Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. OBJECTIVE: This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). METHODS: This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method. RESULTS: The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (ß=.097; P<.001). There was an association between MSDP and TD (ß=.074; P<.001) as well as between TD and COPD (ß=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: ß=.094; P<.001 and indirect: ß=.004; P=.03). The indirect effect remains present in the smoking population (direct: ß=.120; P<.001 and indirect: ß=.002; P=.03). CONCLUSIONS: This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

Indirect estimation of pediatric reference interval via density graph deep embedded clustering.

Establishing reference intervals (RIs) for pediatric patients is crucial in clinical decision-making, and there is a critical gap of pediatric RIs in China. However, the direct sampling technique for establishing RIs is resource-intensive and ethically challenging. Indirect estimation methods, such as unsupervised clustering algorithms, have emerged as potential alternatives for predicting reference intervals. This study introduces deep graph clustering methods into indirect estimation of pediatric reference intervals. Specifically, we propose a Density Graph Deep Embedded Clustering (DGDEC) algorithm, which incorporates a density feature extractor to enhance sample representation and provides additional perspectives for distinguishing different levels of health status among populations. Additionally, we construct an adjacency matrix by computing the similarity between samples after feature enhancement. The DGDEC algorithm leverages the adjacency matrix to capture the interrelationships between patients and divides patients into different groups, thereby estimating reference intervals for the potential healthy population. The experimental results demonstrate that when compared to other indirect estimation techniques, our method ensures the predicted pediatric reference intervals in different age and gender groups are closer to the true values while maintaining good generalization performance. Additionally, through ablation experiments, our study confirms that the similarity between patients and the multi-scale density features of samples can effectively describe the potential health status of patients.

A shared decision-making model in pediatric palliative care: a qualitative study of healthcare providers.

BACKGROUND: Pediatric shared decision-making (SDM) is a fundamental part of family-centered care. Pediatric palliative care (PPC) is one of the more difficult fields for healthcare providers when choosing to utilize SDM. However, to our knowledge, there are still few structured approaches of SDM in PPC. We aimed to build a model of SDM in PPC that achieves better care and outcomes for children and their family members. METHODS: This study is a descriptive phenomenology study. Participants included physicians, nurses, and social workers in the PPC team. Participants were individually interviewed face-to-face or via an online meeting software. Data were collected in semi-structured interviews and analyzed using a thematic framework analysis. RESULTS: In total, 27 healthcare providers were interviewed. The model of SDM in PPC identified three themes, including the participants, the principle and the process of SDM. Decision participants involved the children, parents, the PPC team and others. The decision principle had three sub-themes including type, standard and precondition. The decision process describes the fundamental process of SDM and provides suggestions for mobilizing patients and parents to engage in decision-making and seeking conflict resolution. CONCLUSIONS: This is the first study to develop a SDM model in PPC. This model can provide guidance to PPC teams on SDM practices. In addition, the model contributes to the existing body of knowledge by providing a conceptual model for SDM in the context of PPC.

Evaluation of glomerular filtration rate estimation equations based on serum creatinine in healthy Chinese children and adolescents: a nationwide cross-sectional study.

BACKGROUND: Several equations for glomerular filtration rate (GFR) estimation based on serum creatinine (SCr) have been proposed for children, but most were developed among patients with kidney disease. The association between SCr and GFR may be distorted by kidney dysfunction and thus not applicable to healthy children. This study aimed to evaluate the applicability of existing SCr-based GFR estimation equations in healthy Chinese children. METHODS: GFR estimation equations that developed in healthy children were mainly analysed, including the Flanders Metadata (FM), simple height-independent (Simple), full age spectrum (FAS) and FAS-height equations. The FM equation assumed that GFR is proportional to the ratio of height to SCr. The Simple, FAS and FAS-height equations assumed that the ratio of GFR to population mean is equal to the reciprocal ratio of SCr to population mean (denoted by Q). Estimated GFR were calculated using data of SCr, age, sex and height collected from 12 208 healthy Chinese children aged 3 months to <20 years. The performance of GFR estimation equations was evaluated by the sex and age distribution of the estimated GFR and the deviation from the measured GFR reported by other literatures. RESULTS: The FM and Simple equations performed well in their applicable age of 1 month to 14 years, but presented undesirable sex difference after adolescence. The FAS and FAS-height equations showed reasonable development trend of estimated GFR throughout childhood, and the FAS equation had higher consistency than the FAS-height equation compared with measured GFR in healthy children. The GFR estimated by the FAS equation increased with age before 2 years, and reached the adult level thereafter without important sex difference. CONCLUSIONS: The FAS equation is applicable to healthy Chinese children.

