Autophagy-related long non-coding RNAs act as prognostic biomarkers and associate with tumor microenvironment in prostate cancer.

Aberrant autophagy could promote cancer cells to survive and proliferate in prostate cancer (PCa). LncRNAs play key roles in autophagy regulatory network. We established a prognostic model, which autophagy-related lncRNAs (au-lncRNAs) were used as biomarkers to predict prognosis of individuals with PCa. Depending on au-lncRNAs from the Cancer Genome Atlas and the Human Autophagy Database, a risk score model was created. To evaluate the prediction accuracy, the calibration, Kaplan-Meier, and receiver operating characteristic curves were used. To clarify the biological function, gene set enrichment analyses (GSEA) were performed. Quantitative real-time PCR (qRT-PCR) was employed to determine the au-lncRNAs expression in PCa cell lines and healthy prostate cells for further confirmation. We identified five au-lncRNAs with prognostic significance (AC068580.6, AF131215.2, LINC00996, LINC01125 and LINC01547). The development of a risk scoring model required the utilization of multivariate Cox analysis. According to the model, we categorized PCa individuals into low- and high-risk cohorts. PCa subjects in the high-risk group had a worse disease-free survival rate than those in the low-risk group. The 1-, 3-, and 5-year periods had corresponding areas under curves (AUC) of 0.788, 0.794, and 0.818. The prognosis of individuals with PCa could be predicted by the model with accuracy. Further analysis with GSEA showed that the prognostic model was associated with the tumor microenvironment, including immunotherapy, cancer-related inflammation, and metabolic reprogramming. Four lncRNAs expression in PCa cell lines was greater than that in healthy prostate cells. The au-lncRNA prognostic model has significant clinical implications in prognosis of PCa patient.

Prediction of postoperative curve correction based on the supine radiographs for adult idiopathic scoliosis (AdIS) patients.

BACKGROUND CONTEXT: Preoperative supine radiographs are mandatory in the new adult idiopathic scoliosis (AdIS) classification. Supine radiographs are easily reproducible and highly predictive of side bending radiographs. However, few studies evaluated the use of supine radiographs in predicting postoperative curve correction after posterior spinal fusion (PSF) in AdIS. PURPOSE: To investigate the use of supine and side bending (SB) radiographs in predicting postoperative curve correction in AdIS patients who underwent PSF. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: 93 AdIS patients who underwent PSF between 2022 and 2023 were included. OUTCOME MEASURES: Demographic data were age, gender, height, weight, body mass index (BMI), Risser grade, Lenke curve types and Cobb angles. Main outcome measures were preoperative and immediate postoperative Cobb angle (proximal thoracic [PT], main thoracic [MT] and thoracolumbar/lumbar [TL/L] curves), Supine Cobb angle and Flexibility rate (PT, MT and TL/L), and Correction rate (PT, MT and TL/L). METHODS: Correlation study was performed between Supine Cobb angle vs. postoperative Cobb angle for PT, MT and TL/L curves. A predictive formula was derived from the correlation plots. RESULTS: A total of 93 subjects were included in our study with a median age of 24.7 years and comprised of 80 females (86.0%). Preoperative Supine Cobb angle (r=0.835, r=0.881, r=0.767, p<.001) and preoperative SB Cobb angle (r=0.815, r=0.872, r=0.801, p<.001) showed similar strong positive correlation with postoperative PT, MT and TL/L Cobb angle, but preoperative Supine Cobb angle had slightly stronger correlation in PT and MT, whereas preoperative SB Cobb angle had stronger correlation in TL/L curve. Using the derived predictive formulae, there was a significant, strong, positive correlation between the predicted value and actual value of postoperative standing Cobb angle, (r=0.852, p<.001), with 71.0% of the patients had predicted postoperative Cobb angle from the supine radiographs within 5 degrees of the actual value. CONCLUSION: Both supine radiographs and side bending radiographs had strong predictability of the postoperative Cobb angle for PT, MT and TL/L curves. In 71.0% of patients, the actual postoperative Cobb angle was within 5 degrees of the predicted postoperative Cobb angle using the predictive formulae.

The widths of the medial and lateral pedicle walls in adolescent idiopathic scoliosis (AIS) with major thoracic curves.

