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Abstract Background The Access, Watch, and Reserve (AWaRe) classification of antibiotics was a useful tool to support antibiotic stewardship. However, the AWaRe patterns of antibiotic consumption in Western China were unclear. We aimed to assess the antibiotic consumption patterns using the AWaRe Classification of public hospitals in Sichuan Province Western China. Methods Antibiotic consumption data of year 2020 were obtained from the Sichuan Province Drug Use Monitoring Platform. We measured the antibiotic consumption (DDDs per 1,000 inhabitants per day, DIDs), calculated the proportion of antibiotic use, the ratio of Access to Watch antibiotics and patterns of antibiotic use by using drug utilization 90%. Results This analysis included 4452 public health institutions. The antibiotic consumption rate was 10.39 DIDs (Median 8.50, IQR 7.71–12.96). The proportions of Access antibiotic use and Watch antibiotic use were 46.83% (Median 47.49, IQR 44.16–52.02) and 51.20% (Median 51.43, IQR 45.42–54.61), respectively. The Access-to-Watch index was 0.91 (Median 0.92, IQR 0.81–1.15). Amoxicillin (16.85%), cefuroxime (9.21%), cefixime (8.60%%), levofloxacin (8.11%) and metronidazole (6.16%) were the most consumed antibiotics. Conclusions The proportion of Access antibiotic consumption in Sichuan Western China has not achieved the WHO target of 60%. Overuse of antibiotic is serious in Sichuan. National and regional antibiotics management systems, stewardship programs and surveillance of antibiotic consumption based on AWaRe classification are needed to improve antibiotic consumption patterns, curb antibiotic overuse and combat antimicrobial resistance in Western China.

Abstract Background Medication Treatment Satisfaction (M-TS) from the patients’ perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps. Methods Using PubMed, Embase (Ovid), Cochrane library (Ovid), IPA (Ovid), PsycINFO, Patient-Reported Outcome and Quality of Life Questionnaires biomedical databases, and four Chinese databases, we performed a systematic search for studies addressing the development and validation of PROMs for M-TS. Based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, pairs of reviewers independently assessed the measurement properties of the PROMs and rated the quality of evidence on the measurement properties of each PROM. (The Open Science Framework registration: https://doi.org/10.17605/OSF.IO/8S5ZM ). Results This review identified 69 PROMs for M-TS in 114 studies (four generic, 32 disease-specific, and 33 drug-specific) of which 60 were intended for adults. All provided limited or no information regarding interpretability. Most demonstrated appropriate construct validity including convergent validity (39/69) and discriminative or known-groups validity (40/69) (high to moderate quality of evidence). Only a few provided evidence of sufficient content validity (8/69), structural validity (13/69), and internal consistency (11/69). Of 38 PROMs reporting test–retest reliability, results in 24 provided evidence of satisfactory test–retest reliability (18 with high to moderate, 6 with low to very low quality of evidence). Few PROMs reported responsiveness (16/69). Two generic PROMs (Treatment Satisfaction Questionnaire for Medication initial Version 1.4, TSQM-1.4; Treatment Satisfaction with Medicines Questionnaire, SATMED-Q) and one drug-specific PROM (Insulin Treatment Satisfaction Questionnaire, ITSQ) demonstrated both satisfactory validity and reliability. Conclusions Most existing PROMs for M-TS require further exploration of measurement properties. Reporting guidelines are needed to enhance the reporting quality of the development and validation of PROMs for M-TS.

Abstract Currently, in vitro cultured corneal epithelial transplantation is effective in treating limbal stem cell dysfunction (LSCD). Selecting carriers is crucial for constructing the corneal epithelium through tissue engineering. In this study, the traditional amniotic membrane (AM) was modified, and mesenchymal stem cells (MSCs) were inoculated into the ultra-thin amniotic membrane (UAM) stroma to construct a novel UAM-MSC tissue-engineered corneal epithelial carrier, that could effectively simulate the limbal stem cells (LSCs) microenvironment. The structure of different carriers cultured tissue-engineered corneal epithelium and the managed rabbit LSCD model corneas were observed through hematoxylin–eosin staining. Cell phenotypes were evaluated through fluorescence staining, Western blotting, and RT-qPCR. Additionally, cell junction genes and expression markers related to anti-neovascularization were evaluated using RT-qPCR. Corneal epithelium cell junctions were observed via an electron microscope. The tissue-engineered corneal epithelium culture medium was analyzed through mass spectrometry. Tissue-engineered corneal epithelial cells expanded by LSCs on UAM-MSCs had good transparency. Simultaneously, progenitor cell (K14, PNCA, p63) and corneal epithelial (PAX6) gene expression in tissue-engineered corneal epithelium constructed using UAM-MSCs was higher than that in corneal epithelial cells amplified by UAM and de-epithelialized amniotic membrane. Electron microscopy revealed that corneal epithelial cells grafted with UAM-MSCs were closely connected. In conclusion, the UAM-MSCs vector we constructed could better simulate the limbal microenvironment; the cultured tissue-engineered corneal epithelium had better transparency, anti-neovascularization properties, closer intercellular connections, and closer resemblance to the natural corneal epithelial tissue phenotype.

Abstract Background PCSK9 inhibitors are a novel class of lipid-lowering drugs that have demonstrated favorable efficacy and safety. Evolocumab and alirocumab have been added to China’s National Reimbursement Drug List through the National Drug Price Negotiation (NDPN) policy. This study aims to evaluate the impact of the NDPN policy on the utilization and accessibility of these two PCSK9 inhibitors. Methods The procurement data of evolocumab and alirocumab were collected from 1,519 hospitals between January 2021 and December 2022. We determined the monthly availability, utilization, cost per daily defined dose (DDDc), and affordability of the two medicines. Single-group interrupted time series (ITS) analysis was performed to assess the impact of the NDPN policy on each drug, and multiple-group ITS analysis was performed to compare the differences between them. Results The NDPN policy led to a significant and sudden increase in the availability and utilization of PCSK9 inhibitors, along with a decrease in their DDDc. In the year following the policy implementation, there was an increase in the availability, utilization, and spending, and the DDDc remained stable. The affordability of PCSK9 inhibitors in China have been significantly improved, with a 92.97% reduction in out-of-pocket costs. The availability of both PCSK9 inhibitors was similar, and the DDDc of alirocumab was only $0.23 higher after the intervention. The market share of evolocumab consistently exceeded that of alirocumab. Regional disparities in utilization were observed, with higher utilization in the eastern region and a correlation with per capita disposable income. Conclusions The NDPN policy has successfully improved the accessibility and utilization of PCSK9 inhibitors in China. However, regional disparities in utilization indicate the need for further interventions to ensure equitable medicine access.

Abstract Background Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. Methods This study included 6952 children aged 9–11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers

Abstract Cephalopods can change their skin color by using high‐speed electron transduction among receptors, neural networks, and pigmentary effectors. However, it remains challenging to realize a neuroelectrical transmission system like that found in cephalopods, where electrons/ions transmit on nanoscale, which is crucial for fast adaptive electrochromic tuning. Inspired by that, hereby an ideal, rapidly responsive, and multicolor electrochromic biomimetic skin is introduced. Specifically, the biomimetic skin comprises W18O49 nanowires (NWs) that are either colorless or blue, Au nanoparticles@polyaniline (Au NPs@PANI) ranging from green to pink, and a flexible conductive substrate. As the applied voltage changes from 0.4 V to ‐0.7 V and back to 0 V, the color of the biomimetic skin transforms from green to blue and ultimately to pink. This color change is attributed to the electrically induced redox reaction of Au NPs@PANI and W18O49 NWs, triggered by the transfer of electrons and ions. Furthermore, the high versatility and adaptability of electrical stimulus enable the creation of a highly interactive electrochromic biomimetic skin system through the integration of sensitive acoustic sensors, providing a perfect environment‐responsive platform. This work provides a biomimetic multicolor electrochromic skin that depends on electron/ion transfer on nanoscale, expands potential uses for camouflage skin.

