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Yu-Xiang Deng,1,* Yu-Jie Zhao,2,* Qiao-Hong Nong,3 Hong-Mei Qiu,1 Qiao-Li Guo,1 Hui Hu1 1Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518000, People’s Republic of China; 2Department of Radiotherapy, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518000, People’s Republic of China; 3Department of Oncology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Hu, Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, 518000, People’s Republic of China, Tel +86-755-83923333, Email Sapphiretjmu@163.comBackground: The immune system appears to play a crucial role in how breast cancer responds to chemotherapy. In this study, we investigated a peripheral marker of immune and inflammation named the neutrophil to albumin ratio (NAR) to explore its potential relationship with pathological complete response (pCR) in locally advanced breast cancer patients who underwent neoadjuvant chemotherapy (NAC).Methods: We conducted a retrospective analysis of 212 consecutive breast cancer patients who received NAC. The NAR was calculated by examining the complete blood cell count and albumin level in peripheral blood before starting NAC. Through ROC curve analysis, we determined the optimal cutoff value for NAR as 0.0877. We used Pearson’s chi-square test or Fisher’s exact test to evaluate the relationship between NAR and pCR, as well as other clinical and pathological characteristics. Logistic regression models were employed for univariate and multivariate analyses.Results: The results of both univariate and multivariate logistic regression analyses showed that NAR was associated with tumor pathological regression. The NAR high group had a higher pCR rate compared to the NAR low group (OR 3.127 [95% CI 1.545– 6.328]; p = 0.002).Conclusion: According to this study, it was observed that patients with breast cancer who had high levels of NAR were more likely to achieve pCR when undergoing NAC.Keywords: breast cancer, neoadjuvant chemotherapy, pathological complete response, neutrophil to albumin ratio, predictive factors

Qing Deng1,2 ,* Shu-ping Zhang1,2 ,* Yu-Xuan Deng,1,2 Fang-fen Liu,1,2 Wei Shi,1– 3 Hong-fu Xie,1– 4 Yi Xiao,1,2 Ying-Xue Huang,1,2 Ji Li1– 4 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 3Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan, People’s Republic of China; 4Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying-Xue Huang; Ji LiDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People’s Republic of ChinaTel +86 186 2755 6448; +86 139 7512 3658Fax +86 0731 8432 8888Email 29103866@qq.com; liji_xy@csu.edu.cnBackground: Intense pulsed light (IPL), as a therapeutic approach for rosacea, had advantage in removing erythema and telangiectasia and was gradually accepted by rosacea patients, but there have been few studies on economic evaluation of this therapy.Purpose: This study aimed to detect willingness-to-pay (WTP) of IPL treatment for rosacea and to conduct a benefit–cost analysis (BCA) among the Chinese population, so as to provide an economic reference for doctors to make treatment decisions.Materials and Methods: An observational, cross-sectional study assessed respondent’s demographic characteristics and willingness-to-pay (WTP) of IPL and rosacea patients’ clinical data and Dermatology Life Quality Index (DLQI). WTP was obtained by contingent valuation (CV) method. In brief, contrast figures of three cases treated with IPL (Case1, Case2, and Case3 represented the increasing severity of rosacea) were showed and WTP was inquired. The costs were obtained according the market and compared with WTP (benefits) to get a benefit–cost ratio (BCR). Predictors of cost-effective WTP were identified using the multivariable logistic regression model.Results: A total of 303 rosacea patients and 202 controls were included in the study. The average cost of a single IPL treatment for rosacea was USD 208.04 in Changsha, China. The mean WTP for Case 1, Case 2, and Case 3 was USD 201.57, 214.64, and 221.74, respectively. WTP was statistically lower for Case 1 than that for Case 2 or Case 3 (P< 0.05). The BCRs were 0.85, 1.03, and 1.06 for Case 1, Case 2, and Case 3, respectively. WTP is significantly associated with household monthly income, previous treatment cost, and DLQI after adjustments for demographic characteristics (P< 0.05).Conclusion: IPL is an acceptable treatment for rosacea with moderate to severe erythema. For patients with relatively high income or severely impaired quality of life, IPL is an economically feasible therapy and deserves to be recommended.Keywords: benefit-cost analysis, intense pulsed light, rosacea, willingness-to-pay, economic evaluation

Yuxiang Deng,1,* Jianhong Peng,1,* Yujie Zhao,1 Qiaoqi Sui,1 Ruixia Zhao,2 Zhenhai Lu,1 Miaozhen Qiu,3 Junzhong Lin,1 Zhizhong Pan1 1Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Public Health, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Recent studies have suggested that the lymph node ratio (LNR) is a prognostic indicator for various malignancies. However, LNR has not been evaluated in colorectal liver-only metastasis (CRLM). This study aimed to investigate the prognostic value of LNR in patients with CRLM after curative resection. Patients and methods: We retrospectively investigated the clinicopathologic features of 154 CRLM patients who underwent curative resection between 2005 and 2015. We classified patients into low and high groups based on their LNR by using the X-tile software. Survival curves were plotted through Kaplan–Meier method and compared by log-rank test. Cox proportional hazards analysis was performed to identify the factors associated with recurrence-free survival (RFS) and overall survival (OS). Results: The patients were divided into two groups in which 124 patients were identified as LNR ≤0.33 and 30 patients as LNR >0.33. Compared to low LNR, high LNR was significantly associated with poor 3-year RFS (47.2% vs 16.7%, P=0.001) and OS (72.8% vs 45.3%, P=0.003) rates. Multivariate analysis indicated that the LNR was an independent predictor for 3-year RFS (hazard ratio, 2.124; 95% CI, 1.339–3.368; P=0.001) and OS (HR, 2.287; 95% CI, 1.282–4.079; P=0.005). However, the node (N) stage and lymph node distribution were not significantly associated with the 3-year RFS (P=0.071, P=0.226) or OS (P=0.452, P=0.791) in patients with CRLM. Conclusion: This study demonstrated that LNR was an independent predictor for 3-year RFS and OS in patients with CRLM who underwent curative resection and that its prognostic value was superior to that of N stage and lymph node distribution. Keywords: colorectal cancer, liver metastases, lymph node ratio, N stage, prognosis

Yu-Xiang Deng,1,* Jun-Zhong Lin,1,* Jian-Hong Peng,1,* Yu-Jie Zhao,1 Qiao-Qi Sui,1 Xiao-Jun Wu,1 Zhen-Hai Lu,1 Yuan-Hong Gao,2 Zhi-Fang Zeng,2 Zhi-Zhong Pan1 1Department of Colorectal Surgery, 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Research indicates that cancer-triggered inflammation plays a pivotal role in carcinogenesis. Here, we aimed to evaluate the correlation of lymphocyte-to-monocyte ratio (LMR) before neoadjuvant chemoradiotherapy (CRT) with clinical outcomes in patients with locally advanced rectal cancer (LARC). We retrospectively enrolled 317 consecutive patients with LARC between 2004 and 2013. The optimal cutoff values of LMR were determined using receiver operating curve analysis. Overall survival (OS) and disease-free survival related to the LMR were analyzed using the log-rank test and multivariate Cox regression methods. We found that a low LMR (≤4.91) was prominently correlated with worse prognostic features and a shorter 3-year survival rate of LARC. Moreover, multivariate Cox analysis revealed that elevated LMR was an independent factor for better OS (hazard ratio 0.538, 95% confidence interval 0.292–0.991, P=0.047). In addition, univariate logistic regression analysis showed that the LMR was not associated with tumor pathologic regression. In conclusion, LMR is identified as a valuable prognostic marker for predicting the OS of LARC patients receiving CRT. Keywords: rectal cancer, lymphocyte-monocyte ratio, prognosis, systemic inflammation