BACKGROUND CONTEXT: The widths of medial and lateral pedicle walls in the normal spine of middle-aged and elderly adults have been investigated and these studies found that the medial pedicle wall was thicker than the lateral pedicle wall. However, none had evaluated the widths of medial and lateral pedicle walls on adolescent or young adult scoliotic spines. PURPOSE: This study aims to identify the distribution and variation of medial and lateral pedicle wall widths throughout the different vertebral levels of the scoliotic spine and its differences according to age, gender, body mass index (BMI), maturity, curve types and curve severity in adolescent idiopathic scoliotic (AIS) patients with major thoracic curves. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: A total of 6,230 pedicles (right: 3,064, left: 3,166) from 191 patients were included in this study, with 264 (right: 183, left: 81) fully corticalized pedicles excluded from analysis. OUTCOME MEASURES: Demographic data were age, gender, height, weight, BMI, Risser grade, Lenke curve types and Cobb angles. The main outcome measures were medial and lateral pedicle wall widths. Associations between pedicle wall widths and demographic data were calculated. METHODS: This was a subanalytical retrospective study done on the same patient population as the previously published study on pedicle grading. The data was obtained from the main computed tomography (CT) scan pedicle study dataset. Medial and lateral pedicle wall widths were measured in the axial slices of CT scans from T1 to L5 vertebrae. RESULTS: A total of 6,230 pedicles (right: 3,064, left: 3,166) from 191 patients were included in this study with 264 (right: 183, left: 81) fully corticalized pedicles excluded from analysis. Right-sided medial pedicle wall widths were narrower from T4-T10 (0.75±0.23 mm) compared to T1-T3 (0.89±0.28 mm) and T11-L5 (0.92±0.30 mm). Left-sided medial pedicle wall widths were narrower from T4 to T7 (0.76±0.24 mm) compared to T1-T3 (0.88±0.26 mm) and T8-L5 (0.90±0.27 mm). Medial cortical wall widths were significantly thicker compared to lateral cortical wall widths for all vertebras from T1 to L5 (right medial 0.85±0.28 mm vs. lateral 0.64±0.26 mm (p<.001), left medial 0.86±0.26 mm vs. lateral 0.64±0.26 mm (p<.001)). The left medial pedicle wall widths were marginally significantly (p<.001) thicker than the right side (right medial 0.85±0.28 mm vs. left 0.86±0.26 mm). The main notable significant differences were located at the periapical region of the thoracic curve between T7 to T10 with the left concave medial pedicle width being thicker than the right convex medial pedicle width. The thinnest medial pedicle walls were located at right concave T7 (0.73±0.24 mm) and T8 (0.73±0.23 mm). We generally found no significant associations between the medial and lateral pedicle wall widths with age, gender, BMI, Risser grade, Cobb angle and curve types. CONCLUSIONS: Knowledge on the widths of medial and lateral pedicle walls, their distribution and differences in a scoliotic spine is important for pedicle screw fixation, especially during pedicle probing to find the pedicle channel. The medial pedicle wall widths were significantly thicker than the lateral pedicle wall widths in AIS patients with major thoracic curves. The right concave periapical region had the thinnest medial pedicle walls.

Analysis of duration of different stages of surgery in posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) patients: comparison between severe versus non-severe AIS.

PURPOSE: Prolonged surgical duration in severe adolescent idiopathic scoliosis (AIS) patients is associated with increased blood loss and perioperative complications. The aim of this study was to compare the duration of each stage of posterior spinal fusion (PSF) in severe AIS (Cobb angle ≥ 90°) with non-severe AIS patients. This analysis will identify the most time-consuming stage of PSF and help surgeons formulate strategies to shorten operative time. METHODS: Retrospective study whereby 90 AIS patients (Lenke type 2, 3, 4, and 6) who underwent PSF from 2019 to 2023 were recruited. Twenty-five severe AIS patients were categorized in Gp1 and 65 non-severe AIS patients in Gp2. Propensity score matching (PSM) with one-to-one with nearest neighbor matching (match tolerance 0.05) was performed. Outcomes measured via operation duration of each stage of surgery, blood loss, number of screws, fusion levels and screw density. RESULTS: Twenty-five patients from each group were matched. Total operative time was significantly higher in Gp1 (168.2 ± 30.8 vs. 133.3 ± 24.0 min, p < 0.001). The lengthiest stage was screw insertion which took 58.5 ± 13.4 min in Gp1 and 44.7 ± 13.7 min in Gp2 (p = 0.001). Screw insertion contributed 39.5% of the overall increased surgical duration in Gp1. Intraoperative blood loss (1022.2 ± 412.5 vs. 714.2 ± 206.7 mL, p = 0.002), number of screws (17.1 ± 1.5 vs. 15.5 ± 1.1, p < 0.001) and fusion level (13.1 ± 0.9 vs. 12.5 ± 1.0, p = 0.026) were significantly higher in Gp1. CONCLUSION: Screw insertion was the most time-consuming stage of PSF and was significantly longer in severe AIS. Adjunct technologies such as CT-guided navigation and robotic-assisted navigation should be considered to reduce screw insertion time in severe AIS.