BackgroundRetardation among children is a persistent global health concern. Vitamin deficiency in childhood may contribute to growth retardation; however, its causal effects are not fully understood.ObjectiveHere, we aimed to explore the prediction values of fat-soluble vitamin levels on GR in children aged 1–6 years.Methods614 children aged from 1 to 6 years at Nantong Maternal and Child Care Health Hospital between January 2021 and December 2022 in this retrospective observational study participated in the assessment of developmental status and blood detection of vitamin from peripheral blood (PB). The relationship between vitamin levels and GR was analyzed by Multivariable logistic regression analysis.ResultsDevelopmental assessment results showed that 132 cases from 614 with growth retardation (21.50%). Statistical analysis showed children with GR were more likely to be males (59.45% vs. 40.55%, p = 0.191). The age of children with GR was significantly higher than those without GR (p

Background: Tinnitus treatment remains a global challenge, and current therapeutic approaches are still controversial. This study aims to elucidate the potential mechanisms of Xiao-Chai-Hu-Tang (XCHT) in treating tinnitus through the analysis of network pharmacology, mendelian randomization and molecular docking, and molecular dynamics simulation analysis. We hope to contribute to the research on the target of action of traditional Chinese medicine and exploration of the mechanism of tinnitus. Methods: We utilized network pharmacology to screen potential targets of action of XCHT on tinnitus. Mendelian randomization was employed to determine the causal relationship between potential targets of action and tinnitus. Finally, molecular docking and molecular dynamics simulation with clear targets and the combination of the active ingredient in effectiveness. Results: Through network pharmacology, we identified 38 potential targets of action. Mendelian randomization analysis revealed that HIF1A (OR [95 % CI] = 0.78 [0.65, 0.94], P = 0.008) and CCND1 (OR [95 % CI] = 1.22 [1.00, 1.49], P = 0.04) exhibited significant results with tinnitus. Molecular docking and molecular dynamics simulation of HIF1A and active ingredients demonstrated good binding efficacy. Conclusion: HIF1A may play a key role in the treatment of tinnitus by XCHT, which may play a certain protective role in tinnitus patients and may inhibit the occurrence and development of tinnitus. However, the specific mechanism and effect need to be further studied and verified.

Abstract Parents’ beliefs and attitudes toward their children with Tourette syndrome (TS) influence treatment-seeking behaviors. This study aimed to explore and describe the Chinese parents’ perspectives on the causes of TS for their children. A qualitative study using semi-structured interviews was conducted with the parents of TS patients from a children’s hospital in western China from June to July 2021, and thematic analysis was performed to transcribe interviews and identify themes. A total of 13 participants were interviewed in this study. Five themes were developed in relation to the cognition of the causes of TS in parents, including physical problems, parenting and education problems, mental problems, bad habits, and neurological problems. Due to the insufficient awareness of TS, most parents repeatedly seek medical advice that they regarded the symptoms as physical problems or neurological problems. They generally felt guilty and blamed themselves for their parenting styles and education methods. And some parents attributed it to the poor psychological quality or the bad habits of children. Study findings showed a lack of scientific understanding of the causes of TS among parents further hindered the timely effective treatment for patients and affected the family relationships, which highlights the importance of public education and raising awareness of the disease.

Abstract Background Cancer stem-like capacities are major factors contributing to unfavorable prognosis. However, the associated molecular mechanisms underlying cancer stem-like cells (CSCs) maintain remain unclear. This study aimed to investigate the role of the ubiquitin E3 ligase membrane-associated RING-CH 7 (MARCH7) in bladder cancer cell CSCs. Methods Male BALB/c nude mice aged 4–5 weeks were utilized to generate bladder xenograft model. The expression levels of MARCHs were checked in online databases and our collected bladder tumors by quantitative real-time PCR (q-PCR) and immunohistochemistry (IHC). Next, we evaluated the stem-like capacities of bladder cancer cells with knockdown or overexpression of MARCH7 by assessing their spheroid-forming ability and spheroid size. Additionally, we conducted proliferation, colony formation, and transwell assays to validate the effects of MARCH7 on bladder cancer CSCs. The detailed molecular mechanism of MARCH7/NOD1 was validated by immunoprecipitation, dual luciferase, and in vitro ubiquitination assays. Co-immunoprecipitation experiments revealed that nucleotide-binding oligomerization domain-containing 1 (NOD1) is a substrate of MARCH7. Results We found that MARCH7 interacts with NOD1, leading to the ubiquitin–proteasome degradation of NOD1. Furthermore, our data suggest that NOD1 significantly enhances stem-like capacities such as proliferation and invasion abilities. The overexpressed MARCH7 counteracts the effects of NOD1 on bladder cancer CSCs in both in vivo and in vitro models. Conclusion Our findings indicate that MARCH7 functions as a tumor suppressor and inhibits the stem-like capacities of bladder tumor cells by promoting the ubiquitin–proteasome degradation of NOD1. Targeting the MARCH7/NOD1 pathway could be a promising therapeutic strategy for bladder cancer patients.

Abstract Objective This work compares the marketing authorization, labels and dosage forms of medicines in the WHO Model List of Essential Medicines for Children (EMLc) in China, the Russian Federation and Brazil to urge policymakers to pay more attention to paediatric medication. Methods Medicines were selected from the 8th EMLc. By searching relevant databases, which include different types of medical information in China, the Russian Federation and Brazil, the marketing authorization, labels and dosage forms of paediatric medicines in the three countries were evaluated. Results A total of 485 drug products containing 312 active pharmaceutical ingredients listed in the WHO EMLc were evaluated. Among them, 344 products were approved for use in China, 286 in the Russian Federation and 264 in Brazil. Out of the 344 approved medicines, 317 (92.15%) were authorized for paediatric use in China, 224 (78.32%) in the Russian Federation and 218 (82.58%) in Brazil. In terms of guidance information labelling on drug labels, 75.08%, 83.04% and 88.07% of paediatric drugs approved in China, the Russian Federation and Brazil, respectively, clearly indicated the usage and dosage for paediatric use. Additionally, injections and tablets were the most prevalent dosage forms in these three countries. Conclusion There is still scope for enhancing the marketing authorization and development of dosage forms for paediatric medicines in the three countries. Furthermore, additional measures are being implemented to enhance the information provided on drug labels for children, particularly in China.

Background: Generic substitution policies have been widely implemented worldwide to enhance the accessibility of medications. Nevertheless, certain patients have voiced discontent with these policies. This study aimed to evaluate the patient preferences for generic substitution policies and explore the potential for optimization to enhance patient acceptance.Methods: A discrete choice experiment (DCE) was conducted to estimate the relative importance (RI) of five attributes, including generic consistency evaluation (GCE), reimbursement rate, medication use control, information disclosure, and post-marketing surveillance. Respondents were recruited among inpatients and outpatients in three cities and surveys were conducted face-to-face. Preference coefficients, RI of attributes, and the uptake rate of various policies were computed using a mixed logit model. The interaction effects were also included to examine preference heterogeneity.Results: A total of 302 patients completed the survey. All five attributes significantly impacted policy acceptance. GCE held the highest RI value at 56.64%, followed by reimbursement rate (RI = 12.62%), information disclosure (RI = 12.41%), post-marketing surveillance (RI = 9.54%), and medication use control (RI = 8.80%). Patient preferences varied depending on their gender and income. The patient uptake rate of China’s current policy was only 68.56%. If all generics were to pass GCE without altering the other attributes, the uptake rate of policies would rise to 82.63%. Similarly, implementing information disclosure without changing other attributes would result in a 78.67% uptake rate, which is comparable to the effect of a 10% increase in reimbursement rate for generics (78.81%). Combining these policies could mitigate the adverse effects of mandatory substitution on patient.Conclusion: Chinese patient preferences for generic substitution policies were mainly influenced by GCE. China’s current generic substitution policy has room for further optimization to enhance patient acceptance.

The task of image deblurring is a complex and ill-posed inverse problem, which endeavors to restore a high-fidelity image from its degraded and blurred counterpart. Traditional deblurring methodologies are often confronted with the challenge of maintaining the integrity of image details and edges throughout the restoration procedure. This paper delves into an innovative approach that synergistically harnesses the power of non-local statistical properties and wavelet tight frame based $\ell _{0}$ regularization. The presented model integrates non-local statistical priors pertaining to the image in question into its regularization framework. Meanwhile, it leverages the robustness of wavelet tight frames to counteract the inherent ill-posedness of image deblurring scenarios. This dual strategy results in a more effective preservation of fine details and edges during the deblurring process. Empirical numerical simulations corroborate the efficacy of the presented algorithm. It demonstrates a marked superiority over existing deblurring techniques in terms of quantitative metrics such as Peak Signal-to-Noise Ratio (PSNR), Root Mean Square Error (RMSE), Structural Similarity Index (SSIM), and Universal Image Quality Index (UQI). Consequently, the presented algorithm yields images of enhanced deblurring quality, substantiating its potential in image restoration.

