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Junfeng Ban, Yan Zhang, Xin Huang, Guanghan Deng, Dongzhi Hou, Yanzhong Chen, Zhufen Lu Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China Abstract: Drug delivery carriers can maintain effective therapeutic concentrations in the eye. To this end, we developed lipid nanoparticles (L/NPs) in which the surface was modified with positively charged chitosan, which engaged in hydrogen bonding with the phospholipid membrane. We evaluated in vitro corneal permeability and release characteristics, ocular irritation, and drug dynamics of modified and unmodified L/NPs in aqueous humor. The size of L/NPs was uniform and showed a narrow distribution. Corneal permeation was altered by the presence of chitosan and was dependent on particle size; the apparent permeability coefficient of dexamethasone increased by 2.7 and 1.8 times for chitosan-modified and unmodified L/NPs, respectively. In conclusion, a chitosan-modified system could be a promising method for increasing the ocular bioavailability of unmodified L/NPs by enhancing their retention time and permeation into the cornea. These findings provide a theoretical basis for the development of effective drug delivery systems in the treatment of ocular disease. Keywords: ocular drug delivery system, local bioavailability, dexamethasone, eye drop administration

Many factors can affect delivery mode decisions. Therefore, this study aimed to explore the effects of maternal age, physician's sex, region, income, and hospital type on cesarean section (C/S) delivery rates between 2008 and 2018 in Taiwan. In this population-based cross-sectional study, data were extracted from the Taiwan National Health Insurance Research Database (2 million individuals). The logistic regression method was used to analyze the aforementioned risk factors, and data are expressed as odds ratios (ORs) and 95% confidence intervals. In total, 9826 and 9714 deliveries in 2008 and 2018, respectively, were included in the analysis. The C/S ratio increased from 16.5% (n = 1607) in 2008 to 19.7% (n = 1916) in 2018. A higher C/S risk for women aged >34 years (ORs: 2.835 and 2.225 in 2008 and 2018, respectively) than for those aged ≤34 years was noted in both years. Female physicians had a lower risk of performing C/S than male physicians in 2008 (OR: .762, 95% confidence interval: .625-.928), but this was not apparent in 2018. Higher income levels (>new Taiwan dollar 45,081) and central Taiwan were associated with a lower C/S risk in both years. Private, not-for-profit hospitals had a lower C/S risk in 2008, which was not apparent in 2018. In conclusion, this study revealed a significant increase in C/S rates over the past decade, which was influenced by multiple factors. Maternal age, physician's sex, income status, location, and type of hospital may influence C/S rates. Analyzing these relationships can inform the development of strategies aimed at reducing future C/S rates, and targeted interventions may reduce the C/S rates., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Currently, the number of patients with spinal stenosis is increasing, and most of the patients are found to have a history of smoking in the clinic. In this study, we used the Mendelian randomization (MR) method to investigate the causal relationship between smoking and spinal stenosis., Methods: Genetic loci independently associated with smoking and spinal stenosis in people of European ancestry were selected as instrumental variables using pooled data from large-scale genome-wide association studies (GWAS). Three MR analyses, MR-Egger, Weighted median and inverse variance weighting (IVW), were used to investigate the causal relationship between smoking and spinal stenosis. The results were tested for robustness by heterogeneity and multiplicity tests, and sensitivity analyses were performed using the "leave-one-out" method., Results: The IVW results showed an OR (95% CI) of 2.40 (0.31-18.71), P = .403, indicating that there was no causal relationship between smoking and spinal stenosis. And no heterogeneity and multiplicity were found by the test and sensitivity analysis also showed robust results., Conclusion: In this study, genetic data were analyzed and explored using 2-sample MR analysis, and the results showed that there is a causal relationship between smoking and the occurrence of spinal stenosis, and more studies need to be included., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between multiple sclerosis and spinal stenosis using Mendelian randomization (MR). Genetic loci independently associated with multiple sclerosis and spinal stenosis in people of European origin were selected as instrumental variables using pooled data from genome wide association studies (GWAS). Three MR analyses, MR-Egger, Weighted median and inverse variance weighting (IVW), were used to investigate the causal relationship between multiple sclerosis and spinal stenosis. Heterogeneity and multiplicity tests were performed, and sensitivity analyses were performed using the "leave-one-out" method to explore the robustness of the results. The IVW results showed an OR (95% CI) of 1.05 (1.01-1.08), P = .016, indicating a causal relationship between MS and spinal stenosis. And no heterogeneity and multiplicity were found by the test, and sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using 2-sample MR analysis, and the results showed a causal relationship between multiple sclerosis and the occurrence of spinal stenosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To explore the causal relationship between asthma, allergic rhinitis (AR), and chronic sinusitis (CRS), using two sample Mendelian randomization (MR) analysis, thereby providing foundational evidences for the pathogenesis and treatment of CRS. Methods: The genetic variations in AR and asthma were used as instrumental variables, with genetic data from the Integrated Epidemiology Unit (IEU) Open database. A total of 14 283 asthma and 18 934 AR cases were included, with 98 300 and 64 595 corresponding normal control cases, respectively. For CRS, there were 3 236 CRSwNP and 8 524 CRSsNP, respectively, with 167 849 and 167 849 corresponding normal control cases, respectively. The genetic data were analyzed using the inverse variance weighting method (IVW), MR Egger method, weighted median method, and Cochran's Q-test. Results: The IVW analysis showed that asthma increased the risk of both CRSwNP ( OR =482.8, 95% CI : 57.18-4 077.78, P <0.001) and CRSsNP ( OR =25.73, 95% CI : 9.79-67.56, P <0.001); AR significantly increased the risk of CRSsNP ( OR =5.40, 95% CI : 1.68-17.26, P =0.004), but not CRSwNP ( OR =7.38, 95% CI : 0.80-67.73, P =0.077). Conversely, neither CRSwNP nor CRSsNP increased the risk of asthma or AR. Conclusion: According to Mendelian genetic laws, asthma is a risk factor for CRSwNP and CRSsNP, while AR is a risk factor for CRSsNP.