Crocetin as one of the main components of saffron possesses a lot of pharmacological effects, especially the beneficial effects in the treatment of hyperlipidemia. However, the pharmacokinetics of crocetin in the pathological state of hyperlipidemia has not been reported. In present study, the pharmacokinetics of crocetin in hyperlipidemia rats after oral administration of crocetin was investigated and the possible mechanisms for the pharmacokinetics were explored. High-fat diet was used to induce hyperlipidemia in rats. The pharmacokinetics of crocetin was investigated in hyperlipidemia and normal rats after oral and intravenous administration of crocetin, and the possible mechanisms of the pharmacokinetic changes were investigated in terms of metabolism and absorption using in vitro incubation with liver microsomes and the everted gut sac method, respectively. Results indicated that the AUCs of crocetin in hyperlipidemia rats after oral administration of crocetin were remarkably decreased when compared with those in normal rats. Moreover, crocetin was also metabolized more rapidly in the liver microsomes of hyperlipidemia rats and intestinal absorption of crocetin was significantly reduced in hyperlipidemia rats. It suggested that the remarkably decreased AUCs of crocetin in hyperlipidemia rats might partly result from the result of faster metabolic elimination and reduced absorption of crocetin in the hyperlipidemia pathological state. And the present investigations conducted on rats demonstrate that further investigations into the kinetics of crocetin in humans with hyperlipidemia are necessary in order to ensure an adequate dosage in this indication., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The mitochondrial enzyme arginase-2 (Arg-2) is implicated in the pathophysiology of contrast-induced acute kidney injury (CI-AKI). Therefore, Arg-2 represents a candid target for CI-AKI prevention. Here, layer-by-layer (LbL) assembled renal-targeting polymeric nanoparticles are developed to efficiently deliver small interfering RNA (siRNA), knockdown Arg-2 expression in renal tubules, and prevention of CI-AKI is evaluated. First, near-infrared dye-loaded poly(lactic-co-glycolic acid) (PLGA) anionic cores are electrostatically coated with cationic chitosan (CS) to facilitate the adsorption and stabilization of Arg-2 siRNA. Next, nanoparticles are coated with anionic hyaluronan (HA) to provide protection against siRNA leakage and shielding against early clearance. Sequential electrostatic layering of CS and HA improves loading capacity of Arg-2 siRNA and yields LbL-assembled nanoparticles. Renal targeting and accumulation is enhanced by modifying the outermost layer of HA with a kidney targeting peptide (HA-KTP). The resultant kidney-targeting and siRNA loaded nanoparticles (PLGA/CS/HA-KTP siRNA) exhibit proprietary accumulation in kidneys and proximal tubular cells at 24 h post-tail vein injection. In iohexol-induced in vitro and in vivo CI-AKI models, PLGA/CS/HA-KTP siRNA delivery alleviates oxidative and nitrification stress, and rescues mitochondrial dysfunction while reducing apoptosis, thereby demonstrating a robust and satisfactory therapeutic effect. Thus, PLGA/CS/HA-KTP siRNA nanoparticles offer a promising candidate therapy to protect against CI-AKI., (© 2024 Wiley‐VCH GmbH.)

Background: Colorectal cancer is the second leading cause of cancer-related deaths among digestive tract malignancies, following gastric cancer. Sleep is of great significance for maintaining human health. The incidence of sleep disorders in patients with cancer is approximately twice that observed in the general population. Lack of sleep can prolong hospital stays, increase the likelihood of infection, and increase mortality rates. Therefore, studying the factors related to sleep quality is significant for improving the quality of life of patients with malignant tumors of the digestive tract., Aim: To investigate the relationships among sleep quality, disease uncertainty, and psychological resilience in patients undergoing chemotherapy for digestive tract malignancies., Methods: A total of 131 patients with malignant digestive tract tumors who were treated at Hefei BOE Hospital between April 2021 and September 2022 were selected as research participants. Based on their Pittsburgh Sleep Quality Index (PSQI) scores, participants were divided into either the sleep disorder group (PSQI score > 7) or the normal sleep group (PSQI score ≤ 7). The clinical data-together with the Mishel Uncertainty in Illness Scale for Adults (MUIS-A) and Connor-Davidson Resilience Scale (CD-RISC) scores-were compared., Results: In this study, 78 (59.54%) patients with digestive tract malignancies developed sleep disorders after chemotherapy. Sleep disorder incidence was higher in patients with colorectal cancer than in those with gastric and esophageal cancers ( P < 0.05). The total MUIS-A score and those for each item in the sleep disorder group were higher than those in the normal sleep group. The total CD-RISC score and those for each item in the sleep disorder group were lower than those in the normal sleep group ( P < 0.05). The PSQI scores of patients with malignant digestive tract tumors were positively correlated with the scores for lack of disease information, disease uncertainty, and unpredictability in the MUIS-A and negatively correlated with the scores for tenacity, self-improvement, and optimism in the CD-RISC ( P < 0.05)., Conclusion: Patients undergoing chemotherapy for digestive tract malignancies are prone to sleep problems related to disease uncertainty and psychological resilience. Therefore, interventions can be implemented to improve their sleep quality., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The interfacial instability of the poly(ethylene oxide) (PEO)-based electrolytes impedes the long-term cycling and further application of all-solid-state lithium metal batteries. In this work, we have shown an effective additive 1-adamantanecarbonitrile, which contributes to the excellent performance of the poly(ethylene oxide)-based electrolytes. Owing to the strong interaction of the 1-Adamantanecarbonitrile to the polymer matrix and anions, the coordination of the Li + -EO is weakened, and the binding effect of anions is strengthened, thereby improving the Li + conductivity and the electrochemical stability. The diamond building block on the surface of the lithium anode can suppress the growth of lithium dendrites. Importantly, the 1-Adamantanecarbonitrile also regulates the formation of LiF in the solid electrolyte interface and cathode electrolyte interface, which contributes to the interfacial stability (especially at high voltages) and protects the electrodes, enabling all-solid-state batteries to cycle at high voltages for long periods of time. Therefore, the Li/Li symmetric cell undergoes long-term lithium plating/stripping for more than 2000 h. 1-Adamantanecarbonitrile-poly(ethylene oxide)-based LFP/Li and 4.3 V Ni 0.8 Mn 0.1 Co 0.1 O 2 /Li all-solid-state batteries achieved stable cycles for 1000 times, with capacity retention rates reaching 85% and 80%, respectively., (© 2024. The Author(s).)

The dual-ligand strategy was employed to synthesize a new microporous material, [Zn 3 (SNDC)(AmTAZ) 3 (H 2 O)]·H 2 O·CH 3 CN ( 1 ), incorporating sulfonic acid and amino groups for enhancing gas adsorption and separation. The activated 1 (named 1a ) exhibited selective adsorption of acetylene over carbon dioxide and methane. Hence, the dual-ligand strategy optimized the pore environment and provided an effective approach for pure separation of gases.

Background: Triage is the process of accurately assessing patients' symptoms and providing them with proper clinical treatment in the emergency department (ED). While many countries have developed their triage process to stratify patients' clinical severity and thus distribute medical resources, there are still some limitations of the current triage process. Since the triage level is mainly identified by experienced nurses based on a mix of subjective and objective criteria, mis-triage often occurs in the ED. It can not only cause adverse effects on patients, but also impose an undue burden on the health care delivery system., Objective: Our study aimed to design a prediction system based on triage information, including demographics, vital signs, and chief complaints. The proposed system can not only handle heterogeneous data, including tabular data and free-text data, but also provide interpretability for better acceptance by the ED staff in the hospital., Methods: In this study, we proposed a system comprising 3 subsystems, with each of them handling a single task, including triage level prediction, hospitalization prediction, and length of stay prediction. We used a large amount of retrospective data to pretrain the model, and then, we fine-tuned the model on a prospective data set with a golden label. The proposed deep learning framework was built with TabNet and MacBERT (Chinese version of bidirectional encoder representations from transformers [BERT])., Results: The performance of our proposed model was evaluated on data collected from the National Taiwan University Hospital (901 patients were included). The model achieved promising results on the collected data set, with accuracy values of 63%, 82%, and 71% for triage level prediction, hospitalization prediction, and length of stay prediction, respectively., Conclusions: Our system improved the prediction of 3 different medical outcomes when compared with other machine learning methods. With the pretrained vital sign encoder and repretrained mask language modeling MacBERT encoder, our multimodality model can provide a deeper insight into the characteristics of electronic health records. Additionally, by providing interpretability, we believe that the proposed system can assist nursing staff and physicians in taking appropriate medical decisions., (©Yu-Ting Lin, Yuan-Xiang Deng, Chu-Lin Tsai, Chien-Hua Huang, Li-Chen Fu. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 01.04.2024.)

Objective: We aimed to investigate the value of contrast-enhanced ultrasound (CEUS) in the preoperative prediction of the histological grades and molecular subtypes of breast cancer., Methods: A total of 183 patients with pathologically confirmed breast cancer were included. Contrast enhancement patterns and quantitative parameters were compared in different groups. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of CEUS in the preoperative prediction of pathological characteristics, including histologic grade and molecular subtypes., Results: Heterogeneous enhancement, perfusion defects, and peripheral radial vessels were mostly observed in higher histologic grade (grade III) breast cancer. Heterogeneous enhancement and perfusion defect were the most effective indicators for grade III breast cancer, with the areas under the ROC curve of 0.768 and 0.756, respectively. There were significant differences in the enhancement intensity, post-enhanced margin, perfusion defects, and peripheral radial vessel among the different molecular subtypes of breast cancer (all P < 0.01). Perfusion defects and clear edge after enhancement were the best qualitative criteria for the diagnosis of HER-2 overexpressed and triple-negative breast cancers, and the corresponding areas under the ROC curves were 0.804 and 0.905, respectively. There were significant differences in PE, WiR, WiPI, and WiWoAUC between grade III vs grade I and II breast cancer ( P < 0.05). PE, WiR, WiPI, and WiWoAUC had good efficiency in the diagnosis of high-histologic-grade breast cancer. PE had the highest diagnostic efficiency in Luminal A, while WiPI had the highest diagnostic efficiency in Luminal B subtype breast cancer, and the areas under the ROC curve were 0.825 and 0.838, respectively. WiWoAUC and WiR were the most accurate parameters for assessing triple-negative subtype breast cancers, and the areas under the curve were 0.932 and 0.922, respectively., Conclusion: Qualitative and quantitative perfusion analysis of contrast-enhanced ultrasound may be useful in the non-invasive prediction of the histological grade and molecular subtypes of breast cancers., 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 Li, Su, Deng, Guo, Lun and Hu.)

