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1.
Curr Med Sci ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748371

ABSTRACT

OBJECTIVE: Sepsis is considered a major cause of health loss in children and had high mortality and morbidity. Currently, there is no reliable model for predicting the prognosis of pediatric patients with sepsis. This study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their outcomes. METHODS: This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the Pediatric Intensive Care Unit of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, from January 1, 2019, to December 31, 2021. Risk factors for sepsis were identified by logistic regression analyses. RESULTS: A total of 355 children with sepsis were enrolled, with 333 children (93.8%) in the good prognosis group, and 22 children (6.2%) in the poor prognosis group. Among them, there were 255 patients (71.8%) in the sepsis group, and 100 patients (28.2%) in the severe sepsis group. The length of hospital stay in the poor prognosis group was longer than that in the good prognosis group (P<0.01). The levels of interleukin 1ß (IL-1ß) in the poor prognosis group were higher than those in the good prognosis group (P>0.05), and the platelet (PLT), albumin (ALB), and hemoglobin (Hb) levels were lower in the poor prognosis group (P<0.01). The IL-8 levels in the severe sepsis group were higher than those in the sepsis group (P<0.05). Multiple logistic regression analysis suggested that lower Hb levels, ALB levels, peak PLT counts, and higher IL-1ß levels were independent risk factors for poor prognosis in children with sepsis. CONCLUSION: Lower Hb, ALB, and PLT counts and elevated IL-1ß are independent risk factors for poor prognosis in children with sepsis.

2.
Biophys Rep ; 10(1): 1-14, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38737473

ABSTRACT

The prediction of affinity between TCRs and peptides is crucial for the further development of TIL (Tumor-Infiltrating Lymphocytes) immunotherapy. Inspired by the broader research of drug-protein interaction (DPI), we propose an atom-level peptide-TCR interaction (PTI) affinity prediction model APTAnet using natural language processing methods. APTAnet model achieved an average ROC-AUC and PR-AUC of 0.893 and 0.877, respectively, in ten-fold cross-validation on 25,675 pairs of PTI data. Furthermore, experimental results on an independent test set from the McPAS database showed that APTAnet outperformed the current mainstream models. Finally, through the validation on 11 cases of real tumor patient data, we found that the APTAnet model can effectively identify tumor peptides and screen tumor-specific TCRs.

3.
Eur J Med Chem ; 271: 116417, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38688063

ABSTRACT

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC50 = 0.55 µM) in a hypoxia-reactive element (HRE) luciferase reporter assay. Further pharmacological studies revealed that 17q concentration-dependently blocked hypoxia-induced HIF-1α protein accumulation, reduced inflammation response, inhibited cellular invasiveness and promoted VHL-dependent HIF-1α degradation in human RA synovial cell line. Moreover, 17q improved the pathological injury of ankle joints, decreased angiogenesis and attenuated inflammation response in the adjuvant-induced arthritis (AIA) rat model, indicating the promising therapeutic potential of compound 17q as an effective HIF-1 inhibitor for RA therapy.


Subject(s)
Arthritis, Rheumatoid , Isoquinolines , Signal Transduction , Animals , Humans , Male , Rats , Antirheumatic Agents/pharmacology , Antirheumatic Agents/chemistry , Antirheumatic Agents/chemical synthesis , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Dose-Response Relationship, Drug , Drug Discovery , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Isoquinolines/chemistry , Isoquinolines/pharmacology , Isoquinolines/chemical synthesis , Molecular Structure , Signal Transduction/drug effects , Structure-Activity Relationship , Quinolones/chemical synthesis , Quinolones/chemistry , Quinolones/pharmacology
4.
Biotechnol Adv ; 73: 108364, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38642673

