[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

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*

AIM:To investigate the mechanism by which Shuangdan Mingmu Capsules alleviate retinal inflammatory responses in mice with diabetic retinopathy(DR)through the inhibition of the cGAS-STING signaling pathway.METHODS:SPF C57BL/6J male mice were first randomly divided into two groups: a DR model group(n=30)receiving daily intraperitoneal STZ injections(50 mg/kg)for 5 d, and a normal control group(n=10)receiving equivalent sodium citrate buffer. After successful diabetes induction, the mice were randomly divided into model group, Shuangdan Mingmu Capsules group, and positive drug group, with 10 mice in each group. The Shuangdan Mingmu Capsules group received gavage with Shuangdan Mingmu Capsules solution at a clinically equivalent dose(11.2 g/kg), while the positive drug group received gavage with Calcium Dobesilate solution at an equivalent dose of 11.6 mg/kg. The model group and the normal group received gavage with an equal volume of normal saline. Each group of mice received gavage once daily, and after 8 weeks of intervention treatment, Evans blue staining was used to detect the retinal leakage in each group of mice, HE staining was used to detect changes in the retinal tissue structure, TUNEL staining was used to observe the apoptosis of retinal cells, and immunofluorescence was used to detect the expression levels of retinal Rhodopsin, Opsin, Iba1 and GFAP. Furthermore, Western blot was used to detect the protein expression levels of cGAS, STING, TNF-α, IL-6 and IL-1β in the mouse retina.RESULTS:Compared with the normal group, the model group mice exhibited increased levels of neuroretinal leakage, retinal thinning, and elevated retinal cells apoptosis, accompanied by upregulation of Iba1 and GFAP expression levels in the retina, and downregulation of Rhodopsin and Opsin expression. The protein expression levels of cGAS, STING, TNF-α, IL-6, and IL-1β in the retinal tissue were significantly increased. In contrast to the model group, the Shuangdan Mingmu Capsules group and positive drug group mice showed decreased levels of neuroretinal leakage and retinal cells apoptosis, along with downregulation of Iba1 and GFAP expression levels in the retina, and upregulation of Rhodopsin and Opsin expression. The protein expression levels of cGAS, STING, TNF-α, IL-6, and IL-1β in the retinal tissue were significantly decreased. However, there was no significant difference between the Shuangdan Mingmu Capsules group and the positive drug group.CONCLUSION:Shuangdan Mingmu Capsules exert therapeutic effects on retinal inflammation and early damage in DR mouse models, with the underlying mechanism involving the inhibition of the cGAS-STING signaling pathway.

