken in southern China. The identification of candidate genes associated with traits such as disease resistance, heat tolerance, immunomodulation, and behavioral traits is a significant outcome. These candidate genes may contribute to the understanding of the molecular basis of the adaptation of the southern native chicken to the local environment. It is recommended that these genes be integrated into chicken breeding programs to enhance sustainable agriculture and promote effective conservation and utilization strategies., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: This prospective cohort study, conducted at a high-volume esophageal cancer center from July 2019 to July 2022, aimed to investigate the link between the right gastroepiploic artery (RGEA) length and anastomotic leakage (AL) rates following minimally invasive esophagectomy (MIE). Real-world data on stomach blood supply in the Chinese population were examined., Materials and Methods: A total of 516 cases were enrolled, categorized into two groups based on the Youden index-determined optimal cut-off value for the relative length of RGEA (length of RGEA/length of gastric conduit, 64.69%) through ROC analysis: Group SR (short RGEA) and Group LR (long RGEA). The primary observation parameter was the relationship between AL incidence and the ratio of direct blood supply from RGEA. Secondary parameters included the mean length of the right gastroepiploic artery, greater curvature, and the connection type between right and left gastroepiploic vessels. Patient data were prospectively recorded in electronic case report forms., Results: The study revealed median lengths of 43.60 cm for greater curvature, 43.16 cm for the gastric conduit, and 26.75 cm for RGEA. AL, the most common postoperative complication, showed a significant difference between groups (16.88 vs. 8.84%, P =0.01). Multivariable binary logistic regression identified Group SR and LR (odds ratio: 2.651, 95% CI: 1.124-6.250, P =0.03) and Neoadjuvant therapy (odds ratio: 2.479, 95% CI: 1.374-4.473, P =0.00) as independent predictors of AL., Conclusions: The study emphasizes the crucial role of RGEA length in determining AL incidence in MIE for esophageal cancer. Preserving RGEA and fostering capillary arches between RGEA and LGEA are recommended strategies to mitigate AL risk., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC., Methods: This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS., Results: The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%)., Conclusion: Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Changes in soil nitrogen components in tea gardens affect the soil nitrogen supply capacity and nitrogen cycle. In this study, soil samples were collected from forest land, cultivated land, and tea gardens with different plantation ages (30, 50, and 70 years) to explore the changes in soil nitrogen components and their relationship with physicochemical properties and enzyme activities. The results showed that:① with the increase in tea plantation age, the silt, total phosphorus, and urease and catalase activities gradually increased, whereas the sand, clay, pH, electrical conductivity, soil organic carbon, and the activities of invertase gradually decreased. The alkaline phosphatase activity increased first and then decreased with the increase in tea plantation age, and no significant differences were observed in soil water content and acid phosphatase activity. ② With the increase in tea plantation age, the contents of acid ammonia nitrogen, amino acid nitrogen, and nitrate nitrogen (NO 3 - -N) increased significantly, and the contents of total nitrogen, acid ammonia nitrogen, hydrolyzable unknown nitrogen, and non-hydrolyzable nitrogen in tea gardens were significantly higher than those in forest land. ③ The total phosphorus, alkaline phosphatase, and urease were the main factors affecting soil nitrogen components. Among them, organic nitrogen components were significantly correlated with total phosphorus and alkaline phosphatase, and inorganic nitrogen components were significantly correlated with alkaline phosphatase, whereas total nitrogen had significant correlations with sand, silt, total phosphorus, urease, and alkaline phosphatase.

Shenfu injection (SFI), composed of ginseng and aconite, is a Chinese patent developed from the classic traditional prescription Shenfu Decoction created more than 700 years ago. SFI has been widely used in China for over 30 years for treating cardiovascular diseases. The main components in it include ginsenosides and aconitum alkaloids. In recent years, the role of SFI in the treatment of cardiovascular diseases has attracted much attention. The pharmacological effects and therapeutic applications of SFI in cardiovascular diseases are summarized here, highlighting pharmacological features and potential mechanisms developments, confirming that SFI can play a role in multiple ways and is a promising drug for treating cardiovascular diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Xie, Hu, Tong and Peng.)