Insulin Determines Transforming Growth Factor ß Effects on Hepatocyte Nuclear Factor 4α Transcription in Hepatocytes.

Loss of hepatocyte nuclear factor 4α (HNF4α) expression is frequently observed in end-stage liver disease and associated with loss of vital liver functions, thus increasing mortality. Loss of HNF4α expression is mediated by inflammatory cytokines, such as transforming growth factor (TGF)-ß. However, details of how HNF4α is suppressed are largely unknown to date. Herein, TGF-ß did not directly inhibit HNF4α but contributed to its transcriptional regulation by SMAD2/3 recruiting acetyltransferase CREB-binding protein/p300 to the HNF4α promoter. The recruitment of CREB-binding protein/p300 is indispensable for CCAAT/enhancer-binding protein α (C/EBPα) binding, another essential requirement for constitutive HNF4α expression in hepatocytes. Consistent with the in vitro observation, 67 of 98 patients with hepatic HNF4α expressed both phospho-SMAD2 and C/EBPα, whereas 22 patients without HNF4α expression lacked either phospho-SMAD2 or C/EBPα. In contrast to the observed induction of HNF4α, SMAD2/3 inhibited C/EBPα transcription. Long-term TGF-ß incubation resulted in C/EBPα depletion, which abrogated HNF4α expression. Intriguingly, SMAD2/3 inhibitory binding to the C/EBPα promoter was abolished by insulin. Two-thirds of patients without C/EBPα lacked membrane glucose transporter type 2 expression in hepatocytes, indicating insulin resistance. Taken together, these data indicate that hepatic insulin sensitivity is essential for hepatic HNF4α expression in the condition of inflammation.

A comparison between Boston brace and European braces in the treatment of adolescent idiopathic scoliosis (AIS) patients: a systematic review based on the standardised Scoliosis Research Society (SRS) inclusion criteria for brace treatment.

PURPOSE: To compare the Boston brace and European braces using a standardised Scoliosis Research Society (SRS) inclusion criteria for brace treatment as well as consensus recommendations for treatment outcome. METHODS: This was a systematic review that was carried out using MeSH terminology in our search protocol in PubMed, Cochrane Library, Scopus, Clinicaltrials.gov and Web of Science database between 1976 and 29th of Jan 2023. All studies that were included in this review had applied fully/partially the SRS inclusion criteria for brace wear. Outcome measures were divided into primary and secondary outcome measures. RESULTS: 3830 literatures were found in which 176 literatures were deemed relevant to the study once duplicates were removed and titles and abstracts were screened. Of these literatures, only 15 had fulfilled the eligibility criteria and were included in the study. 8 of the studies were Level IV studies, 5 were Level III studies and 2 studies were Level I studies (1 prospective randomised controlled trial (RCT) and 1 Quasi-RCT). The percentage of patients who avoided surgery for European braces ranged from 88 to 100%, whereas for Boston brace ranged from 70 to 94%. When treatment success was assessed based on the final Cobb angle > 45°, approximately 15% of patients treated with European braces had treatment failure. In contrast, 20-63% of patients treated with Boston brace had curves > 45° at skeletal maturity. The BrAIST study used a cut-off point of 50° to define failure of treatment and the rate of treatment failure was 28%. Curve correction was not achieved in most patients (24-51% of patients) who were treated with the Chêneau brace and its derivatives. However, none of the patients treated with Boston brace achieved curve correction. CONCLUSION: Boston brace and European braces were effective in the prevention of surgery. In addition, curve stabilisation was achieved in most studies. Limitation in current literature included lack of studies providing high level of evidence and lack of standardisation in terms of compliance to brace as well as multidisciplinary management of brace wear.

Variations in the Number of Vertebrae, Prevalence of Lumbosacral Transitional Vertebra and Prevalence of Cervical Rib Among Surgical Patients With Adolescent Idiopathic Scoliosis: An Analysis of 998 Radiographs.

