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1.
J Clin Anesth ; 98: 111574, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39121785

ABSTRACT

STUDY OBJECTIVE: Although a prolonged heart rate-corrected QT interval (QTcI) is associated with an increased risk of mortality in the general population, its prognostic value in surgical patients remains unclear. We aimed to examine whether preoperative QTcI prolongation predicts short-term postoperative outcomes in elderly patients undergoing noncardiac surgery. DESIGN: The study was a retrospective analysis using the TriNetX network database. SETTING: Operating room. INTERVENTION: Assessment and categorization of preoperative QTcI. PATIENTS: Data of patients aged ≥65 years who underwent non-cardiac surgery between 2010 and 2023 were analyzed. MEASUREMENTS: Patients were categorized into four groups based on preoperative QTcI: long (500-600 ms), borderline (460-500 ms), high-normal (420-460 ms) and control (370-420 ms) groups. The groups were compared using a propensity score-matched analysis. The primary outcome was the all-cause 90-day mortality risk. The secondary outcomes included 90-day risks of postoperative new-onset atrial fibrillation (Af), ventricular arrhythmias (VAs), emergency visits, hospital readmissions, and pneumonia. RESULTS: In total, data on 519,929 patients were collected in this study. Pairwise comparisons showed that all QTcI prolongation groups demonstrated a heightened incidence of postoperative mortality, arrhythmias, and other complications compared to the control group. Patients with a long QTcI had a 3-fold higher risk of mortality (hazard ratio [HR] = 3.124, p < 0.001), Af (HR = 3.059, p < 0.001), and VAs (HR = 3.617, p < 0.001) than controls. The risks of emergency visits (HR = 1.287, p < 0.001), hospital readmissions (HR = 1.591, p < 0.001), and pneumonia (HR = 1.672, p < 0.001) were also higher in the long QTcI group than in the control group. A dose-dependent response was evident between QTcI and mortality as well as arrhythmia risk. CONCLUSION: Preoperative QTcI screening effectively risk-stratifies elderly surgical patients, with a QTcI≥500 ms being strongly predictive of short-term postoperative mortality and other complications. Incorporating QTcI assessment into the preoperative evaluation may guide perioperative monitoring and management.


Subject(s)
Electrocardiography , Long QT Syndrome , Postoperative Complications , Humans , Retrospective Studies , Female , Aged , Male , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/diagnosis , Postoperative Complications/mortality , Long QT Syndrome/epidemiology , Aged, 80 and over , Patient Readmission/statistics & numerical data , Heart Rate , Preoperative Period , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/diagnosis , Risk Factors , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Atrial Fibrillation/diagnosis , Incidence , Prognosis
2.
Appl Environ Microbiol ; 90(8): e0012124, 2024 08 21.
Article in English | MEDLINE | ID: mdl-38980046

ABSTRACT

Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs.


Subject(s)
Antivenins , Camelids, New World , Elapid Venoms , Single-Domain Antibodies , Snake Bites , Animals , Single-Domain Antibodies/immunology , Mice , Snake Bites/therapy , Snake Bites/immunology , Antivenins/immunology , Elapid Venoms/immunology , Cell Surface Display Techniques , Naja naja , Peptide Library
3.
BMC Palliat Care ; 23(1): 189, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075384

ABSTRACT

OBJECTIVES: Sexuality is an important dimension of health-related quality of life (HRQOL) in cancer patients. Studies evidence that most patients report impairments of their sexual health related to their disease or its treatment. The Quality of Life Group of the European Organization for the Research and Treatment of Cancer (EORTC) developed a patient reported outcome measure assessing multidimensional aspects of sexual health. The validation study for this instrument revealed heterogenous results for patients in palliative oncological treatment. The aim of this secondary analyses is to examine differences in patient related sexual health outcomes between palliative patients with good performance status (GPS) and those with poor performance status (PPS). METHODS: In this observational cohort study, self-reported sexual health issue scores were compared between the two groups of patients in palliative oncological treatment with GPS vs PPS status. RESULTS: Patients with GPS experienced significantly more sexual satisfaction than patients with PPS (p = 0.015). They reported significantly more treatment effects on their sexual activity (p = 0.005) and suffer more from decreased libido (p = 0.008). Patients with PPS reported significantly more fatigue (p = 0.03) and regarded preservation of sexual activity of higher importance than did patients with GPS (p = 0.049). CONCLUSIONS: Our study demonstrates the importance of sexuality for patients in palliative oncological treatment, especially for those with limited performance status. Considering the patients´ perspective, sexual health reaches beyond physical functioning. Patients in a palliative phase of disease report high levels of psychosexual problems while sexual performance deteriorates. Sexuality is an important aspect of HRQOL for these patients, needs to be addressed by health care providers and sensitively integrated into palliative care plans.