Background: The potential impact of learning curve on long-term health-related quality of life (QoL) after esophagectomy for cancer has not been investigated. The aim of this article is to investigate the relationship between learning curve for McKeown minimally invasive esophagectomy (MIE) and health-related quality of life (QoL) in long-term, disease free survivors up to 10 years after esophageal cancer resection., Methods: Esophageal cancer patients who underwent McKeown MIE between 2009 and 2019 were identified in which 280 who were free of disease at the time of survey and completed health-related QoL and symptom questionnaires, including EORTC QLQ-C30, EORTC QLQ-OES18, and Digestive Symptom Questionnaire. Patients were assessed in 3 cohorts according to the learning phases of expertise reported by our previous study: initial phase; plateau phase, and; experienced phase., Results: Median time from operation to survey was 5.8 years (interquartile range 4.6-8.2). The QLQ-C30 mean scores of functional scales, and symptom scales of respiratory and digestive systems including dyspnea (P = 0.006), shortness of breath (P = 0.003), and dysphagia (P = 0.031) were significantly better in experienced phase group. Furthermore, in the subgroup analyses for patients without postoperative major complications, patients in the initial learning phase remained suffering from more symptoms of dyspnea (P = 0.040) and shortness of breath (P = 0.001)., Conclusion: Esophageal cancer patients undergoing McKeown MIE in initial learning phase tend to suffer from a deterioration in long-term health-related QoL and higher symptomatic burden as compared to experienced learning phase, which did not improved over time and warranted more attention., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Spatial prediction of the concentrations of soil heavy metals (HMs) in cultivated land is critical for monitoring cultivated land contamination and ensuring sustainable eco-agriculture. In this study, 32 environmental variables from terrain, climate, soil attributes, remote-sensing information, vegetation indices, and anthropogenic activities were used as auxiliary variables, and random forest (RF), regression Kriging (RK), ordinary Kriging (OK), and multiple linear regression (MLR) models were proposed to predict the concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in cultivated soils. In comparison to those of RK, OK, and MLR, the RF model had the best prediction performance for As, Cd, Cr, Hg, Pb, and Zn, whereas the OK and RK models had highest prediction performance for Cu and Ni, respectively, showing that R 2 was the highest, and mean absolute error (MAE) and root mean square error (RMSE) were the lowest. The prediction performance of the spatial distribution of soil HMs under different prediction methods was basically consistent. The high value areas of eight HMs concentrations were all distributed in the southern plain area. However, the RF model depicted the details of spatial prediction more prominently. Moreover, the importance ranking of influencing factors derived from the RF model indicated that the spatial variation in concentrations of the eight HMs in Lanxi City were mainly affected by the combined effects of Se, TN, pH, elevation, annual average temperature, annual average rainfall, distance from rivers, and distance from factories. Given the above, random forest models could be used as an effective method for the spatial prediction of soil heavy metals, providing scientific reference for regional soil pollution investigation, assessment, and management.

Background: Lymph nodes along the left recurrent laryngeal nerve (LRLN) is thought to be highly involved in esophageal cancer. Given the unique anatomical positioning of the nerve, performing lymphadenectomy in this region requires advanced techniques within limited working space. Meanwhile, high incidence of morbidity and mortality is associated with lymphadenectomy. Although several methods have been applied to reduce the technical requirement and the incidence of postoperative complication, the optimal method remains controversial., Methods: This study was a single-center, prospective, randomized trial to investigate the utility of lymphadenectomy along the LRLN during the minimally invasive esophagectomy in esophageal squamous cell carcinoma patients by comparing the surgical outcome, postoperative complication, survival rate, and quality of life (QoL) between the retraction method (RM) and the suspension method (SM) in patients with esophageal cancer from June 2018 to November 2020. QoL was assessed according to questionnaire: EQ-5D-5L., Results: Of 94 patients were enrolled and randomized allocated to RM and SM group equally. Characteristics did not differ between groups. The duration of lymph node dissection along LRLN was significant longer in SM group ( P <0.001). No difference was observed about postoperative complications. One of in-hospital death was occurred in each group ( P >0.999). Patients in neither of groups exhibiting difference about 3-year disease-free survival rate ( P =0.180) and overall survival rate ( P =0.430). No difference was observed in postoperative QoL between groups at different time points (all, P >0.05)., Conclusion: Both methods of lymph node dissection along the LRLN during minimally invasive esophagectomy in esophageal squamous cell carcinoma patients are technically feasible and safe. The RM appears more favorable in terms of reducing surgical duration compared to the SM., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Anastomotic leakage (AL) is a severe complication following esophagectomy with high mortality. Perioperative decreased serum albumin level is considered a predictive of AL, however, its impact on AL incidence in patients treated with neoadjuvant chemotherapy (NCT) followed by minimally invasive esophagectomy (MIE) is not well defined., Methods: The data of 318 consecutive esophageal cancer patients who underwent MIE were collected retrospectively from January 2021 to December 2021. The perioperative level of albumin was detected and the baseline of altering levels for albumin was established. The incidence of postoperative complications and survival rate were analyzed between groups., Results: After exclusion, 137 patients were enrolled and assigned to more decreased albumin (MA) and less decreased albumin (LA) groups. The levels of albumin descended significantly after MIE (p < 0.0001). There was no significant difference in the clinicopathologic characteristics or surgical outcomes between groups. The incidence of postoperative AL was 10.2% in MA group and 1.4% in LA group (p = 0.033). Three patients died due to AL in MA group, while no mortality was observed in LA group (p = 0.120). The rate of other postoperative complications was similar between groups. Progression-free survival (PFS) in LA group was a little higher than that in MA group, but it was no significant difference (p = 0.853). Similarly, no difference was observed in overall survival (OS) between groups (p = 0.277)., Conclusions: Severely deficient serum albumin after MIE was an indicator of AL in esophageal cancer patients treated with NCT., Trial Registration: Chinese clinical trial registry: ChiCTR2200066694, registered December14th,2022. https://www.chictr.org.cn/edit.aspx?pid=185067&htm=4 ., (© 2023. The Author(s).)

