Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis, which is primarily transmitted through the respiratory tract, and remains one of the diseases with the highest mortality rate of single-pathogen infections globally. The cell wall polysaccharides of M. tuberculosis are critical for maintaining bacterial structure, mediating pathogenesis, and enabling immune evasion. Lipoarabinomannan (LAM), a key polysaccharide component, has revolutionized non-invasive diagnostic technologies as a TB biomarker, while polysaccharide-based vaccines have emerged as innovative strategies for TB prevention. This review systematically examines the composition, subcellular distribution, and functional roles of M. tuberculosis cell wall polysaccharides in bacterial metabolism, drug resistance, and immune regulation. A particular emphasis is placed on recent advancements in LAM-based diagnostics and vaccine development. Future studies should utilize advanced technologies to precisely characterize the structural features of TB polysaccharides and explore their biological functions, providing a foundation for targeted diagnostic and therapeutic innovations. This article aims to provide reference for advancing both basic research and clinical applications related to M. tuberculosis.

Global public health faces substantial challenges from malignant tumors and infectious diseases. Vaccination provides an approach for treating and preventing these diseases. Oral vaccinations are particularly advantageous in disease treatment and prevention due to their non-invasive nature, high patient compliance, convenience, cost-effectiveness, and capacity to stimulate comprehensive and adaptive immune responses. However, the overwhelming majority of oral vaccines remain in experimental development, struggling with clinical and commercial translation due to their suboptimal efficacy. Thus, enhancing scientists' understanding of the interaction between vaccines and gastrointestinal immune system, creating antigen delivery systems suitable for the gut mucosal environment, developing more potent antigenic epitopes, and using personalized combination therapies are critical for advancing the next generation of oral vaccines. This article explores the fundamental principles and applications of current oral anti-tumor and anti-infective vaccines and discusses considerations necessary for designing future oral vaccines.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Objective: To investigate the health-related quality of life and its influencing factors among urban adults in Hangzhou City, so as to provide the evidence for formulation and assessment of health policy. Methods: A total of 1 800 permanent residents at ages of 18 to 64 years were sampled from Gongshu and Xihu districts, Hangzhou City using a stratified cluster random sampling method from May to August 2022. The health-related quality of life was measured with the EuroQol five-dimensional questionnaire (EQ-5D-5L), and factors affecting health-related quality of life were identified with a Tobit regression model. Results: A total of 1 624 valid questionnaires were recovered, with a response rate of 90.22%, and the respondents included 693 men (42.67%) and 931 women (57.33%). The proportions of difficulty in mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were 1.23%, 0.43%, 0.74%, 11.15% and 8.56%, and the median (interquartile range) of health state utility value and EuroQol Visual Analogue Scale (EQ-VAS) score were 1 (0) and 90 (15) points, respectively. Female (β=-0.050), age of 45 to 64 years (β=-0.067) and development of chronic disease (one chronic disease: β=-0.036; two and more chronic diseases: β=-0.090) were factor affecting of health state utility values, and age of 35 to 44 years (β=-1.945) and 45 to 64 years (β=-3.459), unemployment (β=-1.913), development of chronic disease (one chronic disease: β=-3.444; two and more chronic diseases: β=-8.529), high-level physical activity (β=2.355) and overweight/obesity (β=-1.456) were factors affecting the EQ-VAS score. Conclusions The overall health related quality of life is relatively good among urban adults in Hangzhou City. Gender, age, employment, physical activity, presence of chronic diseases and overweight/obesity may be associated with health-related quality of life among urban adults in Hangzhou City.

OBJECTIVES: To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis. METHODS: Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue. RESULTS: The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05). CONCLUSIONS In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.
Male ; Animals ; Mice ; Mucocutaneous Lymph Node Syndrome/pathology* ; Coronary Vessels/pathology* ; NF-kappa B ; Caspase 3/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Chitinase-3-Like Protein 1 ; von Willebrand Factor/metabolism* ; Mice, Inbred C57BL ; Cadherins

The study of children who experienced with febrile seizures(FS) as a result of COVID-19 infection to gain insight into the clinical characteristics and prognosis of neurological damage, with the aim of improving prevention, diagnosis, and the treatment of neurological complications. This study investigated the clinical features of 53 children with FS who were admitted to Sanya Women and Children’s Hospital from December 1, 2022, to January 31, 2023. The results indicated that the duration of convulsion in the case and control group was 7.90±8.91 and 2.67±1.23 (minutes) respectively. The analysis reveals that convulsions occurred within 24 hours in 39 cases (95.12%) of the case group, and in 8 cases (66.7%) of the control group. The difference was statistically significant (P<0.05). Additionally, the case group presented lower counts of WBC and NEU compared to the control group (p<0.05). The findings indicate that convulsions manifest at earlier stages of COVID-19 in children and the last longer than in the control group. It is therefore crucial for healthcare workers to remain attentive to patients with COVID-19 who report fever within 24 hours, and act promptly to implement preventive measures, particularly in cases of prolonged fever. It is essential to integrate the clinical manifestation, particularly convulsions, and the continuous numerical changes of inflammatory factors to assess COVID-19 linked with febrile seizures. In addition, larger-scale multi-center and systematic research are necessary to aid clinicians in monitoring neuropathological signals and biological targets, enabling more equitable diagnosis and treatment plans.