To investigate the efficacy of chiropractic rehabilitation therapy in Crowe IV developmental dysplasia of the hip (DDH) patients after total hip arthroplasty. Seventy-two patients with Crowe IV type DDH hospitalized in the Department of Orthopedics I of Ya'an Hospital of Traditional Chinese Medicine from January 2021 to June 2023 were selected for the study, and they were divided into 36 cases in the chiropractic rehabilitation therapy group (the treatment group) and 36 cases in the traditional rehabilitation therapy group (the control group) according to the method of randomized grouping. All patients were evaluated at preoperative, 1, 3, and 6 months postoperatively for follow-up, and the muscle strength of the affected limb, the patient's walking gait, the shortened length of the affected limb, the visual analog scale score (VAS score), the Oswestry Dysfunction Index Score (ODI score), the Harris Hip Score, and the degree of pelvic tilt were recorded to evaluate the results of the study. A total of 4 subjects withdrew from the study, 2 in the treatment group, and 2 in the control group. The muscle strength of the affected limb, walking gait, shortened length of the affected limb, VAS score, ODI score, Harris score, and pelvic tilt in the treatment and control groups improved significantly compared with the preoperative period. Comparisons between the 2 groups revealed that at the final follow-up visit, the limp gait of the patients in the treatment group was significantly reduced, the shortened length of the affected limb was significantly reduced, the VAS score was significantly reduced, and the ODI score was significantly reduced, in the treatment group relative to that of the control group, Harris Hip Score was significantly improved, and the degree of pelvic tilt was significantly reduced, but the improvement in muscle strength of the affected limb was not statistically significant. In future clinical practice, we recommend that chiropractic rehabilitation be used as a routine adjunctive treatment after TKA in patients with Crowe IV DDH to optimize outcomes and improve patients' quality of life., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between rheumatoid arthritis (RA) and ankylosing spondylitis using Mendelian randomization (MR). Genetic loci independently associated with RA and ankylosing spondylitis in people of European origin were selected as instrumental variables using pooled data from large-scale genome-wide association studies. Three MR analyses, MR-Egger, weighted median, and inverse variance weighting, were used to investigate the causal relationship between RA and ankylosing spondylitis. Heterogeneity and multiplicity tests were used, and a sensitivity test using the "leave-one-out" method was used to explore the robustness of the results. The inverse variance weighting results showed an OR (95 % CI) of 1.25 (1.11-1.41), P < .001, indicating a causal relationship between RA and ankylosing spondylitis. And no heterogeneity and pleiotropy were found by the test and sensitivity analysis also showed robust results. The present study was conducted to analyze and explore the genetic data using two-sample MR analysis and the results showed that there is a causal relationship between RA and the occurrence of ankylosing spondylitis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense , and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism., 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 Deng, Zhao, Cai, Zhang, Ma, Lv, Jiang, Peng, Wang, Xing and Yu.)

Background: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases., Aim: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD., Methods: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test., Results: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE., Conclusion: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Acute decompensation (AD) of cirrhosis is associated with high short-term mortality, mainly due to the development of acute-on-chronic liver failure (ACLF). Thus, there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from activated innate immune cells and correlated with various inflammatory processes., Aim: To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis., Methods: A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort ( n = 309) and validation cohort ( n = 133). Demographic and clinical data were collected, and serum sTREM-1 was measured at admission. All enrolled patients were followed-up for at least 1 year., Results: In patients with AD and cirrhosis, serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver, coagulation, cerebral and kidney failure. A new prognostic model of AD (P-AD) incorporating sTREM-1, blood urea nitrogen (BUN), total bilirubin (TBil), international normalized ratio (INR) and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease (MELD), MELD-sodium (MELD-Na), chronic liver failure-consortium (CLIF-C) ACLF and CLIF-C AD scores. Additionally, sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up. The ACLF risk score incorporating serum sTREM-1, BUN, INR, TBil and aspartate aminotransferase levels was established and significantly superior to MELD, MELD-Na, CLIF-C ACLF, CLIF-C AD and P-AD in predicting risk of ACLF development., Conclusion: Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising., Methods: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort., Findings: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening., Interpretation: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care., Funding: A full list of funding bodies that contributed to this study can be found in Acknowledgments section., Competing Interests: Declaration of interests JB, QZZ, JZ, FMS, YW, and LW are employees of Berry Oncology Corporation. All the authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

To investigate the causal relationship between obesity and meniscal injuries using Mendelian randomization (MR). Genetic loci independently associated with obesity and meniscal injuries in people of European origin were selected as instrumental variables using pooled data from genome-wide association studies. Three MR analyses, MR-Egger, weighted median and inverse variance weighting, were used to investigate the causal relationship between obesity and meniscal injuries. The results were tested for robustness by heterogeneity and multiplicity tests, and sensitivity analyses were performed using the "leave-one-out" method. The inverse variance weighting results showed an OR (95% CI) of 1.13 (1.04-1.22), P = .003, indicating a causal relationship between obesity and the occurrence of meniscal injuries. And no heterogeneity and multiplicity were found by the test and sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using 2-sample MR analysis, and the results showed that obesity is a risk factor for meniscal injuries., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The aim was to investigate the independent risk factors for postoperative incisional infection in ankle fractures and to establish a nomogram prediction model accordingly. Data were collected from ankle fracture patients in the Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2022. Univariate and multivariate logistic regression analyses were used to determine the independent risk factors for postoperative incisional infection in ankle fractures and to establish the corresponding nomogram. Receiver operating characteristic curves were plotted and area under the curve was calculated, and calibration curves and decision curve analysis were plotted to evaluate the model performance. A total of 722 patients with ankle fractures were included in the study, and 76 patients developed postoperative incisional infections, with an incidence of 10.53%. After univariate and multivariate logistic regression analysis, a total of 5 variables were identified as independent risk factors for postoperative incisional infection in ankle fractures, namely, age ≥ 60 years (OR, 1.885; 95% CI, 1.156-3.045), having diabetes (OR1.625; 95% CI, 1.095-2.876), open fracture (OR, 5.564; 95% CI, 3.099-9.990), albumin < 35 g/L (OR, 2.618; 95% CI, 1.217-4.215), and operative time ≥ 2 hours (OR, 1.606; 95% CI, 1.077-3.247). The nomogram for postoperative incisional infection after ankle fracture constructed in this study has good predictive accuracy and helps orthopedic surgeons to intervene earlier in patients at high risk of postoperative incisional infection after ankle fracture., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between dried fruit intake and meniscal injuries using Mendelian randomization (MR). Data were pooled from large-scale genome wide association studies (GWAS), and genetic loci independently associated with dry fruit intake and meniscal injuries in populations of European origin were selected as instrumental variables. Three MR analyses, inverse variance weighting (IVW), weighted median (WME) and MR-Egger, were used to investigate the causal relationship between dried fruit intake and meniscal injuries. The results were tested for robustness by heterogeneity and multiplicity tests, and sensitivity analyses were performed using the "leave-one-out" method. The IVW results showed an OR (95 % CI) of 0.47 (0.28-0.78), P = .003, indicating a causal relationship between dried fruit intake and meniscus injury. And no heterogeneity and multiplicity were found by the test and sensitivity analysis also showed robust results. The present study used a 2-sample MR analysis, and by analyzing and exploring the genetic data, the study showed that too little intake of dry fruits is a risk factor for meniscal injuries., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between dried fruit intake and frozen shoulder using Mendelian randomization (MR). Genome wide association studies were conducted to pool data and select genetic loci independently associated with dried fruit intake and frozen shoulder in people of European ancestry as instrumental variables. Three MR analyses, inverse variance weighting, weighted median and MR-Egger, were used to investigate the causal relationship between dried fruit intake and frozen shoulder. Heterogeneity and multiplicity tests were used, and sensitivity analyses were conducted using the leave-one-out method to explore the robustness of the results. The inverse variance weighting results showed an OR (95 % CI) of 0.52 (0.34-0.80), P = .003, suggesting that there is a causal relationship between dried fruit intake and frozen shoulder. And no heterogeneity and multiplicity were found by the test and sensitivity analysis also showed robust results. The present study used a two-sample MR analysis, and by analyzing and exploring the genetic data, the study showed that too little intake of dry fruits is a risk factor for developing frozen shoulder., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with disordered lipid and iron metabolism. Our previous study has substantiated the pivotal role of Caveolin-1 (Cav-1) in protecting hepatocytes and mediating iron metabolism in the liver. This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD., Methods: Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study. Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro. Moreover, a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro, respectively, while a high-iron diet was used to construct an in vivo iron overload model. Besides, iron concentration, the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit, Prussian blue staining, Western blotting, immunofluorescence staining, immunohistochemical staining and ELISA. The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining., Results: Significant disorder of lipid and iron metabolism occurred in NAFLD. The expression of Cav-1 was decreased in NAFLD hepatocytes (P < 0.05), accompanied by iron metabolism disorder. Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD, subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver. Further, CD68 + CD163 + macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver, which was contrary to the effect of Cav-1 in hepatocytes. Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers (P < 0.05)., Conclusions: These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis. It is a pivotal molecule for predicting and protecting against the development of NAFLD., (© 2023. The Author(s).)