Background: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited., Methods: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN., Results: Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model., Conclusion: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as National Institutes of Health (NIH) type III prostatitis, is a common disorder with an unclear etiology and no known curative treatments. Based on the presence or absence of leukocytes in expressed prostatic secretion (EPS), CP/CPPS is classified further into IIIa (inflammatory) and IIIb (noninflammatory) subtypes. However, the severity of symptoms is not entirely consistent with the white blood cell (WBC) count. Following the preliminary finding of a link between inflammatory cytokines and CP/CPPS, we performed this clinical study with the aim of identifying cytokines that are differentially expressed according to whether the prostatitis subtype is IIIa or IIIb. We found that granulocyte colony-stimulating factor (G-CSF), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly elevated and interferon-inducible protein-10 (IP-10) and platelet-derived growth factor-BB (PDGF-BB) levels were downregulated in the EPS of patients with type IIIa prostatitis. In a word, it is a meaningful study in which we investigate the levels of various cytokines in EPS according to whether prostatitis is the IIIa or IIIb subtype. The combination of G-CSF, IL-18, MCP-1, IP-10, and PDGF-BB expression levels could form a basis for classification, diagnosis, and therapeutic targets in clinical CP/CPPS., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Introduction: The optimal management strategy for pancreatic trauma remains unclear. We aimed to determine whether the initial nonoperative management (NOM) strategy based on percutaneous drainage combined with endoscopic retrograde cholangiopancreatography guided stent placement would improve outcomes for blunt high-grade pancreatic trauma., Methods: Patients with blunt abdominal trauma who were hemodynamically stable without signs of diffuse peritonitis were consecutively enrolled at a high-volume center. The primary outcome was the occurrence of severe complications (Clavien‒Dindo classification ≥ Ⅲ b ) for patients who underwent initial laparotomy (LAP) versus NOM. Modified Poisson regression was used to model the primary outcome. Propensity score matching and weighting models were included into a regression-based sensitivity analysis., Results: Of 119 patients with grade III/IV pancreatic trauma, 29 patients underwent initial NOM, and 90 underwent initial LAP. The incidence of severe complications in the LAP group was higher than that in the NOM group (65/90 [72.2%] versus 9/29 [31.0%], P < 0.001). In the multivariable modified Poisson regression model, the relative risk for severe complications was decreased in the NOM group (relative risk, 0.52; 95% confidence interval, 0.30-0.90; P = 0.020). The results of the sensitivity analysis were consistent with those of the multivariable analysis. The mean number of reinterventions per patient was 1.8 in the NOM group and 2.6 in the LAP group (P = 0.067)., Conclusions: For blunt high-grade pancreatic trauma patients with stable hemodynamics and no diffuse peritonitis, the NOM strategy was associated with a lower risk of severe complications (Clavien‒Dindo classification ≥ Ⅲ b ) and did not require more invasive reintervention procedures. In high-volume centers with sufficient expertise, percutaneous drainage combined with endoscopic retrograde cholangiopancreatography guided stent placement may serve as an initial reasonable option for selected patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bone morphogenetic protein 9 (BMP9) has been validated as one of the most potent osteoinduction factors, but its underlying mechanism remains unclear. As a member of the matrix metalloproteinase (MMP) family, MMP13 may be involved in regulating the lineage-specific differentiation of mouse embryonic fibroblasts (MEFs). The goal of this study was to determine whether MMP13 regulates the osteoinduction potential of BMP9 in MEFs, which are multipotent progenitor cells widely used for stem cell biology research. In vitro and in vivo experiments showed that BMP9-induced osteogenic markers and/or bone were enhanced by exogenous MMP13 in MEFs, but were reduced by MMP13 knockdown or inhibition. The expression of hypoxia inducible factor 1 alpha (HIF-1α) was induced by BMP9, which was enhanced by MMP13. The protein expression of β-catenin and phosphorylation level of glycogen synthase kinase-3 beta (GSK-3β) were increased by BMP9 in MEFs, as was the translocation of β-catenin from the cytoplasm to the nucleus; all these effects of BMP9 were enhanced by MMP13. Furthermore, the MMP13 effects of increasing BMP9-induced β-catenin protein expression and GSK-3β phosphorylation level were partially reversed by HIF-1α knockdown. These results suggest that MMP13 can enhance the osteoinduction potential of BMP9, which may be mediated, at least in part, through the HIF-1α/β-catenin axis. Our findings demonstrate a novel role of MMP13 in the lineage decision of progenitor cells and provide a promising strategy to speed up bone regeneration., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: To systematically evaluate the correlation between serum osteocalcin levels and cognitive function status in type 2 diabetes mellitus (T2D) patients., Methods: This review was conducted according to the PRISMA guidelines, and was developed and submitted to PROSPERO (CRD42022339295). We comprehensively searched PubMed, EMBASE, Web of Science, Scopus, ProQuest, and Chinese Databases (China National Knowledge Infrastructure, Wan Fang, Chinese Science and Technology Periodical Database, and China Biology Medicine) up to 1 June 2023. 3 investigators performed independent literature screening and data extraction of the included literature, and 2 investigators performed an independent quality assessment of case-control studies using the Newcastle-Ottawa-Scale tool. Data analysis was performed using Review Manager 5.4 software. For continuous various outcomes, mean difference (MD) or standardized MD with 95% confidence intervals (CIs) was applied for assessment by fixed-effect or random-effect model analysis. The heterogeneity test was performed by the Q statistic and quantified using I2, and publication bias was evaluated using a funnel plot., Results: 9 studies with T2D were included (a total of 1310 subjects). Meta-analysis results indicated that cognitive function was more impaired in patients with lower serum osteocalcin levels [MD = 9.91, 95% CI (8.93, -10.89), I2 = 0%]. Serum osteocalcin levels were also significantly different between the 2 groups of T2D patients based on the degree of cognitive impairment [MD = -0.93, 95% CI (-1.09, -0.78), I2 = 41%]. It summarized the statistical correlation between serum osteocalcin and cognitive function scores in patients with T2D at r = 0.43 [summary Fisher's Z = 0.46, 95% CI (0.39, -0.50), I2 = 41%). After sensitivity analysis, the heterogeneity I2 decreased to 0%, indicating that the results of the meta-analysis are more reliable., Conclusion Subsections: Based on a meta-analysis of included studies, we concluded that there is a moderately strong positive correlation between serum osteocalcin levels and patients' cognitive function in T2D. An intervention to increase serum osteocalcin levels can contribute to delaying and improving cognitive decline in patients with T2D., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Few studies have addressed the question of which drain types are more beneficial for patients with pancreatic trauma (PT)., Aim: To investigate whether sustained low negative pressure irrigation (NPI) suction drainage is superior to closed passive gravity (PG) drainage in PT patients., Methods: PT patients who underwent pancreatic surgery were enrolled consecutively at a referral trauma center from January 2009 to October 2021. The primary outcome was defined as the occurrence of severe complications (Clavien-Dindo grade ≥ Ⅲ b ). Multivariable logistic regression was used to model the primary outcome, and propensity score matching (PSM) was included in the regression-based sensitivity analysis., Results: In this study, 146 patients underwent initial PG drainage, and 50 underwent initial NPI suction drainage. In the entire cohort, a multivariable logistic regression model showed that the adjusted risk for severe complications was decreased with NPI suction drainage [14/50 (28.0%) vs 66/146 (45.2%); odds ratio (OR), 0.437; 95% confidence interval (CI): 0.203-0.940]. After 1:1 PSM, 44 matched pairs were identified. The proportion of each operative procedure performed for pancreatic injury-related and other intra-abdominal organ injury-related cases was comparable in the matched cohort. NPI suction drainage still showed a lower risk for severe complications [11/44 (25.0%) vs 21/44 (47.7%); OR, 0.365; 95%CI: 0.148-0.901]. A forest plot revealed that NPI suction drainage was associated with a lower risk of Clavien-Dindo severity in most subgroups., Conclusion: This study, based on one of the largest PT populations in a single high-volume center, revealed that initial NPI suction drainage could be recommended as a safe and effective alternative for managing complex PT patients., Competing Interests: Conflict-of-interest statement: All authors read and approved the final manuscript and declared no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1., Methods: ATRA content was detected with ELISA and HPLC-MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro-computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism., Results: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/β-catenin, and reduced by inhibiting this pathway. β-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1., Conclusions: Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering., (© 2023. Korean Tissue Engineering and Regenerative Medicine Society.)

By using density functional theory calculations combined with the nonequilibrium Green's function method and machine learning, we systematically studied the thermoelectric properties of four kinds of porous graphene nanosheets (PGNS) before and after nitrogen doping. The results show that the thermoelectric performance of porous graphene nanosheets along the armchair or zigzag chiral direction is improved due to the dramatically enhanced power factor caused by nitrogen doping. The calculated ZT values of nitrogen-doped porous graphene nanosheets are boosted by about one order of magnitude compared with those of undoped porous graphene nanosheets at room temperature. More importantly, an anisotropic thermoelectric transport is found in the nitrogen-doped porous graphene nanosheets. The results show that the ZT values of nitrogen-doped porous graphene nanosheets along the zigzag transport direction are nearly 11 times larger than those of them along the armchair transport direction. These results reveal that the thermoelectric properties of porous graphene nanosheets can be well regulated by nitrogen doping, and provide a good theoretical guidance for their application in thermoelectric devices.