Subject(s)
Neoplasms , Palliative Care , Quality of Life , Sexual Health , Humans , Palliative Care/methods , Palliative Care/standards , Palliative Care/psychology , Female , Male , Neoplasms/complications , Neoplasms/psychology , Neoplasms/therapy , Middle Aged , Aged , Cohort Studies , Quality of Life/psychology , Surveys and Questionnaires , Adult , Aged, 80 and over
4.
BMC Womens Health ; 24(1): 343, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38877469

ABSTRACT

BACKGROUND: The primary screening technique for precancerous lesions and cervical cancer is human papillomavirus (HPV) testing, and HPV self-sampling has been shown to be consistent with clinician sampling in terms of the accuracy of the results and may improve cervical cancer screening rates. The aim of this study was to understand the level of awareness, experience, acceptability, and preference for vaginal HPV self-sampling among women in Jiangsu, Zhejiang, and Shanghai, China, and to analyze the possible influencing factors to determine the feasibility of implementing self-sampling. METHODS: Overall, 1793 women were included in the data analysis. A self-administered questionnaire was utilized. In addition to descriptive analysis, univariate and multivariate analyses were used to explore the associations between sociodemographic features, history of cervical cancer screening, and the level of awareness, experience, acceptability, and preference for HPV self-samples. RESULTS: The participants' level of awareness of and experience with HPV self-sampling were moderate. A total of 88.8% of participants rated the acceptability as "high", and self-sampling was preferred by 64.2% of them for cervical cancer screening. People aged 45 to 54 years showed a preference for both clinician sampling(OR = 1.762 (1.116-2.163)) and self-sampling (OR = 1.823 (1.233-2.697)). Those who had graduated from high school or above (OR = 2.305 (1.517-3.503), OR = 2.432 (1.570-3.768), OR = 3.258 (2.024-5.244)) preferred clinician-sampling, and those with a bachelor's degree or above (OR = 1.664 (1.042-2.657)) preferred self-sampling. Middle- and high-income individuals showed no preference for either sampling method (OR < 1). CONCLUSIONS: HPV self-sampling is widely accepted, but awareness, experience and preferences need to be improved. These results may help to adjust public health strategies for the early inclusion of HPV self-sampling as a screening method in national initiatives to prevent cervical cancer.


Subject(s)
Early Detection of Cancer , Health Knowledge, Attitudes, Practice , Papillomavirus Infections , Patient Acceptance of Health Care , Uterine Cervical Neoplasms , Adult , Aged , Female , Humans , Middle Aged , Young Adult , China/epidemiology , Cross-Sectional Studies , Early Detection of Cancer/methods , Early Detection of Cancer/psychology , Human Papillomavirus Viruses , Papillomavirus Infections/diagnosis , Patient Acceptance of Health Care/statistics & numerical data , Patient Acceptance of Health Care/psychology , Patient Preference/statistics & numerical data , Self Care/methods , Self Care/statistics & numerical data , Specimen Handling/methods , Surveys and Questionnaires , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virology , Vaginal Smears/methods , Vaginal Smears/statistics & numerical data
5.
Int Immunopharmacol ; 128: 111476, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38185035