Abstract Rapid and accurate judgment of the rock mass condition is the key to guaranteeing the safety and efficiency of tunnel boring machine (TBM) tunneling. This paper proposes a method for evaluating rock mass parameters based on K-means clustering, grouping tunneling areas according to the values of TBM tunneling parameters. A dataset including rock mass and TBM tunneling data is treated by logistic normalization and principal component analysis (PCA), and large volumes of tunneling data with different features are transformed into appropriate volumes of dimensionless data. K-means clustering is used, samples are grouped according to the values of tunneling data, and the specific ranges as defined by clustering are regarded as the unified evaluated results of each group. Based on the C1 part of the Pearl Delta water resources allocation project, 100 training samples and 30 testing samples were field-collected, and the proposed method was realized by the training samples and verified by the testing samples. The evaluation accuracies of uniaxial compressive strength (UCS), and joint frequency (Jf) were 90%, and 86.7% respectively, demonstrating that the evaluation had acceptable values, and the proposed method was greatly helpful for judging rock conditions.

The prevention of ecological risks is a critical determinant influencing sustainable development. Driven by rapid socio-economic development, the ecosystems of mountainous cities within agro-pastoral transition zones are increasingly vulnerable to complex disturbances, constituting a significant threat to sustainable development and human well-being. To help achieve sustainable development, it is essential to conduct research on addressing and mitigating ecological risks from the perspective of collaborative management networks in mountainous cities. Taking Zhangjiakou as the study area, this paper employed the land use transfer matrix and standard deviation ellipse methods to analyze the dynamic land use changes. Additionally, using Fragstats 4,2 to calculate the landscape indices with land use data, this paper evaluated the landscape ecological risk (LER) from 2000 to 2020. Furthermore, the social network analysis (SNA) method was utilized to explore the spatial correlation characteristics of the LER. The findings indicate that: (1) Cultivated land and grassland were the predominant land use types in Zhangjiakou. During 2000–2020, Zhangjiakou experienced significant changes in land use, dominated by the transfer among cultivated land, forestland, and grassland. It indicated that the issue of unstable ecological land use continued to exist. Affected by human activities, construction land showed a consistent upward trend, primarily concentrated in the urban built-up areas and areas along the Jing-Zhang Railway. (2) The LER of Zhangjiakou was predominantly characterized by low risk, medium risk, and high risk levels. In the transitional areas and foothills, the LER was relatively higher. During 2000–2020, Zhangjiakou showed a declining trend of LER. This suggested that the ecological protection policies in Zhangjiakou were effective, leading to an improvement in the local ecological environment. (3) The LER in Zhangjiakou demonstrated a spatial clustering pattern that exhibited an upward trend, which was supported by both spatial autocorrelation and the SNA analysis. In the LER collaborative management network, Xuanhua, Qiaodong, Qiaoxi, Wanquan and Zhangbei consistently upheld pivotal roles. Based on the number of inward and outward connections, 16 counties in Zhangjiakou were classified into four categories and three zones accompanied by corresponding recommendations. The findings of this study can serve as a valuable reference for subsequent landscape pattern optimization and ecological restoration in Zhangjiakou.

Objectives This study aimed to analyse the current status, trends and risk factors of disease burden from 1990 to 2019 among Chinese children.Design and participants It was a retrospective study on data from the Global Burden of Disease Study 2019 (GBD 2019). Data of disease burden and risk factors were extracted from the GBD 2019. Children were divided into two groups of

Abstract Background The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors offered dyslipidemia patients an alternative to statins for lipid‐lowering treatment. Understanding patient and physician preferences for lipid‐lowering drugs may promote shared decision‐making and improve treatment outcomes. Methods This study utilized an online discrete choice experiment (DCE) to assess the relative importance (RI) of six attributes related to lipid‐lowering drugs, including frequency of administration, mode of administration, reduction of low‐density lipoprotein cholesterol (LDL‐C) level, risk of myopathy, risk of liver damage, and out‐of‐pocket monthly cost. Respondents were recruited from dyslipidemia patients and cardiovascular physicians in China. A mixed logit model and latent class analysis were employed to estimate the preference coefficient, marginal willingness to pay (mWTP), and RI of attributes. Ethical approval has been obtained for this study. Results A total of 708 patients and 507 physicians participated in the survey. Patients prioritized the ‘risk of liver damage’ (RI = 23.6%) with ‘mode of administration’ (RI = 19.2%) and ‘frequency of administration’ (RI = 18.8%) following closely. Contrarily, physicians prioritized the ‘reduction of LDL‐C level’ (RI = 33.5%), followed by ‘risk of liver damage’ (RI = 26.0%) and ‘risk of myopathy’ (RI = 16.1%). Patients placed a higher value on ‘frequency of administration’ (p

BackgroundThe association between benign paroxysmal positional vertigo (BPPV) and various mental disorders is still controversial. This study used the Mendelian randomization (MR) method to clarify the correlation between BPPV and seven mental disorders (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings) to aid in the exploration of BPPV complications and prevention and early treatment of mental disorders.MethodsThe datasets for BPPV and seven mental disorders were obtained from genome-wide association studies (GWASs). Two-sample MR was used to analyze the correlation between exposure (BPPV) and various outcomes (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings). A reverse MR study was also performed. The inverse variance weighting (IVW) method, the MR–Egger method, the simple mode method, the weighted mode method, and the weighted median method were selected.ResultsThe MR analysis and the reverse MR analysis results did not reveal significant associations between BPPV and bipolar disorder, depression, anxiety disorder, schizophrenia, suicidal tendencies, neuroticism, and mood swings. Interestingly, neuroticism (IVW: OR = 1.142, 95% CI: 1.059–1.231, P = 0.001; P-MR-PRESSO adjustment = 0.0002) and mood swings (IVW: OR = 3.119, 95% CI: 1.652–5.884, P = 0.0004) may have a significant association with BPPV. After MR-PRESSO adjustment, there was no horizontal pleiotropy or heterogeneity, and a significant association between neuroticism, mood swings, and BPPV has still been suggested.ConclusionWe conducted MR analysis on genetic data from European populations and discovered a causal relationship between BPPV and the seven mental disorders. Our research findings suggest that BPPV may not have a significant causal relationship with bipolar disorder, depression, anxiety disorder, schizophrenia, or suicidal tendencies. However, neuroticism and mood swings may be risk factors for BPPV.

Abstract Background Nebulized drug delivery is commonly used in pediatric clinical practice. The growing number of literatures have reported the application of nebulized ketamine in pediatric sedation in recent years. This meta-analysis of randomized controlled trials comparing the efficacy and safety of nebulized ketamine versus different pharmacological approaches was conducted to estimate the effects of this technique in pediatric sedation. Methods We searched PubMed, Embase, and Cochrane Library from inception to Feb 2023. All randomized controlled trials used nebulized ketamine as presurgical and pre-procedural sedatives in children were included. Sedative effects and various adverse events were considered as the outcomes. Results Ten studies with 727 pediatric patients were enrolled. Compared to nebulized dexmedetomidine, using of ketamine via nebulization showed similar sedation satisfaction (54.79% vs. 60.69%, RR = 0.88, with 95%CI [0.61, 1.27]), success rate of parental separation (57.27% vs. 73.64%, RR = 0.81, with 95%CI [0.61, 1.08]), and mask acceptability (37.27% vs. 52.73%, RR = 0.71, with 95%CI [0.45, 1.10]). However, the using of combination of two medications (nebulized ketamine plus nebulized dexmedetomidine) was associated with better sedative satisfaction (33.82% vs. 68.11%, RR = 0.50, with 95%CI [0.27, 0.92]) and more satisfactory mask acceptance (45.59% vs. 71.01%, RR = 0.69, with 95%CI [0.56, 0.86]). Compared with nebulized ketamine, using of nebulized dexmedetomidine was associated with less incidence of emergence agitation (18.18% vs. 3.33%, RR = 4.98, with 95%CI [1.88, 13.16]). Conclusions Based on current evidences, compared to nebulized dexmedetomidine, nebulized ketamine provides inconspicuous advantages in pediatric sedation, and it has a relatively high incidence of emergence agitation. Combination of nebulized ketamine and dexmedetomidine might be considered as one preferred option in pediatric sedation as it can provide more satisfactory sedative effects. However, there is insufficient evidence regarding nebulized ketamine versus ketamine administered through other routes and nebulized ketamine versus other sedatives. The overall low or moderate quality of evidence evaluated by the GRADE system also calls for more high-quality studies with larger sample sizes in future. Research registration The protocol of present study was registered with PROSPERO (CRD42023403226).