STUDY DESIGN: Retrospective Study. OBJECTIVE: This study aims to investigate variation in the number of thoracic and lumbar vertebrae, the prevalence of lumbosacral transitional vertebra (LSTV) and the prevalence of cervical ribs among surgical patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Due to variation in the number of thoracic or lumbar vertebrae, inaccurate identification of vertebral levels has been found to be a contributory factor to wrong-level surgery. METHODS: This was a retrospective study on AIS patients who underwent posterior spinal fusion. Demographic and anthropometric data (age, gender, height, weight, and body mass index), radiographic data (Lenke curve type, pre-operative Cobb angle, vertebra numbering of cervical, thoracic, and lumbar spine, presence of LSTV based on the Castellvi classification and the presence of cervical ribs) and clinical data were collected. Data were analysed and reported with mean and standard deviation for quantitative parameters and number and percentage for qualitative parameters. Multinomial logistic regression analyses were performed to identify factors associated with the outcomes of interest. RESULTS: A total of 998 patients met inclusion criteria, of which 135 (13.5%) were males and 863 (86.5%) were females. The vertebrae number varied between 23 to 25 total vertebrae with 24 vertebrae considered as the typical number of vertebrae. The prevalence of atypical number of vertebrae (23 or 25) was 9.8% (98 patients). We found a total of 7 different variations in number of cervical, thoracic, and lumbar vertebrae (7C11T5L, 7C12T4L, 7C11T6L, 7C12T5L, 7C13T4L, 7C12T6L, and 7C13T5L) with 7C12T5L considered as the typical vertebrae variation. The total prevalence of patients with atypical vertebrae variation was 15.5% (155 patients). Cervical ribs were found in 2 (0.2%) patients while LSTV were found in 250 (25.1%) of patients. The odds of 13 thoracic vertebrae were higher in males (OR 5.17; 95% CI: 1.25, 21.39) and the odds of 6 lumbar vertebrae were higher in LSTV (OR 3.93; 95% CI: 2.58, 6.00). CONCLUSION: In this series, we identified a total of 7 different variations in the number of cervical, thoracic, and lumbar vertebrae. The total prevalence of patients with atypical vertebrae variation was 15.5%. LSTV was found in 25.1% of the cohort. It is important to ascertain atypical vertebrae variations rather than the absolute number of vertebrae because variants such as 7C11T6L and 7C13T4L may still have typical numbers of vertebrae in total. However, due to the differences in the number of morphologically thoracic and lumbar vetrebrae, there may still be a risk of inaccurate identification.

Prevalence and sociodemographic predictors of high-risk vaginal human papillomavirus infection: findings from a public cervical cancer screening registry.

INTRODUCTION: High-risk human papillomavirus (HPV) screening is vital for early cervical cancer detection and treatment. With the introduction of the national cervical cancer screening programme and screening registry in Malaysia, there is a need to monitor population-based HPV screening uptake and high-risk HPV prevalence as part of cervical cancer surveillance. OBJECTIVE: To determine the prevalence and sociodemographic factors predicting high-risk HPV infection in Malaysia based on a public, community-based cervical cancer screening registry targeting women at risk of getting HPV infection. METHODS: The study used data from the Malaysian cervical cancer screening registry established by the Family Health Development Division from 2019 to 2021. The registry recorded sociodemographic data, HPV test details and results of eligible women who underwent HPV screening at public primary healthcare facilities. A vaginal sample (via self-sampling or assisted by a healthcare provider) was used for DNA extraction for HPV detection and genotyping. Registry data were extracted and analysed to determine prevalence estimates of high-risk HPV infection. Multifactorial logistic regression analysis was conducted to determine predictors of high-risk HPV infection. All analyses were performed using Stata version 14. RESULTS: The programme screened a total of 36,738 women during the study period. Women who attended the screening programme were mainly from urban areas, aged 30-39 years, and of Malay ethnicity. The prevalence of high-risk HPV infection was 4.53% among women screened, with the yearly prevalence ranging from 4.27 to 4.80%. A higher prevalence was observed among urban settling women, those aged 30-49 years, those of Indian ethnicity, and those without children. The results from logistic regression showed that women from urban areas, lower age groups, of Indian or Chinese ethnicity, and who are self-employed were more likely to be infected with high-risk HPV. CONCLUSION: Targeted and robust strategies to reach identified high-risk groups are needed in Malaysia. In addition, the registry has the potential to be expanded for an improved cervical cancer elimination plan. TRIAL REGISTRATION: Trial registration number: NMRR ID-22-00187-DJU.

YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer.