ABSTRACT

Global sustainable development faces a significant challenge in effectively utilizing CO2. Meanwhile, CO2 biological fixation offers a promising solution. CO2 has the highest oxidation state (+4 valence state), whereas typical multi­carbon chemicals have lower valence states. The Gibbs free energy (ΔG) changes of CO2 reductive reactions are generally positive and this renders it necessary to input different forms of energy. Although biological carbon fixation processes are friendly to operate, the thermodynamic obstacles must be overcome. To make this reaction occur favorably and efficiently, diverse strategies to enhance CO2 biological fixation efficiency have been proposed by numerous researchers. This article reviews recent advances in optimizing CO2 biological fixation and intends to provide new insights into achieving efficient biological utilization of CO2. It first outlines the thermodynamic characteristics of diverse carbon fixation reactions and proposes optimization directions for CO2 biological fixation. A comprehensive overview of the catalytic mechanisms, optimization strategies, and challenges encountered by common carbon-fixing enzymes is then provided. Subsequently, potential routes for improving the efficiency of biological carbon fixation are discussed, including the ATP supply, reducing power supply, energy supply, reactor design, and carbon enrichment system modules. In addition, effective artificial carbon fixation pathways were summarized and analyzed. Finally, prospects are made for the research direction of continuously improving the efficiency of biological carbon fixation.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 476-482, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38660855

ABSTRACT

OBJECTIVE: To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line. METHODS: The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin. The levels of Pgp, p-AKT, and p-mTOR in cells were detected by Western blot. Cell viability was detected by MTT assay. IC50 was computed by SPSS. RESULTS: The doxorubicin-resistant Burkitt lymphoma cell line, RAJI/DOX, was established successfully. The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line. NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line. NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line, and the effect was obvious when it was cooperated with doxorubicin. CONCLUSION: The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line. NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.


Subject(s)
Burkitt Lymphoma , Cell Proliferation , Doxorubicin , Drug Resistance, Neoplasm , Imidazoles , Proto-Oncogene Proteins c-akt , Quinolines , TOR Serine-Threonine Kinases , Humans , Doxorubicin/pharmacology , Cell Line, Tumor , Proto-Oncogene Proteins c-akt/metabolism , Quinolines/pharmacology , TOR Serine-Threonine Kinases/metabolism , Cell Proliferation/drug effects , Imidazoles/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Cell Survival/drug effects , Phosphorylation
6.
Article in English | MEDLINE | ID: mdl-38520514

ABSTRACT

PURPOSE: Our study aims to evaluate the global burden of disease attributable to IPV from 1990 to 2019 at global, regional, national, and socio-demographic index (SDI) levels. Our research question is: What is the global burden of disease attributable to intimate partner violence (IPV) from 1990 to 2019, and how does it vary at global, regional, national, and socio-demographic index (SDI) levels? METHODS: Data parameters for the number of deaths, disability-adjusted life years (DALYs), and age-standardized rate were obtained from the Global Burden of Disease Study 2019. We calculated the percentage change and population attributable fraction with 95% uncertainty intervals. RESULTS: IPV directly accounted for 0.14% [95% UI 0.09%, 0.21%] and 0.32% [95% UI 0.17%, 0.49%] of global all-cause deaths and DALYs in 2019, respectively. The age-standardized deaths and DALYs rates of IPV increased by 12.83% and 4.00% respectively from 1990 to 2019. Women aged 35-39 and 30-34 had the highest deaths and DALYs rate respectively. The highest age-standardized rates of IPV-related deaths and DALYs were observed in Southern Sub-Saharan. Both of deaths and DALYs were high in low-socio-demographic Index (SDI) quintile in 2019. CONCLUSIONS: A higher level of deaths and DALYs attributable to IPV were reported in younger women, in the early 2000s, in Southern Sub-Saharan regions and in low SDI regions. Our study provides policymakers with up-to-date and comprehensive information.

7.
Cell Death Dis ; 15(3): 187, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38443386

ABSTRACT

Colorectal cancer (CRC) is the third most common cancer associated with a poor prognosis. Effective targeted therapy alone or in combination for treating advanced CRC remains to be a major clinical challenge. Here, we propose the therapeutic efficacy and molecular mechanism underlying RC48, a FDA-approved anti-HER2 antibody conjugate via a cleavable linker to the microtubule inhibitor monomethyl auristatin E (MMAE), either alone or in combination with gemcitabine (GEM) in various models of HER2-positive advanced CRC. Our findings demonstrated that HER2 was widely expressed and located on the plasma membrane of CRC patient specimens, PDX xenograft tumors and cell lines. It confirmed that RC48 alone significantly targeted and eradicated HER2 positive CRC tumor in these models. Moreover, we screened a panel of FDA-approved first-line chemotherapy drugs in vitro. We found that GEM exhibited stronger antiproliferative activity compared to the other first-line anti-cancer agents. Furthermore, combination therapy of RC48 and GEM significantly showed synergetic antitumor activity in vitro and in vivo. To gain further mechanistic insights into the combination therapy, we performed RNA-seq analysis. The results revealed that combination treatment of RC48 and GEM regulated multiple signaling pathways, such as PI3K-AKT, MAPK, p53, Foxo, apoptosis, cell cycle and cell senescence, etc., to exert its antitumor activity in CRC cells. Collectively, these preclinical findings demonstrated that RC48 alone or combinational therapy exerted promising antitumor activity, and meriting the preclinical framework for combinational therapy of anti-HER2 drug conjugate drug and chemotherapy drugs for HER2-positive patients with advanced CRC.