Background: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) was manifested as seropositive for PLA2R antibodies (SAb) and/or glomerular PLA2R antigens' (GAg) deposits. According to the test of SAb and GAg, PLA2R-associated MN can be divided into SAb + /GAg-, SAb-/GAg + , and SAb + /GAg + groups. The clinical characteristics and outcomes of the three groups need to be further evaluated., Methods: 184 PLA2R-associated MN patients were enrolled. SAb was measured by enzyme-linked immunosorbent assay with a cut-off value of 14 RU/mL. GAg was detected by immunofluorescence using a paraffin section of renal biopsy samples. Clinical characteristics and the decline of eGFR were compared among the 3 groups., Results: There were 33 SAb + /GAg-, 46 SAb-/GAg +, and 105 SAb + /GAg + PLA2R-associated MN patients reviewed. Clinical characteristics, such as the level of proteinuria, serum albumin, as well as eGFR, were comparable between the SAb + /GAg- and SAb + /GAg + patients. While SAb-/GAg + patients exhibited mild clinical manifestations as evidenced by higher serum albumin (P < 0.001) and lower proteinuria (p = 0.049) compared with SAb + /GAg + patients. After 21.96 ± 7.39 month follow-up, the eGFR decrease was no difference between the SAb + /GAg- and SAb + /GAg + patients. SAb-/GAg + patients had a lower rate of the > 20% eGFR decline as well as a 50% eGFR decline compared with the SAb + /GAg + patients (10.87% vs 30.48%, p = 0.013; 0.00% vs 4.76%, p = 0.324)., Conclusions: Our study showed that the clinical manifestations of SAb + /Gag- patients were the same as those of double-positive patients, while SAb-/GAg + patients exhibited mild clinical manifestations and slower eGFR decline compared to the double-positive patients., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E&#95;2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E&#95;2(PGE&#95;2), prostaglandin F&#95;(2α)(PGF&#95;(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E&#95;2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE&#95;2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF&#95;(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P&lt;0.05 or P&lt;0.01), significantly reduce the uterine and ovarian coefficients(P&lt;0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE&#95;2 content was significantly increased(P&lt;0.05), COX-2, PGF&#95;(2α) and Ca~(2+) content, and PGF&#95;(2α)/PGE&#95;2 was significantly decreased(P&lt;0.05 or P&lt;0.01), and OT content was decreased, while E&#95;2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P&lt;0.05 or P&lt;0.01) and ERα protein expression was upregulated(P&lt;0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P&lt;0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.

The supplementation of soil amendments may not only improve the soil physical and chemical properties but also lead to the accumulation of heavy metals in soil. This experiment included six treatments:control (CK), organic manure (OM), polyacrylamide+organic manure (PAM+OM), straw mulching+organic manure (SM+OM), buried straw+organic manure (BS+OM), and bio-organic manure+organic manure (BM+OM) to explore the effects of different soil amendments on heavy metals and soil enzyme activities in coastal saline land and the relationship between them. The results revealed that compared with that in the CK treatment, the contents of soil Cr, Cu, Ni, and Pb exhibited an upward trend after the supplementation of soil amendments, among which the SM+OM and PAM+OM treatments had the most significant effects on the contents of soil Cr and Cu, respectively, whereas the BM+OM treatment had the most significant effects on the contents of soil Ni and Pb. Compared with those in the CK treatment, the activities of soil invertase and urease increased significantly following supplementation of soil amendments, and the BM+OM treatment had the best effect. The alkaline phosphatase activity exhibited a slightly upward trend after the supplementation of soil amendments, whereas the catalase activity did not change significantly. The redundancy analysis revealed that the first two axes cumulatively accounted for 70.3% of the variability in enzyme activities, and the importance of single soil heavy metals on soil enzyme activity was as follows:Ni>Cu>Cr>Pb.