ABSTRACT

Streptococcus pneumoniae is a clinically relevant pathogen notorious for causing pneumonia, meningitis, and otitis media in immunocompromised patients. Currently, antibiotic therapy is the most efficient treatment for fighting pneumococcal infections. However, an arise in antimicrobial resistance in S. pneumoniae has become a serious health issue globally. To resolve the problem, alternative and cost-effective strategies, such as monoclonal antibody-based targeted therapy, are needed for combating bacterial infection. S. pneumoniae alpha-enolase (spEno1), which is thought to be a great target, is a surface protein that binds and converts human plasminogen to plasmin, leading to accelerated bacterial infections. We first purified recombinant spEno1 protein for chicken immunization to generate specific IgY antibodies. We next constructed two single-chain variable fragments (scFv) antibody libraries by phage display technology, containing 7.2 × 107 and 4.8 × 107 transformants. After bio-panning, ten scFv antibodies were obtained, and their binding activities to spEno1 were evaluated on ELISA, Western blot and IFA. The epitopes of spEno1 were identified by these scFv antibodies, which binding affinities were determined by competitive ELISA. Moreover, inhibition assay displayed that the scFv antibodies effectively inhibit the binding between spEno1 and human plasminogen. Overall, the results suggested that these scFv antibodies have the potential to serve as an immunotherapeutic drug against S. pneumoniae infections.


Subject(s)
Phosphopyruvate Hydratase , Single-Chain Antibodies , Streptococcus pneumoniae , Animals , Humans , Chickens , Peptide Library , Phosphopyruvate Hydratase/immunology , Plasminogen , Recombinant Proteins , Single-Chain Antibodies/immunology , Streptococcus pneumoniae/enzymology , Streptococcus pneumoniae/immunology
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1005924

ABSTRACT

Objective To analyze the clinical characteristics and influencing factors of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) in Hubei province, and to provide a theoretical basis for the diagnosis and treatment of NSCLC patients with COPD. Methods A total of 246 NSCLC patients admitted to our hospital from 2018 to 2020 were selected and divided into control group (without COPD, n=125) and observation group (with COPD, n=121) according to COPD. The clinical characteristics of chest pain, hemoptysis, emasculation, atelectasis and pleural effusion were compared between the two groups. The values of FEV1/FVC, RV/TLC and DLCO in the two groups were measured by pulmonary function detector. The age, gender, smoking, smoking history, proportion of lung squamous cell carcinoma, TNM stage and other clinical data of all subjects were analyzed by self-made survey scale of our hospital. Univariate analysis and logistic regression were used to analyze the risk factors of COPD in NSCLC patients. Results Among 246 NSCLC patients, 121 patients (49.19%) were complicated with COPD, including 76 males and 45 females, and there was a statistical difference between the two groups (χ2=4.891, P>0.05). The average age of the observation group (61.02±4.82) was significantly higher than that of the control group (59.76±4.73) (t=2.069, P0.05). Male (OR=2.982), smoking history (OR=2.623) and lung squamous cell carcinoma (OR=3.147) were risk factors for COPD in NSCLC patients (P<0.05). Conclusions NSCLC patients with COPD are more common in male smokers in Hubei Province, often accompanied by pleural effusion , severe hemoptysis and other symptoms , and their lung function is decreased. Early detection and standardized treatment of COPD in the treatment of NSCLC can improve the prognosis of patients.

7.
J Formos Med Assoc ; 123(1): 78-87, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37400295

ABSTRACT

Periodic mammography and/or sonography examinations are conducted across numerous hospitals nationalwidely, especially for antedees with a positive mammography screening. Despite the regular practice, clinical efficacy of hospital-based breast cancer surveillance remains unclear. Specifically, the impact of surveillance interval upon survival and prognostic surrogates stratified by menopausal status, as well as malignant transition rate should be deciphered. We retrieved cancer registry to ascertain 841 breast cancers with surveillance history through administration data. Healthy controls underwent breast surveillance and were concurrently free of cancer. More benign diseases rather than cancers were identified from premenopausal women (age ≤50 years) with sonography alone within one year, as well as older women (age >50) with both mammography and sonography one to two years before a cancer or benign diagnosis. Among breast cancers, mammography alone during the antecedent one to two years had a protective effect for diagnosing carcinoma in situ rather than invasive cancer (age-adjusted odds ratio: 0.048, P = 0.016). Three-state time homogeneous Markov model showed that hospital-based breast surveillance within 2 years of disease onset reduced the malignant transition rate by 65.16% (59.79-76.74%). The clinical efficacy of breast cancer surveillance was evidenced.