To investigate the causal relationship between ever smoked and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with ever smoked and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between ever smoked and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results of ever smoked showed an OR = 2.49, 95% CI = 1.05-5.91, P = .038, indicating that ever smoked is a risk factor for a frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. This study used two-sample MR analysis to analyze and explore the genetic data, and the results showed a higher prevalence of frozen shoulder in patients with ever smoked, suggesting that active control of ever smoked may reduce the occurrence of frozen shoulder., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between breast cancer and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with breast cancer and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median (WME) and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between breast cancer and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an OR (95% CI) of 1.02 (1.00-1.04), P = .048, indicating that breast cancer is a risk factor for a frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using two-sample MR analysis, and the results showed that the incidence of frozen shoulder was higher in breast cancer patients, suggesting that screening for frozen shoulder in breast cancer patients should be increased., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between depression and frozen shoulder using a Mendelian randomization (MR) approach. Pooled data from a large-scale genome-wide association study were used. Genetic loci that were independent of each other and associated with depression and frozen shoulder in populations of European ancestry were selected as instrumental variables. Inverse variance weighting was used as the primary analysis method. Weighted median and MR-Egger were used as complementary analysis methods to assess causal effects. To explore the causal relationship between depression and frozen shoulder. Sensitivity test analysis was performed using heterogeneity test, multiple validity test, and leave-one-out analysis to explore the robustness of the results. Inverse variance weighting results showed an odds ratio (95% confidence interval) of 1.18 (0.91-1.53), P = .204, indicating that depression was not causally related to the development of frozen shoulder. And the test revealed no heterogeneity and pleiotropy, and the sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using a two-sample MR analysis, and the results showed no causal relationship between depression and the occurrence of frozen shoulder, requiring the inclusion of a larger sample for the study., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between attention deficit and hyperactivity disorder (ADHD) and frozen shoulder using Mendelian randomization (MR). Data were pooled from large-scale genome wide association studies, and genetic loci that were independent of each other and associated with ADHD and frozen shoulder in people of European ancestry were selected as instrumental variables. Three MR analyses, inverse variance weighting, weighted median and MR-Egger, were used to investigate the causal relationship between ADHD and frozen shoulder. Heterogeneity and multiplicity tests were used, and sensitivity analyses were performed using the "leave-one-out" method to explore the robustness of the results. The inverse variance weighting results showed an OR (95 % CI) of 1.12 (1.00-1.25), P = .046, indicating a causal relationship between ADHD and frozen shoulder. And no heterogeneity and multiplicity were found by the test and sensitivity analysis also showed robust results. The present study used a two-sample MR analysis, and by analyzing and exploring the genetic data, the study showed that ADHD is a risk factor for developing frozen shoulder, and patients with ADHD are more likely to suffer from frozen shoulder., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chondrosarcoma is the second most common primary bone malignancy with the highest incidence in middle-aged and elderly people, where distant metastasis (DM) still leads to poor prognosis. The purpose of this study was to construct a nomogram for studying the diagnosis of DM in middle-aged and elderly patients with chondrosarcoma. Data on chondrosarcoma patients aged ≥ 40 years diagnosed from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The data were divided into a training set and an internal validation set according to a 7:3 ratio, and the training set data were screened for independent risk factors for DM in chondrosarcoma patients using univariate and multivariate logistic regression analysis. The screened independent risk factors were then used to build a nomogram. In addition, data from 144 patients with chondrosarcoma aged ≥ 40 years diagnosed in a tertiary hospital in China from 2012 to 2021 were collected as the external validation set. The results were evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis in the training set, internal validation set, and external validation set. A total of 1462 middle-aged and elderly patients with chondrosarcoma were included, and 92 (6.29%) had DM at the time of diagnosis. Independent risk factors for DM in middle-aged and elderly patients with chondrosarcoma included being married (OR: 2.119, 95% CI: 1.094-4.105), histological type of dedifferentiated chondrosarcoma (OR: 1.290, 95% CI: 1.110-1.499), high-grade tumor (OR: 1.511, 95% CI: 1.079-2.115), T3 stage (OR: 4.184, 95% CI: 1.977- 8.858), and N1 staging (OR: 5.666, 95% CI: 1.964-16.342). The area under the receiver operating characteristic curve (AUC) was 0.857, 0.820, and 0.859 in the training set, internal validation set, and external validation set, respectively. The results of the calibration curve and decision curve analysis also confirmed that the established nomogram could accurately predict DM in middle-aged and elderly patients with chondrosarcoma. Married, histological type of dedifferentiated chondrosarcoma, high-grade tumor, T3 stage, and N1 stage are independent risk factors for DM in middle-aged and elderly chondrosarcoma patients, and clinicians should see more attention., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The aim was to study the independent risk factors for chronic low back pain after lumbar compression fractures undergoing percutaneous kyphoplasty (PKP), and to establish a nomogram prediction model accordingly. Data were collected from patients with lumbar compression fractures from January 2017 to December 2021 at the Affiliated Hospital of Xinjiang Medical University. Univariate and multivariate logistic regression analyses were used to determine the independent risk factors for chronic low back pain after receiving PKP for lumbar compression fractures, and the corresponding nomogram was established. Receiver operating characteristic (ROC) curves were plotted and area under the curve (AUC) was calculated, and calibration curves and decision curve analysis (DCA) were plotted to evaluate the model performance. A total of 792 patients with lumbar compression fractures were included in the study, and 188 patients had chronic postoperative low back pain, with an incidence of 23.74%. After univariate and multivariate logistic regression analysis, a total of 5 variables were identified as independent risk factors for chronic low back pain after undergoing PKP for lumbar compression fractures, namely having diabetes (OR, 1.607; 95% CI, 1.157-3.205), preoperative T value < -2.5 SD (OR, 2.697; 95% CI, 1.417-5.021), multiple lumbar fractures (OR, 1.815; 95% CI, 1.415-3.201), lumbar compression ≥ 50% (OR, 2.854; 95% CI, 1.411-6.524), and bone cement leakage (OR, 2.911; 95% CI, 1.715-6.817). The nomogram for chronic low back pain after PKP for lumbar compression fractures constructed in this study has good predictive accuracy and helps orthopedic surgeons to intervene earlier in patients at high risk of chronic low back pain after undergoing PKP for lumbar compression fractures., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