Liver fibrosis refers to a reversible event of repair and reconstruction following injury due to various etiologies, and its continuous development will lead to cirrhosis and liver cancer. Abnormal alterations in intestinal microbiota can hasten the development of hepatic fibrosis and damage. Veronicastrum latifolium (Hemsl.) Yamazaki (VLY) is a classic drug applied extensively for managing acute and chronic hepatitis, liver cirrhosis and ascites in ethnic minority areas of Guizhou Province, China, which possesses broad-spectrum pharmacological activities. In view of the crucial role of intestinal microbiota in the development of liver fibrosis, the present study attempted to investigate the effects of VLY aqueous extract on ameliorating CCl 4 -elicited liver fibrosis in mice and on intestinal microbiota and to explore its possible mechanism. Phytochemical analysis showed that VLY water extract contained a variety of components, particularly rich in organic acids and their derivatives, flavonoids, phenolic acids, nucleotides and their derivatives, carbohydrates and other compounds. VLY water extract remarkably alleviated CCl 4 -induced liver damage and fibrosis in mice, improved liver histology, and improved liver function abnormalities. VLY water extract also inhibited the activation of hepatic stellate cells and invasion of intrahepatic inflammatory cells. Additionally, sequencing the 16 s rDNA gene revealed that VLY water extract changed the intestinal microbiota composition in liver fibrotic mice. It elevated the Firmicutes/Bacteroidota ratio and enriched the relative Lactobacillus richness, which is capable of mitigating fibrosis and inflammation in impaired liver. In summary, through modulation of inflammation and intestinal microbiota, VLY water extract can reduce the CCl 4 -elicited liver fibrosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: To evaluate effectiveness of concurrent radiotherapy in esophageal cancer patient treated with neoadjuvant therapy., Methods: The data of 1026 consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent minimally invasive esophagectomy (MIE) were retrospectively collected. The main inclusion criteria were patients with locally advanced (cT2-4N0-3M0) ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by MIE, and divided into two groups according to different neoadjuvant strategies. Propensity score matching was performed to improve the comparability between the two groups., Results: After exclusion and matching, 141 patients were enrolled retrospectively: 92 received NCT, and 49 received NCRT. No difference in clinicopathologic characteristics or incidence of adverse events between groups. A shorter operation time (215.7 ± 35.5 min) (p < 0.001), less blood loss (111.2 ± 67.7 ml) (p = 0.0007) and a greater number of lymph nodes retrieved (33.8 ± 11.7) (p = 0.002) were observed in NCT group than in NCRT group. The incidence of postoperative complications was similar between groups. Although patients in NCRT group had better pathological complete response (16, 32.7%) (p = 0.0026) and ypT0N0 (10, 20.4%) (p = 0.0002) rates, there was no significant difference in 5-year progression-free survival (p = 0.1378) or disease-specific survival (p = 0.1258) between groups., Conclusions: Compared with NCRT, NCT has certain advantages in that it can simplify the surgical procedure and decrease the surgical technique required without compromising the surgical oncological outcomes and long-term survival of patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To compare the perioperative outcomes from McKeown minimally invasive esophagectomy (MIE) when performed in three-dimensional versus two-dimensional visualization system, and investigate the learning curve of a single surgeon who implemented three-dimensional McKeown MIE., Methods: A total of 335 consecutive cases (three-dimensional or two-dimensional) were identified. Perioperative clinical parameters were compared and cumulative sum learning curve was plotted. Propensity score matching was used to reduce selection bias from confounding factors., Results: Patients in three-dimensional group were associated with more chronic obstructive pulmonary disease (23.9% vs 3.0%, p < 0.01). After propensity score matching (108 matched patients in each groups), this finding was no longer statistically significant. Comparing to two-dimensional group, significant improvement in total retrieved lymph nodes (28 vs 33, p = 0.003) was observed in three-dimensional group. In addition, more lymph nodes around the right recurrent laryngeal nerve were harvested in three-dimensional group than that in two-dimensional group (p = 0.045). However, there were no significantly differences were found between the two groups in terms of other intraoperative parameters (e.g., operative time) and postoperative relevant outcomes (e.g., lung infection). Furthermore, the change point in the cumulative sum learning curves for intraoperative blood loss and thoracic procedure time was 33 procedures, respectively., Conclusion: Three-dimensional visualization system appears to be superior in performing lymphadenectomy during McKeown MIE to that of a two-dimensional technique. For surgeons proficient in performing two-dimensional McKeown MIE, the learning curve for a three-dimensional procedure appears to begin near proficiency after more than 33 cases., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Heat stress is a major problem that constrains pig productivity. Understanding and identifying adaptation to heat stress has been the focus of recent studies, and the identification of genome-wide selection signatures can provide insights into the mechanisms of environmental adaptation. Here, we generated whole-genome re-sequencing data from six Chinese indigenous pig populations to identify genomic regions with selection signatures related to heat tolerance using multiple methods: three methods for intra-population analyses (Integrated Haplotype Score, Runs of Homozygosity and Nucleotide diversity Analysis) and three methods for inter-population analyses (Fixation index (F ST ), Cross-population Composite Likelihood Ratio and Cross-population Extended Haplotype Homozygosity). In total, 1 966 796 single nucleotide polymorphisms were identified in this study. Genetic structure analyses and F ST indicated differentiation among these breeds. Based on information on the location environment, the six breeds were divided into heat and cold groups. By combining two or more approaches for selection signatures, outlier signals in overlapping regions were identified as candidate selection regions. A total of 163 candidate genes were identified, of which, 29 were associated with heat stress injury and anti-inflammatory effects. These candidate genes were further associated with 78 Gene Ontology functional terms and 30 Kyoto Encyclopedia of Genes and Genomes pathways in enrichment analysis (P < 0.05). Some of these have clear relevance to heat resistance, such as the AMPK signalling pathway and the mTOR signalling pathway. The results improve our understanding of the selection mechanisms responsible for heat resistance in pigs and provide new insights of introgression in heat adaptation., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS ( HR =1.069, 95% CI : 1.005-1.137, P =0.035) and ΔLVEF ( HR =0.935, 95% CI : 0.878-0.995, P =0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 ( P =0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P =0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P =0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.

As a member of Ubiquitin-specific protease subfamily, ubiquitin specific protease 7 (USP7) has been reported to participate in a variety of cellular processes, including cell cycle, apoptosis, DNA damage response, and epigenetic modification. However, its function in preimplantation embryos is still obscure. To investigate the functions of USP7 during preimplantation embryo development, we used siRNA to degrade endogenous USP7 messenger RNA. We found that USP7 knockdown significantly decreased the development rate of mouse early embryos. Moreover, depletion of USP7 induced the accumulation of the DNA lesions and apoptotic blastomeres in early embryos. In addition, USP7 knockdown caused an abnormal H3K27me3 modification in 2-cell embryos. Overall, our results indicate that USP7 maintains genome stability perhaps via regulating H3K27me3 and DNA damage, consequently controlling the embryo quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The invasion of Spartina alterniflora poses a great threat to coastal wetland ecosystems. In this study, the stoichiometric characteristics of soil carbon, nitrogen, and phosphorus under a Spartina alterniflora invasion were explored using ANOVA in a coastal wetland in Hangzhou Bay, and the driving coupling relationship between soil environmental factors and soil C:N:P stoichiometric characteristics of the coastal wetland were further explored based on the redundancy analysis (RDA), boosted regression tree (BRT), and partial least squares-structural equation (PLS-SEM) model. The results showed that:① after the invasion of Spartina alterniflora , soil N:P and total nitrogen (TN) in the wetland increased significantly, and with the increase in invasion time, TN and N:P decreased significantly, whereas soil organic carbon (SOC), C:N, and C:P increased significantly. ② The RDA model revealed that the main factors affecting the stoichiometric characteristics of topsoil C:N:P were SOC>electrical conductivity (EC)>TN in winter and SOC>bulk density (BD)>TN in summer. ③ The BRT model showed that under the invasion of Spartina alterniflora , TN was the key factor affecting soil C:N and N:P, and SOC was the key factor affecting C:P. ④ The PLS-SEM model showed that clay and water content directly affected SOC, thus affecting C:N and C:P; the clay and EC directly affected total phosphorus (TP), thus affecting N:P and C:P; and the EC directly affected TN, thus affecting C:N and N:P. In conclusion, the invasion of Spartina alterniflora had a significant impact on soil C:N:P stoichiometric characteristics in the study area. Soil physical properties and nutrient content directly or indirectly affected soil C:N:P stoichiometric characteristics to varying degrees.