Subject(s)
Colorectal Neoplasms , Immunoconjugates , Humans , Immunoconjugates/pharmacology , Immunoconjugates/therapeutic use , Phosphatidylinositol 3-Kinases , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Antibodies , Gemcitabine
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 219-224, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38387925

ABSTRACT

OBJECTIVE: To investigate possible mechanism on protien LMP1 expressed by EBV inducing plasmablast differentiation of DLBCL cell via the mTORC1 pathway. METHODS: The expression levels of LMP1 protein, CD38 and the phosphorylation levels of p70S6K in EBV+ and EBV- DLBCL cell lines were detected by Western blot. Cell lines overexpressing LMP1 gene stablely were constructed and LMP1 gene was silenced by RNAi. The expression of LMP1 gene was verified by RT-qPCR. The expression levels of LMP1 and CD38 and the phosphorylation levels of p70S6K in each group were detected by Western blot. RESULTS: Compared with EBV-DLBCL cells, the expression of LMP1 was detected on EBV +DLBCL cells (P =0.0008), EBV +DLBCL cells had higher phosphorylation levels of p70S6K (P =0.0072) and expression levels of CD38(P =0.0091). Compared with vector group, the cells of LMP1OE group had higher expression levels of LMP1 and CD38 (P =0.0353; P <0.0001), meanwhile molecular p70S6K was phosphorylated much more(P =0.0065); expression of LMP1 mRNA was verified(P <0.0001). Compared with si-NC group, expression level of LMP1 protein(P =0.0129) was not detected and phosphorylated p70S6K disappeared of LMP1KO group (P =0.0228); meanwhile, expression of CD38 decreased,although there was no significant difference (P =0.2377). CONCLUSION: LMP1 promotes DLBCL cells plasmablast differentiation via activating mTORC1 signal pathway.


Subject(s)
Herpesvirus 4, Human , Ribosomal Protein S6 Kinases, 70-kDa , Humans , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Signal Transduction , Cell Line , Viral Matrix Proteins/genetics , Viral Matrix Proteins/metabolism
9.
Biomed Pharmacother ; 169: 115865, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37972469

ABSTRACT

The inhibitory effects of Chinese medicine Pocoa (PCPs) with different carboxyl group (-COOH) contents on oxidative damage and inflammatory response of renal epithelial cells and the influence of -COOH content in polysaccharides were investigated. HK-2 cell damage model was established by nanocalcium oxalate crystals (nanoCOM), and then PCPs with -COOH contents of 2.56% (PCP0), 7.48% (PCP1), 12.07% (PCP2), and 17.18% (PCP3) were used to protect the cells. PCPs could inhibit the damage of nanoCOM to HK-2 cells, increase cell viability, restore cytoskeleton and morphology, and improve lysosomal integrity. PCPs can reduce the oxidative stress response of nanoCOM to cells, inhibit the opening of mPTP and cell necrotic apoptosis, reduce the level of Ca2+ ions in cells, the production of ATP and MDA, and increase SOD expression. PCPs can also reduce the cellular inflammatory response caused by oxidative damage, and reduce the expression of nitric oxide (NO), inflammatory factors TNF-α, IL-6, IL-1ß and MCP-1, as well as the content of inflammasome NLRP3. After protection, PCPs can inhibit the endocytosis of nanoCOM crystals by cells. With the increase in -COOH content in PCPs, its ability to inhibit nanoCOM cell damage, reduce oxidative stress, reduce inflammatory response, and inhibit crystal endocytosis increases, that is, PCP3 with the highest -COOH content, shows the best biological activity. Inhibiting cell damage and inflammation and reducing a large amount of endocytosis of crystals by cells are beneficial to inhibit the formation of kidney stones.