Neutrophils resist ferroptosis and promote breast cancer metastasis through aconitate decarboxylase 1.

Metastasis causes breast cancer-related mortality. Tumor-infiltrating neutrophils (TINs) inflict immunosuppression and promote metastasis. Therapeutic debilitation of TINs may enhance immunotherapy, yet it remains a challenge to identify therapeutic targets highly expressed and functionally essential in TINs but under-expressed in extra-tumoral neutrophils. Here, using single-cell RNA sequencing to compare TINs and circulating neutrophils in murine mammary tumor models, we identified aconitate decarboxylase 1 (Acod1) as the most upregulated metabolic enzyme in mouse TINs and validated high Acod1 expression in human TINs. Activated through the GM-CSF-JAK/STAT5-C/EBPß pathway, Acod1 produces itaconate, which mediates Nrf2-dependent defense against ferroptosis and upholds the persistence of TINs. Acod1 ablation abates TIN infiltration, constrains metastasis (but not primary tumors), bolsters antitumor T cell immunity, and boosts the efficacy of immune checkpoint blockade. Our findings reveal how TINs escape from ferroptosis through the Acod1-dependent immunometabolism switch and establish Acod1 as a target to offset immunosuppression and improve immunotherapy against metastasis.

Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study.

PURPOSE: Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. PATIENTS AND METHODS: This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. RESULTS: We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm (P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm (P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). CONCLUSION: HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.

Retrospective analysis of cataract surgery outcomes in China from 2009 to 2018: from a national registry system data.

OBJECTIVE: To evaluate patients' benefits after cataract surgery and to form recommendations for Chinese national health policy decision makers and administration departments based on the quality of cataract treatments. METHOD: An observational study based on real-world data source from the National Cataract Recovery Surgery Information Registration and Reporting System. RESULTS: A total of 14 157 463 original records were reported from 1 July 2009 to 31 December 2018. The factors that influenced the 3-day postsurgical best-corrected visual acuity (BCVA), the primary outcome, were analysed by logistic regression analysis. We found that a history of hypertension (OR=0.916) or diabetes (OR=0.912), presurgical pupil abnormality (OR=0.571) and high intraocular pressure (OR=0.578) were harmful to the postsurgical BCVA improvement (BCVA ≥6/20), while male sex (OR=1.113), better presurgical BCVA level (OR=5.996 for ≥6/12-<6/7.5 and OR=2.610 for >6/60-<6/12 taken ≤6/60 as reference), age-related cataract (OR=1.825) and intraocular lens implantation (OR=1.886) were statistically beneficial to the postsurgical BCVA improvement. Compared with extracapsular cataract extraction (ECCE) with large incision, the ECCE with small incision (OR value=1.810) and the phacoemulsification (OR=1.420) significantly improved the benefit probability. CONCLUSION: ECCE with small incision has comparable effects on postsurgical BCVA improvement of phacoemulsification. Therefore, ECCE could be an alternative cataract surgical treatment in economically underdeveloped areas in China, provided the surgeons are adequately trained.

Targeting the chromatin effector Pygo2 promotes cytotoxic T cell responses and overcomes immunotherapy resistance in prostate cancer.