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by 99m Tc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with 18 F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with 18 F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and 18 F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and 18 F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs . (35.7%±13.9%), P =0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P =0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 ( P =0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group ( n =36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group ( n =64) (all P <0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.

Background: Anlotinib is a novel oral small-molecule tyrosine kinase inhibitor (TKI), which can inhibit angiogenesis. The purpose of this study was to evaluate the efficacy and safety of anlotinib combined with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC)., Methods: This phase II clinical trial included 40 patients with metastatic TNBC who had previously received anthracycline and/or taxane treatment. All patients received anlotinib combined with chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and safety., Results: During May 1, 2019 and April 30, 2022, there were 40 patients enrolled in this study. The median PFS and median OS were 8.8 months (95% confidence interval [CI] 6.5-11.1 months) and 19.0 months (95% CI, 12.1-25.9 months), respectively. The ORR, CBR and DCR were 40.0% (16/40), 85.0% (34/40) and 95.0% (38/40), respectively. Cox univariate and multivariate analyses demonstrated that having more than 3 metastatic sites (p = 0.001; p = 0.020) was an independent and meaningful unfavorable prognostic factor for PFS. 37.5% of patients had grade 3 to 4 treatment-related adverse events (TRAEs). The grade 3 to 4 TRAEs included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%) and thrombocytopenia (2.5%). None of the patients withdrew from the study or died due to TRAEs., Conclusion: In this single-arm study, the treatment of metastatic TNBC with anlotinib combined with chemotherapy showed certain efficacy, and its toxicity was acceptable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Xie, Chen, Zhang, Chen, Bai, Lan, Song, Guo and Du.)

Irritable bowel syndrome (IBS) is a common refractory disease. Chinese medicine (CM) has remarkable efficacy and advantages on the treatment of IBS. This review summarized the articles focusing on the treatment of IBS with CM to sum up the latest treatment methods for IBS and the underlying mechanisms. Literature analysis showed that prescriptions, acupuncture, and moxibustion are the primary methods of CM treatment for IBS. The potential mechanism centers on the regulation of the enteric nervous system, the alleviation of visceral hypersensitivity, the stability of intestinal flora, and the regulation of the immune system., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: A substantial need for effective and safe treatment options is still unmet for patients with heavily pre-treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Herein, we assessed the efficacy and safety of pyrotinib plus trastuzumab and chemotherapy in patients with heavily treated HER2-positive MBC., Methods: In this single-arm exploratory phase II trial, patients with HER2-positive MBC previously treated with trastuzumab plus lapatinib or pertuzumab, received pyrotinib plus trastuzumab and chemotherapy. The primary end point was progression-free survival (PFS) in the total population (TP). Secondary end points included PFS in the subgroup with brain metastases (Sub-BrM), confirmed objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), exploration of predictive factors of PFS, and safety., Results: Between November 1, 2018, and March 31, 2021, 40 patients were eligible for this study. The median PFS reached 7.5 months (95% confidence interval [CI] 4.7 to 9.9 months) and 9.4 months (95% CI 6.6 to 12.1 months) in the TP and Sub-BrM, respectively. ORR was 50.5% (20/40). CBR was 75.5% (30/40) and DCR reached 97.5% (39/40). Cox univariate and multivariate analyses demonstrated that liver or/and lung metastases was the significant adverse prognostic factor for PFS (p = 0.018; p = 0.026; respectively). The most frequent grade 3 or 4 treatment-related adverse events were diarrhea, neutropenia and leukopenia. No new safety signals were observed., Conclusion: Pyrotinib plus trastuzumab and chemotherapy offered a promising option with manageable safety profile for heavily pre-treated HER2-positive MBC, especially for those without liver or/and lung metastases., (© 2022. The Author(s).)