TFIIB-related factor 1 (BRF1) is an important transcription factor. It specifically regulates the transcription of RNA polymerase III-dependent genes (RNA Pol III genes). The products of these genes are some small non-coding RNAs, including transfer RNAs (tRNAs) and 5S ribosomal RNAs (5S rRNA). The transcription levels of tRNAs and 5S rRNA vary with changes in intracellular BRF1 amounts. tRNAs and 5S rRNA play a crucial role in determining protein synthesis. Studies have demonstrated that dysregulation of tRNAs and 5S rRNA is closely related to cell growth, proliferation, transformation, and even tumorigenesis. BRF1 is a key factor determining the generation of tRNAs and 5S rRNA. Increasing BRF1 expression enhances cell proliferation and transformation, promoting tumor development. In contrast, repressing BRF1 activity decreases the rates of cell proliferation and transformation, and inhibits tumor growth. High levels of BRF1 are found in the samples of patients suffering from hepatocellular carcinoma, breast cancer, gastric carcinoma, lung cancer, prostate carcinoma, and other cancers. It indicates that high levels of BRF1 are closely related to the occurrence of human cancer and may be a common landmark of tumors. But there is discrepancy in the regulatory mechanisms and signaling pathways of BRF1 overexpression in different cancers. In general, high levels of BRF1 in patients suffering from cancer show short survival period and poor prognosis. However, there is one exception, namely breast cancer. Approximate 80% of cases of breast cancer are estrogen receptor-positive (ER+) and 20% are ER-. The cases with high levels of BRF1 reveal longer survival period and better prognosis after they accepted the hormone treatment by Tamoxifen (Tam), compared to the cases with low level BRF1. It seems like a contradiction. Most of the cases with high levels of BRF1 belong to ER+ status. Tam has been used to treat ER+ cases of breast cancer after diagnosis and surgery. Thus, hormone therapy, such as Tam, is more effective on these patients. This is because, on one hand, that Tam competes with E2 (17β-estradiol) to bind to estrogen receptor α (ERα), but does not dissociate to occupy the receptors, blocking E2 binding to this receptor and inhibiting its biological effects. On other hand, Tam can inhibit the expression of BRF1, leading to a decline of intracellular BRF1 levels. Therefore, the actual levels of BRF1 are lower in the patients with ER+ breast cancer. It appears the prognosis of the high BRF1 expression cases better than that of the low BRF1 expression cases. Myocardial hypertrophy manifests magnification of cardiomyocyte volume rather than number increasing in the postnatal heart. Myocardial hypertrophy is a critical risk factor underlying cardiovascular diseases. No matter how myocardial hypertrophy occur, it will ultimately lead to myocardial dysfunction and heart failure. Hypertrophic growth of cardiomyocytes requires a large amount of protein synthesis to meet its needs of cardiomyocyte growth. Animal models and cell experiments have shown that myocardial hypertrophy stimulates a significant increase in BRF1 expression and transcription of tRNAs and 5S rRNA. Interestingly, elevated levels of BRF1 are found in the myocardium tissues of patients with myocardial hypertrophy. These studies demonstrate that BRF1 indeed plays a critical role in myocardial hypertrophy. In summary, high levels of BRF1 are found in patients suffering from different cancers and myocardial hypertrophy. It implies that BRF1 is a promising biological target of cancer and cardiomyopathy. BRF1 is expected to become a common biomarker for early diagnosis and prognostic observation of different human cancers. It is also an important biomarker for the diagnosis and treatment of cardiomyopathy. BRF1 not only holds an important position in the field of basic medical research but also has great prospects for translational medicine. In the present article, we summarize the progress on studies of BRF1 expressions in cancer and cardiomyopathy, proposes future research directions. It is a new research area. Here, we emphasize the significancy of BRF overexpression in the two huge diseases of human, cancer and cardiomyopathy to raise people's attention to this field.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused significant mental distress in populations globally. At the frontline of the pandemic, emergency departments (EDs) are the prime setting to observe the effects of the pandemic on the mental health of the population. We aimed to describe the trend of mental health-related ED attendances at an acute hospital in Singapore before and during the various stages of the COVID-19 pandemic. METHODS: This is a retrospective, descriptive study of patients who presented to the ED between 1 January 2019 and 31 December 2020. Patients diagnosed with mental health-related systematised nomenclature of medicine who visited the ED during this period were identified and were placed into mental health diagnosis categories for analysis. A comparison was made between patients who presented before the pandemic (2019) and during the pandemic (2020). RESULTS: During the study periods, we identified 1,421 patients, of whom 27 were excluded due to non-mental health-related diagnoses, leaving 1,394 patients for analysis. There was a 36.7% increase in mental health-related ED presentations from 2019 to 2020. The proportion of higher-acuity mental health-related ED attendances and number of suicide attempts also increased. CONCLUSION Our study described an increase in the proportion of high-acuity mental health-related ED attendances during the COVID-19 pandemic. Emergency physicians must be cognisant of the effects of the pandemic on mental health. Further research should be conducted to better equip the healthcare system for handling all aspects of the pandemic.
Humans ; COVID-19/psychology* ; Emergency Service, Hospital/statistics & numerical data* ; Retrospective Studies ; Singapore/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Mental Disorders/diagnosis* ; Mental Health ; SARS-CoV-2 ; Tertiary Care Centers ; Pandemics ; Aged ; Suicide, Attempted/statistics & numerical data* ; Young Adult ; Adolescent