Subject(s)
Calcium Oxalate , Nanoparticles , Humans , Calcium Oxalate/metabolism , Oxidative Stress , Polysaccharides/pharmacology , Polysaccharides/chemistry , Inflammation/drug therapy , Nanoparticles/chemistry
10.
Mar Drugs ; 21(11)2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37999396

ABSTRACT

Phycobiliproteins (PBPs) are natural water-soluble pigment proteins, which constitute light-collecting antennae, and function in algae photosynthesis, existing in cyanobacteria, red algae, and cryptomonads. They are special pigment-protein complexes in algae with a unique structure and function. According to their spectral properties, PBPs can be mainly divided into three types: allophycocyanin, phycocyanin, and PE. At present, there are two main sources of PBPs: one is natural PBPs extracted from algae and the other way is recombinant PBPs which are produced in engineered microorganisms. The covalent connection between PBP and streptavidin was realized by gene fusion. The bridge cascade reaction not only improved the sensitivity of PBP as a fluorescent probe but also saved the preparation time of the probe, which expands the application range of PBPs as fluorescent probes. In addition to its function as a light-collecting antenna in photosynthesis, PBPs also have the functions of biological detection, ion detection, and fluorescence imaging. Notably, increasing studies have designed novel PBP-based far-red fluorescent proteins, which enable the tracking of gene expression and cell fate.


Subject(s)
Fluorescent Dyes , Phycobiliproteins , Photosynthesis
11.
BMC Public Health ; 23(1): 1995, 2023 10 13.
Article in English | MEDLINE | ID: mdl-37833684

ABSTRACT

BACKGROUND: Subjective memory impairment (SMI) is common in older people. The aim of this study was to investigate the factors influencing SMI among older people in China, with specific focus on the interaction effect of midday napping duration and depressive symptoms on the risk of SMI. METHODS: Using a dataset representative of the Chinese population from a longitudinal study of health and retirement in China, subjects with SMI were screened using the question "how do you feel about your memory now?" and the Mini-Mental State Examination. A logistic regression model was applied to explore the factors affecting SMI. Additive and multiplicative models were used to analyze the interaction effect of midday napping duration and depressive symptoms on the risk of SMI. RESULTS: We enrolled 8,254 subjects included and the incidence of SMI was 63.9%. Depressive symptoms, nap time, and physical activity were influencing factors of SMI. Midday napping duration and depressive symptoms had positive additive interaction effects on the risk of SMI. When extended-length naps and depressive symptoms coexisted, the risk of SMI was 1.06 times greater than that for either alone (RERI, relative excess risk due to interaction = 0.27, 95% CI = 0.07-0.43; AP, attributable proportion = 0.14, 95% CI = 0.01-0.23; S, synergy index = 1.06, 95% CI = 0.57-1.62). When short naps and depressive symptoms coexisted, the risk of SMI was 1.2 times higher than that for either alone (RERI = 0.12, 95% CI=-0.14-0.39; AP = 0.13, 95% CI=-0.07-0.22; S = 1.20, 95% CI = 0.79-1.82). LIMITATIONS: Since this was a cross-sectional study, the cause-and-effect relationships between the associated variables cannot be inferred. CONCLUSIONS: The interaction effect that exists between nap time and depressive symptoms in older people is important for the identification and early intervention of people at risk for SMI.


Subject(s)
Depression , Retirement , Humans , Aged , Longitudinal Studies , Risk Factors , Depression/epidemiology , Cross-Sectional Studies , Sleep , China/epidemiology
12.
Front Nutr ; 10: 1117028, 2023.
Article in English | MEDLINE | ID: mdl-37771755