The noninflamed microenvironment in prostate cancer represents a barrier to immunotherapy. Genetic alterations underlying cancer cell-intrinsic oncogenic signaling are increasingly appreciated for their role in shaping the immune landscape. Recently, we identified Pygopus 2 (PYGO2) as the driver oncogene for the amplicon at 1q21.3 in prostate cancer. Here, using transgenic mouse models of metastatic prostate adenocarcinoma, we found that Pygo2 deletion decelerated tumor progression, diminished metastases, and extended survival. Pygo2 loss augmented the activation and infiltration of cytotoxic T lymphocytes (CTLs) and sensitized tumor cells to T cell killing. Mechanistically, Pygo2 orchestrated a p53/Sp1/Kit/Ido1 signaling network to foster a microenvironment hostile to CTLs. Genetic or pharmacological inhibition of Pygo2 enhanced the antitumor efficacy of immunotherapies using immune checkpoint blockade (ICB), adoptive cell transfer, or agents inhibiting myeloid-derived suppressor cells. In human prostate cancer samples, Pygo2 expression was inversely correlated with the infiltration of CD8+ T cells. Analysis of the ICB clinical data showed association between high PYGO2 level and worse outcome. Together, our results highlight a potential path to improve immunotherapy using Pygo2-targeted therapy for advanced prostate cancer.

Chinese pediatric and adolescent reference intervals of vitamin E based on real-world physical examination data.

OBJECTIVES: To establish the reference interval (RI) of vitamin E for Chinese children and adolescents. MATERIALS AND METHODS: Serum tocopherol samples were examined using high performance liquid chromatography in third-party clinical laboratory institutions. Using real-world data from multi-center clinical laboratory institutions in China, the distribution parameters of vitamin E levels were described and the RI was calculated using three algorithms. RESULTS: A total of 756,766 cases were included in the analysis, including 435,561 males and 321,205 females. The median of vitamin E in infants younger than 4 years of age initially increased but subsequently decreased; while its levels in children between 4 and 11 years of age remained relatively stable despite progressing in age (approximately 7.4-7.8 mg/L). After the start of puberty, the difference, relative to sex, gradually became apparent, and the median vitamin E levels in females was higher than in males. The differences of vitamin E levels between different regions and samples in different seasons had no clinical significance. The RI of vitamin E for children aged 0-18 years in China was 4.5-11.1 mg/L based on expectation-maximization algorithm. The RI established by the Hoffmann method was 4.6-12.8 mg/L. CONCLUSION: The age- and sex-specific RIs of vitamin E were established by an indirect approach. The RIs established by EM algorithms could be used as an alternative to establish RIs based on real-world data.

Is the Tradeoff between Folic Acid or/and Multivitamin Supplementation against Birth Defects in Early Pregnancy Reconsidered? Evidence Based on a Chinese Birth Cohort Study.

BACKGROUND: Several studies have reported conflicting results on the association between maternal exposure to folic acid (FA) and/or multivitamin (MV) supplements and the risk of birth defects (BDs), especially for different subtypes of BDs. The present study aimed to identify the association between maternal exposure to FA or/and MV and BDs in offspring. METHODS: In the Chinese Birth Cohort Study initiated from 20 November 2017, 120,652 pregnant women completed follow-up until 20 August 2021. The participants were classified into four groups: without exposure to FA and MV, exposure to only FA, exposure to only MV, and exposure to FA and MV. Birth defects were coded by the International Classification of Diseases (ICD)-10. In order to explore the structural relationship between maternal FA or MV supplements and BDs, directed acyclic graphs were drawn. Then, an inverse probability treatment weighting was utilized to reduce the systematic differences in the baseline characteristics among the different groups. Lastly, a two-level mixed-effect log binomial regression analysis was used to estimate the relative risk (RR) value of the different subtypes of BDs under different exposures to FA and/or MV. RESULTS: Compared with the maternal group without exposure to FA and MV, the RR values of nervous system defects, face, ear, and neck defects, limb defects, and CHDs in the maternal group with only FA supplementation were less than 1.0, but they were not statistically significant. The RR values of genitourinary defects, abnormal chromosomes, and oral clefts were more than 1.0, and they were also not statistically significant. However, the risk of genitourinary defects (RR: 3.22, 95% CI: 1.42-7.29) and chromosomal abnormalities (RR: 2.57, 95% CI: 1.16-5.73) in the maternal group with only MV supplementation increased more than those in the maternal group without exposure to FA and MV. In addition, the RR values of all subtypes of BDs in the maternal group with exposure to FA and MV were closer to 1.0 than those in maternal group with exposure to only MV, but they were not statistically significant. CONCLUSIONS: It was indicated that the simultaneous supplementation of FA and MV in early pregnancy may have an interaction for the prevention of BDs and may have inconsistent effects for different subtypes of BDs. At the same time, excessive FA supplementation in pregnant women may increase the risk of BDs in their offspring. Although the mechanism is not clear, this evidence reminded us that more trade-offs are necessary for formulating strategies for the prevention of BDs with FA and/or MV supplementation in early pregnancy.