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

Objective: To clarify the values of autotaxin (ATX) in patients with primary biliary cholangitis (PBC) and PBC-related hepatocellular carcinoma (HCC). Methods: 179 patients with PBC were selected from prospective cohorts of autoimmune liver diseases at the time of first diagnosis of PBC in Department of Hepatology, the Fifth Medical Center of PLA General Hospital, from January 2016 to January 2018, all patients with PBC received UDCA therapy, primary endpoint was event of HCC, the follow-up period was censored at the date of HCC. The relationship between level of ATX and clinical features in patients with PBC and its potential value in predicting disease progression and PBC-related HCC were analyzed. Results: The ATX level in the peripheral blood of patients with PBC was significantly higher than that of alcoholic liver cirrhosis(ALC) (t = 3.278, P = 0.001) and healthy controls(HC) (t = 6.594, P < 0.001), however, when comparing PBC to non-PBC related HCC, no significant difference was found between the groups(t=-0.240, P = 0.811). Consistent with peripheral blood levels, histochemical staining indicated that ATX in the liver of patients with PBC was significantly higher than that of HC (Z=-3.633, P < 0.001) and ALC (Z=-3.283, P < 0.001), and the expression of ATX in PBC with advanced histological stage was significantly higher than PBC with early stage (Z=-2.018, P = 0.034). The baseline ATX level in PBC patients without developing to HCC during follow-up had significant difference to patients with developing to HCC (228.451 ± 124.093 ng/ml vs 301.583 ± 100.512 ng/ml, t = 2.339, P = 0.021). The result in multivariate logistic regression analysis showed that ATX were independent predictors of PBC related HCC(OR 1.245, 95%CI 1.097-1.413). The optimal critical value of peripheral blood ATX level at baseline for predicting HCC was 235.254 ng/ml, with the cut-off value of 0.714 in AUC of the ROC (95% CI was 0.597~ 0.857), sensitivity and specificity were 84.6% and 59.0%, respectively. Conclusion: ATX level was significantly higher in PBC patients over controls, and it's concentration was correlated with UDCA efficacy and fibrosis stage. ATX has potential values in predicting disease progression and PBC-related HCC.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

Abstract: Objective To investigate the willingness to receiving multitarget stool DNA (MT-sDNA) testing and factors affecting the payment among individuals receiving colonoscopy screening, so as to provide the evidence for the formulation and health economic evaluation of colorectal cancer screening strategies. Methods: Individuals at ages of 40 to 75 years that received colonoscopy screening in The Affiliated Hospital of Ningbo University Medical School from August 2021 to March 2022 were sampled. Participants' demographics, living behaviors, family history, willingness to receive MT-sDNA testing and willingness to pay for MT-sDNA testing were collected using questionnaire surveys, and factors affecting the willingness to receive and pay for MT-sDNA testing were analyzed using a multivariable logistic regression model. Results : A total of 546 respondents were enrolled, with a mean age of (56.25±8.66) years and including 282 men (51.65%). There were 504 respondents that were willing to receiving MT-sDNA testing (92.31%) and 480 that were willing to pay for the MT-sDNA testing (88.24%). Multivariable logistic regression analysis showed that a family history of colorectal cancer in first-degree relatives (OR=0.246, 95%CI: 0.068-0.888), history of hemorrhoids (OR=0.300, 95%CI: 0.109-0.826) resulted in low willingness to receive MT-sDNA testing, and recognizing the reliability of MT-sDNA testing (OR=5.749, 95%CI: 1.480-22.323), considering no difficulty in sampling for MT-sDNA testing (OR=32.042, 95%CI: 6.666-154.021) and considering a difficulty in sampling for MT-sDNA testing (OR=20.278, 95%CI: 4.405-93.354) resulted in high willingness to receive MT-sDNA testing, while recognizing the reliability of MT-sDNA testing (OR=5.003, 95%CI: 1.761-14.216), concern about the reliability of MT-sDNA testing (OR=4.166, 95%CI: 1.285-13.501), considering no difficulty in sampling for MT-sDNA testing (OR=6.558, 95%CI: 2.105-20.428) and considering a difficulty in sampling for MT-sDNA testing (OR=5.820, 95%CI: 1.810-18.720) resulted in high willingness to pay for the MT-sDNA testing among individuals receiving colonoscopy screening. Conclusion A family history of colorectal cancer in first-degree relatives, history of hemorrhoids and awareness of MT-sDNA testing are factors affecting the willingness to receive and pay for the MT-sDNA testing among individuals receiving colonoscopy screening.