ABSTRACT

Background: Elderly patients have a high risk of developing postoperative cognitive dysfunction (POCD). Gastrointestinal disorders, such as constipation, in the elderly population may be involved in the pathogenesis of neurological disorders by promoting inflammatory responses due to a 'leaky gut'. General anesthetic sevoflurane may impair gastrointestinal function in elderly patients to trigger neurological complications following surgery. Therefore, we hypothesized that elderly individuals with gastrointestinal dysfunction may be more vulnerable to sevoflurane and consequently develop POCD. Methods: Aged mice were randomly divided into four groups: control (CTRL), CTRL+sevoflurane (Sev), slow transit constipation (STC), and STC + Sev. Mice in the STC and STC + Sev groups were intra-gastrically administrated loperamide (3 mg/kg, twice a day for 7 days) to induce a slow transit constipation (STC) model determined with fecal water content and the time of first white fecal pellet, whereas mice in the other groups received the similar volume of saline. One week later, mice in the CTRL+Sev group and STC + Sev group received 2% sevoflurane for 2 h. The gut permeability evaluated with 4-kDa fluorescein isothiocyanate (FITC)-dextran, serum cytokines, microglia density, TLR4/NF-κB signaling expression, and POCD-like behavioral changes were determined accordingly. Results: The loperamide-induced STC mice had decreased fecal water content and prolonged time of first white fecal pellet. Sevoflurane exposure caused significantly increased gut permeability and serum cytokines, as well as the activation of microglia and the TLR4/NF-κB signaling pathway in the prefrontal cortex of the aged STC mice. Sevoflurane also caused cognitive impairment and emotional phenotype abnormality in aged STC mice. Conclusion: Aged STC mice were more vulnerable to sevoflurane anesthesia and consequently developed POCD-like behavioral changes. Our data suggest that gastrointestinal disorders including constipation may contribute to the development of POCD.

13.
Front Public Health ; 11: 1116616, 2023.
Article in English | MEDLINE | ID: mdl-37719741

ABSTRACT

Background: The prevalence of mental distress is common for medical students in China due to factors such as the long duration of schooling, stressful doctor-patient relationship, numerous patient population, and limited medical resources. However, previous studies have failed to provide a comprehensive prevalence of these mental disorders in this population. This meta-analysis aimed to estimate the prevalence of common mental disorders (CMDs), including depression, anxiety, and suicidal behaviors, among medical students in China. Methods: We conducted a systematic search for empirical studies on the prevalence of depression, anxiety, suicide attempt, suicide ideation, and suicide plan in Chinese medical students published from January 2000 to December 2020. All data were collected pre-COVID-19. The prevalence and heterogeneity estimations were computed by using a random-effects model and univariate meta-regression analyses. Results: A total of 197 studies conducted in 23 provinces in China were included in the final meta-analysis. The prevalence data of depression, anxiety, suicide attempt, suicide ideation, and suicide plan were extracted from 129, 80, 21, 53, and 14 studies, respectively. The overall pooled crude prevalence for depression was 29% [38,309/132,343; 95% confidence interval (CI): 26%-32%]; anxiety, 18% (19,479/105,397; 95% CI: 15%-20%); suicide ideation, 13% (15,546/119,069; 95% CI: 11%-15%); suicide attempt, 3% (1,730/69,786; 95% CI: 1%-4%); and suicide plan, 4% (1,188/27,025; 95% CI: 3%-6%). Conclusion: This meta-analysis demonstrated the high prevalence of CMDs among Chinese medical students. Further research is needed to identify targeted strategies to improve the mental health of this population.


Subject(s)
COVID-19 , Mental Disorders , Students, Medical , Humans , Physician-Patient Relations , Prevalence , Mental Disorders/epidemiology , China/epidemiology
14.
Brain Res ; 1820: 148561, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37657750

ABSTRACT

BACKGROUND: Schizophrenia is characterised by neurotrophic, neuroelectrophysiological and cognitive dysfunction. However, there exists a paucity of research examining the association between serum brain-derived neurotrophic factor (BDNF) concentration, resting electroencephalogram (EEG) gamma activity, and cognitive impairment in individuals diagnosed with schizophrenia. METHODS: In this study, 87 first-episode schizophrenia patients and 75 healthy controls were assessed. Measurements were conducted to determine the levels of BDNF, resting EEG γ-activity at left and right frontal pole EEG electrodes respectively (FP1/FP2) leads, and cognitive function as assessed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia MATRICS Consensus Cognitive Battery (MCCB). Comparisons were made between the patient group and the control group, revealing lower BDNF levels, lower T-scores for 7 MCCB cognitive items, and higher EEG γ-activity among patients when compared to controls. RESULTS: According to the correlation analysis, there were significant associations observed in the patient group. BDNF levels were found to be correlated with EEG γ activity as well as T-scores of speed of processing (SoP), verbal learning (VeL), and reasoning problem-solving (RPS). Moreover, EEG γ activity showed an association with both the total score of the Positive and Negative Syndrome Scale (PANSS) and T-score of SoP. These findings suggest a potential relationship between BDNF levels, EEG γ activity, cognitive domains, and clinical symptoms in individuals with first-episode schizophrenia. CONCLUSIONS: In conclusion, our findings demonstrate the coexistence of neurobiochemical and electrophysiological abnormalities alongside cognitive dysfunction during the early stages of schizophrenia. These findings provide valuable insights into the mechanism of cognitive impairment in schizophrenia. By highlighting the simultaneous occurrence of these factors, our study contributes to a better understanding of the complex nature of schizophrenia and emphasizes the importance of studying its cognitive aspects.