Clinicians' practices and attitudes regarding advance care planning in mainland China: A multicenter cross-sectional survey.

OBJECTIVES: This study aims to explore clinicians' practices and attitudes regarding advance care planning (ACP) in mainland China. METHODS: This study was a multicenter cross-sectional survey. Clinicians from tertiary hospitals in Beijing, Guangxi, and Inner Mongolia were invited to participate in the study. A questionnaire was formulated based on related literature to obtain information including demographic characteristics, and practices and attitudes toward ACP. RESULTS: The total number of participants included 285 clinicians. The data response rate was 84.57%. Most of the clinicians had an inadequate understanding of ACP. Only a few clinicians had experience in participating or witnessing an ACP or related end-of-life discussions. Among 285 clinicians, 69.82% of clinicians were willing to introduce ACP to patients. Two hundred and thirty-eight (83.51%) clinicians wanted more education on ACP. Almost all clinicians believed that patients had the right to know about their diagnosis, prognosis, and available care options. Most clinicians (82.11%) regarded that ACP was partially feasible in mainland China. If clinicians had a serious illness, almost everyone was willing to find out their true health status and decide for themselves, and 81.40% wanted to institute an ACP for themselves. The biggest barriers to the use of ACP in mainland China were cultural factors. Statistical analysis revealed that some or good understanding level (P = 0.0052) and practical experience (P = 0.0127) of ACP were associated with the positive willingness. SIGNIFICANCE OF RESULTS: ACP is still in its infancy in mainland China. Clinicians had inadequate understanding and minimal exposure to ACP. Most clinicians recognized the value and significance of ACP and had a positive attitude toward ACP. Clinicians need to be provided with education and training to promote their ACP practices. Culturally appropriate ACP processes and documents need to be developed based on Chinese culture and Chinese needs.

N-Heterocyclic Carbene Silver Complex Modified Polyacrylonitrile Fiber/MIL-101(Cr) Composite as Efficient Chiral Catalyst for Three-Component Coupling Reaction.

Complex asymmetric synthesis can be realized by the chiral induction of amino acids in nature. It is of great significance to design a new biomimetic catalytic system for asymmetric synthesis. In this context, we report the preparation and characterization of the composite of polyacrylonitrile fiber (PANF) and metal-organic framework to catalyze the chiral synthesis of propargylamines. A confined microenvironment is established with N-heterocyclic carbene (NHC) silver complex-supported PANF and D-proline-encapsulated MIL-101(Cr). This novel supported catalyst demonstrated high activity in addition to excellent stereoselectivity in the three-component reaction between alkynes, aldehydes, and amines (A3). The regeneration can be realized by adsorption of D-proline again when the stereoselectivity decreases after recycle uses. By regulating the confined microenvironment on the composite, the activity and selectivity of the catalytic system are improved with turnover numbers of up to 2800 and 98% ee. The biomimetic catalytic system to A3 coupling reaction is systematically studied, and the synergistic catalytic mechanism between NHC-Ag and D-proline in the confined microenvironment is revealed.

Detection of pediatric drug-induced kidney injury signals using a hospital electronic medical record database.