Ferroptosis is a regulated cell death process initiated by iron-dependent phospholipid peroxidation and is mainly suppressed by GPX4-dependent and FSP1-dependent surveillance mechanisms. However, how the ferroptosis surveillance system is regulated during cancer development remains largely unknown. Here, we report that the YTHDC1-mediated m6A epigenetic regulation of FSP1 alleviates the FSP1-dependent ferroptosis suppression that partially contributes to the tumor suppressive role of YTHDC1 in lung cancer progression. YTHDC1 knockdown promoted the lung tumor progression and upregulated FSP1 protein level that resulted in ferroptosis resistance of lung cancer cells. Silencing FSP1 abrogated YTHDC1 knockdown-induced proliferation increase and ferroptosis resistance. Mechanistically, YTHDC1 binding to the m6A sites in the FSP1 3'-UTR recruited the alternative polyadenylation regulator CSTF3 to generate a less stable shorter 3'-UTR contained FSP1 mRNA, whereas YTHDC1 downregulation generated the longer 3'-UTR contained FSP1 mRNA that is stabilized by RNA binding protein HuR and thus led to the enhanced FSP1 protein level. Therefore, our findings identify YTHDC1 as a tumor progression suppressor in lung cancer and a ferroptosis regulator through modulating the FSP1 mRNA stability and thus suggest a ferroptosis-related therapeutic option for YTHDC1high lung cancer.

What is the prevalence and distribution of narrow dysplastic and fully corticalized pedicles in Asian adolescent idiopathic scoliosis patients with major main thoracic curves? A computed tomography scan analysis of 6,494 pedicles.

BACKGROUND CONTEXT: Patients with adolescent idiopathic scoliosis (AIS) have higher prevalence of abnormal or dysplastic pedicles. PURPOSE: To investigate the prevalence and distribution of narrow dysplastic and fully corticalized pedicles in Asian AIS patients with major main thoracic curves. DESIGN: Retrospective study. PATIENT SAMPLE: A total of 6,494 pedicles in 191 patients were measured and evaluated. OUTCOME MEASURES: The primary outcomes measures were the pedicle width measurements (total transverse pedicle width, transverse cancellous width, total transverse cortical width) and classification of pedicles. Demographic data (age, gender, height, weight, body mass index), proximal thoracic Cobb angle, main thoracic Cobb angle and lumbar Cobb angle were also obtained. METHODS: AIS patients with major (largest Cobb angle) main thoracic curves and had computed tomography (CT) scans prior to corrective spine surgery were reviewed. The pedicles were classified as Grade A: cancellous channel >4 mm; Grade B: cancellous channel 2 to 4 mm; Grade C: cancellous channel <2 mm or corticalized pedicle >4 mm; Grade D: corticalized pedicle ≤4 mm. Grades B, C, and D were dysplastic pedicles while grades C and D were narrow dysplastic pedicles. RESULTS: The prevalence of dysplastic pedicles (grades B, C, and D) was 61.7%. There were 22.6% narrow dysplastic pedicles (grades C and D) and 4.1% fully corticalized pedicles (grade D). In the thoracolumbar region, there was a sharp transition from larger and less dysplastic pedicles at T11 and T12 to narrower and more dysplastic pedicles at L1 and L2 (narrow dysplastic pedicles at T11: 3.1%, T12: 3.1%, L1: 39.8% and L2: 23.6%). Higher prevalences of narrow dysplastic pedicles were located at right T3 to T5 (71.2%-83.7%) and left T7-T9 (51.3%-61.2%). Higher prevalences of fully corticalized pedicles were located at right T3 to T5 (20.9%-34.0%) and left T7 to T8 (11.0%-12.0%). These were the concave pedicles of proximal thoracic and main thoracic curves, respectively. CONCLUSION: There were 95.9% pedicles with cancellous channels (grades A, B, and C) can allow pedicle screw fixation and only 4.1% fully corticalized pedicles (grade D) that require an alternative method of fixation. For grade C pedicles (18.5%), pedicle screws can still be attempted with caution. Precautions should also be observed at the L1 and L2 levels as there was a transition to narrower pedicles.

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation.