Poly ADP-ribose polymerase inhibitor (PARPi) treatment is effective in triple-negative breast cancer (TNBC) with BRCA mutation. However, its efficacy in BRCA-proficient TNBC remains unexplored. It is, therefore, an exciting proposition to broaden the indication of PARPi for BRCA-proficient TNBC patients. Chemokine receptor (CXCR4) is a transmembrane G protein-coupled receptor, which is involved in cell migration, proliferation, apoptosis, and damage repair, and it initiates many signalling pathways. Although administration of CXCR4 inhibitor alone is not ideal as a target drug, it can play a strong synergistic role in combination with other drugs. We explored the effect of CXCR4 and PARP1 on tumour cell proliferation, migration, metastasis, and apoptosis in vitro and in vivo and found that a CXCR4 inhibitor, AMD3100, enhanced the anti-tumour effect of PARP1 inhibitor, olaparib, on BRCA-proficient TNBC. When CXCR4 was inhibited and silenced, DNA damage repair and DNA replication fork activity were suppressed by up-regulating caspase-3-mediated increase in PARP1 cleavage; in combination with the inhibition of PARP1, AMD3100 resulted in the accumulation of fatal DNA damage and induction of apoptosis. This combination regimen can be effective against BRCA-proficient TNBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The endothelium is the critical barrier that controls transendothelial communications. Blood vessels in cancer tissue are poorly developed and highly permeable. However, it is poorly understood how circulating cancer cells released through these "leaky" vessels break the intact vasculature of remote organs to metastasize. We investigated the roles of cancer cell-derived extracellular vesicles (CEVs) in regulating cancer metastasis by analyzing samples from gastric cancer patients, performing in vitro experiments, and studying mouse models. We made several novel observations. First, the rate of metastasis was closely associated with plasma levels of CEVs in patients with gastric cancer. Second, cultured endothelial cells endocytosed CEVs, resulting in cytoskeletal rearrangement, low expression of the junction proteins cadherin and CD31, and forming large intercellular gaps to allow the transendothelial migration of cancer cells. The dynamin inhibitor Dynasore prevented these CEV-induced changes of endothelial cells by blocking CEVs endocytosis. Third, CEVs disrupted the endothelial barrier of cancer-bearing mice to promote cancer metastasis. Finally, lactadherin promoted the clearance of circulating CEVs to reduce metastasis. These results demonstrate the essential role of CEVs in promoting the metastasis of gastric cancer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Carthamus tinctorius is proved potent in treating ischemic stroke. Flavonoids, such as safflower yellow, hydroxysafflor yellow A(HSYA), nicotiflorin, safflower yellow B, and kaempferol-3-O-rutinoside, are the main substance basis of C. tinctorius in the treatment of ischemic stroke, and HSYA is the research hotspot. Current studies have shown that C. tinctorius can prevent and treat ischemic stroke by reducing inflammation, oxidative stress, and endoplasmic reticulum stress, inhibiting neuronal apoptosis and platelet aggregation, as well as increasing blood flow. C. tinctorius can regulate the pathways including nuclear factor(NF)-κB, mitogen-activated protein kinase(MAPK), signal transducer and activator of transcription protein 3(STAT3), and NF-κB/NLR family pyrin domain containing 3(NLRP3), and inhibit the activation of cyclooxygenase-2(COX-2)/prostaglandin D2/D prostanoid receptor pathway to alleviate the inflammatory development during ischemic stroke. Additionally, C. tinctorius can relieve oxidative stress injury by inhibiting oxidation and nitrification, regulating free radicals, and mediating nitric oxide(NO)/inducible nitric oxide synthase(iNOS) signals. Furthermore, mediating the activation of Janus kinase 2(JAK2)/STAT3/suppressor of cytokine signaling 3(SOCS3) signaling pathway and phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt)/glycogen synthase kinase-3β(GSK3β) signaling pathway and regulating the release of matrix metalloproteinase(MMP) inhibitor/MMP are main ways that C. tinctorius inhibits neuronal apoptosis. In addition, C. tinctorius exerts the therapeutic effect on ischemic stroke by regulating autophagy and endoplasmic reticulum stress. The present study reviewed the molecular mechanisms of C. tinctorius in the treatment of ischemic stroke to provide references for the clinical application of C. tinctorius.

Background: Clinical benefits of neoadjuvant Anlotinib for locally advanced esophageal squamous cell carcinoma (ESCC) remains unclear. This study evaluated the efficacy and safety of neoadjuvant Anlotinib plus chemotherapy followed by minimally invasive esophagectomy (MIE) for the treatment of patients with locally advanced ESCC., Methods: Patients with locally advanced ESCC were randomly assigned to neoadjuvant Anlotinib combined with chemotherapy (Anlotinib group) or neoadjuvant chemoradiotherapy alone (nCRT group) with an allocation ratio of 1:1. The primary endpoint was the R0 surgical resection rate. Secondary endpoints included postoperative pathologic stage, complete response (CR) rate, and safety. Safety was assessed by adverse events (AEs) and postoperative complications., Results: From August 2019 to August 2021, 93 patients were assigned to the nCRT or Anlotinib group. Of the 93 patients, 79 underwent MIE and were finally included in the per-protocol set (nCRT group: n=39; Anlotinib group: n=40). The R0 resection rate was 97.4% for nCRT versus 100.0% for Anlotinib group ( p >0.05). Compared with the nCRT group, patients in the Anlotinib group had shorter total operation duration (262.2 ± 39.0 vs. 200.7 ± 25.5 min, p =0.010) and less blood loss (161.3 ± 126.7 vs. 52.4 ± 39.3 mL, p <0.001). No significant differences were found in the postoperative pathologic stage between the Anlotinib group and nCRT group (all p >0.05). Besides, the incidences of AEs (80.0% vs. 92.3%) and postoperative complications (22.5% vs. 30.8%) were similar between the two groups (all p >0.05)., Conclusions: Neoadjuvant Anlotinib plus chemotherapy had a similar safety profile and pathologic response, but better surgical outcomes than nCRT for locally advanced ESCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Li, Xie, Bao, Hao, Long, Wang, Zhong and Guo.)