Subject(s)
Breast Neoplasms , Female , Humans , Aged , Middle Aged , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/epidemiology , Mammography , Ultrasonography , Physical Examination , Treatment Outcome , Mass Screening , Early Detection of Cancer
8.
Org Biomol Chem ; 22(3): 482-485, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38108209

ABSTRACT

An iodine-mediated cyclization has been developed to 4-aryl-NH-1,2,3-triazoles, with p-toluenesulfonyl hydrazide and sulfamic acid used as nitrogen sources. Sulfamic acid plays a crucial role in this reaction by both acting as a substrate and providing an acidic environment. This reaction offers a metal- and azide-free strategy to access NH-1,2,3-triazoles.

9.
Life (Basel) ; 13(10)2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37895346

ABSTRACT

With the advent of direct-acting antiviral agents (DAA) in the recent few years, hepatitis C virus (HCV) infection has become a curable infectious disease. Successful clearance of HCV could lead to improvement of both hepatic and extrahepatic outcomes, such as complications of cirrhosis, hepatocellular carcinoma, cardiovascular diseases, and incident diabetes. However, challenges persist in reaching the HCV elimination goals of the World Health Organization by 2030. Among these challenges are identifying those already infected or undiagnosed subjects, re-linking to the care of known but untreated HCV-infected subjects, and developing strategies to enhance treatment rates and compliance in specific or high-risk populations. In addition, issues of post-DAA viral clearance, including avoiding or preventing reinfection in high-risk populations and surveillance of hepatocellular carcinoma, are important to consolidate the treatment's short- and long-term efficacies. In the current DAA era, treatment is the most effective prevention strategy not only in its excellent efficacy and safety but also in preventing HCV spread. All of the surveillance or measures should center on DAA treatment in clinical practice.

10.
JMIR Aging ; 6: e45442, 2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37792460

ABSTRACT

BACKGROUND: Ikigai (meaning or purpose in life) is a concept understood by most older adults in Japan. The term has also garnered international attention, with recent academic attempts to map it to concepts in the Western well-being literature. In addition, efforts to use social and home robots to increase well-being have grown; however, they have mostly focused on hedonic well-being (eg, increasing happiness and decreasing loneliness) rather than eudaimonic well-being (eg, fostering meaning or purpose in life). OBJECTIVE: First, we explored how Japanese older adults experience ikigai and relate these to concepts in the Western well-being literature. Second, we investigated how a home robot meant to promote ikigai is perceived by older adults. METHODS: We used a mixed methods research design-including 20 interviews with older adults, a survey of 50 older adults, and 10 interviews with family caregivers. For interviews, we asked questions about older adults' sources of ikigai, happiness, and social support, along with their perception of the robot (QT). For surveys, a number of well-being scales were used, including 2 ikigai scales-ikigai-9 and K-1-and 6 Patient-Reported Outcomes Measurement Information System scales, measuring meaning and purpose, positive affect, satisfaction with participation in social roles, satisfaction with participation in discretionary social activities, companionship, and emotional support. Questions related to the perception and desired adoption of the robot and older adults' health status were also included. RESULTS: Our results suggest that health is older adults' most common source of ikigai. Additionally, although self-rated health correlated moderately with ikigai and other well-being measures, reported physical limitation did not. As opposed to social roles (work and family), we found that ikigai is more strongly related to satisfaction with discretionary social activities (leisure, hobbies, and friends) for older adults. Moreover, we found that older adults' sources of ikigai included the eudaimonic aspects of vitality, positive relations with others, contribution, accomplishment, purpose, and personal growth, with the first 3 being most common, and the hedonic aspects of positive affect, life satisfaction, and lack of negative affect, with the first 2 being most common. However, the concept of ikigai was most related to eudaimonic well-being, specifically meaning in life, along the dimension of significance. Finally, we found that Japanese older adults have high expectations of a home robot for well-being, mentioning that it should support them in a multitude of ways before they would likely adopt it. However, we report that those with the highest levels of meaning, and satisfaction with their leisure life and friendships, may be most likely to adopt it. CONCLUSIONS: We outline several ways to improve the robot to increase its acceptance, such as improving its voice, adding functional features, and designing it to support multiple aspects of well-being.

