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*

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

RNA-binding protein human antigen R(HuR)is a protein product of the embryonic lethal abnormal vision gene(ELAVL).It is widely expressed in human cells and primarily regulates mRNA stability through post-transcriptional mecha-nisms,particularly by binding to AU-enriched elements(AR-Es).Recent studies have indicated that HuR interacts with non-coding RNAs to participate in the regulation of gene expression,including long non-coding RNAs,circular RNAs,microRNAs,and vault RNAs.The interactions between HuR and these ncR-NAs play a crucial role in the occurrence and development of va-rious diseases,including tumors.Since there are already reviews summarizing the research on tumors,this review mainly focuses on summarizing the role of HuR-ncRNA interactions in diseases other than tumors.

RNA-binding protein human antigen R(HuR)is a protein product of the embryonic lethal abnormal vision gene(ELAVL).It is widely expressed in human cells and primarily regulates mRNA stability through post-transcriptional mecha-nisms,particularly by binding to AU-enriched elements(AR-Es).Recent studies have indicated that HuR interacts with non-coding RNAs to participate in the regulation of gene expression,including long non-coding RNAs,circular RNAs,microRNAs,and vault RNAs.The interactions between HuR and these ncR-NAs play a crucial role in the occurrence and development of va-rious diseases,including tumors.Since there are already reviews summarizing the research on tumors,this review mainly focuses on summarizing the role of HuR-ncRNA interactions in diseases other than tumors.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

In order to promote the regional homogeneous diagnosis of electrocardiogram (ECG), in April 2020, a tertiary hospital in Xinjiang led the establishment of a specialty alliance for regional telediagnosis of ECG that conforms to the regional characteristics of Xinjiang based on the " Internet+ specialty alliance" model. The specialty alliance had built a telediagnosis platform of ECG based on the regional five level remote network system, achieving telediagnosis services of static ECG, dynamic ECG, and dynamic blood pressure, and providing technical support for integrated management of ECG diagnosis data and remote training. The leading hospital and alliance member units carried out diversified " online+ offline" cooperation through the platform, covering telediagnosis, training, suitable technology sharing, scientific research collaboration, and discipline construction, achieving the sinking and sharing of high-quality diagnostic resources in tertiary hospital, and promoting the homogenization of regional ECG diagnosis. As of December 2023, the leading hospital had signed specialty alliance agreements with 56 medical institutions and telediagnosis cooperation agreements with 37 primary medical and health institutions, completed 28 217 cases of telediagnosis, conducted more than 50 academic activities, and promoted 6 new technologies/projects. This specialty alliance achieved good results, which could provide references for other public hospitals to promote the development of specialty alliances.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the effects of α1-antitrypsin(AAT)on motor function in adult mice with immature brain white matter injury.Methods Five-day-old C57BL/6J mice were randomly assigned to the sham surgery group(n=27),hypoxia-ischemia(HI)+ saline group(n=27),and HI+AAT group(n=27).The HI white matter injury mouse model was established using HI methods.The HI+AAT group received intraperitoneal injections of AAT(50 mg/kg)24 hours before HI,immediately after HI,and 72 hours after HI;the HI+saline group received intraperitoneal injections of the same volume of saline at the corresponding time points.Brain T2-weighted magnetic resonance imaging scans were performed at 7 and 55 days after modeling.At 2 months of age,adult mice were evaluated for static,dynamic,and coordination parameters using the Catwalk gait analysis system.Results Compared to the sham surgery group,mice with HI injury showed high signal intensity on brain T2-weighted magnetic resonance imaging at 7 days after modeling,indicating significant white matter injury.The white matter injury persisted at 55 days after modeling.In comparison to the sham surgery group,the HI+saline group exhibited decreased paw print area,maximum contact area,average pressure,maximum pressure,paw print width,average velocity,body velocity,stride length,swing speed,percentage of gait pattern AA,and percentage of inter-limb coordination(left hind paw → left front paw)(P<0.05).The HI+saline group showed increased inter-paw distance,percentage of gait pattern AB,and percentage of phase lag(left front paw → left hind paw)compared to the sham surgery group(P<0.05).In comparison to the HI+saline group,the HI+ AAT group showed increased average velocity,body velocity,stride length,and swing speed(right front paw)(P<0.05).Conclusions The mice with immature brain white matter injury may exhibit significant motor dysfunction in adulthood,while the use of AAT can improve some aspects of their motor function.[Chinese Journal of Contemporary Pediatrics,2024,26(2):181-187]

Purpose: This study investigated the adjunctive effect of light-emitting diodes (LEDs) in the treatment of experimental periodontitis. Methods: Experimental periodontitis was induced by placing ligatures around the mandibular second, third, and fourth premolars of 6 beagles for 3 months. After ligature removal, periodontitis progressed spontaneously for 2 months. The animals’ hemimandibles were allocated among the following 3 groups: 1) no treatment (control), 2) scaling and root planing (SRP), and 3) SRP with LED irradiation at 470-nm and 630-nm wavelengths (SRP/LED). The probing pocket depth (PPD) and gingival recession (GR) were measured at baseline, 6 weeks, and 12 weeks. The clinical attachment level (CAL) was calculated. After 12 weeks, histological and histomorphometric assessments were performed. The distances from the gingival margin to the apical extent of the junctional epithelium (E) and to the connective tissue (CT) attachment were measured, as was the total length of soft tissue (ST). Results: PPD and CAL increased at 12 weeks compared with baseline in the control group (6.31±0.43 mm to 6.93±0.50 mm, and 6.46±0.60 mm to 7.61±0.78 mm, respectively). PPD and CAL decreased at 12 weeks compared with baseline in the SRP group (6.01±0.59 to 4.81±0.65 mm, and 6.51±0.98 to 5.39±0.93 mm, respectively). PPD and CAL decreased at 12 weeks compared with baseline in the SRP/LED group (6.03±0.39 to 4.46±0.47 mm, and 6.11±0.47 to 4.78±0.57 mm, respectively). The E/ST and CT/ST ratios significantly differed among the 3 groups (P<0.05). The clinical parameters and histologic findings demonstrated that 470-nm and 630-nm wavelength LED irradiation accompanying SRP could improve treatment results. Conclusions Within the study limitations, 470 nm and 630 nm wavelength LED irradiation might provide additional benefits for periodontitis treatment.