Objective: To explore the synergic mechanism of ginsenoside Rg 1 (Rg 1 ) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs., Methods: The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg 1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg 1 for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na + ], potassium ions [K + ] and calcium ions [Ca 2+ ] levels, and Nav1.5, Kv4.2, and RyR 2 genes expressions in each group were examined., Results: For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg 1 had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg 1 significantly decreased the level of intracellular Ca 2+ (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg 1 significantly decreased the level of intracellular Ca 2+ via regulating Nav1.5, RyR 2 expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg 1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg 1 significantly inhibited the level of intracellular Na + (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg 1 significantly inhibited the level of intracellular K + (P<0.01) via regulating Nav1.5, Kv4.2, RyR 2 expressions in impaired NRCMs., Conclusion: Rg 1 inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na + ], [K + ], and [Ca 2+ ]., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The efficacy and tolerability of eribulin mesylate, a synthetic halichondrin B analog, in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes have been established. Acute-on-chronic liver failure (ACLF) is a clinical syndrome manifesting as acute and severe hepatic derangement resulting from varied insults in patients with established chronic liver disease or cirrhosis who did not previously receive eribulin. A middle-aged woman diagnosed with MBC and diffuse liver metastases who was pretreated with multi-line chemotherapy received eribulin as eighth-line chemotherapy and presented with hepatic encephalopathy, rapid bilirubin elevation, and significant coagulation dysfunction on day 4 in cycle 1. The patient was diagnosed with ACLF induced by eribulin. Therefore, ACLF may be a lethal and rare adverse event when patients with chronic liver metastases receive eribulin treatment, and clinicians' awareness should be increased for optimal prevention and prompt diagnosis and treatment.

Rhein, one of the main active components of rhubarb (Dahuang) and Polygonum multiflorum (Heshouwu), has a wide range of effective pharmacological effects. Recently, increasing studies have focused on its potential hepatorenal toxicity, but the cardiotoxicity is unknown. In this study, we found that the IC 50 of rhein to H9c2 cells at 24 h and 48 h were 94.5 and 45.9μmol/L, respectively, with positive correlation of dose-toxicity and time-toxicity. After the treatment of rhein (106, 124 and 132μmol/L), the number of H9c2 cells decreased significantly, and the morphology of H9c2 cells showed atrophy, round shape and wall detachment. Moreover, the proportion of apoptotic cells in H9c2 cells treated with rhein was significantly increased in a dose-dependent manner. And rhein induced S phase arrest of H9c2 cells and inhibited cell proliferation. Rhein up-regulated ROS, LDH levels and low MMP but down-regulated SOD content in H9c2 cells. Additionally, the results showed that the cardiac function LVEF and LVFS of rhein high-medium-low dose groups (350, 175, 87.5 mg/kg) were significantly reduced. And the contents of Ca 2+ , cTnT, CK and LDH in serum of KM mice were significantly up-regulated by rhein. Furthermore, western blot results suggested that rhein the above effects via promoting Fas-induced apoptosis pathway in vitro and in vivo. In general, rhein may cause cardiotoxicity via Fas-induced apoptosis pathway in vivo and in vitro, which provides reference for the safe use of medicinal plant containing rhein and its preparations., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To compare the clinical effects of two different hydroxyapatite bone graft materials in maxillary sinus lifting surgery with bone grafting and implantation at the same time., Methods: Seventy-two patients with implantation in the maxillary posterior dental area and insufficient bone mass admitted to the First Affiliated Hospital of Bengbu Medical College were collected from March 2018 to April 2019, and they were divided into experimental group(n=36) and control group(n=36) by random number table. Patients in the control group used hydroxyapatite composite material, while patients in the experimental group used nano-hydroxyapatite composite material. The clinical effects, bone increment and bone density changes of the two groups of implants were compared, and postoperative implant stability and complications of the two groups were compared. Statistical analysis was performed with SPSS 18.0 software package., Results: The survival rate of implants in the experimental group was significantly higher than that in the control group at 24 months (P＜0.05). Alveolar bone resorption in the experimental group was significantly lower than the control group 6 months after surgery(P＜0.05). The bone mineral density of implants in the experimental group was significantly higher than the control group 6 months and 12 months after operation(P＜0.05). The implant stability coefficient value of the experimental group was significantly higher than the control group 12 months after operation(P＜0.05). There was no significant difference in the total complication rate between the two groups(P＞0.05)., Conclusions: In maxillary sinus lift, the survival rate of nano-hydroxyapatite composite material implanted in the same period is high, which can improve postoperative bone metabolism and increase implant stability with good safety.