Abstract We aimed to evaluate the prevalence of medication adherence, assess the association between guardians’ mental health and medication adherence for children seen at outpatient department from western China, and identify characteristics associated with nonadherence. We conducted a cross-sectional survey. Participants were recruited by consecutive sampling from the outpatient of the West China Second Hospital from October 2021 to April 2022. The Morisky Medication Adherence Scale (MMAS-8) was used to evaluate patients’ medication adherence. A multivariate linear regression model was used to analyze influencing factors. 1206 children with a mean age of 6.02 ± 3.86 years were included. Seventeen percent (208/1206) of patients showed good adherence, 24.7% (298/1206) showed moderate adherence, and 58% (700/1206) showed poor adherence. Thirty-five percent (428/1206) of guardians had anxiety. Factors that influenced medication adherence included anxiety score of guardian (P = 0.030), education level of guardian (P = 0.003), annual household income (P = 0.001), and days the patient is on the medication (P = 0.023). A majority of children seen at outpatient department from West China had low medication adherence, and depression and anxiety among guardians were common. Implementing health education measures will be important for improving medication adherence in future.

Abstract Background Evidence of drug-induced liver injury is abundant in adults but is lacking in children. Our aim was to identify suspected drug signals associated with pediatric liver injury. Methods Hepatic adverse events (HAEs) among children reported in the Food and Drug Administration Adverse Event Reporting System were analyzed. A descriptive analysis was performed to summarize pediatric HAEs, and a disproportionality analysis was conducted by evaluating reporting odds ratios (RORs) and proportional reporting ratios to detect suspected drugs. Results Here, 14,143 pediatric cases were reported, specifically 49.6% in males, 45.1% in females, and 5.2% unknown. Most patients (68.8%) were 6–18 years old. Hospitalization ranked first among definite outcomes (7,207 cases, 37.2%). In total, 264 disproportionate drug signals were identified. The top 10 drugs by the number of reports were paracetamol (1,365; ROR, 3.6; 95% confidence interval (CI), 3.4–3.8), methotrexate (878; ROR, 2.5; 95% CI, 2.3–2.7), vincristine (649; ROR, 3.0; 95% CI, 2.8–3.3), valproic acid (511; ROR, 3.2; 95% CI, 2.9–3.6), cyclophosphamide (490; ROR, 2.4; 95% CI, 2.2–2.6), tacrolimus (427; ROR, 2.4; 95% CI, 2.2–2.7), prednisone (416; ROR, 2.1; 95% CI, 1.9–2.3), prednisolone (401; ROR, 2.3; 95% CI, 2.1–2.5), etoposide (378; ROR, 2.3; 95% CI, 2.1–2.6), and cytarabine (344; ROR, 2.8; 95% CI, 2.5–3.2). After excluding validated hepatotoxic drugs, six were newly detected, specifically acetylcysteine, thiopental, temazepam, nefopam, primaquine, and pyrimethamine. Conclusions The hepatotoxic risk associated with 264 signals needs to be noted in practice. The causality of hepatotoxicity and mechanism among new signals should be verified with preclinical and clinical studies.

Bone metabolism is a process in which osteoclasts continuously clear old bone and osteoblasts form osteoid and mineralization within basic multicellular units, which are in a dynamic balance. The process of bone metabolism is affected by many factors, including diet. Reasonable dietary patterns play a vital role in the prevention and treatment of bone-related diseases. In recent years, dietary patterns have changed dramatically. With the continuous improvement in the quality of life, high amounts of sugar, fat and protein have become a part of people’s daily diets. However, people have gradually realized the importance of a healthy diet, intermittent fasting, calorie restriction, a vegetarian diet, and moderate exercise. Although these dietary patterns have traditionally been considered healthy, their true impact on bone health are still unclear. Studies have found that caloric restriction and a vegetarian diet can reduce bone mass, the negative impact of a high-sugar and high-fat dietary (HSFD) pattern on bone health is far greater than the positive impact of the mechanical load, and the relationship between a high-protein diet (HPD) and bone health remains controversial. Calcium, vitamin D, and dairy products play an important role in preventing bone loss. In this article, we further explore the relationship between different dietary patterns and bone health, and provide a reference for how to choose the appropriate dietary pattern in the future and for how to prevent bone loss caused by long-term poor dietary patterns in children, adolescents, and the elderly. In addition, this review provides dietary references for the clinical treatment of bone-related diseases and suggests that health policy makers should consider dietary measures to prevent and treat bone loss.

Abstract Objectives The main objective of this study is to evaluate the methodological quality and reporting quality of living systematic reviews (LSRs) on Coronavirus disease 2019 (COVID-19), while the secondary objective is to investigate potential factors that may influence the overall quality of COVID-19 LSRs. Methods Six representative databases, including Medline, Excerpta Medica Database (Embase), Cochrane Library, China national knowledge infrastructure (CNKI), Wanfang Database, and China Science, Technology Journal Database (VIP) were systematically searched for COVID-19 LSRs. Two authors independently screened articles, extracted data, and then assessed the methodological and reporting quality of COVID-19 LSRs using the "A Measurement Tool to Assess systematic Reviews-2" (AMSTAR-2) tool and "Preferred Reporting Items for Systematic reviews and Meta-Analyses" (PRISMA) 2020 statement, respectively. Univariate linear regression and multivariate linear regression were used to explore eight potential factors that might affect the methodological quality and reporting quality of COVID-19 LSRs. Results A total of 64 COVID-19 LSRs were included. The AMSTAR-2 evaluation results revealed that the number of "yes" responses for each COVID-19 LSR was 13 ± 2.68 (mean ± standard deviation). Among them, 21.9% COVID-19 LSRs were rated as "high", 4.7% as "moderate", 23.4% as "low", and 50% as "critically low". The evaluation results of the PRISMA 2020 statement showed that the sections with poor adherence were methods, results and other information. The number of "yes" responses for each COVID-19 LSR was 21 ± 4.18 (mean ± standard deviation). The number of included studies and registration are associated with better methodological quality; the number of included studies and funding are associated with better reporting quality. Conclusions Improvement is needed in the methodological and reporting quality of COVID-19 LSRs. Researchers conducting COVID-19 LSRs should take note of the quality-related factors identified in this study to generate evidence-based evidence of higher quality.

Abstract A distinct population of skeletal stem/progenitor cells (SSPCs) has been identified that is indispensable for the maintenance and remodeling of the adult skeleton. However, the cell types that are responsible for age-related bone loss and the characteristic changes in these cells during aging remain to be determined. Here, we established models of premature aging by conditional depletion of Zmpste24 (Z24) in mice and found that Prx1-dependent Z24 deletion, but not Osx-dependent Z24 deletion, caused significant bone loss. However, Acan-associated Z24 depletion caused only trabecular bone loss. Single-cell RNA sequencing (scRNA-seq) revealed that two populations of SSPCs, one that differentiates into trabecular bone cells and another that differentiates into cortical bone cells, were significantly decreased in Prx1-Cre; Z24 f/f mice. Both premature SSPC populations exhibited apoptotic signaling pathway activation and decreased mechanosensation. Physical exercise reversed the effects of Z24 depletion on cellular apoptosis, extracellular matrix expression and bone mass. This study identified two populations of SSPCs that are responsible for premature aging-related bone loss. The impairment of mechanosensation in Z24-deficient SSPCs provides new insight into how physical exercise can be used to prevent bone aging.

Abstract Background Tyrosine kinase inhibitors combined with conventional chemotherapy (CC) in treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) has achieved promising efficacy and safety outcomes. The study was conducted to compare the cost-effectiveness between imatinib (HANSOH Pharma, Jiangsu, China) and dasatinib (CHIATAI TIANQING Pharma, Jiangsu, China) in treating pediatric Ph-positive ALL when combined with CC from the perspective of the health system in China. Methods A Markov model was established to simulate a hypothetical cohort of pediatric Ph-positive ALL patients receiving imatinib or dasatinib, combined with CC. The model was designed using a 10-year horizon, a 3- month cycle, and a 5% discount rate. Three health states were included: alive with progression-free survival, progressed disease, and death. Patient characteristics and transition probabilities were estimated based on clinical trials. Other relevant data, such as direct treatment costs and health utility data were extracted from published literature and Sichuan Province’s centralized procurement and supervision platform. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the results. The willingness-to-pay (WTP) was set as three times China’s GDP per capita in 2021. Results In the base-case analysis, the total medical costs were $89,701 and $101,182, and the quality-adjusted life years (QALYs) gained were 1.99 and 2.70, for imatinib and dasatinib regimens, respectively. The incremental cost-effectiveness ratio for dasatinib versus imatinib was $16,170/QALY. The probabilistic sensitivity analysis indicated that treatment with dasatinib combined with CC achieved a 96.4% probability of cost-effectiveness at a WTP threshold of $37,765/QALY. Conclusions Dasatinib combined with CC is likely to be a cost-effective strategy compared to imatinib combination therapy for pediatric Ph-positive ALL in China at a WTP threshold of $37,765/QALY.