To investigate the causal relationship between metformin use and osteoporosis and different subtypes of osteoporosis using a 2-sample Mendelian randomization method. Data from genome-wide association studies were analyzed, with the exposure factor being metformin and the outcome variables being osteoporosis and different subtypes. Mendelian randomization was performed using Inverse Variance Weighted (IVW), MR-Egger, and weight median (WM) methods, and heterogeneity tests, horizontal multivariate analyses, and sensitivity analyses were performed. The IVW method analysis with metformin and osteoporosis showed P = 1.53E-04, OR (95%CI) = 1.81E-02 (2.27E-02-1.44E-01); the IVW method analysis with metformin and postmenopausal osteoporosis with pathologic fracture showed P = 2.22E-01, OR (95%CI) = 4.89E-02 (3. 83E-04-6.23E + 00); the IVW method using metformin with osteoporosis with pathological fracture showed that P = 2.14E-01, OR (95%CI) = 1.64E + 00(5.78E-02-6.44E-04); the IVW method using metformin with pharmacological osteoporosis with pathological fracture showed that P = 9. 83E- 01, OR (95%CI) = 1.11E + 00 (3.99E-05-3.11E + 04); IVW method of metformin use and pharmacological osteoporosis showed that P = 5.99E-01, OR (95%CI) = 2.27E + 01 (2.00E-04-2.57E + 06); there is a causal relationship between metformin use and osteoporosis, but there is no causal relationship between metformin use and postmenopausal osteoporosis with pathological fracture, osteoporosis with pathological fracture, pharmacological osteoporosis, and pharmacological osteoporosis with pathological fracture, and metformin use is a protective factor for osteoporosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chondrosarcoma is the second largest bone malignancy after osteosarcoma and mainly affects middle-aged adults, where patients with distant metastasis (DM) often have a poor prognosis. Although nomograms have been widely used to predict distant tumor metastases, there is a lack of large-scale data studies for the diagnostic evaluation of DM in chondrosarcoma. Data on patients diagnosed with chondrosarcoma from 2004 to 2015 were obtained from the Surveillance, Epidemiology, and End Results database. Independent risk factors for having DM from chondrosarcoma were screened using univariate and multivariate logistics regression analysis. A nomogram was created to predict the probability of DM from the screened independent risk factors. The nomogram was then validated using receiver operating characteristic curves and calibration curves. A total of 1870 chondrosarcoma patients were included in the study after data screening, of which 157 patients (8.40%) had DM at the time of diagnosis. Univariate and multivariate logistic regression analysis screened four independent risk factors, including grade, tumor number, T stage, and N stage. receiver operating characteristic curves and calibration curves showed good accuracy of the nomogram in both training and validation sets. The current study screened for independent risk factors for DM from chondrosarcoma, which will help clinicians evaluate patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction and Hypothesis: Child delivery mode may be associated with pelvic floor disorders. We explored the association between different delivery modes and later development of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) in Taiwanese women., Methods: This was a retrospective population-based cohort study. Women who delivered babies between January 1, 2000, and December 31, 2018, were selected for this study. The study used Taiwan's National Health Insurance (NHI) Research Database. After propensity score matching, 51,587 women who underwent cesarean section (C/S) and 51,587 women who underwent vaginal delivery (VD) were recruited. Primary outcomes were the presence of SUI and POP after delivery., Results: The incidence of SUI (1.6/1000 person-years) and POP (1.5/1000 person-years) was higher in the VD group than in the C/S group (0.8 and 0.6 in 1000 person-years). VD was associated with an increased risk of SUI [hazard ratio (HR): 2.79, 95% confidence interval (CI): 2.45-3.17] and POP (HR: 1.96, 95% CI: 1.75-2.19) compared to C/S. We also found that age (HR: 1.06, 95% CI: 1.05-1.08 in SUI, HR: 1.08, 95% CI: 1.07-1.09 in POP) and Charlson Comorbidity Index (CCI) (HR: 1.28, 95% CI: 1.12-1.46 in SUI, HR: 1.27, 95% CI: 1.13-1.43 in POP) were associated with an increased risk of SUI and POP. The cumulative incidence of SUI and POP was higher in the VD group than in the C/S group (log-rank test, P < 0.05)., Conclusions: The current study was the largest retrospective cohort study regarding the influence of delivery mode on SUI and POP so far. VD was found to be associated with an increased risk of SUI and POP compared with C/S. Postpartum care for pelvic physical therapy should be provided particularly to women undergoing VD., (© 2023. The International Urogynecological Association.)