11.
Nanomaterials (Basel) ; 13(15)2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37570508

ABSTRACT

We reported the photoconduction properties of tungsten disulfide (WS2) nanoflakes obtained by the mechanical exfoliation method. The photocurrent measurements were carried out using a 532 nm laser source with different illumination powers. The results reveal a linear dependence of photocurrent on the excitation power, and the photoresponsivity shows an independent behavior at higher light intensities (400-4000 Wm-2). The WS2 photodetector exhibits superior performance with responsivity in the range of 36-73 AW-1 and a normalized gain in the range of 3.5-7.3 10-6 cm2V-1 at a lower bias voltage of 1 V. The admirable photoresponse at different light intensities suggests that WS2 nanostructures are of potential as a building block for novel optoelectronic device applications.

12.
J Org Chem ; 88(13): 8034-8041, 2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37319302

ABSTRACT

A tandem reaction for the synthesis of phenanthrenes from arynes and α-(bromomethyl)styrenes is reported. The transformation proceeds via an ene reaction of α-(bromomethyl)styrenes with arynes, followed by a [4 + 2] cycloaddition reaction. The reaction generates 9-benzylphenanthrene derivatives in moderate to excellent yields.


Subject(s)
Phenanthrenes , Styrenes , Cycloaddition Reaction , Cyclization
13.
Gastrointest Endosc ; 98(5): 755-764, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37356632

ABSTRACT

BACKGROUND AND AIMS: Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. METHODS: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. RESULTS: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded. CONCLUSIONS: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).

14.
J Obstet Gynaecol ; 43(1): 2204942, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37129887

ABSTRACT

This aim of this study was to investigate women's knowledge about HPV along with their experience and acceptability of self-sampling in Jiangsu province, China. A total of 862 women aged 25-63 years old from Jiangsu province who purchased an HPV self-sampling test kit were invited to complete a questionnaire designed by the authors. Participants had high acceptability for HPV self-sampling with a mean score of 4.2 (95% [CI], 4.1-4.22) out of 5 points. 27% of participants preferred clinician-sampling, 33% preferred self-sampling, other 40% expressed no preference. Women with good knowledge about HPV and with a good experience with HPV self-sampling were more acceptable for self-sampling (P < 0.05). The biggest concern about HPV self-sampling of the participants includes 'specimens' spoilage', 'incorrect sampling', 'can't get results in time', and so on. HPV self-sampling can be used to improve cervical cancer screening coverage and participation rates in China.


Cancer screening and can be an alternative primary screening for cervical cancer.•What the results of this study add? This study adds new findings about Chinese women's experience and acceptability of HPV self-sampling. We found that most women had high acceptability for HPV self-sampling in Jiangsu province, China, and high knowledge about HPV as well as good•What is already known on this subject? HPV self-sampling testing was proven to be useful for improving the uptake rate of cervical experience of self-sampling can improve the acceptability for self-sampling in women.•What the implications are of these findings for clinical practice and/or further research? Further research should assess the acceptability of women with less education or who never screened.


Subject(s)
Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Adult , Middle Aged , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & control , Cross-Sectional Studies , Early Detection of Cancer/methods , Papillomavirus Infections/prevention & control , China , Specimen Handling/methods , Papillomaviridae , Self Care/methods , Mass Screening/methods , Patient Acceptance of Health Care
15.
Int Immunopharmacol ; 120: 110277, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37196558

ABSTRACT

Overexpression of human alpha-enolase (hEno1)has been reported in a wide range of cancers and is tightly associated with poor prognosis, making it a remarkable biomarker and therapeutic target. In this study, polyclonal yolk-immunoglobulin (IgY) antibodies purified from hEno1-immunized chickens showed a noticeable specific humoral response. Phage display technology was used to construct two antibody libraries of IgY gene-derived single-chain variable fragments (scFvs) containing 7.8 × 107 and 5.4 × 107 transformants, respectively. Phage-based ELISA indicated that specific anti-hEno1 clones were significantly enriched. The nucleotide sequences of scFv-expressing clones were determined and classified into seven groups either in the short linker or the long linker. Moreover, higher mutation rates were revealed in the CDR regions, especially in the CDR3. Three distinguish antigenic epitopes were identified on the hEno1 protein. The binding activities of selected anti-hEno1 scFv on hEno1-positive PE089 lung cancer cells were confirmed using Western blot, flow cytometry, and immunofluorescence assay. In particular, hEnS7 and hEnS8 scFv antibodies significantly suppressed the growth and migration of PE089 cells. Taken together, these chicken-derived anti-hEno1 IgY and scFv antibodies have great potential to develop diagnostic and therapeutic agents for the treatment of lung cancer patients with high expression levels of hEno1 protein.