Abstract Background Access to essential medicines is a vital component of universal health coverage. The low availability of essential medicines for children (EMC) has led the World Health Organization (WHO) to issue a number of resolutions calling on member states on its improvement. But its global progress has been unclear. We aimed to systematically evaluate the progress of availability of EMC over the past decade across economic regions and countries. Methods We searched eight databases from inception to December 2021 and reference lists to identify included studies. Two reviewers independently conducted literature screening, data extraction and quality evaluation. This study was registered with PROSPERO, CRD42022314003. Results Overall, 22 cross-sectional studies covering 17 countries, 4 income groups were included. Globally, the average availability rates of EMC were 39.0% (95%CI: 35.5-42.5%) in 2009–2015 and 43.1% (95%CI: 40.1-46.2%) in 2016–2020. Based on the World Bank classification of economic regions, income was not proportional to availability. Nationally, the availability rate of EMC was reasonable and high (> 50%) in only 4 countries, and low or very low for the rest 13 countries. The availability rates of EMC in primary healthcare centers had increased, while that for other levels of hospitals slightly declined. The availability of original medicines decreased while that of generic medicines was stable. All drug categories had not achieved the high availability rate. Conclusion The availability rate of EMC was low globally, with slight increase in the last decade. Continuous monitoring and timely reporting of the availability of EMC are also needed to facilitate targets setting and inform relevant policy making.

Objectives: This study aimed to investigate the prevalence and influencing factors of medication adherence in children with central precocious puberty (CPP), and provide references for clinical practice.Methods: Children under 12 years of age with CPP and their caregivers at a women’s and children’s hospital were selected for a cross-sectional study from February to May 2023, and a questionnaire was used to collect basic characteristics of pediatric patients and their caregivers, information of medication, cognition of medication, and medication adherence. The 8-item Morisky Medication Adherence Scale (MMAS-8) was adopted to assess medication adherence, and the potential influencing factors were explored by univariate and multivariate analyses.Results: A total of 125 valid questionnaires were collected. The medication adherence rate of children with CPP reported by caregivers was 76.0%. The univariate analysis showed that the percentage of parental caregivers (p = 0.027), the age of caregivers (p = 0.029), the education level of caregivers (p = 0.001), the financial burden (p < 0.000), the incidence of adverse effects (p = 0.008), and the cognition of medication including the importance of medication (p = 0.002), the dosage of medication (p = 0.002), the adverse effects of medication (p = 0.007), the harm of non-compliance with medication (p < 0.000), and the evaluation of the price of medication (p = 0.003) in the poor adherence group were significantly inferior to those in the better adherence group. The multivariate analysis showed that the higher incidence of adverse effects (p = 0.20), not understanding the harm of non-compliance with medication (p = 0.004), and evaluation of the price of medication as expensive (p = 0.043) were independent risk factors for poor medication adherence.Conclusion: Medication adherence in children with CPP is relatively better, and the factors leading to poor medication adherence are mainly on the caregivers of pediatric patients. It is recommended to increase the health education among caregivers of children with CPP to enhance the cognition of the condition and medication, and further improve the therapeutic efficacy for CPP.

Abstract Though triazole antifungals are the first choice for preventing and treating invasive fungal infections, periostitis caused by voriconazole has been described in emerging case reports; however, no studies exist on this association in real-world clinical settings. Our study aimed to identify the association between periostitis and triazole antifungals by analyzing data from the FDA Adverse Event Reporting System (FAERS). We extracted and analyzed reports on the association between periostitis and triazole antifungals in FAERS from the first quarter of 2004 to the second quarter of 2022 using OpenVigil 2.1. Disproportionality analysis was performed to evaluate the association between periostitis and triazole antifungals, and chi-squared (χ2), relative reporting ratio (RRR), reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural networks (BCPNN) of information components (IC) were reported. In total, 143 patients experienced periostitis while using voriconazole. Disproportionality analysis identified an association between periostitis and voriconazole (χ2 = 82,689.0, RRR = 583.6, 95%CI [472.4, 721.1], PRR = 1808.9, 95%CI [1356.0, 2412.9], ROR = 1831.7, 95%CI [1371.6, 2446.3], IC = 9.2, 95%CI [8.6, 9.8]). However, no safety signals were observed between periostitis and other triazole antifungals. When stratified by sex and age, disproportionality analysis identified positive signals between periostitis and voriconazole. The possible association between periostitis and voriconazole should attract sufficient attention in clinical practice. Alternative treatment with other triazole antifungals can be considered, and causality needs to be verified in further prospective studies.

The genus Bruguiera, a member of the Rhizophoraceae family, is predominantly found in coastal areas as a mangrove plant, boasting a rich and diverse community of endophytes. This review systematically compiled approximately 496 compounds derived from both the Bruguiera genus and its associated endophytes, including 152 terpenoids, 17 steroids, 16 sulfides, 44 alkaloids and peptides, 66 quinones, 68 polyketides, 19 flavonoids, 38 phenylpropanoids, 54 aromatic compounds, and 22 other compounds. Among these, 201 compounds exhibited a spectrum of activities, including cytotoxicity, antimicrobial, antioxidant, anti-inflammatory, antiviral, antidiabetic, insecticidal and mosquito repellent, and enzyme inhibitory properties, etc. These findings provided promising lead compounds for drug discovery. Certain similar or identical compounds were found to be simultaneously present in both Bruguiera plants and their endophytes, and the phenomenon of their interaction relationship was discussed.

ObjectiveThis study aims to preliminarily assess the oncological and reproductive outcomes of fertility preservation treatment using conization combined with pelvic node evaluation in young patients with early-stage cervical cancer (ECC) through meta-analysis.MethodsIn this meta-analysis, we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to 0 7/02/2023.ResultsThere were 17 relevant studies with a total of 620 patients included, of which 444 patients received conization combined with pelvic node evaluation. The combined pregnancy rate was 45.4% (95% CI: 0.34–0.57), the combined live birth rate was 33.9% (95% CI: 0.26–0.42), the combined miscarriage rate was 4.8% (95% CI: 0.02–0.092), the combined preterm delivery rate was 5.1% (95% CI: 0.02–0.092), and the combined recurrence rate was 1.9% (95% CI: 0.006–0.035), which did not significantly differ from that of patients who received radical surgery (OR: 0.689, 95% CI: 0.506–0.938).ConclusionCervical conization combined with pelvic lymph node evaluation for fertility preservation in young ECC patients can achieve oncological outcomes similar to radical surgery while improving pregnancy success rates and preserving postoperative fertility. In summary, fertility preservation treatment using cervical conization combined with pelvic lymph node evaluation may be considered as a viable option for young ECC patients with strong fertility preservation desire, resulting in better pregnancy and live birth outcomes.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier PROSPERO (CRD42023423432).

Abstract Background Gestational weight gain (GWG) criteria recommended by the Institute of Medicine may not be appropriate for Asians. Our aims are to investigate the association between GWG and adverse pregnancy outcomes, and to propose optimal total GWG and rates of GWG for Chinese women. Methods Prospective data of 51,125 mother-child pairs from 27 hospitals and community health care centers from Guizhou, Yunnan and Sichuan provinces in China between 2014 and 2018 were analyzed. Generalized Additive Models were performed to determine the associations of GWG with the risk of aggregated adverse outcomes (gestational diabetes mellitus, preeclampsia, cesarean delivery, stillbirth, preterm birth, macrosomia, large for gestational age, and small for gestational age). The range that did not exceed a 2.5% increase from the lowest risk of aggregated adverse outcomes was defined as the optimal GWG range. Results Among all participants, U-shaped prospective association was found between GWG and the risk of aggregated adverse pregnancy outcomes. The optimal GWG range of 8.2–13.0 kg was proposed for underweight, 7.3–12.5 kg for normal weight, and 2.0–9.4 kg for overweight/obese women. Meanwhile, a higher GWG rate in the first two trimesters than that in the last trimester was suggested, except for overweight/obese women. After stratified by maternal age, mothers ≥35 years were suggested to gain less weight compared to younger mothers. Conclusions To keep a balance between maternal health and neonatal growth, optimal GWG ranges based on Asia-specific BMI categories was suggested for Chinese women with different pre-gravid BMIs and maternal ages.