Background: Drug-induced kidney injury (DIKI) is one of the most common complications in clinical practice. Detection signals through post-marketing approaches are of great value in preventing DIKI in pediatric patients. This study aimed to propose a quantitative algorithm to detect DIKI signals in children using an electronic health record (EHR) database. Methods: In this study, 12 years of medical data collected from a constructed data warehouse were analyzed, which contained 575,965 records of inpatients from 1 January 2009 to 31 December 2020. Eligible participants included inpatients aged 28 days to 18 years old. A two-stage procedure was adopted to detect DIKI signals: 1) stage 1: the suspected drugs potentially associated with DIKI were screened by calculating the crude incidence of DIKI events; and 2) stage 2: the associations between suspected drugs and DIKI were identified in the propensity score-matched retrospective cohorts. Unconditional logistic regression was used to analyze the difference in the incidence of DIKI events and to estimate the odds ratio (OR) and 95% confidence interval (CI). Potentially new signals were distinguished from already known associations concerning DIKI by manually reviewing the published literature and drug instructions. Results: Nine suspected drugs were initially screened from a total of 652 drugs. Six drugs, including diazepam (OR = 1.61, 95%CI: 1.43-1.80), omeprazole (OR = 1.35, 95%CI: 1.17-1.54), ondansetron (OR = 1.49, 95%CI: 1.36-1.63), methotrexate (OR = 1.36, 95%CI: 1.25-1.47), creatine phosphate sodium (OR = 1.13, 95%CI: 1.05-1.22), and cytarabine (OR = 1.17, 95%CI: 1.06-1.28), were demonstrated to be associated with DIKI as positive signals. The remaining three drugs, including vitamin K1 (OR = 1.06, 95%CI: 0.89-1.27), cefamandole (OR = 1.07, 95%CI: 0.94-1.21), and ibuprofen (OR = 1.01, 95%CI: 0.94-1.09), were found not to be associated with DIKI. Of these, creatine phosphate sodium was considered to be a possible new DIKI signal as it had not been reported in both adults and children previously. Moreover, three other drugs, namely, diazepam, omeprazole, and ondansetron, were shown to be new potential signals in pediatrics. Conclusion: A two-step quantitative procedure to actively explore DIKI signals using real-world data (RWD) was developed. Our findings highlight the potential of EHRs to complement traditional spontaneous reporting systems (SRS) for drug safety signal detection in a pediatric setting.

Reference intervals of 14 biochemical markers for children and adolescence in China: the PRINCE study.

OBJECTIVES: The Pediatric Reference Intervals in China (PRINCE) was initiated to establish the reference intervals (RIs) of Chinese children, as well as to make it possible to compare the variability of biochemical markers among countries internationally. METHODS: Healthy participants, aged up to 20 years, from 11 provinces across China, were enrolled in PRINCE and according to a standard screening procedure, that included a questionnaire survey, physical examinations and laboratory tests. Fasting venous blood specimens were collected. All serum specimens were analyzed with Cobas C702 in the center laboratory, i.e. clinical laboratory of Beijing Children's Hospital, with certified qualification (ISO15189). The nonparametric method recommended by Clinical Laboratory Standards Institute guidelines, was used to calculate the age- and sex-specified RIs. RESULTS: Among the 15,150 participants enrolled, 12,352 children (6,093 males and 6,259 females) were included to calculate RIs. The RIs for total protein, albumin, globulin, calcium, phosphate, potassium, sodium, chlorine, alkaline phosphatase, γ-glutamyl transpeptadase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were established by age- or sex-partitions. Most biochemical markers displayed larger variability and higher dispersion during the periods between 28 days and 1 year old, and included 4-6 age partitions commonly during 1 to <20 years old. In addition, differences of RIs between sexes usually occurs around the initiation of puberty at 12-13 years old. CONCLUSIONS: The age- and sex-specified RIs of 14 biochemical markers in PRINCE study can provide a solid reference, which will be transferred into relevant RIs for other clinical laboratory's platforms according to the CLSI guidelines.

Dual crosslinking of folic acid-modified pectin nanoparticles for enhanced oral insulin delivery.