Subject(s)
Lung Neoplasms , Phosphopyruvate Hydratase , Single-Chain Antibodies , Animals , Humans , Cell Surface Display Techniques , Chickens , Enzyme-Linked Immunosorbent Assay , Peptide Library , Phosphopyruvate Hydratase/immunology
16.
Indian J Dermatol Venereol Leprol ; 89(2): 189-194, 2023.
Article in English | MEDLINE | ID: mdl-36332095

ABSTRACT

BACKGROUND: Melasma is a chronic skin condition that adversely impacts quality of life. Although many therapeutic modalities are available there is no single best treatment for melasma. Oral tranexamic acid has been used for the treatment of this condition but its optimal dose is yet to be established. OBJECTIVES: We used network meta-analysis to determine the optimal dose of oral tranexamic acid for the treatment of melasma. METHODS: We conducted a comprehensive search of all studies of oral tranexamic acid for the treatment of melasma up to September 2020 using PubMed, EMBASE and the Cochrane Library database. The quality of the studies was evaluated using the Jadad score and the Cochrane's risk of bias assessment tool. Only high quality randomised controlled trials were selected. Some studies lacked standard deviation of changes from baseline and these were estimated using the correlation coefficient obtained from another similar study. RESULTS: A total of 92 studies were identified of which 6 randomized controlled trials comprising 599 patients were included to form 3 pair-wise network comparisons. The mean age of the patients in these studies ranged from 30.3 to 46.5 years and the treatment duration ranged from 8 to 12 weeks. The Jadad scores ranged from 5 to 8. The optimal dose and duration of oral tranexamic acid was estimated to be 750 mg per day for 12 consecutive weeks. LIMITATIONS: Some confounding factors might not have been described in the original studies. Although clear rules were followed, the Melasma Area and Severity Index and the modified Melasma Area and Severity Index were scored by independent physicians and hence inter-observer bias could not be excluded. CONCLUSION: Oral tranexamic acid is a promising drug for the treatment of melasma. This is the first network meta-analysis to determine the optimal dose of this drug and to report the effects of different dosages. The optimal dose is 250 mg three times per day for 12 weeks, but 250 mg twice daily may be an acceptable option in poorly adherent patients. Our findings will allow physicians to balance drug effects and medication adherence. Personalized treatment plans are warranted.


Subject(s)
Melanosis , Tranexamic Acid , Humans , Infant , Network Meta-Analysis , Quality of Life , Melanosis/diagnosis , Melanosis/drug therapy , Administration, Oral , Treatment Outcome , Randomized Controlled Trials as Topic
18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-970906

ABSTRACT

OBJECTIVE@#To explore the clinical phenotype and genetic basis for a Chinese pedigree affected with Oral-facial-digital syndrome type I (OFD1).@*METHODS@#A pedigree with OFD1 who presented at Hebei General Hospital on March 17, 2021 was selected as the subject. Clinical data of the child was collected. Trio-whole exome sequencing (trio-WES) was carried out for the proband and members of her pedigree, and candidate variant was verified by Sanger sequencing.@*RESULTS@#The proband has featured hypotelorism, broad nasal root, flat nasal tip, lobulated tongue, tongue neoplasia, camptodactyly of left fifth finger, syndactyly of right fourth and fifth fingers, and delayed intellectual and language development. Trio-WES revealed that the proband and her daughter, sister and mother have harbored a heterozygous c.224A>G (p.Asn75Ser) variant of the OFD1 gene. The same variant was not found among healthy members from her pedigree.@*CONCLUSION@#The c.224A>G (p.Asn75Ser) variant probably underlay the OFD1 in this pedigree. Above discovery has enriched the spectrum of OFD1 gene variants.