Abstract Background Diet quality in early childhood has a long-term impact on health outcomes. However, there are scarce dietary indexes for Chinese preschool children, and the existing indexes had limited validity and reliability. This study thus aimed to develop a dietary index for preschool children based on the Chinese Dietary Guideline and Chinese Dietary Reference Intakes and to assess their overall diet quality using the China Health and Nutrition Survey (CHNS). Methods The Chinese Preschooler Dietary Index (CPDI) included 11 components, covering 9 food group components and two nutrient components. The total scores of CPDI ranged from 0 to 90, with a higher score indicating greater diet quality. This study assessed the diet quality of 1742 preschoolers aged two to five years old from CHNS using the CPDI. Dietary intake data were obtained using three-day 24-h diet recalls, and sociodemographic information was also collected. Cochran-Mantel-Haensel (CMH) test was used to explore the association between demographic and CPDI total scores. The principal component analysis, correlation analysis and Cronbach’s alpha were used to evaluate the relative reliability and validity of the CPDI. Finally, a stepwise multiple regression analysis was performed to explore potential influencing factors of CPDI. Results Among the 1742 CHNS preschool children, more than 70% resided in rural areas and 41.2% of the sample were raised in a low-income family. The mean CPDI score of the preschoolers was 38.8 ± 12.9. Higher diet scores were correlated with higher energy and nutrient intake. Children with higher age (β = 0.93, SE = 0.26, P = 0.0003), raised in a home with higher household income (β = 3.11, SE = 0.27, P

Abstract Background Intranasal midazolam and ketamine have been widely used as sedative premedication in children. It is difficult to determine which one yields better sedative effects for clinical practice. We conducted the present meta-analysis by summarizing the evidences to evaluate the efficacy and safety of intranasal midazolam versus intranasal ketamine as sedative premedication in pediatric patients. Methods We searched PubMed, Embase, and Cochrane Library from inception to April 2022. All randomized controlled trials (RCTs) used intranasal midazolam and ketamine as sedatives in children were enrolled. The risk of bias in RCTs was assessed by Cochrane risk of bias tool. Condition of parental separation, anesthesia induction or facemask acceptance, sedation level, different hemodynamic parameters and adverse events were considered as the outcomes in our study. Results A total of 16 studies with 1066 patients were enrolled. Compared with midazolam, administration of intranasal ketamine might be associated with severer changes in hemodynamics parameters including mean blood pressure (SMD = -0.53, with 95% CI [-0.93, -0.13]) and heart rate (HR) (SMD = -1.39, with 95% CI [-2.84, 0.06]). Meanwhile, administration of intranasal midazolam was associated with more satisfactory sedation level (61.76% vs 40.74%, RR = 1.53, with 95%CI [1.28, 1.83]), more rapid onset of sedation (SMD = -0.59, with 95%CI [-0.90, -0.28]) and more rapid recovery (SMD = -1.06, with 95%CI [-1.83, -0.28]). Current evidences also indicated that the differences of various adverse effects between two groups were not significant. Conclusions Given that administration of midazolam via intranasal route provides more satisfactory sedative level with less fluctuation of hemodynamics parameters and more rapid onset and recovery, it might be considered as the preferred sedative premedication for pediatric patients compared to ketamine. However, the widespread evidences with low or moderate quality indicated that superiority of intranasal midazolam in pediatric sedation needs to be confirmed by more studies with high quality and large sample size in future. Trial registration The protocol of present study was registered with PROSPERO (CRD42022321348).

Objective Spliced X-Box binding protein 1 (sXBP1) modulates malignant cell activities and enhances the bortezomib sensitivity in multiple myeloma (MM) cells, while its clinical value in MM patients remains elusive. Hence, the current study aimed to explore this issue, particularly the correlation of sXBP1 with treatment outcomes of bortezomib-based therapy in MM patients.Methods Totally, 97 newly-diagnosed MM patients undergoing bortezomib-based therapy, 20 disease controls (DCs), and 20 health controls (HCs) were enrolled. Bone marrow plasma cell samples were acquired to determine sXBP1 by RT-qPCR.Results sXBP1 was lowest in MM patients, followed by DCs, and highest in HCs (P

Sentiment analysis is the mining of information sentiment tendency, which is mainly used for public opinion monitoring, commodity review analysis, and information retrieval.With the rapid development of social media, the volume of text data has shown explosive growth, and text sentiment analysis has become one of the important research hotspots in the field of natural language processing.At the same time, due to the characteristics of massive, time-varying, unstructured and strongly correlated sentiment data, visual analysis techniques that can present sentiment tendencies intuitively and efficiently are widely used in this field.The recent research on visual analysis of sentiment was reviewed, and according to the presentation form “topic words”, “association”, “evolution”, “spatial and temporal distribution” four aspects of text sentiment visual analysis methods were described, and future sentiment analysis techniques as well as text sentiment visual analysis research were foreseen.

Objectives: To compare the effectiveness and safety of the new antiepileptic drug, lacosamide (LCM) with Levetiracetam, for the treatment of focal epilepsy in children.Methods: This study was a cohort study. Children with focal epilepsy who received LCM or Levetiracetam treatment in West China Second Hospital of Sichuan University were recruited and followed up for 12 months. Changes in the frequency of epilepsy, 50% and 75% responder rates, and seizure freedom rates from baseline to the maintenance period and adherence score were assessed. In addition, adverse events (AEs) were recorded.Results: 92 patients completed the study, and were divided into two groups: LCM (n = 46) and Levetiracetam (n = 46). Participants were aged from 2 to 16.3 years, with a mean epilepsy duration of 2.57 years. The average maintenance dose of LCM was 5.03 ± 1.91 mg/kg/d after the titration period. There was no significant difference between the two groups in terms of the mean seizure frequency during subsequent visits at 1, 3,6, 9, 12 months. There was significant difference between the two groups in terms of the 50% responder rate at 6 months. No serious AEs were reported in both groups. The vast majority of patients had good adherence (adherence score = 4) in the LCM group.Conclusion: LCM is effective as adjunctive therapy in children with epilepsy and has good safety, tolerability and adherence. Large sample size studies with long-term follow-up are needed in the future to comprehensively evaluate the use of LCM in children.Clinical Trial Registration: [https://www.chictr.org.cn/showproj.html?proj=41041], identifier [ChiCTR1900024507].

Background: The concept of prescribing cascades has been proposed for more than 20 years, but the research progress and cognitive level varied in different countries. The aim of this study was to systematically evaluate the current status of relevant original research on prescribing cascades, and to provide references for further research and continuous improvement in clinical practice.Methods: We searched three English databases and four Chinese databases from inception until January 2022. Relevant studies about prescribing cascades meeting the eligibility criteria were extracted independently by two reviewers, and a descriptive analysis was conducted to compare the methods and outcomes of the included studies.Results: A total of 32 studies involving 7,075,200 patients in 11 countries were included, including 13 cross-sectional studies, 11 case reports, 7 cohort studies, and 1 case-control study. The target population was mainly elderly people (24 studies). The purpose of the included studies could be divided into three categories: prevention (4 studies), identification (17 studies), and resolution (11 studies) of prescribing cascades. 49 prescribing cascade routes were identified and mainly attributed to the cardiovascular system, most primary diseases of which were dementia, the initial medications of prescribing cascades were mainly calcium channel blockers, and two to six drugs were involved in the prescribing cascade routes.Conclusion: Prescribing cascades have attracted more attention internationally and current studies have mainly focused on the elderly and their cardiovascular diseases and nervous diseases, but still not yet formed integral research in other special populations of drug use, such as children and pregnant women. It is necessary to further conduct in-depth studies with a broader range, and to establish a series of effective measures to decrease the incidence of prescribing cascades in the high-risk group of drug use.