Background: Early Identifying and characterizing patients with diabetic macular edema (DME) is essential for individualized treatment and outcome optimization. This study aimed to timely investigate optical coherence tomography (OCT) biomarkers of DME refractory to intravitreal anti-vascular endothelial growth factor (VEGF) therapy., Methods: We retrospective reviewed 72 eyes from 44 treatment-naïve patients who were treated with intravitreal anti-VEGF for DME. OCT scans prior to anti-VEGF were evaluated for serous retinal detachment (SRD), size of outer nuclear layer cystoid changes, diffuse retinal thickening, integrity of the inner segment-outer segment (IS-OS) junction, quantity and location of hyperreflective foci, vitreomacular interface abnormalities, and epiretinal membrane (ERM). The Baseline best-corrected visual acuity (BCVA) and central macular thickness was recorded at baseline and 4 months after treatment with anti-VEGF. The main outcome measure was the correlation between spectral-domain OCT measurements and BCVA response at baseline and after anti-VEGF treatment (mean change from baseline; ≥ 10 Early Treatment Diabetic Retinopathy Study letters in BCVA)., Results: Partially continuous IS-OS layers (partially vs. completely continuous: β, -0.138; Wald chi-square, 16.392; P<0.001) was predictor of better response to anti-VEGF treatment. In contrast, ERM (present vs. absent ERM: β, 0.215; Wald chi-square, 5.921; P=0.015) and vitreomacular traction (vitreomacular traction vs. posterior vitreous detachment: β=0.259; Wald chi-square=5.938; P=0.015) were the predictors of poor response. The improvement of BCVA trended toward the OCT predictive value of central macular thickness reduction; however, this was not significant., Conclusion: Partially continuous IS-OS layers is predictive of better response to anti-VEGF therapy in DME. Meanwhile, ERM is a significant predictor of poor response., 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 Hsieh, Deng, Chang, Chang and He.)

Photoinduced relaxation processes at interfaces are intimately related to many fields such as solar energy conversion, photocatalysis, and photosynthesis. Vibronic coupling plays a key role in the fundamental steps of the interface-related photoinduced relaxation processes. Vibronic coupling at interfaces is expected to be different from that in bulk due to the unique environment. However, vibronic coupling at interfaces has not been well understood due to the lack of experimental tools. We have recently developed a two-dimensional electronic-vibrational sum frequency generation (2D-EVSFG) for vibronic coupling at interfaces. In this work, we present orientational correlations in vibronic couplings of electronic and vibrational transition dipoles as well as the structural evolution of photoinduced excited states of molecules at interfaces with the 2D-EVSFG technique. We used malachite green molecules at the air/water interface as an example, to be compared with those in bulk revealed by 2D-EV. Together with polarized VSFG and ESHG experiments, polarized 2D-EVSFG spectra were used to extract relative orientations of an electronic transition dipole and vibrational transition dipoles at the interface. Combined with molecular dynamics calculations, time-dependent 2D-EVSFG data have demonstrated that structural evolutions of photoinduced excited states at the interface have different behaviors than those in bulk. Our results showed that photoexcitation leads to intramolecular charge transfer but no conical interactions in 25 ps. Restricted environment and orientational orderings of molecules at the interface are responsible for the unique features of vibronic coupling., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Many photoinduced excited states' relaxation processes and chemical reactions occur at interfaces and surfaces, including charge transfer, energy transfer, proton transfer, proton-coupled electron transfer, configurational dynamics, conical intersections, etc. Of them, interactions of electronic and vibrational motions, namely, vibronic couplings, are the main determining factors for the relaxation processes or reaction pathways. However, time-resolved electronic-vibrational spectroscopy for interfaces and surfaces is lacking. Here we develop interface/surface-specific two-dimensional electronic-vibrational sum frequency generation spectroscopy (2D-EVSFG) for time-dependent vibronic coupling of excited states at interfaces and surfaces. We further demonstrate the fourth-order technique by investigating vibronic coupling, solvent correlation, and time evolution of the coupling for photoexcited interface-active molecules, crystal violet (CV), at the air/water interface as an example. The two vibronic absorption peaks for CV molecules at the interface from the 2D-EVSFG experiments were found to be more prominent than their counterparts in bulk from 2D-EV. Quantitative analysis of the vibronic peaks in 2D-EVSFG suggested that a non-Condon process participates in the photoexcitation of CV at the interface. We further reveal vibrational solvent coupling for the zeroth level on the electronic state with respect to that on the ground state, which is directly related to the magnitude of its change in solvent reorganization energy. The change in the solvent reorganization energy at the interface is much smaller than that in bulk methanol. Time-dependent center line slopes (CLSs) of 2D-EVSFG also showed that kinetic behaviors of CV at the air/water interface are significantly different from those in bulk methanol. Our ultrafast 2D-EVSFG experiments not only offer vibrational information on both excited states and the ground state as compared with the traditional doubly resonant sum frequency generation and electronic-vibrational coupling but also provide vibronic coupling, dynamical solvent effects, and time evolution of vibronic coupling at interfaces., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The electrochemical conversion of CO 2 represents a promising way to simultaneously reduce CO 2 emissions and store chemical energy. However, the competition between CO 2 reduction (CO 2 R) and the H 2 evolution reaction (HER) hinders the efficient conversion of CO 2 in aqueous solution. In water, CO 2 is in dynamic equilibrium with H 2 CO 3 , HCO 3 - , and CO 3 2- . While CO 2 and its associated carbonate species represent carbon sources for CO 2 R, recent studies by Koper and co-workers indicate that H 2 CO 3 and HCO 3 - also act as proton sources during HER ( J. Am. Chem. Soc. 2020, 142 , 4154-4161, ACS Catal. 2021, 11 , 4936-4945, J. Catal. 2022, 405 , 346-354), which can favorably compete with water at certain potentials. However, accurately distinguishing between competing reaction mechanisms as a function of potential requires direct observation of the non-equilibrium product distribution present at the electrode/electrolyte interface. In this study, we employ vibrational sum frequency generation (VSFG) spectroscopy to directly probe the interfacial species produced during competing HER/CO 2 R on Au electrodes. The vibrational spectra at the Ar-purged Na 2 SO 4 solution/Au interface, where only HER occurs, show a strong peak around 3650 cm -1 , which appears at the HER onset potential and is assigned to OH - . Notably, this species is absent for the CO 2 -purged Na 2 SO 4 solution/gold interface; instead, a peak around 3400 cm -1 appears at catalytic potential, which is assigned to CO 3 2- in the electrochemical double layer. These spectral reporters allow us to differentiate between HER mechanisms based on water reduction (OH - product) and HCO 3 - reduction (CO 3 2- product). Monitoring the relative intensities of these features as a function of potential in NaHCO 3 electrolyte reveals that the proton donor switches from HCO 3 - at low overpotential to H 2 O at higher overpotential. This work represents the first direct detection of OH - on a metal electrode produced during HER and provides important insights into the surface reactions that mediate selectivity between HER and CO 2 R in aqueous solution., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Objectives: To investigate the relationship between systemic inflammatory response and short-term mortality in patients with non-cirrhotic chronic severe hepatitis (CSH) by using several indicators of inflammation including neutrophil-to-lymphocyte ratio (NLR), neutrophil (NEU), white blood cell (WBC), platelet-to lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR)., Methods: Data were collected from two prospectively enrolled CATCH-LIFE noncirrhotic cohorts. Cox regression analysis was used to investigate the association between systemic inflammatory biomarkers and 90-day liver transplant (LT)-free mortality. A generalized additive model (GAM) was used to illustrate the quantitative curve relationship between NLR and 90-day LT-free mortality. Kaplan-Meier method was used to estimate the 90-year LT-free survival., Results: The prevalence of CSH was 20.5% (226/1103). The 28-day and 90-day LT-free mortality rates were 17.7% and 26.1%, respectively, for patients with non-cirrhotic CSH. Patients with no infection accounted for 75.0% of all CSH patients, and NLR was independently associated with 90-day LT-free mortality. NLR of 2.9 might be related to disease deterioration in CSH patients without infection., Conclusions: NLR may be an independent risk factor for 90-day LT-free mortality in patients with non-cirrhotic chronic liver disease. A NLR of 2.9 as the cut-off value can be used to predict disease aggravation in CSH patients without infection., (© 2022 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.)

