BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

OBJECTIVES: To investigate the level of neuropsychological development in large for gestational age (LGA) infants at the age of 12 months. METHODS: The infants, aged 12 to <13 months, who attended the Outpatient Service of Child Care in the First Affiliated Hospital of Shandong First Medical University from December 2021 to June 2023, were enrolled as subjects. According to the gestational age and birth weight, they were divided into preterm appropriate for gestational age (AGA) group, preterm LGA group, early term AGA group, early term LGA group, full-term AGA group, and full-term LGA group. A modified Poisson regression analysis was used to investigate the association between LGA and neuropsychological development outcome at 12 months of age. RESULTS: After adjustment for confounding factors, compared with the full-term AGA group at the age of 12 months, the full-term LGA group had a significant increase in the risk of language deficit (RR=1.364, 95%CI: 1.063-1.750), the early term LGA group had significant increases in the risk of abnormal gross motor, fine motor, language, and the preterm LGA group had significant increases in the risk of abnormal language, social behavior, and total developmental quotient (P<0.05); also, the early term AGA group had higher risks of developmental delay across all five attributes and in total developmental quotient at the age of 12 months (P<0.05); except for the language attribute, the preterm AGA group had higher risks of developmental delay in the other 4 attributes (P<0.05). CONCLUSIONS The neuropsychological development of LGA infants with different gestational ages lags behind that of full-term AGA infants at 12 months of age, and follow-up and early intervention of such infants should be taken seriously in clinical practice.
Infant, Newborn ; Infant ; Child ; Humans ; Birth Weight ; Infant, Large for Gestational Age ; Infant, Small for Gestational Age ; Gestational Age ; Child Health

Objective: To explore the application of up-conversing phosphor technology (UPT) to detect pathogenic organisms in the air. Methods: The performance of UPT was verified with Staphylococcus aureus, Yersinia pestis and Escherichia coli O157 as simulated strains, including stability, specificity, sensitivity and response time tests; Air particle sampler is used to collect air samples in the field microenvironment test chamber, and UPT is used for detection. At the same time, compared with the traditional culture method, the practicability of UPT is verified. Results: The coefficient of variation in laboratory was 9.62% and 8.02% when the concentration of 10⁷ CFU/ml and 10⁸ CFU/ml were detected by UPT. The results were less than the allowable target, and the detection system had good stability. The specificity of UPT was verified by Staphylococcus aureus. The results showed that no non-Staphylococcus aureus was detected, and the positive detection rate of different kinds of Staphylococcus aureus was 100%. The specificity of the detection system was good. The sensitivity of UPT for detecting Staphylococcus aureus was 10⁴ CFU/ml. Detection sensitivity of Yersinia pestis ≥10³ CFU/ml; The detection sensitivity of Escherichia coli O157 is ≥10³ CFU/ml, and the response time of UPT to bacteria is within 15 min (all 10 min 15 s). The detection results of bacteria contentration in the air of the on-site microenvironment test cabin by UPT showed that when the concentration of Escherichia coli O157 in the air reached above 10⁴ CFU/m³, the detection results of UPT were positive, and with the increase of air concentration, the numerical concentration measured by UPT showed an upward trend, which was positively correlated with the concentration of bacteria in the air. Conclusion: UPT may be feasible as a rapid method to evaluate the species and contentration of pathogenic organisms in the air.
Humans ; Sensitivity and Specificity ; Technology

The concept of ethnic medicine is divided into a broad sense and a narrow sense. The broad concept refers to the traditional medicine of the Chinese nation, and the narrow concept refers to the traditional medicine of Chinese ethnic minorities. The external medicine is one of the main forms of ethnic medicine, and it is also the important content of ethnic medicine for external use, which is widely used in clinical practice. As the theory of ethnic medicine is unique, the application methods have certain characteristics, which are the key technical parts of clinical practice. However, the existing traditional Chinese medicine consensus formulation me-thods cannot meet the needs of the consensus formulation of the external ethnic medicine. Therefore, the methods suitable for expert consensus on external ethnic medicine are required. This article took Expert opinion on clinical application of Baimai Ointment as an exa-mple, and explorde a reasonable, effective, multi-dimensional, and multi-stage method to formulate expert consensus on the external ethnic medicine. In this research, three-dimensional sources of information, including ancient classics, clinical research evidence, and expert application experiences, were systematically and scientifically collected. After organization and analysis, the information was formed into comprehensive evidence. In a formal consensus meeting, part of the recommendations reached consensus. As to the issues that did not reach agreement, in-depth interviews were used to explore the reasons for the differences and resolve the disagreements. Finally, unanimous recommendations were reached. There are common problems during the formulation process of Expert opinion on clinical application of Baimai Ointment. This study is expected to provide references for the formulation of expert consensus on other external ethnic medicine.
Humans ; Biological Products ; Consensus ; Drugs, Chinese Herbal