The efficient coverage of underwater wireless sensor networks (UWSNs) has become increasingly important because of the scarcity of underwater node resources. Complex underwater environments, water flow forces, and undulating seabed reduce the coverage effect of underwater nodes, even leading to coverage holes in UWSNs. To solve the problems of uneven coverage distribution and coverage holes, a three-dimensional iterative enhancement algorithm is proposed for UWSN coverage hole recovery using intelligent search followed by virtual force. Benefiting from biological heuristic search algorithms, improved particle swarm optimization is applied for node pre-coverage. With the change in iteration times, the adaptive inertia weight, acceleration factor, and node position are constantly updated. To avoid excessive coverage holes caused by search falling into local optimum, underwater nodes are considered as particles in the potential field whose virtual forces are calculated to guide nodes towards higher coverage positions. In addition, based on the optimal node location obtained by the proposed algorithm, the monitoring area is divided based on the clustering idea. The underwater routing protocol DBR based on depth information is subsequently used to optimize node residual energy, and its average is calculated comprehensively and compared with the other three coverage algorithms using the DBR routing protocol. Based on the experimental data, after 100 iterations, the coverage rates for BES, 3D-IVFA, DABVF, and the proposed algorithm are 83.28%, 88.85%, 89.31%, and 91.36%, respectively. Moreover, the proposed algorithm is further verified from the aspects of different node numbers, coverage efficiency, node movement trajectory, coverage hole, and average residual energy of nodes, which provides conditions for resource development and scientific research in marine environments.

Abstract Bumetanide, a drug being studied in autism spectrum disorder (ASD) may act to restore gamma-aminobutyric acid (GABA) function, which may be modulated by the immune system. However, the interaction between bumetanide and the immune system remains unclear. Seventy-nine children with ASD were analysed from a longitudinal sample for a 3-month treatment of bumetanide. The covariation between symptom improvements and cytokine changes was calculated and validated by sparse canonical correlation analysis. Response patterns to bumetanide were revealed by clustering analysis. Five classifiers were used to test whether including the baseline information of cytokines could improve the prediction of the response patterns using an independent test sample. An immuno-behavioural covariation was identified between symptom improvements in the Childhood Autism Rating Scale (CARS) and the cytokine changes among interferon (IFN)-γ, monokine induced by gamma interferon and IFN-α2. Using this covariation, three groups with distinct response patterns to bumetanide were detected, including the best (21.5%, n = 17; Hedge’s g of improvement in CARS = 2.16), the least (22.8%, n = 18; g = 1.02) and the medium (55.7%, n = 44; g = 1.42) responding groups. Including the cytokine levels significantly improved the prediction of the best responding group before treatment (the best area under the curve, AUC = 0.832) compared with the model without the cytokine levels (95% confidence interval of the improvement in AUC was [0.287, 0.319]). Cytokine measurements can help in identifying possible responders to bumetanide in ASD children, suggesting that immune responses may interact with the mechanism of action of bumetanide to enhance the GABA function in ASD.

BackgroundToripalimab is the first domestic anti-tumor programmed death 1 antibody marketed in China. The CHOICE-01 trial (identifier: NCT 03856411) demonstrated that toripalimab plus chemotherapy can significantly improve the clinical outcomes of advanced non-small cell lung cancer (NSCLC) patients. However, whether it is cost-effective remains unknown. Given the high cost of combination therapy, a cost-effectiveness analysis of toripalimab plus chemotherapy (TC) versus chemotherapy alone (PC) for the first-line treatment of patients with advanced NSCLC is required.MethodsA partitioned survival model was adopted to predict the course of disease in advanced NSCLC patients on TC or PC from the perspective of the Chinese healthcare system over a 10-year horizon. The survival data were obtained from the CHOICE-01 clinical trial. Cost and utility values were obtained from local hospitals and kinds of literature. Based on these parameters, the incremental cost-effectiveness ratio (ICER) of TC vs. PC was measured, and one-way sensitivity analyses, probabilistic sensitivity analyses (PSA), and scenario analyses were performed to assess the robustness of the model.ResultsIn the base case, TC was associated with an incremental cost of $18510 and an incremental quality-adjusted life year (QALY) of 0.57 compared with PC, resulting in an ICER of $32237/QALY which was lower than the willingness to pay (WTP) threshold ($37654/QALY), TC was cost-effective. The health utility value of progression-free survival, the price of toripalimab, and the cost of best supportive care were factors that significantly influenced the ICER, but no change in any of them could change the model result. TC showed a 90% probability of being a cost-effective option at a WTP threshold of $37,654/QALY. In the 20 and 30-year time horizons, the results remained unchanged and TC remained cost-effective when the second-line treatment was switched to docetaxel.ConclusionAt a WTP threshold of $37,654 per QALY, TC was cost-effective compared to PC for patients with advanced NSCLC in China.

Background: Tuberculosis continues to be a significant global burden. Purified protein derivative of tuberculin (TB-PPD) is one type of tuberculin skin test (TST) and is used commonly for the auxiliary diagnosis of tuberculosis. The recombinant Mycobacterium tuberculosis fusion protein (EC) test is a new test developed in China.Objective: Evaluate the long-term economic implications of using the EC test compared with the TB-PPD test to provide a reference for clinical decision-making.Methods: The target population was people at a high risk persons of being infected with Mycobacterium tuberculosis. The outcome indicator was quality-adjusted life years (QALY). A cost–utility analysis was used to evaluate the long-term economic implications of using the EC test compared with the TB-PPD test. We employed a decision tree–Markov model from the perspective of the whole society within 77 years.Results: Compared with the TB-PPD test, the EC test had a lower cost but higher QALY. The incremental cost–utility ratio was −119,800.7381 CNY/QALY. That is, for each additional QALY, the EC test could save 119,800.7381 CNY: the EC test was more economical than the TB-PPD test.Conclusion: Compared with the TB-PPD test, the EC test would be more economical in the long term for the diagnosis of M. tuberculosis infection according our study.

Background: Essential medicine is a vital component to assure universal access to quality healthcare. However, the trend of affordability to essential medicines in China and its regional differences were not yet fully understood. This study aimed to systematically evaluate the price and affordability of essential medicines, their progress, and regional distribution in China in the last decades.Methods: We searched seven databases and three websites for potentially eligible studies from inception until March 2022. Studies on the price and affordability of essential medicines investigated in China were included. Median and interquartile range (IQR) was used to describe the price and affordability of essential medicines, and compared in three periods, before 2009, from 2009 to 2014, and from 2015 to 2019. Subgroup analysis was performed to examine the price and affordability by regions, health facilities, and ATC categories of medicines. The study was registered with PROSPERO (CRD42022310173).Results: A total of 65 studies including 11,639 health facilities investigated between 2006 and 2019 were included in this review. Median price ratios (MPR) and affordability of essential medicines were reported in 44 studies and 50 studies, respectively. The median MPRs of essential medicines in China was 1.59 (IQR: 5.39), with a tendency to rise first and then fall from 2006 to 2019. And the median affordability was equal to 0.88 (IQR: 2.58) days’ wage of the lowest paid unskilled government worker, but steadily rose from 2006 to 2019. Subgroup analysis showed that the affordability in the western region (1.40, IQR: 2.88), urban area (0.95, IQR: 2.80), private sector (0.90, IQR: 2.30), of originator brands (OB) (2.90, IQR: 6.68), and antineoplastic and immunomodulating agents (5.68, IQR: 56.47) were worse than their counterparts.Conclusion: The prices of essential medicine were higher than international level, the overall affordability of essential medicines in China is acceptable but poor in the western region, for OB drugs and anti-cancer medicines. Further national essential medicine policies are needed to reduce regional disparities and improve the affordability of expensive drugs.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails

ObjectivesRecombinant Mycobacterium tuberculosis fusion protein (EC) was anticipated to be used for the scale-up of clinical application for diagnosis of Mycobacterium tuberculosis infection in China, but it lacked a head-to-head economic evaluation based on the Chinese population. This study aimed to estimate the cost-utility and the cost-effectiveness of both EC and tuberculin pure protein derivative (TB-PPD) for diagnosis of Mycobacterium tuberculosis infection in the short term.MethodsFrom a Chinese societal perspective, both cost-utility analysis and cost-effectiveness analysis were performed to evaluate the economics of EC and TB-PPD for a one-year period based on clinical trials and decision tree model, with quality-adjusted life years (QALYs) as the utility-measured primary outcome and diagnostic performance (including the misdiagnosis rate, the omission diagnostic rate, the number of patients correctly classified, and the number of tuberculosis cases avoided) as the effective-measured secondary outcome. One-way and probabilistic sensitivity analyses were performed to validate the robustness of the base-case analysis, and a scenario analysis was conducted to evaluate the difference in the charging method between EC and TB-PPD.ResultsThe base-case analysis showed that, compared with TB-PPD, EC was the dominant strategy with an incremental cost-utility ratio (ICUR) of saving 192,043.60 CNY per QALY gained, and with an incremental cost-effectiveness ratio (ICER) of saving 7,263.53 CNY per misdiagnosis rate reduction. In addition, there was no statistical difference in terms of the omission diagnostic rate, the number of patients correctly classified, and the number of tuberculosis cases avoided, and EC was a similar cost-saving strategy with a lower test cost (98.00 CNY) than that of TB-PPD (136.78 CNY). The sensitivity analysis showed the robustness of cost-utility and cost-effectiveness analysis, and the scenario analysis indicated cost-utility in EC and cost-effectiveness in TB-PPD.ConclusionThis economic evaluation from a societal perspective showed that, compared to TB-PPD, EC was likely to be a cost-utility and cost-effective intervention in the short term in China.