Pectin-based drug delivery systems hold great potential for oral insulin delivery, since they possess excellent gelling property, good mucoadhesion and high stability in the gastrointestinal (GI) tract. However, lack of enterocyte targeting ability and premature drug release in the upper GI tract of the susceptible ionic-crosslinked pectin matrices are two major problems to be solved. To address these issues, we developed folic acid (FA)-modified pectin nanoparticles (INS/DFAN) as insulin delivery vehicles by a dual-crosslinking method using calcium ions and adipic dihydrazide (ADH) as crosslinkers. In vitro studies indicated insulin release behaviors of INS/DFAN depended on COOH/ADH molar ratio in the dual-crosslinking process. INS/DFAN effectively prevented premature insulin release in simulated GI fluids compared to ionic-crosslinked nanoparticles (INS/FAN). At an optimized COOH/ADH molar ratio, INS/DFAN with FA graft ratio of 18.2% exhibited a relatively small particle size, high encapsulation efficiency and excellent stability. Cellular uptake of INS/DFAN was FA graft ratio dependent when it was at/below 18.2%. Uptake mechanism and intestinal distribution studies demonstrated the enhanced insulin transepithelial transport by INS/DFAN via FA carrier-mediated transport pathway. In vivo studies revealed that orally-administered INS/DFAN produced a significant reduction in blood glucose levels and further improved insulin bioavailability in type I diabetic rats compared to INS/FAN. Taken together, the combination of dual crosslinking and FA modification is an effective strategy to develop pectin nano-vehicles for enhanced oral insulin delivery.

Signal Detection of Pediatric Drug-Induced Coagulopathy Using Routine Electronic Health Records.

Background: Drug-induced coagulopathy (DIC) is a severe adverse reaction and has become a significantly increased clinical problem in children. It is crucial to the detection of the DIC safety signal for drug post-marketing scientific supervision purposes. Therefore, this study aimed to detect potential signals for DIC in children using the routine electronic medical record (EMR) data. Methods: This study extracted EMR data from Beijing Children's Hospital between 2009 and 2020. A two-stage modeling method was developed to detect the signal of DIC. We calculated the crude incidence by mining cases of coagulopathy to select the potential suspected drugs; then, propensity score-matched retrospective cohorts of specific screened drugs from the first stage were constructed and estimated the odds ratio (OR) and 95% confidence interval (CI) using conditional logistic regression models. The current literature evidence was used to assess the novelty of the signal. Results:In the study, from a total of 340 drugs, 22 drugs were initially screened as potentially inducing coagulopathy. In total, we identified 19 positive DIC associations. Of these, potential DIC risk of omeprazole (OR: 2.23, 95% CI: 1.88-2.65), chlorpheniramine (OR:3.04, 95% CI:2.56-3.60), and salbutamol sulfate (OR:1.36, 95% CI:1.07-1.73) were three new DIC signals in both children and adults. Twelve associations between coagulopathy and drugs, meropenem (OR: 3.38, 95% CI: 2.72-4.20), cefoperazone sulbactam (OR: 2.80, 95% CI: 2.30-3.41), fluconazole (OR: 2.11, 95% CI: 1.71-2.59), voriconazole (OR: 2.82, 95% CI: 2.20-3.61), ambroxol hydrochloride (OR: 2.12, 95% CI: 1.74-2.58), furosemide (OR: 2.36, 95% CI: 2.08-2.67), iodixanol (OR: 2.21, 95% CI: 1.72-2.85), cefamandole (OR: 1.82, 95% CI: 1.56-2.13), ceftizoxime (OR: 1.95, 95% CI: 1.44-2.63), ceftriaxone (OR: 1.95, 95% CI: 1.44-2.63), latamoxef sodium (OR: 1.76, 95% CI: 1.49-2.07), and sulfamethoxazole (OR: 1.29, 95% CI: 1.01-1.64), were considered as new signals in children. Conclusion: The two-stage algorithm developed in our study to detect safety signals of DIC found nineteen signals of DIC, including twelve new signals in a pediatric population. However, these safety signals of DIC need to be confirmed by further studies based on population study and mechanism research.

Prevalence and burden of chronic cough in China: a national cross-sectional study.