AIM To study the chemical constituents from the water fraction of rhizoma of Smilax trinervula Miq.and their biological activities.METHODS Polyamide,silica gel,Sephadex LH-20,ODS and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT mothod,and the inhibitory activities on α-glucosidase were determined by PNPG method.RESULTS Eleven compounds were isolated and identified as tyrosine(1),uridine(2),2-(2',3',4'-trihydroxybutyl)-6-(2",3",4"-trihydroxybutyl)-pyrazine(3),2-(1',2',3',4'-tetrahydroxybutyl)-6-(2",3",4"-trihydroxybutyl)-pyrazine(4),2-(1',2',3',4'-tetrahydroxybutyl)-5-(2",3",4"-trihydroxybutyl)-pyrazine(5),uracil(6),2-(1',2',3',4'-tetrahydroxybutyl)-5-(1",2",3",4"-tetrahydroxybutyl)-pyrazine(7),dioscin(8),shikimic acid(9),pyrazine(10),3,4-dihydroxyphenyethyl alcohol 8-O-β-D-glycopyranoside(11).The IC50 values of compounds 8 to human breast cancer cell MCF-7 was(2.36±0.26)μg/mL,and the IC50 values of compounds 3-5 and 7 to α-glucosidase were(1.54±0.15)-(10.53±0.38)μg/mL.CONCLUSION Compounds 1-7,10 are isolated from Smilax genus for the first time,and compound 9,11 are first isolated from this plant.Compound 8 has anti-tumor activity,and compounds 3-5,7 have α-glucosidase inhibitory activities.

Juvenile idiopathic arthritis(JIA)is the most prevalent joint disease in childhood.The disease is defined as arthritis of unknown etiology,involving one or more joints,with onset before the age of 16 years and symptomatic duration of more than 6 weeks.Temporomandibular joint(TMJ)arthritis is a common manifestation of JIA,but it often develops insidiously.Failing to diag-nose and treat it promptly may lead to maxillofacial dysfunction and dentofacial deformity,and negatively affect the patient's quality of life.Therefore,early diagnosis and disease management of TMJ arthritis are crucial.This article reviews the occurrence of JIA-TMJ arthritis and its progress in clinical diagnosis and disease treatment in recent years,aiming to provide some reference for den-tists in the clinical diagnosis and treatment of JIA.

Objective:To compare the clinical efficacy of Minimally Invasive Surgery (MIS) and traditional Posterior Spinal Fusion (PSF) in treating children with paralytic scoliosis with pelvic obliquity (PSPO) following spinal cord injury.Methods:A retrospective analysis was conducted on the data of 25 patients with PSPO who underwent surgical treatment at the Drum Tower Hospital affiliated with Nanjing University Medical School from January 2017 to June 2023. The cohort included 4 males and 21 females, aged 12.3±2.8 years (range 9-14 years). Patients were divided into the MIS group (12 cases) and the PSF group (13 cases). Radiological parameters were measured preoperatively, postoperatively, and at the last follow-up. Surgical time, intraoperative blood loss, intraoperative blood transfusion volume, length of hospital stay, total hospitalization costs, and complications were recorded. The Scoliosis Research Society questionnaires-22 (SRS-22) Chinese version were used to assess patient satisfaction and efficacy.Results:There were no statistically significant differences between the MIS and PSF groups in age, gender, Risser sign, preoperative Cobb angle for scoliosis, pelvic tilt angle, or local kyphosis angle ( P>0.05). The MIS group demonstrated surgical time of 176±30 minutes, intraoperative blood loss of 300±70 ml, blood transfusion volume of 280±175 ml, and total hospitalization costs of 87'800± 13'300 yuan, all of which were lower than PSF group, with values of 280±91 minutes, 1'433±116 ml, 1'351±996 ml, and 14'8400±26'100 yuan, respectively. These differences were statistically significant ( t=3.789, P=0.001; t=29.328, P<0.001; t=3.667, P=0.001; t=7.271, P<0.001). In the MIS group, preoperative, postoperative, and last follow-up Cobb angles were 79.11°±6.74°, 35.86°±4.98°, and 36.27°±4.84° respectively; pelvic tilt angles were 24.79°±5.58°, 9.18°±3.32°, and 8.79°±2.94°; local kyphosis angles were 38.84°±4.18°, 12.96°±4.87°, and 11.43°±6.08°, respectively. Postoperative and last follow-up angles were significantly reduced compared to preoperative values, with statistically significant differences ( P<0.05). In the PSF group, preoperative, postoperative, and last follow-up Cobb angles were 82.06°±9.26°, 34.75°±5.14°, and 35.15°±5.04° respectively; pelvic tilt angles were 26.60°±6.21°, 10.12°±3.21°, and 9.91°±2.97°; local kyphosis angles were 40.92°±7.04°, 10.92°±7.26°, and 14.02°±5.58°, respectively. Differences from preoperative to postoperative measurements were statistically significant ( P<0.05). At the last follow-up, both groups showed no significant loss of scoliosis correction, and there were no statistically significant differences between the groups postoperatively or at the last follow-up ( P>0.05). In the MIS group, one case of superficial surgical site infection and one case of postoperative atelectasis occurred. In the PSF group, two cases of deep surgical site infection, one case of poor screw placement, and two cases were transferred to the ICU postoperatively due to excessive intraoperative bleeding. Preoperative SRS-22 total scores were 2.0±0.6 for PSF and 2.1±0.4 for MIS. Postoperative SRS-22 total scores (excluding satisfaction) were 3.0±0.5 for PSF and 2.9±0.3 for MIS. The within-group differences from preoperative to postoperative were statistically significant ( P<0.05), while the between-group differences from preoperative to postoperative were not statistically significant ( P>0.05). Conclusion:Compared to the PSF technique, MIS can shorten surgery time, reduce intraoperative blood loss and perioperative complications, and decrease hospitalization costs. MIS can achieve similar early clinical efficacy.