Background: Autoimmune liver disease (AILD) has been considered a relatively uncommon disease in China, epidemiological data for AILD in patients with cirrhosis and acute decompensation (AD) is sparse., Aim: To investigate the prevalence, outcome and risk factors for AILD in cirrhotic patients complicated with AD in China., Methods: We collected data from patients with cirrhosis and AD from two prospective, multicenter cohorts in hepatitis B virus endemic areas. Patients were regularly followed up at the end of 28-d, 90-d and 365-d, or until death or liver transplantation (LT). The primary outcome in this study was 90-d LT-free mortality. Acute-on-chronic liver failure (ACLF) was assessed on admission and during 28-d hospitalization, according to the diagnostic criteria of the European Association for the Study of the Liver (EASL). Risk factors for death were analyzed with logistic regression model., Results: In patients with cirrhosis and AD, the overall prevalence of AILD was 9.3% (242/2597). Prevalence of ACLF was significantly lower in AILD cases (14%) than those with all etiology groups with cirrhosis and AD (22.8%) ( P < 0.001). Among 242 enrolled AILD patients, the prevalence rates of primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and PBC-AIH overlap syndrome (PBC/AIH) were 50.8%, 28.5% and 12.0%, respectively. In ACLF patients, the proportions of PBC, AIH and PBC/AIH were 41.2%, 29.4% and 20.6%. 28-d and 90-d mortality were 43.8% and 80.0% in AILD-related ACLF. The etiology of AILD had no significant impact on 28-d, 90-d or 365-d LT-free mortality in patients with cirrhosis and AD in both univariate and multivariate analysis. Total bilirubin (TB), hepatic encephalopathy (HE) and blood urea nitrogen (BUN) were independent risk factors for 90-d LT-free mortality in multivariate analysis. The development of ACLF during hospitalization only independently correlated to TB and international normalized ratio., Conclusion: AILD was not rare in hospitalized patients with cirrhosis and AD in China, among which PBC was the most common etiology. 90-d LT-free mortality were independently associated with TB, HE and BUN., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest in this manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study was designed to explore the effect and mechanism of Gegen Qinlian Decoction(GQD) on cardiac function of diabetic mice with damp-heat syndrome. The db/db diabetic mice were exposed to the damp-heat environment test chamber for inducing the damp-heat syndrome. Forty-eight six-week-old db/db mice were randomly divided into six groups, namely the db/db diabetic model group, db/db diabetic mouse with damp-heat syndrome(db/db-dh) group, db/db diabetic mouse with damp-heat syndrome treated with low-dose GQD(db/db-dh+GQD-L) group, db/db-dh+GQD-M(medium-dose) group, db/db-dh+GQD-H(high-dose) group, and db/db-dh+lipro(liprostatin-1, the inhibitor of ferroptosis) group, with eight six-week-old db/m mice classified into the control group. The results showed that mice presented with the damp-heat syndrome after exposure to the &quot;high-fat diet&quot; and &quot;damp-heat environment&quot;, manifested as the elevated fasting blood glucose, reduced food intake, low urine output, diarrhea, listlessness, loose and coarse hair, and dark yellow and lusterless fur. However, the intragastric administration of the high-dose GQD for 10 weeks ameliorated the above-mentioned symptoms, inhibited myocardial hypertrophy and fibrosis, and improved the cardiac diastolic function of db/db-dh mice. qPCR suggested that GQD regulated the expression of ferroptosis-related genes, weakened the lipid peroxidation in the myocardium, and up-regulated glutathione peroxidase 4(GPX4) expression in comparison with those in the db/db-dh group. At the same time, the ferroptosis inhibitor liprostatin-1 significantly improved the cardiac function and reversed the cardiac remodeling of db/db-dh mice. It can be concluded that the damp-heat syndrome may aggravate myocardial ferroptosis and accelerate cardiac remodeling of db/db mice, thus leading to diastolic dysfunction. GQD is able to improve cardiac remodeling and diastolic function in diabetic mice with damp-heat syndrome, which may be related to its inhibition of myocardial ferroptosis.