Background: Chronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD). Methods: A representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded. Results: Chronic cough was found in 3.6% (95% CI 3.1-4.1) of Chinese adults, 2.4% (95% CI 1.9-3.1) of those aged 20-49 years and 6.0% (95% CI 5.3-6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p<0.0001) and more emergency visits (p=0.0042) and hospital admissions (p=0.0002). Furthermore, the impact of chronic cough on PCS score was more significant in those aged 50 years or older, or with COPD (p=0.0018 or 0.0002, respectively), with the impact on hospital admission being more significant in those with COPD or with SAD (p=0.0026 or 0.0065, respectively). Conclusions: Chronic cough is prevalent in China and is associated with a poorer health status, especially in individuals aged 50 years or older and those with the diagnosis of COPD or SAD.

Optimal cut-off value of serum procalcitonin in predicting bacterial infection induced acute exacerbation in chronic obstructive pulmonary disease: A prospective observational study.

OBJECTIVE: To explore the optimal cut-off value of serum procalcitonin (PCT) level in predicting bacterial infection in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: 204 hospitalized patients with AECOPD were enrolled in this study. Their diagnoses and treatments followed routine protocols in Fu-Xing Hospital affiliated to Capital Medical University, Beijing, China. Extra blood samples were taken for serum PCT level testing and the results were blinded to the treating physicians. On discharge, clinical data were collected and the treating physicians made comprehensive analyses to determine whether the AECOPD were triggered by respiratory tract bacterial infection or non-bacterial causes according to the "new diagnostic criteria" defined in this study. In the AECOPD patients with bacterial infection, treating physicians decided whether they had bacterial pneumonia based on imaging studies. Receiver operating characteristic curve (ROC) was used to analyze the accuracy of serum PCT level in predicting bacterial infection. RESULTS: In the 173 AECOPD patients who did not have pneumonia, 115 had evidences of bacterial infection while 58 did not. The median PCT levels were 0.1(0.08, 0.18) ng/ml and 0.07 (0.05, 0.08) ng/ml for each group, which were statistically different. The proposed optimal cut-off value of serum PCT level in predicting bacterial infection was 0.08 ng/mL according to this study, with a sensitivity of 81%, specificity of 67% and area under the ROC curve (AUC) of 0.794. There were 31 AECOPD patients diagnosed with pneumonia, their median PCT level was 0.23 ng/mL. CONCLUSIONS: The serum PCT levels slightly increased in the majority of hospitalized patients with AECOPD compared with reference range. When PCT level was ≥0.08 ng/mL, AECOPD was more likely to be caused by bacterial infection. A significantly elevated PCT levels may indicate combination of AECOPD and bacterial pneumonia.

Awareness about laryngopharyngeal reflux disease among Chinese otolaryngologists: a nationwide survey.

OBJECTIVES: This study aimed to investigate the status of the current knowledge about laryngopharyngeal reflux disease (LPRD) among Chinese otolaryngologists. DESIGN: Multi-centre cross-sectional survey. SETTING: 220 medical centres in different regions of China. PARTICIPANTS: A total of 2254 otolaryngologists from 220 medical centres in China who were successfully on-site surveyed between November 2019 and December 2020. MAIN OUTCOME MEASURES: Awareness about LPRD included knowledge about risk factors, symptoms, laryngoscope signs, related diseases, current diagnostic methods and treatments. RESULTS: The percentage of participants who had heard of LPRD was 96.4%, with academic conferences as the most common source of information (73.3%). The most commonly known risk factor, symptom, laryngoscope sign, related disease, diagnostic method and treatment were alcohol consumption (44.0%), pharyngeal foreign body sensation (66.9%), hyperaemia (52.4%), pharyngolaryngitis (54.8%), pH monitoring (47.6%) and medication (82.1%), respectively. Only 28.3% of all participants knew that 24 h pH or multichannel intraluminal impedance pH monitoring was the most accurate diagnostic test. As many as 73.1% of all participants knew that proton pump inhibitors were the first-line treatment drugs. An analysis of the overall status of awareness using a scoring system suggested that otolaryngologists were better aware owing to more access, working at 3A hospitals, and postgraduate or above educational background (all p<0.05). CONCLUSION: Although the majority of Chinese otolaryngologists had heard of LPRD, their overall awareness about the disease was not encouraging. More efforts are needed to increase the knowledge about LPRD among this group of physicians. TRIAL REGISTRATION NUMBER: ChiCTR1900025581.