BACKGROUND: Globally, despite prostate cancer (PCa) representing second most prevalent malignancy in male, the precise molecular mechanisms implicated in its pathogenesis remain unclear. Consequently, elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies, ultimately advancing the management of PCa. METHODS: A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University. The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa. The expression of aspartoacylase (ASPA) in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques. To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis, a comprehensive set of in vitro and in vivo assays were conducted, including orthotopic and tumor-bearing mouse models (n = 8 for each group). A combination of experimental approaches, such as Western blotting, luciferase assays, immunoprecipitation assays, mass spectrometry, glutathione S-transferase pull-down experiments, and rescue studies, were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa. The Student's t-test was employed to assess the statistical significance between two distinct groups, while one-way analysis of variance was utilized for comparisons involving more than two groups. A two-sided P value of less than 0.05 was deemed to indicate statistical significance. RESULTS: ASPA was identified as a novel inhibitor of PCa progression. The expression of ASPA was found to be significantly down-regulated in PCa tissue samples, and its decreased expression was independently associated with patients' prognosis (HR = 0.60, 95% CI 0.40-0.92, P = 0.018). Our experiments demonstrated that modulation of ASPA activity, either through gain- or loss-of-function, led to the suppression or enhancement of PCa cell proliferation, migration, and invasion, respectively. The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models. Mechanistically, ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets, JNK1/2 and C-Jun, in both PCa cells and mouse models, in an enzyme-independent manner. Importantly, the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models. Moreover, we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples, suggesting a potential regulatory role of ASPA in modulating LYN signaling. CONCLUSION: Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

Effect of supplementary private health insurance on inpatient utilisation: Evidence from Malaysia.

Supplementary private health insurance (PHI) provides better access to healthcare, improves health outcomes, potentially lowers the costs for health systems and supports the social security system. Improperly regulated PHI, however, may aggravate inequity of access towards preferential care and encourage moral hazard among PHI purchasers, altering the health-seeking behaviour, which is often observed through the pattern of health care utilisation. We investigated the effect of PHI ownership on private inpatient care utilisation, its frequency of admission and length of stay by conducting secondary data analysis of the Malaysian National Health Morbidity Survey (NHMS) 2015 data, a nationally representative community health survey. Malaysian adults 18 years of age and above who utilised inpatient healthcare facilities were included. In this cross-sectional study, we addressed the endogeneity effect of health insurance by employing instrumental variable estimation and a two-stage residual inclusion analysis. We found a significant increase in private inpatient utilisation among those who owned PHI compared to those who did not (ß = 4.39, p < 0.001). There was no significant difference in the frequency of admission and length of stay. The increase in private inpatient utilisation among PHI owners may reflect the demand for timely care and hospitality provided by the private sector, potentially exacerbating the moral hazard behaviour among PHI owners. Further exploration of this issue could impact future healthcare systems financing designs and PHI regulation.

Astragalin ameliorates renal injury in diabetic mice by modulating mitochondrial quality control via AMPK-dependent PGC1α pathway.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus, and oxidative stress and mitochondrial dysfunction play an important role in this process. It has been shown that aldose reductase (ALR2) catalyzes NADPH-dependent reduction of glucose to sorbitol, resulting in oxidative stress and mitochondrial dysfunction in diabetic patients. Astragalin (AG), a flavonoid extracted from Thesium chinense Turcz., shows an inhibitory activity on ALR2. In this study, we investigated the therapeutic effects of AG against renal injury in streptozocin (STZ)-induced diabetic mouse model. Diabetic mice were orally administered AG (5, 10 mg·kg-1·d-1) for 4 weeks. We showed that AG treatment greatly improved the proteinuria and ameliorated renal pathological damage without affecting the elevated blood glucose in diabetic mice. Furthermore, AG treatment significantly suppressed highly activated ALR2, and reduced oxidative stress in the kidney of diabetic mice and in high glucose and lipids-stimulated HK2 cells in vitro. We demonstrated that AG treatment modulated mitochondrial quality control and ameliorated apoptosis, boosting mitochondrial biogenesis, maintaining mitochondrial dynamic homeostasis, and improving energy metabolism disorder in vivo and in vitro. In high glucose and lipids-stimulated HK2 cells, we found that AG (20 µM) restored the phosphorylation level of AMPK, and upregulated the expression and transcriptional activity of PGC1α, whereas treatment with H2O2, blockade of AMPK with Compound C or knockdown of AMPKα with siRNA abolished the protective effect of AG on mitochondrial function, suggesting that antioxidant effects and activation of AMPK-dependent PGC1α pathway might be the molecular mechanisms underlying the protective effects of AG on mitochondrial quality control. We conclude that AG could be a promising drug candidate for the treatment of diabetic renal injury through activating AMPK.

A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1.

SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors.

A Comparison Between the Perioperative Outcomes of Female Adolescent Idiopathic Scoliosis (AIS) Versus Adult Idiopathic Scoliosis (AdIS) Following Posterior Spinal Fusion: A Propensity Score Matching Analysis Involving 425 Patients.