Subject(s)
Humans , Female , Pedigree , Orofaciodigital Syndromes/genetics , East Asian People , Phenotype , Heterozygote , Mutation , China
19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-991078

ABSTRACT

Objective:To investigate the influences of Dixon anus preserving surgery on the curative effect, anorectal function and stress response of patients with low rectal cancer.Methods:A total of 150 patients with low rectal cancer admitted to Zhangjiakou Fifth Hospital from May 2016 to March 2019 were retrospective analysis as the study subjects. According to the different surgical methods, the patients were divided into the study group (75 cases) and the control group (75 cases). The patients in the study group received Dixon operation, and the patients in the control group received Miles operation. The general condition of operation, postoperative urination function, stress response [C reactive protein (CRP), interleukin-6 (IL-6), cortisol (Cor) and adrenocorticotropic hormone (ACTH)], anorectal function [anal resting pressure (ARP), maximal squeeze pressure (MSP), anal longest contraction time (ALCT)], quality of life (PAC-QOL score), postoperative complications, local recurrence rate, distant metastasis rate, 3-year tumor free survival rate and 3-year overall survival rate were compared between the two groups.Results:The operation time, intraoperative blood loss and postoperative drainage volume in the study group were lower than those in the control group: (172.28 ± 23.45) min vs. (189.57 ± 23.68) min, (177.39 ± 21.23) ml vs. (191.35 ± 22.67) ml, (342.36 ± 52.89) ml vs. (489.42 ± 63.33) ml, there were statistical differences ( P<0.05). The levels of CRP, IL-6, Cor and ACTH in the study group were lower than those in the control group: (22.35 ± 4.75) mg/L vs. (35.65 ± 5.28) mg/L, (58.74 ± 15.11) μg/L vs. (79.63 ± 20.23) μg/L, (145.36 ± 27.48) ng/L vs. (156.48 ± 32.55) ng/L, (44.58 ± 5.27) ng/L vs. (49.62 ± 5.68) ng/L, there were statistical differences ( P<0.05). The urination function and anorectal function of the patients in the study group were obviously better than those in the control group 6 months after operation, and the PAC-QOL score was obviously lower than that in the control group: (22.53 ± 2.86) scores vs. (27.54 ± 3.21) scores ( P<0.05); there was no obvious difference between the study group and the control group in the incidence of postoperative complications, local recurrence rate, distant metastasis rate, 3-year tumor free survival rate and 3-year total survival rate ( P>0.05). Conclusions:Dixon operation is effective in the treatment of low rectal cancer. It can preserve the anorectal function of patients to the greatest extent, protect urination function, reduce stress reaction of patients, and it is more conducive to rapid rehabilitation of patients.

20.
Front Immunol ; 14: 1292019, 2023.
Article in English | MEDLINE | ID: mdl-38288120

ABSTRACT

Background: Nectin-4 is a novel biomarker overexpressed in various types of cancer, including breast cancer, in which it has been associated with poor prognosis. Current literature suggests that nectin-4 has a role in cancer progression and may have prognostic and therapeutic implications. The present study aims to produce nectin-4-specific single-chain variable fragment (scFv) antibodies and evaluate their applications in breast cancer cell lines and clinical specimens. Methods: We generated recombinant nectin-4 ectodomain fragments as immunogens to immunize chickens and the chickens' immunoglobulin genes were amplified for construction of anti-nectin-4 scFv libraries using phage display. The binding capacities of the selected clones were evaluated with the recombinant nectin-4 fragments, breast cancer cell lines, and paraffin-embedded tissue sections using various laboratory approaches. The binding affinity and in silico docking profile were also characterized. Results: We have selected two clones (S21 and L4) from the libraries with superior binding capacity. S21 yielded higher signals when used as the primry antibody for western blot analysis and flow cytometry, whereas clone L4 generated cleaner and stronger signals in immunofluorescence and immunohistochemistry staining. In addition, both scFvs could diminish attachment-free cell aggregation of nectin-4-positive breast cancer cells. As results from ELISA indicated that L4 bound more efficiently to fixed nectin-4 ectodomain, molecular docking analysis was further performed and demonstrated that L4 possesses multiple polar contacts with nectin-4 and diversity in interacting residues. Conclusion: Overall, the nectin-4-specific scFvs could recognize nectin-4 expressed by breast cancer cells and have the merit of being further explored for potential diagnostic and therapeutic applications.


Subject(s)
Neoplasms , Single-Chain Antibodies , Animals , Single-Chain Antibodies/genetics , Nectins , Biomarkers, Tumor , Molecular Docking Simulation , Chickens
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