Background and Aims: Desert plants possess excellent water-conservation capacities to survive in extreme environments. Cuticular wax plays a pivotal role in reducing water loss through plant aerial surfaces. However, the role of cuticular wax in water retention by desert plants is poorly understood., Methods: We investigated leaf epidermal morphology and wax composition of five desert shrubs from north-west China and characterized the wax morphology and composition for the typical xerophyte Zygophyllum xanthoxylum under salt, drought and heat treatments. Moreover, we examined leaf water loss and chlorophyll leaching of Z. xanthoxylum and analysed their relationships with wax composition under the above treatments., Key Results: The leaf epidermis of Z. xanthoxylum was densely covered by cuticular wax, whereas the other four desert shrubs had trichomes or cuticular folds in addition to cuticular wax. The total amount of cuticular wax on leaves of Z. xanthoxylum and Ammopiptanthus mongolicus was significantly higher than that of the other three shrubs. Strikingly, C31 alkane, the most abundant component, composed >71 % of total alkanes in Z. xanthoxylum, which was higher than for the other four shrubs studied here. Salt, drought and heat treatments resulted in significant increases in the amount of cuticular wax. Of these treatments, the combined drought plus 45 °C treatment led to the largest increase (107 %) in the total amount of cuticular wax, attributable primarily to an increase of 122 % in C31 alkane. Moreover, the proportion of C31 alkane within total alkanes remained >75 % in all the above treatments. Notably, the water loss and chlorophyll leaching were reduced, which was negatively correlated with C31 alkane content., Conclusion: Zygophyllum xanthoxylum could serve as a model desert plant for study of the function of cuticular wax in water retention because of its relatively uncomplicated leaf surface and because it accumulates C31 alkane massively to reduce cuticular permeability and resist abiotic stressors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Metabolic reprogramming is a common feature of glioblastoma (GBM) progression and metastasis. Altered lipid metabolism is one of the most prominent metabolic alterations in cancer. Understanding the links between phospholipid remodeling and GBM tumorigenesis may help develop new anticancer strategies and improve treatments to overcome drug resistance. We used metabolomic and transcriptomic analyses to systematically investigate metabolic and molecular changes in low-grade glioma (LGG) and GBM. We then re-established the reprogrammed metabolic flux and membrane lipid composition in GBM based on metabolomic and transcriptomic analyses. By inhibiting Aurora A kinase via RNA interference (RNAi) and inhibitor treatment, we investigated the effect of Aurora A kinase on phospholipid reprogramming LPCAT1 enzyme expression and GBM cell proliferation in vitro and in vivo. We found that GBM displayed aberrant glycerophospholipid and glycerolipid metabolism compared with LGG. Metabolic profiling indicated that fatty acid synthesis and uptake for phospholipid synthesis were significantly increased in GBM compared to LGG. The unsaturated phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels were significantly decreased in GBM compared to LGG. The expression level of LPCAT1, which is required for the synthesis of saturated PC and PE, was upregulated in GBM, and the expression of LPCAT4, which is required for the synthesis of unsaturated PC and PE, was downregulated in GBM. Notably, the inhibition of Aurora A kinase by shRNA knockdown and treatment with Aurora A kinase inhibitors such as Alisertib, AMG900, or AT9283 upregulated LPCAT1 mRNA and protein expression in vitro. In vivo, the inhibition of Aurora A kinase with Alisertib increased LPCAT1 protein expression. Phospholipid remodeling and a reduction in unsaturated membrane lipid components were found in GBM. Aurora A kinase inhibition increased LPCAT1 expression and suppressed GBM cell proliferation. The combination of Aurora kinase inhibition with LPCAT1 inhibition may exert promising synergistic effects on GBM.

Background: Drug-induced acute kidney damage (DI-AKI) is a clinical phenomenon of rapid loss of kidney function over a brief period of time as a consequence of the using of medicines. The lack of a specialized treatment and the instability of traditional kidney injury markers to detect DI-AKI frequently result in the development of chronic kidney disease. Thus, it is crucial to continue screening for DI-AKI hub genes and specific biomarkers., Methods: Differentially expressed genes (DEGs) of group iohexol, cisplatin, and vancomycin's were analyzed using Limma package, and the intersection was calculated. DEGs were then put into String database to create a network of protein-protein interactions (PPI). Ten algorithms are used in the Cytohubba plugin to find the common hub genes. Three DI-AKI models' hub gene expression was verified in vivo and in vitro using PCR and western blot. To investigate the hub gene's potential as a biomarker, protein levels of mouse serum and urine were measured by ELISA kits. The UUO, IRI and aristolochic acid I-induced nephrotoxicity (AAN) datasets in the GEO database were utilized for external data verification by WGCNA and Limma package. Finally, the Elisa kit was used to identify DI-AKI patient samples., Results: 95 up-regulated common DEGs and 32 down-regulated common DEGs were obtained using Limma package. A PPI network with 84 nodes and 24 edges was built with confidence >0.4. Four hub genes were obtained by Algorithms of Cytohubba plugin, including TLR4, AOC3, IRF4 and TNFAIP6. Then, we discovered that the protein and mRNA levels of four hub genes were significantly changed in the DI-AKI model in vivo and in vitro . External data validation revealed that only the AAN model, which also belonged to DI-AKI model, had significant difference in these hub genes, whereas IRI and UUO did not. Finally, we found that plasma TLR4 levels were higher in patients with DI-AKI, especially in vancomycin-induced AKI., Conclusion: The immune system and inflammation are key factors in DI-AKI. We discovered the immunological and inflammatory-related genes TLR4, AOC3, IRF4, and TNFAIP6, which may be promising specific biomarkers and essential hub genes for the prevention and identification of DI-AKI., 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 Deng, Liu, Qiu, Tang, Que, Li, Gu, Zhou, Wu, Zhou, Yin and Zuo.)

This study aimed to obtain a better understanding on the environmental behavior of As in paddy soil and to reveal the influence mechanisms of different environmental factors on the availability of As in the soil solution. The effects of pH, calcium, and phosphate on the solubility and speciation distribution of As in the paddy soil collected from Zhuzhou of Hunan province were studied by combining the adsorption experiments with the NOM-CD model. The results showed that the minimum concentration of soluble As in the soil was at approximately a pH of 6.0, which was mainly affected by both electrical interactions and site competition between Ca 2+ , PO 4 3- , As(Ⅲ), and As(Ⅴ). The adsorption of As onto soil particles could be increased by an increase in Ca 2+ in the soil system, leading to the decrease in soluble As concentration. This effect became significant at a higher pH, because adsorbed Ca 2+ increased the positive charge on (hydr)oxide surfaces. With phosphate addition, the reduction in As(Ⅴ) in the soil was inhibited at pH<5.5, whereas it was promoted at pH>5.5. Moreover, the concentration of soluble As(Ⅲ) and As(Ⅴ) in the soil solution was dramatically increased with the addition of phosphate owing to the competitive adsorption between As and phosphate. At a lower background of Ca 2+ , there was a higher fraction of As(Ⅲ) in the soil either with or without phosphate addition. This phenomenon might be caused by the higher bioavailability of phosphorus in soil at a lower concentration of Ca 2+ , which favors the dissimilatory reduction of As or iron (hydr)oxides. The results indicated that the NOM-CD model could predict the influence of pH, calcium, and phosphate on the solubility and speciation distribution of As in paddy soil and reveal its main mechanisms. Therefore, the NOM-CD model would provide the quantitative and scientific method for evaluating the risk of As in soils or other solid-water systems.

Studies reported the positive and negative osteogenic effects of MEG3 in mesenchymal stem cells (MSCs). This study aims at clarifying the osteogenic potential of MEG3 and the underlying mechanism. Bone morphogenetic protein 9- (BMP9-) transfected MSCs were recruited as an osteogenic model in vitro , and ectopic bone formation were used in vivo to explore the effect of MEG3 on osteogenesis. We found that overexpression of MEG3 facilitated BMP9-induced osteogenic markers, ALP activities, and matrix mineralization. However, knockdown of MEG3 attenuated BMP9-induced osteogenic markers. MEG3 increased the phosphorylation of GSK-3 β and the protein level of β -catenin. Pyruvate dehydrogenase kinase 4 (PDK4) can also combine with GSK-3 β and increase the latter phosphorylation. Moreover, MEG3 increased the mRNA level of PDK4. The ceRNA analysis showed that MEG3 may regulate the expression of PDK4 via microRNA 532-5p (miR-532-5p). The MEG3-enhanced GSK-3 β / β -catenin axis can be attenuated by miR-532-5p, and miR-532-5p inhibitor partly rescued endogenous PDK4 and MEG3-mediated expression of PDK4. MEG3 may potentiate PDK4 and GSK-3 β / β -catenin by inhibiting miR-532-5p., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2023 Yuan-Yuan Yang et al.)

Mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple lineages, making MSC transplantation a promising option for bone regeneration. Both matricellular proteins and growth factors play an important role in regulating stem cell fate. In this study, we investigated the effects of matricellular protein SMOC2 (secreted modular calcium-binding protein 2) on bone morphogenetic protein 9 (BMP9) in mouse embryonic fibroblasts (MEFs) and revealed a possible molecular mechanism underlying this process. We found that SMOC2 was detectable in MEFs and that exogenous SMOC2 expression potentiated BMP9-induced osteogenic markers, matrix mineralization, and ectopic bone formation, whereas SMOC2 knockdown inhibited these effects. BMP9 increased the levels of p-FAK and p-AKT, which were either enhanced or reduced by SMOC2 and FAK silencing, respectively. BMP9-induced osteogenic markers were increased by SMOC2, and this increase was partially abolished by silencing FAK or LY290042. Furthermore, we found that general transcription factor 2I (GTF2I) was enriched at the promoter region of SMOC2 and that integrin β 1 interacted with SMOC2 in BMP9-treated MEFs. Our findings demonstrate that SMOC2 can promote BMP9-induced osteogenic differentiation by enhancing the FAK/PI3K/AKT pathway, which may be triggered by facilitating the interaction between SMOC2 and integrin β 1., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023 Wen-Ge He et al.)

Bone morphogenetic protein 9 (BMP9) is an effective osteogenic factor and a promising candidate for bone tissue engineering. The osteoblastic potential of BMP9 needs to be further increased to overcome its shortcomings. However, the details of how BMP9 triggers osteogenic differentiation in mesenchymal stem cells (MSCs) are unclear. In this study, we used real-time PCR, western blot, histochemical staining, mouse ectopic bone formation model, immunofluorescence, immunoprecipitation, and chromatin immunoprecipitation to investigate the role of pyruvate dehydrogenase kinase 4 (PDK4) in BMP9-induced osteogenic differentiation of C3H10T1/2 cells, as well as the underlying mechanism. We found that PDK4 was upregulated by BMP9 in C3H10T1/2 cells. BMP9-induced osteogenic markers and bone mass were increased by PDK4 overexpression, but decreased by PDK4 silencing. β-catenin protein level was increased by BMP9, which was enhanced by PDK overexpression and decreased by PDK4 silencing. BMP9-induced osteogenic markers were reduced by PDK4 silencing, which was almost reversed by β-catenin overexpression. PDK4 increased the BMP9-induced osteogenic markers, which was almost eliminated by β-catenin silencing. Sclerostin was mildly decreased by BMP9 or PDK4, and significantly decreased by combined BMP9 and PDK4. In contrast, sclerostin increased significantly when BMP9 was combined with PDK4 silencing. BMP9-induced p-SMAD1/5/9 was increased by PDK4 overexpression, but was reduced by PDK4 silencing. PDK4 interacts with p-SMAD1/5/9 and regulates the sclerostin promoter. These findings suggest that PDK4 can increase the osteogenic potential of BMP9 by enhancing Wnt/β-catenin signaling via the downregulation of sclerostin. PDK4 may be an effective target to strengthen BMP9-induced osteogenesis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The rapid development of synthesis and fabrication techniques has opened up a research upsurge in two-dimensional (2D) material heterostructures, which have received extensive attention due to their superior physical and chemical properties. Currently, thermoelectric energy conversion is an effective means to deal with the energy crisis and increasingly serious environmental pollution. Therefore, an in-depth understanding of thermoelectric transport properties in 2D heterostructures is crucial for the development of micro-nano energy devices. In this review, the recent progress of 2D heterostructures for thermoelectric applications is summarized in detail. Firstly, we systematically introduce diverse theoretical simulations and experimental measurements of the thermoelectric properties of 2D heterostructures. Then, the thermoelectric applications and performance regulation of several common 2D materials, as well as in-plane heterostructures and van der Waals heterostructures, are also discussed. Finally, the challenges of improving the thermoelectric performance of 2D heterostructures materials are summarized, and related prospects are described., (© 2022 IOP Publishing Ltd.)

By employing Cu(CH 3 CN) 4 PF 6 as the catalyst and tert -butyl hydroperoxide as the oxidant, we realized a three-component radical selenosulfonation of substituted maleimides, sulfonyl hydrazides, and diphenyl diselenides, providing a series of 3,4-selenosulfonylated succinimides in moderate to good yields. This reaction features broad substrate scopes, high functional-group tolerability, and feasibility of gram-scale synthesis, enabling one-step construction of C-SO 2 and C-Se bonds under mild reaction conditions. Preliminary mechanistic studies support the free-radical-induced pathway.

Plastic pollution is a global concern and an issue in environmental governance. Based on the updated "Plastic Prohibition/Restriction Order" issued recently in China, the present study systematically reviewed the implementation effectiveness of the "Plastic Prohibition/Restriction Order" since 2007. Furthermore, we summarized plastics in China and plastic waste management progress policies. Additionally, three deficiencies of the updated "Plastic Prohibition/Restriction Order" were discussed:policy formulation, implementation, and supervision. Some positive recommendations were provided based on the available reports, such as integrating plastic pollution into national basic laws and regulation systems, building a network platform for public attendance, and coordinating the publicity of the "Plastic prohibition/Restriction Order" with the public interest. Besides these measurements, some points about plastic waste management in the future were also highlighted, such as the "blind area" in small retail stores, the rational sharing of environmental protection responsibility, new materials and processes, and recycling and disposal systems for plastic wastes. Most importantly, the present study could provide ideas for policy-makers to address plastic pollution at its sources.

Objective: To systematically evaluate the efficacy and safety of different doses of antiviral drugs in the treatment of herpes zoster. Methods: PubMed, EMBASE, Cochrane Library, VIP, CNKI and WanFang database up to April 9, 2022 were searched. Two reviewers selected the studies according to inclusion and exclusion criteria, and the Cochrane bias risk assessment tool was used for quality evaluation. Data were analyzed by Revman 5.4 software for meta-analysis. The qualitative data used relative risk ( RR ) as the effect index, and the quantitative data used mean difference ( MD ) as the effect index. The point estimates and 95 %CI of each effect were given. Results: Fourteen randomized controlled trials with 1 831 patients were included in the study. Compared with the 200 mg acyclovir with five times a day, the 800 mg can improve the effective rate, shorten the blister stopping time ( MD =-1.29, 95 %CI :-1.62- -0.96, P< 0.001), relieve the pain faster ( MD =-2.73, 95 %CI :-4.37- -1.09, P= 0.001), shorten the scabbing time ( MD =-2.42, 95 %CI :-2.96- -1.89, P< 0.001) without increasing the adverse reaction rate ( RR= 1.64, 95 %CI :0.80-3.36, P= 0.17); Compared with the 300 mg valaciclovir with twice daily, the 900-1 000 mg valaciclovir with three times a day can improve the effective rate( RR= 1.17, 95 %CI :1.04-1.32, P= 0.007), shorten the blister stopping time ( MD =-1.53, 95 %CI :-2.54- -0.51, P= 0.003), relieve the pain faster ( MD =-1.04, 95 %CI :-1.30- -0.77, P< 0.001), shorten the scabbing time ( MD =-1.78, 95 %CI :-2.80- -0.76, P< 0.001), reduce the incidence of postherpetic neuralgia( RR= 0.28, 95 %CI :0.15-0.52, P< 0.001) without increasing the adverse reaction rate ( RR= 1.47, 95 %CI :0.93-2.32, P= 0.10); In immunocompromised patients, compared with 1 000 mg valaciclovir with three times a day, 2 000 mg cannot significantly improve the treatment efficacy. There was no significant difference among the efficacy of 250 mg, 500 mg and 750 mg famciclovir, three times a day, in the treatment of herpes zoster. Conclusion: The 800 mg acyclovir with five times a day; 900-1 000 mg valaciclovir and 250 mg famciclovir with three times a day, are better choices in the treatment of herpes zoster.