STUDY DESIGN: Retrospective propensity score matching (PSM) study. OBJECTIVE: To investigate the perioperative outcomes comparing adolescent idiopathic scoliosis (AIS) and adult idiopathic scoliosis (AdIS) patients following posterior spinal fusion (PSF). METHODS: 425 female AIS and AdIS patients who were operated (between January 2015 to March 2020) using a dual attending surgeon strategy were stratified into G1 (AIS aged 10-16 years old) and G2 (AdIS > 20 years old). PSM analysis with one-to-one, nearest neighbor matching technique with match tolerance of 0.001 was used to matched 357 AIS patients to 68 AdIS patients. Operation duration, intraoperative blood loss (IBL), blood loss percentage, hemoglobin drift, blood salvaged, postoperative wound length, allogenic blood transfusion requirement, postoperative hospital stay, postoperative Cobb, correction rate and postoperative complications were documented and reported. RESULTS: Following PSM, G1 and G2 each had 50 patients with comparable and balanced covariates. As anticipated, G2 patients were heavier, taller and had higher body mass index compared to G1 patients (P < 0.05). We could not find any significant differences in the perioperative outcome comparing this 2 groups. AIS and AdIS patients had similar operation duration (125.9 ± 27.2 min vs 127.3 ± 37.8 min), IBL (749.8 ± 315.7 ml vs 723.8 ± 342.1 ml) and length of hospital stay (3.3 ± 0.4 days vs 3.5 ± 0.8 days) (P > 0.05). Hemoglobin drift and amount of blood salvaged were comparable (P > 0.05). G2 had stiffer curves. There was a trend toward a lower correction rate in G2 in the immediate postoperative period, however it did not reach statistical significance (61.8 ± 11.2% vs. 66.3 ± 11.6%, P = 0.051). No patients required blood transfusion and none had any postoperative complications. CONCLUSION: Adolescent and adult female scoliosis patients had comparable perioperative outcome following PSF surgery that was carried out using a dual attending surgeon strategy.

Preoperative "Cervical Axis" Deviation Increases the Risk of Distal Adding-On Following Surgery in Lenke 1 and 2 Adolescent Idiopathic Scoliosis Patients.

STUDY DESIGN: Retrospective. PURPOSE: To evaluate the relationship between shoulder/ neck imbalance with distal adding-on phenomenon and to identify other risk factors in Lenke 1 and 2 (non-AR curves) adolescent idiopathic scoliosis (AIS) patients. METHODS: 100 Lenke 1 and 2 AIS patients with lowest instrumented vertebra (LIV) cephalad to or at L1 were recruited. Medial shoulder/ neck balance was represented by T1-tilt and cervical axis (CA). Lateral shoulder balance was represented by clavicle angle (Cla-A) and radiographic shoulder height (RSH). Distal adding-on phenomenon was diagnosed when there was disc wedging below LIV of >5o at final follow-up. Predictive factors and odds ratio were derived using univariate and multivariate logistic regression analysis. RESULTS: Mean age of this cohort was 15.9 ± 4.4 years. Mean follow-up duration was 30.9 ± 9.6 months. Distal adding-on phenomenon occurred in 19 patients (19.0%). Only Risser grade, preoperative CA and final follow-up lumbar Cobb angle were the independent factors. A positive preoperative CA deviation increased the odds of distal adding-on by 5.4 times (95% CI 1.34-21.51, P = 0.018). The mean immediate postoperative T1-tilt, CA, RSH and Cla-A were comparable between the group with distal adding-on and the group without. CONCLUSION: Distal adding-on phenomenon occurred in 19.0% of patients. Preoperative "Cervical Axis" was an important factor and it increased the risk of distal adding-on by 5.4 times. Other significant predictive factors were Risser grade and lumbar Cobb angle at final follow-up. Immediate postoperative shoulder or neck imbalance was not a significant factor for postoperative distal adding-on phenomenon.