15.
Front Med (Lausanne) ; 10: 1128766, 2023.
Article in English | MEDLINE | ID: mdl-37529246

ABSTRACT

Background: Upper esophageal cancer (UEC) is rare in both Eastern and Western countries. The epidemiological characteristics and long-term survival of UEC patients are less known. In addition, the choice of optimal treatment for UEC has been controversial. Methods: Cases of UEC (C15.3 and C15.0) arising during the period from 1973 to 2013 were identified and selected using the SEER database. Student's t-test and Pearson's chi-square test were used to compare the differences in parameters among different groups. Esophageal cancer-specific survival (ECSS) and overall survival (OS) rates were calculated by using the Kaplan-Meier method. Cox proportional hazard regression was used to analyze predictive factors. Results: In the past 40 years, the cases of UEC have gradually increased, and the proportion of adenocarcinoma (AD) has gradually increased (from 3.6% to 11.8%, p < 0.001). There has been a significant increase (1973-1982 vs. 2004-2013) in median OS (7 months vs. 10 months, p < 0.001) and median ECSS (7 months vs. 11 months, p < 0.001) among UEC patients from 1973 to 2013. For the impact of different treatments, the results showed that the ECSS and OS of surgery without radiation (SWR) and radiation plus surgery (R+S) were superior to those of radiation without surgery (RWS). Subgroup analysis showed that ECSS and OS were highest among patients treated with SWR compared with R+S and RWS for patients with localized disease. For regional disease, ECSS and OS were highest among patients with R+S compared with SWR or RWS. Among patients with regional-stage squamous cell carcinoma (SCC), OS was higher with neoadjuvant radiotherapy or adjuvant radiotherapy compared with SWR. Multivariate analysis showed that radiotherapy sequence was dependently associated with OS among patients with regional-stage SCC. Conclusion: Although the long-term survival of UEC remains poor, it has gradually increased since 1973. This should be closely related to the improvement of medical care over the past 40 years. Different treatment methods have a great influence on the long-term survival of UEC. For localized diseases, surgery may be a better choice. For regional disease, surgery plus adjuvant or neoadjuvant radiotherapy may be more beneficial to improve the long-term prognosis of UEC patients.

16.
Biosensors (Basel) ; 13(8)2023 Aug 04.
Article in English | MEDLINE | ID: mdl-37622876

ABSTRACT

Detecting foodborne pathogens on-site is crucial for ensuring food safety, necessitating the development of rapid, cost-effective, highly sensitive, and portable devices. This paper presents an integrated microfluidic biosensing system designed for the rapid and sensitive detection of Salmonella typhimurium (S. typhimurium). The biosensing system comprises a microfluidic chip with a versatile valve, a recombinase polymerase amplification (RPA) for nucleic acid detection, and a customized real-time fluorescence detection system. The versatile valve combines the functions of an active valve and a magnetic actuation mixer, enabling on-demand mixing and controlling fluid flow. Quantitative fluorescence is processed and detected through a custom-built smartphone application. The proposed integrated microfluidic biosensing system could detect Salmonella at concentrations as low as 1.0 × 102 copies/µL within 30 min, which was consistent with the results obtained from the real-time quantitative polymerase chain reaction (qPCR) tests. With its versatile valve, this integrated microfluidic biosensing system holds significant potential for on-site detection of foodborne pathogens.