Objectives: Patients with acute-on-chronic liver failure (ACLF) have a high risk of infection after liver transplantation (LT). In this study, we aimed to evaluate the prevalence of early post-LT infection (within one month after LT) in recipients with ACLF, and to compare the survival rate between patients with or without post-LT infection., Methods: Patients with ACLF who underwent LT between January 2015 and December 2017 were retrospectively included. Characteristics of the patients, prevalence, site and pathogen of post-LT infection, and its risk factors were evaluated., Results: A total of 62 patients with ACLF developed bacterial or fungal infection after LT. The 30-day, 90-day, and 1-year survival rates in the infected group were found to be significantly lower than those in the non-infected group (67.7% vs 98.5%, 64.5% vs 97.7%, and 48.4% vs 95.4%; all P  < 0.001). The most common pathogens involved were carbapenem-resistant gram-negative organisms, including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter lwoffi. Multivariate analysis demonstrated that reoperation and length of intensive care unit stay were independently associated with post-LT infection. In addition, living donor LT and early allograft dysfunction were independently associated with 30-day all-cause mortality, whereas red blood cell transfusion and post-LT infection were independently associated with all-cause 30-day and 90-day mortality after LT., Conclusions: Early infection after LT is a major prognostic factor in patients with ACLF. Constant vigilance for the risk factors of early infection after LT is needed for timely diagnosis and prompt intervention., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Rosacea is a common chronic facial inflammatory skin disease. However, treatment for "difficult-to-treat rosacea" cases has not been established. This 48-week, prospective, observational study analyzed patients who underwent three non-insulated fractional microneedle radiofrequency (NFMRF) sessions at 2-month intervals. Therapy efficacy, epidermal barrier function, and side effects were evaluated. 34 subjects completed the trial. NFMRF resulted in CEA score reduction from 2.65 ± 0.59 to 1.56 ± 0.50 (P < 0.001) and mean DLQI reduction from 16.70 ± 3.55 to 10.48 ± 2.92 (P < 0.001). The successes of CEA (44.12 vs. 2.94%), IGA (91.67 vs. 25.00%), and flushing (58.82 vs. 26.47%) were observed. Among 34 patients, 22 reported "excellent" or "good" improvement and 30 were "very" or "relatively" satisfied. Skin barrier results revealed that hemoglobin content significantly decreased from 376.47 ± 71.29 at visit 0 to 161.32 ± 52.86 at visit 3. 2 of 30 patients followed-up at 6 months had a relapse at 18 and 20 weeks, respectively. No serious side effects were observed. NFMRF alone results in visible improvement and has great efficacy for difficult-to-treat rosacea without compromising patient safety or damaging the skin barrier., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recently, a ternary-layered material BiOCl has elicited intense interest in photocatalysis, environmental remediation, and ultraviolet light detection because of its unique band gap of around 3.6 eV, low toxicity, and earth abundance. In particular, Gibson et al. reported a measurement of the in-plane thermal conductivity of BiOCl experimentally using a four-point-probe method [Science, 373, 1017-1022 ( 2021 )], which is only 1.25 W/m K at 300 K. Motivated by the work, we studied the thermoelectric property of monolayer BiOCl using first-principles calculations combined with the Boltzmann transport equation. The calculated phonon thermal conductivity of monolayer BiOCl is 3 W/m K at 300 K, which is far below that of other promising 2D thermoelectric materials like graphyne and MoS 2 . A comprehensive analysis of phonon modes is conducted to reveal the low thermal conductivity. Moreover, the maximal ZT value is as high as 1.8 at 300 K and 5.7 at 800 K for the p-type doping with the 2 × 10 15 cm -2 concentration. More importantly, we found that the thermoelectric efficiency of such 2D materials is significantly enhanced to 8 at 800 K by applying 1.5% tensile strain, which clearly outperforms that of the reported 2D thermoelectric material SnSe. The results shed light on the promising application in medium-temperature (600-900 K) thermoelectric devices.

Long non-coding RNA (lncRNA) miR-17-92a-1 cluster host gene (MIR17HG) is oncogenic in several cancers. This study was aimed to probe into its expression characteristics and biological functions in retinoblastoma (RB) and to explore its role in regulating microRNA-155-5p (miR-155-5p) and hypoxia-inducible factor-1α (HIF-1α). In this study, paired RB samples were collected, and expression levels of MIR17HG, miR-155-5p, and HIF-1α were examined by quantitative real-time polymerase chain reaction (qRT-PCR); the proliferation, migration, and invasion of RB cells were detected by cell counting kit-8 (CCK-8) and transwell assays; qRT-PCR and Western blot were used to analyze the changes of miR-155-5p expression and HIF-1α expression. We found that MIR17HG expression was significantly up-regulated in RB samples, which was negatively correlated with miR-155-5p expression. The proliferation, migration, and invasion of RB cells were promoted by MIR17HG overexpression but inhibited by MIR17HG knockdown. MiR-155-5p suppressed the proliferation, migration, and invasion of RB cells. MIR17HG positively regulated the expression of HIF-1α on both mRNA and protein levels in RB cells. Additionally, miR-155-5p was identified as a target of MIR17HG. The data in this study suggest that MIR17HG exerts oncogenic effects in RB via the miR-155-5p/HIF-1α axis., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

The design and control of spintronic devices is a research hotspot in the field of electronics, and pure carbon-based materials provide new opportunities for the construction of electronic devices with excellent performance. Using density functional theory in combination with nonequilibrium Green's functions method, we design spin filter devices based on Penta-hexa-graphene (PHG) nanoribbons-a carbon nanomaterial in which the intrinsic magnetic moments combines with edge effects leading to a half-metallic property. Spin-resolved electronic transport studies show that such carbon-based devices can achieve nearly 100% spin filtering effect at low bias voltages. Such SEF can resist the influence of hydrogen passivation at different positions, but hardly survive under a hydrogen-rich environment. Our analysis show that the perfect SEF transport properties are caused by the magnetic and electronic properties of PHG nanoribbons, especially the magnetic moments on the quasi- sp 3 carbons. These interesting results indicate that PHG nanomaterials have very prominent application prospects in future spintronic devices., (© 2022 IOP Publishing Ltd.)

Although various treatments have been proposed for the management of rosacea, achieving complete remission of persistent erythema remains challenging. Short-wave radiofrequency (SWRF) treatment has been shown to repair skin barriers and reduce chronic inflammation. However, limited studies have evaluated the effectiveness of SWRF treatment for erythematotelangiectatic rosacea (ETR). A prospective, open-label pilot study using SWRF therapy was conducted on 30 patients with mild-to-moderate ETR. During the first stage, the patients underwent a single, full-face treatment and were evaluated before and after the session, as well as on the 7th and 15th day post-treatment. During the second stage, ten treatment sessions were administered, and the patients were evaluated before and after the tenth session, as well as 1 month after the treatment. Adverse events were recorded during each treatment session, and the patients were followed up for 3 months after the last session. Twenty-eight patients completed the entire trial. On the 7th day after the single treatment, the global score (total score of flushing, persistent erythema, and telangiectasia) of ETR improved from 5.23 ± 1.09 to 4.00 ± 0.76 relative to the baseline value (p < 0.05); moreover, the overall treatment satisfaction improved from 7.27 ± 0.89 to 4.90 ± 0.91 (p < 0.05). 1 month after the tenth treatment session, the global score improved from 5.30 ± 1.01 to 3.85 ± 0.93 (p < 0.05), and the overall treatment satisfaction improved from 7.13 ± 0.85 to 5.17 ± 1.19 (p < 0.05). During the 3 month follow-up period, there were two cases of recurrence. Therefore, this report indicates that SWRF might be an effective auxiliary treatment for mild-to-moderate ETR., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Several new isostructural lanthanide metal-organic frameworks (Ln-MOFs), {[Ln 2 (L) 3 DMA 4 ]·2DMA} n ( 1-Ln , where Ln = Eu, Tb, or Eu x Tb 1- x ), were first constructed via the solvothermal reactions of 4,6-di(4-carboxyphenyl)pyrimidine and Ln 3+ ions. 1-Ln exhibits a 4-connected two-dimensional framework endowed with uncoordinated Lewis base sites. An exploration of luminescence sensing demonstrated 1-Eu can be used for the selectivity detection of dimetridazole and metronidazole antibiotics in other antibiotics, blood plasma, and urine, acting as an exceptional recyclable luminescent probe. More importantly, the luminescent inks of 1-Ln are invisible, color adjustable, and stabilized, which may greatly improve their anticounterfeiting applications.

In order to reveal the pollution and risk level of phthalic acid esters (PAEs) in Qiandao Lake, six types of PAEs in 17 sampling points (in Qiandao Lake and its inflowing rivers) in dry and wet seasons were detected. The results showed that six types of PAEs were detected in both dry and wet seasons, with the concentrations of 0.98-5.33 μg·L -1 (average concentration 2.63 μg·L -1 ) in the dry season and 3.22-17.88 μg·L -1 (average concentration 7.99 μg·L -1 ) in the wet season. In terms of the detection rate and concentration of each monomer PAEs, DiBP, DBP, and DEHP were the main PAEs components in the water body. The measured value of DBP at 10 sampling points and its average mass concentration in the wet season were higher than the national standard (3 μg·L -1 ). Principal component analysis indicated that the main sources of PAEs were personal care products, plastics, and domestic waste. The pollution level of PAEs in Qiandao Lake was at a high level at home and abroad. The health risk assessment results in Qiandao Lake showed that the non-carcinogenic risk index of PAEs in the study area was less than 1, which would not produce non-carcinogenic risks to the human body. The carcinogenic risk index of children exceeded 10 -6 at some points, indicating that it may pose carcinogenic risks to children, to which more attention should be paid.