Patients' Perception and Satisfaction on Neck and Shoulder Imbalance in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To evaluate the perception and satisfaction among adolescent idiopathic scoliosis (AIS) patients on Neck Tilt with Medial Shoulder Imbalance and Lateral Shoulder Imbalance. METHODS: Lenke 1 and 2 AIS patients were stratified into 6 groups of preoperative/ postoperative Balanced (B), Lateral Shoulder Imbalance (LSI) (>2 cm), and Neck Tilt with Medial Shoulder Imbalance (NT) (Grade 3). Patients were interviewed using Modified Neck and Shoulder Appearance and SRS-22r questionnaires. T1 tilt, Cervical Axis (CA), Clavicle Angle (Cla-A) and Radiographic Shoulder Height (RSH) were measured. RESULTS: A total of 120 Lenke 1 and 2 AIS patients were recruited. NT patients were aware and unhappy with their abnormal neck with medial shoulder appearances (P < .001). Similarly, LSI patients were aware and unhappy with their abnormal lateral shoulder appearances (P < .001). NT group had larger preoperative/ postoperative T1 tilt (9.2 ± 5.0°; 9.5 ± 5.3°) and CA (4.6 ± 3.1°; 7.0 ± 2.0°) (P < .01). LSI group had larger preoperative/ postoperative Cla-A (4.8 ± 2.8°; 4.0 ± 1.3°) and RSH (20.1 ± 9.4 mm; 17.0 ± 6.6 mm) (P < .001). Postoperative B group scored higher in overall SRS-22r scores, self-image and satisfaction domains (4.2 ± 0.3; 4.0 ± 0.5; 4.4 ± 0.5) while preoperative LSI scored the lowest comparatively (3.5 ± 0.4; 2.4 ± 0.5; 3.3 ± 0.5) (P < .001). CONCLUSION: NT and LSI were major concerns among AIS patients. Both NT and LSI groups were unhappy with their appearances. NT group had larger T1 tilt/ CA whereas LSI group had larger Cla-A/ RSH. Postoperative B group scored higher in overall SRS-22r scores, self-image and satisfaction domains.

COVID-19 clusters in Malaysia: characteristics, detection methods and modes of early transmission.

Objective: Effective prevention and control measures are essential to contain outbreaks of infectious diseases, such as coronavirus disease (COVID-19). Understanding the characteristics of case clusters can contribute to determining which prevention and control measures are needed. This study describes the characteristics of COVID-19 case clusters in Malaysia, the method used to detect a cluster's index case and the mode of early transmission, using the seven cluster categories applied in Malaysia. Methods: This cross-sectional study collected publicly available data on COVID-19 clusters occurring in Malaysia from 1 March 2020 to 31 May 2021. The characteristics of cases were described by category, and their associations with several outcomes were analysed. Descriptive analyses were performed to explore the method used to detect the index case and the mode of early transmission, according to cluster category. Results: A total of 2188 clusters were identified. The workplace cluster category had the largest proportion of clusters (51.5%, 1126/2188 clusters), while the custodial settings category had the largest median cluster size (178 cases per cluster) and longest median duration of cluster (51 days). The high-risk groups category had the highest mortality. There were significant differences in cluster size, duration and rate of detection across the categories. Targeted screening was most commonly used to detect index cases, especially in custodial settings, and in imported and workplace clusters. Household-social and social-workplace contacts were the most common modes of early transmission across most categories. Discussion: Targeted screening might effectively reduce the size and duration of COVID-19 clusters. Measures to prevent and control COVID-19 outbreaks should be continually adjusted based on ongoing assessments of the unique context of each cluster.

Erratum: Unified Approach to Polarons and Phonon-Induced Band Structure Renormalization [Phys. Rev. Lett. 129, 076402 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.129.076402.

Virtual reality for pain and anxiety of pediatric oncology patients: A systematic review and meta-analysis.

Objective: The aim of this paper is to systematically evaluate the effects of virtual reality (VR) on pain, anxiety, and fear symptoms of pediatric patients with cancer. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, CINAHL, and four Chinese medical databases were searched from January 1, 1975, to February 22, 2022. Randomized controlled trials on the effects of VR technology on pediatric cancer patients were searched. Two researchers independently screened literatures, extracted data, and evaluated literature quality according to inclusion and exclusion criteria, and meta-analysis was performed by RevMan 5.3. Results: A total of 379 children with cancer were included in six randomized controlled trials. Overall, there were significant differences in favor of VR in pain (MD â€‹= â€‹-4.82, 95% CI [-7.74, -1.89], P＜0.01; I 2 ​= â€‹95%, P＜0.01), anxiety (SMD â€‹= â€‹-1.47, 95% CI â€‹[​-2.46, -0.48], P＜0.01; I 2  â€‹= â€‹92%, P＜0.01), and fear (MD â€‹= â€‹-1.25, 95% CI [-1.78,0.72], P＜0.01; I 2  â€‹= â€‹0%, P â€‹= â€‹0.69). Conclusions: VR is beneficial to improve the pain, anxiety, and fear mood of pediatric cancer patients. Larger sample sizes and more rigorous studies are needed.