Objective:To evaluate the relationship between postoperative changes in femoral head coverage (FHC) after S 2-Alar-Iliac (S 2AI) screw fixation and the development of sagittal imbalance during follow-up in patients with adult spinal deformity (ASD), providing insights for clinical assessment and treatment strategies. Methods:A consecutive cohort of 98 ASD patients who underwent S2AI fixation between September 2019 and September 2021 was retrospectively analyzed. Patients were divided into two groups based on changes in femoral head coverage (ΔFHC): the FHC-C group (upper quartile ΔFHC, 25 cases) and the FHC-NC group (lower quartile ΔFHC, 24 cases). Additionally, patients were classified into proximal junctional kyphosis (PJK) and non-PJK groups based on their clinical outcomes at the last follow-up. Standing full-spine anteroposterior and lateral X-rays were taken preoperatively, postoperatively, and at the two-year follow-up to measure and document the following spinal parameters: Cobb angle, proximal lumbar lordosis (PLL), distal lumbar lordosis (DLL), lumbar lordosis (LL), lordosis distribution index (LDI), sagittal vertical axis (SVA), coronal balance distance (CBD), thoracic kyphosis (TK), T 1 pelvic angle (T 1PA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL, and proximal junctional angle (PJA). Parameters related to hip joint coverage included: femoral head coverage (FHC), lateral center-edge angle (LCE angle), acetabular index (AI), Sharp angle, and extrusion index (EI). Comparisons of radiographic indicators between the two groups were performed at preoperative, postoperative, and final follow-up assessments. The visual analogue scale (VAS) was used to evaluate the hip pain and back pain. Results:At final follow-up, the incidence of PJK was significantly higher in the FHC-NC group [37.5% (9/24)] compared to the FHC-C group [16.0% (4/25)] (χ 2=3.952, P=0.042). Moreover, the increase in sagittal vertical axis (ΔSVA) was significantly greater in the FHC-NC group (35.9±44.7 mm vs. 14.6±31.8 mm, t=2.216, P=0.031). Patients with PJK had significantly higher preoperative T 1PA (36.8°±10.8° vs. 31.9°±18.4°, t=2.150, P=0.034) and lower immediate postoperative ΔFHC (1.7%±1.5% vs. 3.3%±2.5%, t=2.987, P=0.004), as well as lower changes in lateral center-edge angle during follow-up (0.3°±3.0° vs. 1.1°±8.9°, t=2.334, P=0.022). Pearson correlation analysis revealed significant negative correlations between postoperative ΔFHC and both ΔSVA ( r=-0.374, P=0.008) and proximal junctional angle changes (ΔPJA, r=-0.429, P=0.006). Additionally, increases in VAS leg pain scores correlated negatively with immediate postoperative FHC ( r=-0.314, P=0.025) and ΔFHC ( r=-0.298, P=0.031). Logistic regression indicated that immediate postoperative ΔFHC was a protective factor against PJK [ OR=0.722, 95% CI (0.541, 0.963), P=0.009), with a ROC-determined optimal ΔFHC cut-off of 3.90% (AUC=0.723, Youden index=0.847). Conclusions:Postoperative evaluation of femoral head coverage is clinically important for ASD patients undergoing S2AI screw fixation. A pre-to-post ΔFHC below 3.90% may indicate reduced hip compensation capacity, increasing risks for hip pain, sagittal imbalance progression, and PJK postoperatively.