Owing to the small number of patients with tyrosine hydroxylase (TH) deficiency, no genotype-phenotype correlations have yet been identified. To investigate the genotype-phenotype correlation of R233H mutation in TH deficiency, we analyzed the clinical manifestations and treatment responses of four patients with the R233H homozygous mutation. Thirty-eight additional patients, available from the literature, known to be homozygous or heterozygous for the R233H mutation, were combined with the four cases from our hospital. Data for a total of 42 patients were retrieved. Our four patients showed clinical presentation consistent with Type A TH deficiency, and responded well to levodopa therapy, with an improvement in clinical symptoms within 1-2 weeks. In the 42 patients, 20 of 42 patients (48%) were homozygous and 22 (52%) were heterozygous for the R233H mutation. Of the 20 patients who were homozygous for the R233H mutation, a majority (80%) suffered from Type A TH deficiency. Of the 8 patients that were heterozygous for the R233H/the mutation located downstream of exon 11, 7 patients (86%) suffered from Type B TH deficiency. Of the 7 patients who were heterozygous for the R233H/nonsense mutation, 6 (86%) suffered from Type B TH deficiency. Genotype-phenotype correlation of R233H mutation was observed in TH deficiency. The homozygous R233H mutation frequently manifests as Type A TH deficiency, whereas R233H/nonsense mutation or any mutation located downstream of exon 11 manifests as Type B TH deficiency., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P <0.001). Univariate analysis found that the bilobar distribution of liver tumors ( P =0.003), elevated baseline carcinoembryonic antigen (CEA) levels ( P =0.024), tumor invasion of the portal vein ( P =0.001), number of metastatic tumor>8 ( P <0.001), non-FOLFOXIRI ( P =0.005), and no targeted therapy ( P =0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P =0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P =0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P =0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P =0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

Osteoporosis is a common systemic bone disease caused by the imbalance between osteogenic activity and osteoclastic activity. Aged women are at higher risk of osteoporosis, partly because of estrogen deficiency. However, the underlying mechanism of how estrogen deficiency affects osteoclast activity has not yet been well elucidated. In this study, GSE2208 and GSE56815 datasets were downloaded from GEO database with 25 PreH BMD women and 25 PostL BMD women in total. The RRA algorithm determined 38 downregulated DEGs and 30 upregulated DEGs. Through GO analysis, we found that downregulated DEGs were mainly enriched in myeloid cell differentiation, cytokine-related functions while upregulated DEGs enriched in immune-related biological processes; pathways like Notch signaling and MAPK activation were found in KEGG/Rectome pathway database; a PPI network which contains 66 nodes and 91 edges was constructed and three Modules were obtained by Mcode; Correlation analysis helped us to find highly correlated genes in each module. Moreover, three hub genes FOS, PTPN6, and CTSD were captured by Cytohubba. Finally, the hub genes were further confirmed in blood monocytes of ovariectomy (OVX) rats by real-time PCR assay. In conclusion, the integrative bioinformatics analysis and real-time PCR analysis were utilized to offer fresh light into the role of monocytes in premenopausal osteoporosis and identified FOS, PTPN6, and CTSD as potential biomarkers for postmenopausal osteoporosis., 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 Deng, He, Cai, Jiang, Yang, Dan, Luo, Du, Chen and He.)

Diabetes mellitus, a metabolic disease characterized by chronically elevated blood glucose levels, affects about 29 million Americans and more than 422 million adults all over the world. Particularly, type 2 diabetes mellitus (T2DM) accounts for 90-95% of the cases of vascular disease and its prevalence is increasing due to the rising obesity rates in modern societies. Although multiple factors associated with diabetes, such as reduced red blood cell (RBC) deformability, enhanced RBC aggregation and adhesion to the endothelium, as well as elevated blood viscosity are thought to contribute to the hemodynamic impairment and vascular occlusion, clinical or experimental studies cannot directly quantify the contributions of these factors to the abnormal hematology in T2DM. Recently, computational modeling has been employed to dissect the impacts of the aberrant biomechanics of diabetic RBCs and their adverse effects on microcirculation. In this review, we summarize the recent advances in the developments and applications of computational models in investigating the abnormal properties of diabetic blood from the cellular level to the vascular level. We expect that this review will motivate and steer the development of new models in this area and shift the attention of the community from conventional laboratory studies to combined experimental and computational investigations, aiming to provide new inspirations for the development of advanced tools to improve our understanding of the pathogenesis and pathology of T2DM.

Objective: To investigate the clinical features in patients with iridocorneal endothelial (ICE) syndrome. Methods: A retrospective case series study. Data of clinical manifestations of patients with ICE syndrome including clinical subtypes, presenting visual acuity, clinical features and secondary glaucoma were collected from January 2014 to May 2020 in the Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University. The Wald's Chi-square test of generalized estimating equations was performed to analyze the differences in three clinical subtypes. Results: A total of 127 eyes of 114 subjects (64 females and 50 males) were included. Mean±SD age at presentation was (49±13) years. There were 53 patients (46.5%) with Chandler's syndrome (CS), 36 patients (31.6%) with progressive iris atrophy (PIA), 24 patients (21.0%) with Cogan-Reese syndrome (CRS) and one patient (0.9%) with an undetermined subtype. And 101 patients (88.6%) had uniocular ICE syndrome. Approximately 81.7% (49/60), 56.1% (23/41) and 41.7% (10/24) of eyes presented visual acuity <0.3 in patients with CS, PIA and CRS, respectively. Corneal edema was most common in CS (52.5%, 32/61), followed by PIA (29.3%, 12/41) and CRS (20.8%, 5/24). Corectopia was found in 95.8% (23/24) of eyes with CRS, 95.1% (39/41) of eyes with PIA and 78.7% (48/61) of eyes with CS. Polycoria was observed in 29.3% (12/41) of eyes with PIA, 3.3% (2/61) of eyes with CS and 8.3% (2/24) of eyes with CRS. Ectropion uvea was most common in CRS (54.2%, 13/24), followed by 16.4% (10/61) in CS and 12.2% (5/41) in PIA. Glaucoma was found in 94 eyes (74.0%, 94/127). Among them, 60.7% (37/61) of CS, 80.5% (33/41) of PIA and 95.8% (23/24) of CRS had secondary glaucoma. The difference of presenting visual acuity, corneal edema, corectopia, polycoria, ectropion uveae and secondary glaucoma in three clinical subtypes all had statistical significance (Wald χ 2 =13.87, 10.77, 965.78, 11.45, 15.00, 222.04; all P <0.05). And 86.2% of eyes (81/94) had glaucoma surgeries and 41 eyes (43.6%, 41/94) had the intraocular pressure well controlled with various interventions. Conclusions: ICE syndrome is mostly uniocular and more common in middle-aged patients. CS is the most common clinical subtype with poor presenting visual acuity. About 3/4 of eyes have secondary glaucoma, and the majority of them require surgical interventions, but prognoses are discouraging.

Background: The positive predictive value (PPV) of high risk factor questionnaire (HRFQ) plus fecal immunochemical test (FIT) as preliminary screening strategy for colorectal-related neoplasia is relatively low. We aim to explore independent factors associated with PPVs of HRFQ combined FIT for selecting high risk individuals for colonoscopy., Methods: A total of 6971 residents were enrolled in a community-based screening program. Participants who had positive results of HRFQ and/or FIT and subsequently received colonoscopy were involved. The associations of socio-demographic factors, lifestyle behaviors, and high risk factors of colorectal cancer with PPVs of HRFQ, FIT, and their combination were evaluated by multivariable logistic regression models., Results: Among 572 involved cases, 249 (43.5%) colorectal neoplasms were detected by colonoscopy, including 71 advanced adenoma (12.4%) and 9 colorectal cancer (CRC) (1.6%). The PPVs of preliminary screening were 43.5% for total colorectal neoplasms, 14.0% for advanced neoplasm, and 1.6% for CRC. Adding positive HRFQ to FIT could improve the PPV from 3.5 to 8.0% for detecting CRC. Preliminarily screened positive individuals who were males [adjusted odds ratio (AOR): 1.95, 95% CI 1.31, 2.90; p  < 0.001], elders (> 60 years) (AOR: 1.70, 95% CI 1.17, 2.46; p  = 0.005), or ex-/current smokers (AOR: 3.04, 95% CI 1.31, 7.09; p  = 0.10) had higher odds of PPVs of detecting colorectal neoplasms., Conclusions: Combining HRFQ and FIT could largely improve PPVs for screening advanced neoplasm and CRC. Gender and age-specific FIT cut-off values as well as initiating ages for CRC screening might be recommended to improve the accuracy and effectiveness of current screening algorithm., (© 2022. The Author(s).)

Hydrogen sulfide and biothiol molecules such as Cys and GSH acted important roles in many physiological processes. To simultaneously detect and distinguish them was quite necessary by a suitable fluorescent probe. A novel chemosensor 4-(4-(benzo[d]thiazol-2-yl)-2-methoxyphenoxy)-7-nitrobenzo[c][1,2,5]oxadiazole (BMNO) was designed to detect H 2 S/Cys/GSH using the combination of nitrobenzofurazan (NBD) and benzothiazole fluorophores linked by a facile ether bond. The probe BMNO was developed for simultaneous identification of H 2 S, Cys and GSH. Noticeably, the color changes (from colorless to light purple, light orange and light yellow) of probe BMNO solutions for sensing H 2 S, Cys and GSH could be observed by naked eyes, respectively. The probe BMNO exhibited high selectivity and sensitivity for H 2 S, Cys and GSH showing distinct optical signal with detection limit as low as 0.15 μM, 0.03 μM and 0.14 μM, respectively. The sensing mechanism was clarified by spectrum analysis and some controlled experiments. In addition, these outstanding properties of probe BMNO enabled its practical applications in detection H 2 S in beer, and in cell imaging for Cys and GSH as well., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aimed to evaluate the effect of four exercise modalities on patients with nonalcoholic fatty liver disease (NAFLD)., Materials and Methods: Databases of CNKI, Wanfang, VIP, Web of Science, PubMed, Cochrane Library, Medline, and Embase were searched for relevant studies. The literature search was restricted to those published between January 2010 and June 2021. Randomized controlled trials of exercise interventions on NAFLD were collected. Data were presented as statistical graphics using ADDIS 1.16.5 and R-Studio 4.1., Results: Seventeen controlled studies analyzing 1627 patients with NAFLD were included. Patients were divided into the control group (n=688), aerobic training group (AT, n=554), resistance training group (RT, n=232), high-intensity interval training group (HIIT, n=53), and aerobic training with resistance training group (AT+RT, n=100). Results of the statistical analysis showed that the combined exercise intervention had the most significant effect on the total serum cholesterol of patients' mean difference [MD=0.47(0.23, 0.73), p<0.05]. Levels of alanine aminotransferase and aspartate aminotransferase were improved, but no significant difference was found in their levels in the four groups of exercise intervention. The intervention effect of the four exercises on blood lipid and liver enzymes in patients with NAFLD was in the order of AT+RT > HIIT > RT > AT > control., Conclusions: Exercise interventions are recommended as stand-alone or adjunctive therapy. For patients with NAFLD who can tolerate various exercises, priority should be given to AT+RT exercise 4-5 times per week. The exercise intensity should be 50%-70% of the maximum heart rate and performed for >3 months to improve the effectiveness of the exercise supervision intervention.