Subject(s)
Recombinases , Salmonella typhimurium , Microfluidics , Catheters , Food Safety
17.
Nat Commun ; 14(1): 5163, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37620378

ABSTRACT

Chirality has been a property of central importance in physics, chemistry and biology for more than a century. Recently, electrons were found to become spin polarized after transmitting through chiral molecules, crystals, and their hybrids. This phenomenon, called chirality-induced spin selectivity (CISS), presents broad application potentials and far-reaching fundamental implications involving intricate interplays among structural chirality, topological states, and electronic spin and orbitals. However, the microscopic picture of how chiral geometry influences electronic spin remains elusive, given the negligible spin-orbit coupling (SOC) in organic molecules. In this work, we address this issue via a direct comparison of magnetoconductance (MC) measurements on magnetic semiconductor-based chiral molecular spin valves with normal metal electrodes of contrasting SOC strengths. The experiment reveals that a heavy-metal electrode provides SOC to convert the orbital polarization induced by the chiral molecular structure to spin polarization. Our results illustrate the essential role of SOC in the metal electrode for the CISS spin valve effect. A tunneling model with a magnetochiral modulation of the potential barrier is shown to quantitatively account for the unusual transport behavior.

18.
Proteins ; 91(12): 1771-1778, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37638558

ABSTRACT

We describe the modeling method for RNA tertiary structures employed by team AIchemy_RNA2 in the 15th Critical Assessment of Structure Prediction (CASP15). The method consists of the following steps. Firstly, secondary structure information was derived from various manually-verified sources. With this information, the full length RNA was fragmented into structural modules. The structures of each module were predicted and then assembled into the full structure. To reduce the searching conformational space, an RNA structure was organized into an optimal base folding tree. And to further improve the sampling efficiency, the energy surface was smoothed at high temperatures during the Monte Carlo sampling to make it easier to move across the energy barrier. The statistical potential energy function BRiQ was employed during Monte Carlo energy optimization.


Subject(s)
Algorithms , RNA , RNA/chemistry , Protein Conformation , Monte Carlo Method
19.
Ann Hum Biol ; 50(1): 1-8, 2023 Feb.
Article in English | MEDLINE | ID: mdl-37401376

ABSTRACT

BACKGROUND: Schizophrenia spectrum disorder (SSD) is a common mental disorder causing severe and chronic disability. Epigenetic changes in genes related to the hypothalamic-pituitary-adrenal (HPA) axis are believed to play an important role in SSD pathogenesis. The methylation status of the corticotropin-releasing hormone (CRH) gene, which is central to the HPA axis, has not been investigated in patients with SSD. AIM: We investigated the methylation status of the coding region of the CRH gene (hereafter, CRH methylation) using peripheral blood samples from patients with SSD. SUBJECTS AND METHODS: We used sodium bisulphite and MethylTarget to determine CRH methylation after collecting peripheral blood samples from 70 patients with SSD who had positive symptoms and 68 healthy controls. RESULTS: CRH methylation was significantly increased in patients with SSD, especially in male patients. CONCLUSIONS: Differences in CRH methylation were detectable in the peripheral blood of patients with SSD. Epigenetic abnormalities in the CRH gene were closely related to positive symptoms of SSD, suggesting that epigenetic processes may mediate the pathophysiology of SSD.


Subject(s)
DNA Methylation , Schizophrenia , Humans , Male , Corticotropin-Releasing Hormone/genetics , Corticotropin-Releasing Hormone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Schizophrenia/genetics , Pituitary-Adrenal System/metabolism
20.
J Integr Neurosci ; 22(4): 93, 2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37519158

ABSTRACT

BACKGROUND: As an objective method to detect the neural electrical activity of the brain, electroencephalography (EEG) has been successfully applied to detect major depressive disorder (MDD). However, the performance of the detection algorithm is directly affected by the selection of EEG channels and brain regions. METHODS: To solve the aforementioned problems, nonlinear feature Lempel-Ziv complexity (LZC) and frequency domain feature power spectral density (PSD) were extracted to analyze the EEG signals. Additionally, effects of different brain regions and region combinations on detecting MDD were studied with eyes closed and opened in a resting state. RESULTS: The mean LZC of patients with MDD was higher than that of the control group, and the mean PSD of patients with MDD was generally lower than that of the control group. The temporal region is the best brain region for MDD detection with a detection accuracy of 87.4%. The best multi brain regions combination had a detection accuracy of 92.4% and was made up of the frontal, temporal, and central brain regions. CONCLUSIONS: This paper validates the effectiveness of multiple brain regions in detecting MDD. It provides new ideas for exploring the pathology of MDD and innovative methods of diagnosis and treatment.

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