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective:To study the policy framework and core content of assistive technology (AT) services, compare the current status of AT in countries with different levels of development, and discuss the future development of international policies and services of AT. Methods:Based on the policy and theoretical framework of AT of the United Nations (UN) and World Health Organization (WHO), the policy framework and main contents of international AT services were analyzed; the policies, assistive products and service development of AT services in countries with different levels of development worldwide were compared; and the policy and innovative technology development hotspots of international AT were explored. Results:AT service is an important component of rehabilitation services, and the development of AT services is a key step toward achieving the UN Sustainable Development Goal 3, "Ensure healthy lifestyles and promote the well-being of people of all ages". UN and WHO advocated AT services policy. The framework is based on the UN Convention on the Rights of Persons with Disabilities (CRPD) on articles related to AT, and WHO documents of AT and rehabilitation, such as World Report on Disability, the Global Plan of Action on Disability, Rehabilitation in the Health System, and Rehabilitation in the Health System: A Guide to Action, as well as WHA 71.8 on Assistive Technology, Improving Access to Assistive Technology. The core elements of the international AT policy aim to build integrated, people-centered health services, emphasize the integration of AT into the health system and rehabilitation services, establish and develop AT services in six building blocks of WHO health system, thereby improving access to quality AT to achieve universal health coverage. Further in the fields of technology and service innovation, it proposed to establish a 5P model. High-income countries and low- and middle-income countries are facing many difficulties and large differences in AT service policies, assistive product provision, and service coverage. In the future, adoption of the 5P model proposed by WHO for policy and service delivery and technological changes, and the innovation of assistive product development and AT service models will be the hot spots of AT development. Conclusion:The policy on AT at international level is centered on the concept of UN CRPD and is based on prospect of policy documents issued by the UN and WHO on AT services, with the core objective of developing AT services to provide timely, appropriate, and affordable to persons with disabilities, aging, and people needed to improve their health, quality of life and well-being. It proposes to integrate AT into universal health coverage and to deliver AT service through primary health care in order to achieve the UN SDG 3 goal with full coverage of AT. It proposes to integrate AT into rehabilitation services, i.e. leadership and governance, financing, AT professionals, AT delivery, medicine and technology, and health information system monitoring AT services. There are differneces in AT products and AT delivery due to the globel differneces in economic and social development levels and challenges in access to AT services. It is necessary to develop relevant policies, planning and innovations in assistive products and AT services. AT development in the future will focus on the 5P model of AT to implement reforms in the field of product and service delivery as well as technological innovation in order to improve the coverage, availability, accessibility and affordability, integrate AT into the health system within the framework of universal health coverage, achieve full coverage of universal AT services, and enhance the quality of AT and improve consumers' well-being.

Objective:To study the prevalence of people with disability, and the demand, service policies and service system for assistive technology (AT) services in Australia. Methods:Referring to policy recommendation and indicators in World Health Organizaion's Rehabilitation in Health Systems, Australia's assistive technology service policy framework, services development and trend of development were analyzed by the means of content analysis and development research. Results:There are about 4.4 million people with disability in Australia, of which 1.4 million (32%) with severe or profound disabilities. Federal, state and territorial governments have respectively issued legislation, policy and related service project, including the National Disability Strategy, National Disability Agreement, the National Disability Insurance Scheme, National Standards for Disability Services and others assistance programs to support disability services. There are about two million Australians with disabilities received AT services support from the mentioned programme and scheme. Australia provides more than ten thousands kinds of AT appliances per year, covering all kinds of products in WHO's Priority Assistive Products List. Conclusion:Australia has developed a federal National Disability Strategy, AT service policies and standards, and established federal and state AT insurance and financial support programs for people with disabilities based on the unmet needs of AT services, and federal and state networks for AT services have been established, and service coordination mechanisms at federal and state levels have been established through the National Disability Agreement, covering all types of people with demand of AT in Australia. It meets the requirements of the policy recommendations and assessment indicators in the WHO's Rehabilitation in Health Systems policy guidelines involving AT services. The future development areas in AT will focus on the fields of policy development, ICF implementation, service delivery system, upgrading of service quality and standard, and new technology application.

