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.].

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Background With the events reporting on odors in drinking water, odorous substances in water have become a hot topic in water quality analysis. Due to the low concentration of the odor threshold and the complexity of the odor components in water, it is difficult to make accurate qualitative and quantitative analysis. So it is necessary to develop a highly sensitive and accurate qualitative and quantitative analysis method. Objective To establish a method for simultaneous determination of four odorous substances, including dimethyl disulfide, dimethyl trisulfide, 2-methylisoborneol, and geosmin in water by purge and trap-gas chromatography-tandem mass spectrometry. Methods A certain amount of water sample was stored in the sample vial of a purge and trapinstrument. Through nitrogen purging, the odorous substances in water were purged out and enriched in the trap. Subsequently, the odorous substances were rapidly released at high temperatures after heating the trap, and then carried by carrier gas into gas chromatograph. After temperature programming, the substances were separated by an Agilent DB-624 capillary chromatographic column (30 m×0.25 mm, 1.4 μm) and determined by tandem mass spectrometry in multiple reaction monitoring modes, with internal standard method for quantification. The current project optimized purge time, sodium chloride concentration in water sample, desorption temperature, desorption time, and split ratio during the experimental process. Under the optimized experimental conditions, the standard curve, detection limit, and quantification limit were validated. Recovery tests with spiking concentrations of 5.0, 10.0, 30.0, 80.0 ng·L⁻¹ and precision tests were conducted on water samples. Finally, the established method was applied to detect odorous substances in source water, finished water, and pipeline water in Deqing County of Huzhou City. Result After the optimization, the purge time was 20 min, the desorption temperature was 280 ℃, the desorption time was 2 min, the split ratio was 10∶1, and no sodium chloride was added during the purge process. Under the optimized experimental conditions, the calibration curves for the four odorous substances showed an excellent linearity in the range of 1 to 100 ng·L⁻¹ (R>0.999), with 0.3 ng·L⁻¹ limit of detection and 1.0 ng·L⁻¹ limit of quantitation. The average recoveries were from 85.5% to 102.4% and relative standard deviations (RSD) from 1.6% to 5.2%. After applying this method to detect local source water, finished water, and pipeline water, it was found that the positive rates of 2-methylisoborneo, and geosmin were relatively high, while the positive rates of dimethyl disulfide and dimethyl trisulfide were relatively low. Only one sample of source water tested positive for dimethyl disulfide, and all samples were negative for dimethyl trisulfide. Conclusion Combined with the superiority of purge and trap and tandem mass spectrometry, the method has the advantages of easy to perform, strong anti-interference ability, good accuracy and precision, which meet the limit requirements of the four odorous substances in the expanded indices and reference indices of Hygienic standards for drinking water (GB 5749-2022). It also provides technical support for water quality assessment and analysis of odorous substances.

Based on the theory of "one qi circulation" founded by HUANG Yuanyu， the core disease mechanism of colorectal cancer is the innate spleen deficiency and stomach qi failing to bear downward， which leads to the turbidity assemble in large intestine， forming the carcinoma toxin， and ultimately transforms into colorectal cancer. The treatment should base on recovering the circulation of qi， Huangya Decoction （黄芽汤） as the basic formula， the circulation of qi ascending and descending as the base， adjusting ascending and descending together with Xiaqi Decoction （下气汤）， and differentiating the syndrome on yin-yang excess-deficiency； for spleen-kidney yang deficiency syndrome， treated with Tianhun Decoction （天魂汤） to supplement liver， kidney and assist yang； for liver-kidney yin deficiency syndrome， treated wtih Dipo Decoction （地魄汤） to supplement lung， kidney， and assist yang. They jointly prompt one qi circulation to provide the thoughts for the treatment of colorectal cancer by traditional Chinese medicine.

Objective To explore the influence of gender on the prognosis of patients with atrial fibrillation(AF)undergoing left atrial appendage occlusion(LAAO).Methods All non-valvular AF patients who were admitted in our hospital and underwent LAAO from August 2014 to August 2021 were enrolled and grouped according to gender.Their general information,including gender,age,comorbid underlying diseases,and results of transthoracic echocardiography and transesophageal echocardiography(TEE)were collected.The incidences of device-related thrombosis(DRT),pericardial tamponade,stroke,bleeding,hospitalization for heart failure,and cardiac death were recorded during follow-up.The influence of gender on the prognosis of these patients was analyzed.Results There were totally 673 patients with non-valvular AF were enrolled,including 366 males and 307 females,at a mean age of 68.2±9.4 years.When compared with the male patients,the female ones had a higher CHA2DS2-VASc score(P＜0.01),but smaller proportions of history of stroke,average compression ratio of occluders,and incidence of residual shunt(＜3 mm)after occlusion(P＜0.05).In 45～60 d after surgery,TEE revealed that there were 17 cases of DRT,including 8 males(2.2％)and 9 females(2.9％),though without statistical difference between the groups.Among the 17 DRT cases,1 experienced stroke,and the incidence of stroke was 5.9％in those with DRT and 0.5％without.There were 4 cases of postoperative pericardial tamponade,including 1 in the male group and 3 in the female group(no significant difference),and all of them were improved after pericardial puncture and fluid extraction.During the follow-up period of 40.2±20.5 months,no obvious differences were observed between the 2 groups in terms of stroke,bleeding,hospitalization for heart failure,and cardiogenic death.Conclusion Gender shows no significant effect on the prognosis of patients with non-valvular AF after LAAO.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

Humans ; Multiple Myeloma/genetics* ; Neoplasm, Residual/diagnosis* ; Flow Cytometry ; High-Throughput Nucleotide Sequencing

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.
Humans ; Male ; Young Adult ; Adult ; Middle Aged ; MicroRNAs/genetics* ; Signal Transduction/genetics* ; Spermatozoa/metabolism* ; Gene Expression Profiling

OBJECTIVE: To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI). METHODS: A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581). RESULTS: Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371). CONCLUSIONS For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.