Paddy soils are widely considered a main source of methane (CH 4 ) and nitrous oxide (N 2 O). Comprehensively evaluating CH 4 and N 2 O emissions from double-rice systems in tropical regions with different water irrigation and fertilizer applications is of great significance for addressing greenhouse gas emissions from such systems in China. In this study, eight treatments were evaluated:conventional irrigation-PK fertilizer (D-PK), conventional irrigation-NPK fertilizer (D-NPK), conventional irrigation-NPK+organic fertilizer (D-NPK+M), conventional irrigation-organic fertilizer (D-M), continuous flooding-PK fertilizer (F-PK), continuous flooding-NPK fertilizer (F-NPK), continuous flooding-NPK+organic fertilizer (F-NPK+M), and continuous flooding-organic fertilizer (F-M). CH 4 and N 2 O emissions in double-rice fields in tropical region of china were monitored in situ by closed static chamber-chromatography method and crop yields as well as global warming potential (GWP) and greenhouse gas intensity (GHGI) were determined. The results show that:① The cumulative CH 4 emissions from early rice and late rice are 10.3-78.9 kg·hm -2 and 84.6-185.5 kg·hm -2 , respectively. Compared with F-PK and F-NPK treatments, F-NPK+M and F-M treatments significantly increased the cumulative emissions of CH 4 from early rice season. Under the same fertilizer conditions, the cumulative CH 4 emissions under continuous flooding condition were significantly higher than that under conventional irrigation condition. Irrigation and fertilization had extremely significant effects on CH 4 emission in the early rice season. ② The cumulative N 2 O emissions across all treatments were 0.18-0.76 kg·hm -2 in early rice season and 0.15-0.58 kg·hm -2 in late rice season, respectively. During early rice season, compared with F-PK, F-NPK significantly increased the cumulative N 2 O emission; however, compared with D-PK, D-NPK, D-NPK+M, and D-M treatments significantly increased the cumulative N 2 O emissions. Compared with F-PK, other three treatments under continuous flooding condition significantly increased N 2 O cumulative emission in late rice season; compared with D-PK, D-NPK, and D-M treatment significantly increased the cumulative N 2 O emission. Irrigation and fertilization had significant impacts on N 2 O emissions in late rice season, and fertilization had significant impacts on N 2 O emission in early rice season. ③ Early and late rice yields were 7310.7-9402.4 kg·hm -2 and 3902.8-7354.6 kg·hm -2 , respectively. Early rice yields in both F-NPK and F-M treatments were significantly higher than those in F-PK, D-PK, and D-NPK treatments. Compared with PK, the other three fertilization treatments under the same irrigation condition significantly increased late rice yield. The GWP and GHGI in early rice season were 580.8-2818.5 kg·hm -2 and 0.08-0.30 kg·kg -1 , respectively. There was no significant difference in GWP among four fertilizer treatments under conventional irrigation condition in the early rice season. However, F-NPK+M and F-M treatments had a significant increase in GWP compared with F-PK. The GHGI in F-NPK+M and F-M treatments were significantly higher than that in other treatments. The GWP and GHGI in late rice season were 3091.6-6334.2 kg·hm -2 and 0.50-1.23 kg·kg -1 , respectively. Irrigation significantly affected GWP and GHGI in both early and late rice seasons but fertilization had no significant impact on GWP and GHGI in late rice season. ④ Correlation analysis results showed that soil NH 4 + -N content and soil temperature below 5 cm soil layer had an extremely significant negative correlation with CH 4 emissions. Soil pH was extremely significant positive correlated with CH 4 emissions but significantly negatively correlated with N 2 O emission. Soil NH 4 + -N and NO 3 - -N concentrations were extremely significantly negatively correlated with N 2 O emission. Given crop yield, GWP, GHGI, and D-NPK+M can be recommended for local water and fertilizer management to reduce greenhouse gas emissions while maintaining rice yields.

Background: Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Patients with GIOP are susceptible to fractures and the subsequent delayed bone union or nonunion. Thus, effective drugs and targets need to be explored. In this regard, the present study aims to reveal the possible mechanism of the anti-GIOP effect of all-trans retinoic acid (ATRA)., Methods: Bone morphogenetic protein 9 (BMP9)-transfected mesenchymal stem cells (MSCs) were used as an in vitro osteogenic model to deduce the relationship between ATRA and dexamethasone (DEX). The osteogenic markers runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin were detected using real-time quantitative polymerase chain reaction, Western blot, and immunofluorescent staining assay. ALP activities and matrix mineralization were evaluated using ALP staining and Alizarin Red S staining assay, respectively. The novel genes associated with ATRA and DEX were detected using RNA sequencing (RNA-seq). The binding of the protein-DNA complex was validated using chromatin immunoprecipitation (ChIP) assay. Rat GIOP models were constructed using intraperitoneal injection of dexamethasone at a dose of 1 mg/kg, while ATRA intragastric administration was applied to prevent and treat GIOP. These effects were evaluated based on the serum detection of the osteogenic markers osteocalcin and tartrate-resistant acid phosphatase 5b, histological staining, and micro-computed tomography analysis., Results: ATRA enhanced BMP9-induced ALP, RUNX2 expressions, ALP activities, and matrix mineralization in mouse embryonic fibroblasts as well as C3H10T1/2 and C2C12 cells, while a high concentration of DEX attenuated these markers. When DEX was combined with ATRA, the latter reversed DEX-inhibited ALP activities and osteogenic markers. In vivo analysis showed that ATRA reversed DEX-inhibited bone volume, bone trabecular number, and thickness. During the reversal process of ATRA, the expression of retinoic acid receptor beta (RARβ) was elevated. RARβ inhibitor Le135 partly blocked the reversal effect of ATRA. Meanwhile, RNA-seq demonstrated that serine protease inhibitor, clade A, member 3N (Serpina3n) was remarkably upregulated by DEX but downregulated when combined with ATRA. Overexpression of Serpina3n attenuated ATRA-promoted osteogenic differentiation, whereas knockdown of Serpina3n blocked DEX-inhibited osteogenic differentiation. Furthermore, ChIP assay revealed that RARβ can regulate the expression of Serpina3n., Conclusion: ATRA can reverse DEX-inhibited osteogenic differentiation both in vitro and in vivo, which may be closely related to the downregulation of DEX-promoted Serpina3n. Hence, ATRA may be viewed as a novel therapeutic agent, and Serpina3n may act as a new target for GIOP.

To reveal the Beijing-Hangzhou Grand Canal natural water chemistry characteristics and the influence of human activities, river samples from Xuzhou to Jiaxing were collected in 2019-2020. Simultaneously, the water chemistry data of the canal from 1959 to 1962 and 1975 to 1977 in the Suzhou, Wuxi, and Changzhou sections and the recent social and economic data of the major cities along the canal were collected and analyzed. The results showed that the type of hydrochemistry in the study area was mainly influenced by the weathering of carbonate rocks in the basin, but K + +Na + accounted for 40.39% of the cation equivalent concentration, which was higher than that in ordinary surface water, thereby indicating that the natural hydrochemistry of the canal had been significantly affected by human factors. Spatially, the major ion mass concentrations, total hardness, and total alkalinity of the Grand Canal from Xuzhou station to the downstream area tended to decrease overall, but the parameters at Wuxi and Suzhou stations increased significantly. It was found that Na + and SO 4 2- were increased by approximately 16 and 12 times and total dissolved solids was increased by nearly 3 times by analyzing the 60 years of water chemistry of the Suzhou, Wuxi, and Changzhou sections. The current (Ca 2+ +Mg 2+ )/HCO 3 - ratio in the Suzhou, Wuxi, and Changzhou sections is generally greater than 1, which is significantly higher than that from 1959 to 1962, thereby reflecting the results of human activities. According to the analysis of the social and economic development of the Grand Canal, this change was the result of the accelerated weathering of carbonate rocks in the basin caused by the sulfur oxides discharged by human activities. Further statistical analysis showed that urban domestic sewage and industrial wastewater discharge were the main driving factors causing chemical salinization of natural water in the Grand Canal. This study can provide a scientific basis for coordinating urban development and protecting the water ecological environment of the Grand Canal Basin.