Background: Aorto-esophageal injury is a rare but life-threatening complication of esophageal foreign bodies, which typically requires open surgery. The best way to treat patients with this condition remains unclear. To date, few reports have described an aortic wall directly penetrated by a sharp foreign body. Here, we present a rare case of a fishbone completely embedded in the esophageal muscularis propria and directly piercing the aorta, which was successfully treated by endoscopy and thoracic endovascular aortic repair (TEVAR)., Case Summary: We report the case of a 71-year-old man with a 1-d history of retrosternal pain after eating fish. No abnormal findings were observed by the emergency esophagoscopy. Computed tomography showed a fishbone that had completely pierced through the esophageal mucosa and into the aorta. The patient refused to undergo surgery for personal reasons and was discharged. Five days after the onset of illness, he was readmitted to our hospital. Endoscopy examination showed a nodule with a smooth surface in the middle of the esophagus. Endoscopic ultrasonography confirmed a fishbone under the nodule. After performing TEVAR, we incised the esophageal mucosa under an endoscope and successfully removed the fishbone. The patient has remained in good condition for 1 year., Conclusion: Incising the esophageal wall under endoscope and extracting a foreign body after TEVAR may be a feasible option for cases such as ours., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: High mobility group box 1 (HMGB1) released by neurons and microglia was demonstrated to be an important mediator in depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which could lead to the imbalance of two different metabolic approaches in kynurenine pathway (KP), thus enhancing glutamate transmission and exacerbating depressive-like behaviors. Evidence showed that HMGB1 signaling might be regulated by Connexin (Cx) 36 in inflammatory diseases of central nervous system (CNS). Our study aimed to further explore the role of Cx36 in depressive-like behaviors and its relationship with HMGB1., Methods: After 4-week chronic stress, behavioral tests were conducted to evaluate depressive-like behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Western blot analysis and immunofluorescence staining were used to observe the expression and location of Cx36. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the concentrations of inflammatory cytokines. And the excitability and inward currents of hippocampal neurons were recorded by whole-cell patch clamping., Results: The expression of Cx36 was significantly increased in hippocampal neurons of mice exposed to CUMS, while treatment with glycyrrhizinic acid (GZA) or quinine could both down-regulate Cx36 and alleviate depressive-like behaviors. The proinflammatory cytokines like HMGB1, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were all elevated by CUMS, and application of GZA and quinine could decrease them. In addition, the enhanced excitability and inward currents of hippocampal neurons induced by lipopolysaccharide (LPS) could be reduced by either GZA or quinine., Conclusions: Inhibition of Cx36 in hippocampal neurons might attenuates HMGB1-mediated depressive-like behaviors induced by CUMS through down-regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

The selectivity and activity of the carbon dioxide reduction (CO 2 R) reaction are sensitive functions of the electrolyte cation. By measuring the vibrational Stark shift of in situ-generated CO on Au in the presence of alkali cations, we quantify the total electric field present at catalytic active sites and deconvolute this field into contributions from (1) the electrochemical Stern layer and (2) the Onsager (or solvation-induced) reaction field. Contrary to recent theoretical reports, the CO 2 R kinetics does not depend on the Stern field but instead is closely correlated with the strength of the Onsager reaction field. These results show that in the presence of adsorbed (bent) CO 2 , the Onsager field greatly exceeds the Stern field and is primarily responsible for CO 2 activation. Additional measurements of the cation-dependent water spectra using vibrational sum frequency generation spectroscopy show that interfacial solvation strongly influences the CO 2 R activity. These combined results confirm that the cation-dependent interfacial water structure and its associated electric field must be explicitly considered for accurate understanding of CO 2 R reaction kinetics., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Here, through applying 2,6-bis(4'-carboxyl-phenyl)pyridine (H 2 L), a rigid ligand featuring both carboxylic acid and pyridine groups, a new coordination polymer containing Na(I) has been generated with the reaction between H 2 L ligand and NaNO 3 in a water and DMF mixed solvent, and its chemical composition is [Na 2 L] n . Furthermore, the antiproliferative activity of Na(I) complex against the HXO-Rb44 retinoblastoma cells was detected with CCK-8 assay. Hoechst staining along with Annexin V-FITC/PI revealed that Na(I) complex induces the HXO-Rb44 retinoblastoma cells apoptosis. Flow cytometry analysis of reactive oxygen species (ROS) showed that Na(I) complex significantly increases the level of intracellular ROS. Importantly, western blot analysis revealed that Na(I) complex might induce apoptosis through inactivation of PI3K/AKT/mTOR pathway., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Jun Zhang et al.)

Interactions of electronic and vibrational degrees of freedom are essential for understanding excited-states relaxation pathways of molecular systems at interfaces and surfaces. Here, we present the development of interface-specific two-dimensional electronic-vibrational sum frequency generation (2D-EVSFG) spectroscopy for electronic-vibrational couplings for excited states at interfaces and surfaces. We demonstrate this 2D-EVSFG technique by investigating photoexcited interface-active ( E )-4-((4-(dihexylamino) phenyl)diazinyl)-1-methylpyridin-1- lum (AP3) molecules at the air-water interface as an example. Our 2D-EVSFG experiments show strong vibronic couplings of interfacial AP3 molecules upon photoexcitation and subsequent relaxation of a locally excited (LE) state. Time-dependent 2D-EVSFG experiments indicate that the relaxation of the LE state, S 2 , is strongly coupled with two high-frequency modes of 1,529.1 and 1,568.1 cm -1 Quantum chemistry calculations further verify that the strong vibronic couplings of the two vibrations promote the transition from the S 2 state to the lower excited state S 1 We believe that this development of 2D-EVSFG opens up an avenue of understanding excited-state dynamics related to interfaces and surfaces., Competing Interests: The authors declare no competing interest.

Purpose: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear., Experimental Design: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC ( n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study., Results: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone., Conclusions: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation., (©2021 American Association for Cancer Research.)

Vibronic coupling is believed to play an important role in siglet fission, wherein a photoexcited singlet exciton is converted into two triplet excitons. In the present study, we examine the role of vibronic coupling in singlet fission using polarized transient absorption microscopy and ab initio simulations on single-crystalline pentacene. It was found that singlet fission in pentacene is greatly facilitated by the vibrational coherence of a 35.0 cm -1 phonon, where anisotropic coherence persists extensively for a few picoseconds. This coherence-preserving phonon that drives the anisotropic singlet fission is made possible by a unique cross-axial charge-transfer intermediate state. In the same fashion, this phonon was also found to predominantly drive the quantum decohence of a correlated triplet pair to form a decoupled triplet dimer. Moreover, our transient kinetic experimental data illustrates notable directional anisotropicity of the singlet fission rate in single-crystalline pentacene.