Purpose: Unplanned intraoperative hypothermia (UIH) is a frequent but preventable complication of surgery. Accurate identification of UIH risk factors allows nurses to minimize its negative outcomes. This study aimed to investigate the risk factors for UIH in adult surgical patients., Design: Systematic review and meta-analysis METHODS: We comprehensively searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Ovid Embase, and ClinicalTrials.gov from their inception until December 31, 2020 to identify available, related studies in English. Two authors independently extracted data from these studies. Data analysis was performed using Review Manager Version 5.3., Results: This meta-analysis included 12 studies involving 15,010 patients. The combined results showed that age [mean difference (MD) = 4.85, P < .0001; I 2  = 94%], body mass index (MD = - 0.76, P = .001; I 2  = 59%), ambient temperature [odds ratio (OR) = 0.82, P < .001; I 2  = 54%], preoperative systolic blood pressure (MD = -14.68, P < .00001; I 2  = 30%), preoperative heart rate (MD = - 13.25, P < .00001; I 2  = 0%), duration of anesthesia (>2 h; OR = 2.67, P < .001; I 2  = 0%), and intravenous fluid administration >1,000 mL (OR = 2.02, P = .01; I 2  = 77%) were significantly associated with a higher risk of UIH., Conclusions: Our study demonstrated that various risk factors contribute to the development of UIH. Perioperative nurses should understand these risk factors in order to apply evidence-based procedures and improve patient outcomes. Due to the substantial clinical heterogeneity across studies, further studies are needed to verify these findings., (Copyright © 2021 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Background: The proteinuria remission in hepatitis B virus-associated glomerulonephritis (HBV-GN) patients with massive proteinuria treated with antiviral therapy was low. Tacrolimus (TAC) is effective in primary nephropathy and can inhibit HBV infection by inhibiting HBV binding to sodium taurocholate cotransporting polypeptide on liver cells. This study evaluated the efficacy and safety of TAC combined with ETV compared with entecavir (ETV) monotherapy in HBV-GN., Methods: Patients diagnosed with HBV-GN were recruited for this prospective, randomized, controlled, multicenter, single-blinded study in China. Patients were given TAC and ETV therapy (the TAC+ETV group) or placebo and ETV therapy (the ETV group) for 26 weeks. The efficacy endpoints included proteinuria remission, including complete and partial remission (CR and PR), the change of 24-hour proteinuria (24 h UP) and HBV DNA titer. The safety endpoints were the incidence of HBV virologic breakthrough and adverse events., Results: There were 14 patients in the TAC+ETV group and 17 patients in the ETV group. In the intention-to-treat analyses, 64.3% (9/14) of patients in the TAC+ETV group and 58.8% (10/17) in the ETV group achieved PR or CR at 26 weeks (P=0.38). At week 14, 42.9% (6/14) and 41.2% (7/17) of patients in the TAC+ETV group and the ETV group, respectively, achieved PR or CR (P=0.23). At week 26, the 24 h UP had decreased by 2.63±6.33 g from baseline in the TAC+ETV group and 1.42±4.34 g in the ETV group (P=0.55). The serum albumin increased by 11.1±7.30 g/L from baseline in the TAC+ETV group and 3.81±5.09 g/L in the ETV group (P<0.001). Log10 HBV DNA decreased by 1.49±2.04 from baseline in the TAC+ETV group and 2.47±2.08 in the ETV group (P=0.37); 28.6% (4/14) patients had HBV DNA virologic breakthrough in the ETV group, while none in the TAC+ETV group (P=0.29)., Conclusions: In adult HBV-GN patients, TAC and ETV combination therapy may significantly improve serum albumin levels without increasing the risk of HBV reactivation compared with entecavir monotherapy., Trial Registration: ClinicalTrials.gov Identifier NCT03062813.

Objective: To investigate the urinary small molecular metabolites and their metabolic characteristics of patients with hepatocellular carcinoma (HCC). Methods: High throughput ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to detect the small molecular metabolites in urine of healthy control ( n =10), patients with hepatic hemangioma ( n =10) and patients with HCC ( n =10). The orthogonal projections to latent structures-discriminant analysis (OPLS-DA), hierarchical cluster analysis of multivariate analysis and univariate analysis were used to analyze the differential metabolites of the three groups. Results: The metabolic profiles of the three groups showed that the total of 381 differential metabolites were identified and divided into 96 up-regulated metabolites and 285 down-regulated metabolites. There were 55 urinary metabolites specifically related to HCC. Twenty-one of them were significantly up-regulated, including Acetyl-DL-Leucine, Ala Asp, HoPhe-Gly-OH, while 34 were significantly down-regulated, including Selenocystathionine, Met Trp Met Cys, Valsartan acid and so on. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the differential metabolites were mainly enriched in glutamine/glutamate metabolism, lysine biosynthesis, tricarboxylic acid cycle and purine metabolism. Conclusions: The occurrence of HCC is accompanied by the abnormalities of multiple metabolites and metabolic pathways. The analysis of the characteristic metabolic profile of urine in patients with HCC is helpful to find metabolic markers and potential therapeutic targets for liver cancer.

Background: The prognostic benefit of extensive lymphadenectomy remains controversial in esophageal squamous cell carcinoma (ESCC). The purpose of this retrospective study was to investigate the potential effect of solitary mediastinal (SM) lymph node metastasis and solitary celiac (SC) lymph node metastasis on the short- and long-term outcomes for patients who underwent minimally invasive McKeown esophagectomy., Methods: From September 2009 to December 2020, a total of 934 cases were diagnosed with ESCC and underwent minimally invasive McKeown esophagectomy in our department; 223 cases met the inclusion and exclusion criteria. Propensity score matching (PSM) was utilized to contrast the postoperative results and long-term survival of Group 1 (SM) and Group 2 (SC). Univariate and multivariate Cox proportional hazards regression analyses were used on possible predictors of survival., Results: One hundred forty-seven patients were available for outcome comparison after PSM. The postoperative results were not significantly different between the two groups. In terms of long-term survival, the 5-year disease-free survival (DFS) was 37.6% and 57.3% ( p = 0.191) and 5-year disease-specific survival (DSS) was 39.7% and 68.4% ( p = 0.028) for Group 1 (SM) and Group 2 (SC), respectively. Univariate and multivariate Cox proportional hazards regression analyses showed that body mass index (BMI), pathologic stage (pStage), and SC/SM grouping had significant hazard ratios (HRs), which suggested that SC is associated with better DSS., Conclusion: This cohort study showed that SC lymph node metastasis has a better long-term survival compared with SM lymph node metastasis in esophagectomy of ESCC. The results challenge the current understanding and need confirmation in further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Bao, Wang, Zhao, Long, Xie and Guo.)