Objective:To explore systematic implementation of World Health Organization Family International Classifications (WHO-FICs) in the field of rehabilitation: the theoretical and policy framework at macro level, governance and management mechanism at meso level, and implementation modules at micro levels, respectively. Methods:The policy and theoretical framework of rehabilitation development was discussed based on the international rehabilitation policy documents of WHO, mainly as World Report on Disability, Global Action Plan on Disability and Rehabilitation in Health Service System. Protocol and roadmap of systematic implementation of WHO-FICs, including International Classification of Diseases (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHIβ-2) was proposed. Results:With the use of WHO-FICs, the theoretical and policy framework of rehabilitation was constructed, and the contents and principles of modern rehabilitation services were clarified at macro-level. Rehabilitation is an important part of health service, there are six building blocks: i.e. leadership and governance, financing, human resources for health, service providing, medical technology and health information system. It proposed to use knowledge management system of WHO-FICs, including the classification, nomenclature, definitions, descriptions, terminology and coding systems, to standardize rehabilitation evaluation and statistics. The management and governance system of rehabilitation should be implemented using WHO-FICs. Rehabilitation services are based on the bio-psycho-social model and implemented the principles of people-centered and functioning-oriented. The systematic implementation of WHO-FICs in rehabilitation abide by the model of "Evaluation (ICHI)－Evaluation, Description, Classification and Coding of Functioning (ICF)－Disease Classification, Diagnosis and Coding (ICD)－Rehabilitation Intervention (ICHI)", and with the standardized process of "Evaluation (Functioning and unmet needs)－Diagnose (Disease and Functioning)－Planning of Rehabilitation－Intervention－Evaluation of Outcome". The mic-modules of implementation of WHO-FICs in rehabilitation had been constructed. There were 28 categories of diseases, 7 categories of functioning and 6 categories of rehabilitation interventions in rehabilitation proposed by International Society of Physical and Rehabilitation Medicine. According to ICD-11 and ICF, it proposed to use WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), Brief Model Disability Survey (MDS-B) and VB40 Generic Functioning Domains (VB40), and the ICF core-sets in evaluation of functioning and rehabilitation outcome. The implementation of WHO-FICs in management of medical records and reporting realized the standardized management of medical record, encoding of diseases, functioning and intervention, reporting of performance, and provided tools for billing, reimbursement and payment management of rehabilitation. It proposed to develop WHO-FICs based clinical data sets and big data to implement functioning-related Diagnosis Related Groups and case-mix statistics. Conclusion:With the systematic implementation of WHO-FICs in rehabilitation, the policy and theoretical framework at macro level had been developed. The mechanism of management and governance at meso level had been explored. The application modules and approaches at micro level had been established. A scientific and effective overall solution had been proposed to enhance the scientific, standardized, refined and informatization level, strengthen the level and governance capacity, and improve the quality, safety and the coverage of rehabilitation services.

OBJECTIVE: To investigate the nutritional status of children with cerebral palsy (CP) and the clinical effectiveness of Subjective Global Nutritional Assessment (SGNA) in nutritional assessment of hospitalized children with CP. METHODS: A total of 208 children with CP, aged 1-5 years, who were hospitalized from April to October 2019 were enrolled as subjects. SGNA was used to investigate nutritional status, and the Z-score method recommended by the World Health Organization was used as a reference standard to validate the clinical effectiveness of SGNA. RESULTS: The detection rate of malnutrition in children with CP was 42.3% by SGNA and 39.4% by the Z-score method (P>0.05). The application of SGNA showed high consistency between different evaluators (κ=0.621, P<0.001). With the Z-score method as the reference standard, SGNA had a sensitivity of 80.5%, a specificity of 82.5%, a positive predictive value of 75.0%, and a negative predictive value of 86.7%, and high consistency was observed between the two evaluation methods (κ=0.622, P<0.001). SGNA was moderately consistent with weight-for-age Z-score and height-for-age Z-score (κ=0.495 and 0.478 respectively, P<0.001) and was poorly consistent with weight-for-height Z-score (κ=0.197, P<0.05). CONCLUSIONS There is a relatively high incidence rate of malnutrition in children with CP. SGNA can be used as a tool to assess the nutritional status of children with CP.
Cerebral Palsy ; Child ; Child, Hospitalized ; Child, Preschool ; Humans ; Infant ; Malnutrition ; Nutrition Assessment ; Nutritional Status ; Treatment Outcome

Objective To explore the feasibility of monitoring blood pressure via superficial temporal artery catheterization in neonates,which may provide more ways to monitor arterial blood pressure of neonates.Methods By lottery method,64 neonates from NICU who met inclusion criteria and needed arterial blood pressure monitoring were randomly divided into two groups.Thirty-two cases in the experimental group were treated with superficial temporal artery catheterization,while 32 cases in the control group were treated with radial artery catheterization.The success rate of one-time catheterization,indwelling time of catheter,blood pressure and the rate of complications were compared between two groups.Results There were no significant differences between two groups in the success rate of one-time catheterization,indwelling time of catheter,systolic blood pressure and the rate of complications (P＞0.05).Results showed there was significant difference in diastolic blood pressure between two groups(P＜ 0.05).Conclusion Compared with radial artery blood catheterization,neonatal superficial temporal artery catheterization showed equivalent effect,which made it more convenient for observing condition of neonates.