Structures, kinetics, and chemical reactivities at interfaces and surfaces are key to understanding many of the fundamental scientific problems related to chemical, material, biological, and physical systems. These steady-state and dynamical properties at interfaces and surfaces require even-order techniques with time-resolution and spectral-resolution. Here, we develop fourth-order interface-/surface-specific two-dimensional electronic spectroscopy, including both two-dimensional electronic sum frequency generation (2D-ESFG) spectroscopy and two-dimensional electronic second harmonic generation (2D-ESHG) spectroscopy, for structural and dynamics studies of interfaces and surfaces. The 2D-ESFG and 2D-ESHG techniques were based on a unique laser source of broadband short-wave IR from 1200 nm to 2200 nm from a home-built optical parametric amplifier. With the broadband short-wave IR source, surface spectra cover most of the visible light region from 480 nm to 760 nm. A translating wedge-based identical pulses encoding system (TWINs) was introduced to generate a phase-locked pulse pair for coherent excitation in the 2D-ESFG and 2D-ESHG. As an example, we demonstrated surface dark states and their interactions of the surface states at p-type GaAs (001) surfaces with the 2D-ESFG and 2D-ESHG techniques. These newly developed time-resolved and interface-/surface-specific 2D spectroscopies would bring new information for structure and dynamics at interfaces and surfaces in the fields of the environment, materials, catalysis, and biology.

Background & Aims: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD., Methods: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the Chinese AcuTe on CHronic LIver FailurE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n = 2600 patients) and July 2018 through January 2019 (n = 1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD., Results: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P = .04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared with patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P < .001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P < .001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT., Conclusions: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension. ClinicalTrials.gov no: NCT02457637 and NCT03641872., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The growth of aerosol particles in the atmosphere is related to chemical reactions in the gas and particle phases and at aerosol particle surfaces. While research regarding the gas and particle phases of aerosols is well-documented, physical properties and chemical reactivities at aerosol particle surfaces have not been studied extensively but have long been recognized. In particular, in situ measurements of aerosol particle surfaces are just emerging. The main reason is a lack of suitable surface-specific analytical techniques for direct measurements of aerosol particles under ambient conditions. Here we develop in situ surface-specific electronic sum frequency scattering (ESFS) to directly identify spectroscopic behaviors of molecules at aerosol particle surfaces. As an example, we applied an ESFS probe, malachite green (MG). We examined electronic spectra of MG at aerosol particle surfaces and found that the polarity of the surfaces is less polar than that in bulk. Our quantitative orientational analysis shows that MG is orientated with a polar angle of 25°-35° at the spherical particle surfaces of aerosols. The adsorption free energy of MG at the aerosol surfaces was found to be -20.75 ± 0.32 kJ/mol, which is much lower than that at the air/water interface. These results provide new insights into aerosol particle surfaces for further understanding the formation of secondary organic aerosols in the atmosphere.

Domestic scholars recognize that patients have a "pre-hepatic failure" before they progress to sub-acute and acute-on-chronic liver failure stage, which is also the golden window for effective clinical intervention, so early identification and intervention during this period can reduce the incidence and mortality of liver failure. The Guidelines for the Diagnosis and Treatment of Liver Failure (2018 Edition) issued by the Chinese Medical Association clearly defines the "pre-stage" of liver failure. And from the perspective of pathophysiological mechanism, the pre-hepatic failure corresponds to the stage of acute liver injury/acute decompensation, inflammation factor/ immunologic derangement. This article briefly introduces the research progress on substantive connotation and pathogenesis of pre-hepatic failure, and puts forward some problems to be explored in the future.

High even-order surface/interface specific spectroscopy has the potential to provide more structural and dynamical information about surfaces and interfaces. In this work, we developed a novel fourth-order interface-specific two-dimensional electronic sum frequency generation (2D-ESFG) for structures and dynamics at surfaces and interfaces. A translating wedge-based identical pulses encoding system (TWINs) was introduced to generate phase-locked pulse pairs for coherent pump beams in 2D-ESFG. As a proof-of-principle experiment, fourth-order 2D-ESFG spectroscopy was used to demonstrate couplings of surface states for both n -type and p -type GaAs (100). We found surface dark state within the bandgap of the GaAs in 2D-ESFG spectra, which could not be observed in one-dimensional ESFG spectra. To our best knowledge, this is a first demonstration of interface-specific two-dimensional electronic spectroscopy. The development of the 2D-ESFG spectroscopy will provide new structural probes of spectral diffusion, conformational dynamics, energy transfer, and charge transfer for surfaces and interfaces.

Singlet fission is believed to improve the efficiency of solar energy conversion by breaking up the Shockley-Queisser thermodynamic limit. Understanding of triplet excitons generated by singlet fission is essential for solar energy exploitation. Here we employed transient absorption microscopy to examine dynamical behaviors of triplet excitons. We observed anisotropic recombination of triplet excitons in hexacene single crystals. The triplet exciton relaxations from singlet fission proceed in both geminate and non-geminate recombination. For the geminate recombination, the different rates were attributed to the significant difference in their related energy change based on the Redfield quantum dissipation theory. The process is mainly governed by the electron-phonon interaction in hexacene. On the other hand, the non-geminate recombination is of bimolecular origin through energy transfer. In the triplet-triplet bimolecular process, the rates along the two different optical axes in the a - b crystalline plane differ by a factor of 4. This anisotropy in the triplet-triplet recombination rates was attributed to the interference in the coupling probability of dipole-dipole interactions in the different geometric configurations of hexacene single crystals. Our experimental findings provide new insight into future design of singlet fission materials with desirable triplet exciton exploitations.

We identified fosA3 at a rate of 2.6% in 310 Salmonella isolates from food animals in Guangdong province, China. The fosA3 gene was genetically linked to diverse antibiotic resistance genes (ARGs), including mcr-1 , bla CTX-M-14/55 , oqxAB , and rmtB These gene combinations were embedded in heterogeneous fosA3 -containing multidrug resistance regions on the transferable ST3-IncHI2 and F33:A-:B- plasmids and the chromosome. This indicated a great flexibility of fosA3 cotransmission with multiple important ARGs among Salmonella species., (Copyright © 2020 American Society for Microbiology.)

The effects of hydrophobic solutes on the structure of the surrounding water have been a topic of debate for almost 70 years. However, a consistent description of the physical insight into the causes of the anomalous thermodynamic properties of alcohol-water mixtures is lacking. Here we report experimental results that combined temperature-dependent linear and femtosecond infrared spectroscopy measurements to explore the water structural transformation in concentrated alcohol-water solutions. Experiments show that the enhancement of water structure arises around microhydrophobic interfaces at room temperature in the solutions. As temperature increases, this ordered water structure disappears and a surface topography-dependent new disordered water structure arises at concentrated solutions of large alcohols. The water structural transformation is dependent on not only the length of the alkyl chain but also the clustering of the alcohols. A more-ordered-than-water structure can transform into a less-ordered-than-water structure.