Introduction For improving and optimising drug use in children, we previously developed a tool (including a series of criteria for identifying potentially inappropriate prescribing in children) by literature review and the two-round Delphi technique to prevent inappropriate medication prescriptions at the prescribing stage.Objective To assess the prevalence of potentially inappropriate prescription (PIP) among hospitalised children and explore risk factors associated with PIP.Design A retrospective cross-sectional study.Setting A tertiary children’s hospital in China.Participants Hospitalised children with complete medical records who received drug treatment and discharged from 1 January to 31 December 2021.Outcome measures We evaluated the medication prescriptions by using a series of previously developed criteria for detecting the prevalence of PIP in hospitalised children and used logistic regression to explore the risk factors (including sex, age, number of drugs, number of comorbidities, days of hospitalisation and admission departments) for PIP in children.Results A total of 87 555 medication prescriptions for 16 995 hospitalised children were analysed, and 19 722 PIPs were detected. The prevalence of PIP was 22.53%, and 36.92% of the children had at least one PIP during hospitalisation. The department with the highest prevalence of PIP was the surgical department (OR 9.413; 95% CI 5.521 to 16.046), followed by the paediatric intensive care unit (PICU; OR 8.206; 95% CI 6.643 to 10.137). ‘Inhaled corticosteroids for children with respiratory infections but without chronic respiratory diseases’ was the most frequent PIP. Logistic regression results showed that PIP was more likely to occur in male patients (OR 1.128, 95% CI 1.059 to 1.202) and younger patients (

With China entering the era of high-quality development, it is of vital importance to improve strategic decision quality (SDQ) of state-owned enterprises (SOEs). As one of the most basic strategic decisions in the process of SOEs reform, position evaluation (PE) is seldom studied from the perspective of strategic decision. Instead of adopting the single decision-making body of traditional SDQ evaluation, a new PE model based on the multi-level strategic decision-making body and aiming at the dynamic balance between strategic stability and strategic change is constructed under the WSC (i.e., “Who”-“Should do”-“Can do”) framework combining top-down strategy and bottom-up strategy. Compared with the traditional model, the three key phases of this new PE model are establishing decision-making body, determining weight of bodies, and optimizing subject weights by K-means. The empirical results show that the model can comprehensively consider the opinions of senior, middle and grass-roots employees by reasonably optimizing subject weights, so as to effectively optimize the existing PE in SDQ of SOEs. This provides a direction for the SDQ optimization of SOEs and a new idea for SDQ evaluation research.

BackgroundEssential medicines are the backbone of healthcare and meet the priority healthcare needs of the population. However, approximately one-third of the global population does not have access to essential medicines. Although China formulated essential medicine policies in 2009, the progress of availability of essential medicines and regional variations remains unknown. Therefore, this study was conducted to evaluate the availability of essential medicines, their progress, and regional distribution in China in the last decade.MethodsWe searched eight databases from their inception to February 2022, relevant websites, and reference lists of included studies. Two reviewers selected studies, extracted data, and evaluated the risk of bias independently. Meta-analyses were performed to quantify the availability of essential medicines, their progress, and regional distribution.ResultsOverall 36 cross-sectional studies conducted from 2009 to 2019 were included, with regional data for 14 provinces. The availability of essential medicines in 2015–2019 [28.1%, 95% confidence interval (CI): 26.4–29.9%] was similar to that in 2009–2014 (29.4%, 95% CI: 27.5–31.3%); lower in the Western region (19.8%, 95% CI: 18.1–21.5%) than Eastern (33.8%, 95% CI: 31.6–36.1%) and Central region (34.5%, 95% CI: 30.6–38.5%); very low for 8 Anatomical Therapeutic Chemical (ATC) categories (57.1%), and low for 5 categories (35.7%) among all ATC groups.ConclusionThe availability of essential medicines in China is low compared with the World Health Organization goal, has not changed much in the last decade, is unequal across regions, and lacks data for half of provinces. For policy-making, the monitoring system of the availability of essential medicines is to be strengthened to enable long-term surveillance, especially in provinces where the data has been missing. Meanwhile, Joint efforts from all stakeholders are warranted to improve the availability of essential medicines in China toward the universal health coverage target.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=315267, identifier: PROSPERO CRD42022315267.

Background: At present, only one systematic review has investigated the effect of levothyroxine (LT4) in the treatment of euthyroid pregnant women with thyroid autoimmunity, but some problems [such as merging different types of research for meta-analysis, lacking neonatal outcomes, and so on] exist in this study, satisfactory results can not be provided. So, this systematic review was performed to investigate the effect of LT4 in euthyroid pregnant women with thyroid autoimmunity, in the hope of providing more comprehensive evidence for clinical use.Methods: Medline (Ovid), Embase (Ovid), and Cochrane Central Register of Controlled Trials were electronically searched from database inception to March 2022. We included cohort studies and RCTs that evaluated the impact of LT4 therapy on pregnancy and neonatal outcomes in euthyroid pregnant women with thyroid autoimmunity. Meta-analyses of different types of studies were performed separately, and meta-analyses were further performed by only including researches with low and moderate risk of bias. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the quality of evidence, and used TSA to test the sufficiency of the evidence.Results: Finally, 2,901 euthyroid pregnant women with thyroid autoimmunity in six RCTs and five cohort studies were included. In all outcomes, no statistically significant differences were found between LT4 group and control group, including miscarriage [RR = 0.85, 95%CI (0.69,1.05), p = 0.14, I2 = 1%], preterm birth [RR = 0.80, 95%CI (0.59,1.08), p = 0.14, I2 = 0%], preeclampsia [RR = 0.68, 95%CI (0.12, 3.91), p = 0.66, I2 = 0%], placenta abruption [Peto’ OR = 0.14, 95%CI (0.00, 6.94), p = 0.32, I2 = 0%], birth weight [MD = -36.00, 95%CI (-170.41, 98.41), p = 0.60, I2 = 0%], gestational age at delivery [MD = -0.10, 95%CI (-0.61, 0.41), p = 0.70, I2 = 0%] and neonatal admission [RR = 1.33, 95%CI (0.21, 8.58), p = 0.76, I2 = 0%]. The results for all outcomes were insufficient and inconclusive as demonstrated by TSA. The GRADE assessments showed that the quality of evidence of 4 outcomes (miscarriage, preterm birth, birth weight and gestational age at delivery) were moderate, and 3 outcomes (preeclampsia, placenta abruption and neonatal admission) were low or very low.Conclusion: For pregnancy and neonatal outcomes in euthyroid pregnant women with thyroid autoimmunity, we did not find benefit of LT4 treatment in this study.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022346745, identifier CRD42022346745.

Abstract Background A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. Methods PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. Results Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. Conclusion Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.

Abstract Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells (BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2 (Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling. RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging.

TBM tunnelling trajectory adjustment is a significant issue in guaranteeing a tunnel project. This paper proposes a theoretical method of trajectory adjustment aimed at synchronously reducing bias angle and distance. The proposed method can be divided into three steps. First, the need for manual intervention in the tunnelling trajectory is determined based on the current bias angle and distance. Next, if manual intervention is required, a theoretical relationship is established using the current bias angle and distance as an input and the rotated angle of the TBM main beam as an output. Finally, a series of constraints according to the normal working conditions of the TBM are incorporated into the method. These constraints ensure that the method remains within the acceptable range of TBM operation. Using mechanical parameters such as the cutterhead diameter and cutter spacing of the TBM used in the sixth section of the Qingdao Metro Project, a model suitable for the project is established, and the model is modified by the tunnelling trajectory data collected in the field. This method provides a reference for TBM drivers to use to correct the tunnelling trajectory while considering the specific conditions of the project.