Iron burden and endocrine complications in transfusion-dependent thalassemia patients In Sarawak, Malaysia: a retrospective study.

INTRODUCTION: Thalassaemia is one of the major health problems in Malaysia. With safe blood transfusion regime, the lifespan of patients with transfusion-dependent thalassaemia (TDT) has improved but at the cost of a higher risk of developing endocrine disorders. It is crucial for us to monitor the iron overload to prevent end organ damage. This study aims to evaluate the iron burden and prevalence of endocrinopathies in patients with TDT in Sarawak. MATERIALS AND METHODS: This retrospective cohort study was conducted between January 2020 to June 2020 in six government hospitals in Sarawak. A total of 89 patients with TDT, aged 10 years and above, were recruited. RESULTS: Out of the 89 patients, there were 54 males (60.7%) and 35 females (39.3%) with a median age of 21 years (range 10.0-65.0). Sixty-seven (75.3%) patients had betathalassaemia major and 15 (16.9%) patients had haemoglobin E beta-thalassaemia (HbE beta-thalassaemia), remaining seven patients had other genotypes. Thirty-one (34.8%) patients had mean serum ferritin 2500ng/ml and above, and 44 (66.6%) had liver iron concentration (LIC) ≥7mg/g. The prevalence of endocrine disorders in our cohort was 69.7%. The most common endocrinopathies were short stature (n=46, 51.7%), followed by hypogonadism (n=24, 26.9%), delayed puberty (n=23, 25.8%), hypothyroidism (n=10, 11.2%), diabetes mellitus (n=9, 10.1%), impaired glucose tolerance (n=6, 6.7%) and hypoparathyroidism (n=3, 3.3%). Endocrinopathies were significantly associated with age (p=0.01), age at initiating regular blood transfusion (p<0.01) and duration of regular blood transfusion (p<0.01). CONCLUSION: Our data shows that the development of endocrinopathies in TDT can be time dependent. Early detection of endocrine-related complications and prompt treatment with iron chelation therapy are important to improve morbidity and mortality. A multidisciplinary approach with good patient-doctor collaboration is the key to improving patient care in our settings.

[Annual progress of interventional diagnosis and treatment of tuberculosis in 2023].

A series of studies on the interventional diagnosis and treatment of tuberculosis(TB)were carried out by domestic and foreign researchers in 2023. The combination of minimally invasive interventional procedures with endoscopes, guidance, material acquisition techniques by multiple ways and multichannel and highly accurate laboratory testing techniques is becoming more and more widely practiced clinically, which has played an important role in the accurate diagnosis of problematic TB. Diagnostic procedures for pulmonary TB, tracheobronchial TB, mediastinal lymphatic TB and extrapulmonary TB included conventional flexible bronchoscopy and specific types of bronchoscopy(ultrathin bronchoscopy and endobronchial ultrasound), transbronchial needle aspiration biopsy, endobronchial ultrasound and virtual bronchoscopic navigation system-guided forceps biopsy, thoracoscopic cryobiopsy of pleura, percutaneous biopsy, and so on. The time to diagnosis has been significantly reduced and the diagnostic efficacy has been improved by the clinical specimen detection using either Gene Xpert MTB/RIF, Ultra, loop-mediated isothermal amplification, metagenomic next-generation sequencing, or nanopore sequencing, etc. Interventional therapy was focused on the following diseases: pulmonary TB with massive hemoptysis, tracheobronchial TB, pleural TB and TB-related fistulas. Interventional treatment of tracheobronchial TB mainly included the application of rigid bronchoscopy, bronchoscopic cold and thermal ablation treatment, endoscopic clamp, dilatations of narrow airway with balloon and stent placement, etc. The interventional treatment of pulmonary TB complicated by massive hemoptysis included endovascular embolization, coated stent placement, etc. Interventional treatment of pleural TB involved the application of thoracoscopy, endoscopic forceps, the implantation of stent and other occlusive devices and the closure of fistulas with autologous fat transplantation. In this article, we reviewed the progress of interventional diagnosis and treatment of TB by the search of published literatures from October 2022 to September 2023.

[Establishment and efficiency test of a clinical prediction model of bronchopulmonary dysplasia associated pulmonary hypertension in very premature infants].

Objective: To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants. Methods: This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1st, 2015 to December 31st, 2021 of the Seventh Medical Center of the People's Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children's Hospital from January 1 st, 2020 to December 31st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks' corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model's discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results: A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95%CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions: A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

[Risk factors for pulmonary atelectasis in adults with tracheobronchial tuberculosis].

Objective: To investigate the risk factors for pulmonary atelectasis in adults with tracheobronchial tuberculosis(TBTB). Methods: Clinical data of adult patients (≥18 years old) with TBTB from February 2018 to December 2021 in Public Health Clinical Center of Chengdu were retrospectively analyzed. A total of 258 patients were included, with a male to female ratio of 1∶1.43. The median age was 31(24, 48) years. Clinical data including clinical characteristics, previous misdiagnoses/missed diagnoses before admission, pulmonary atelectasis, the time from symptom onset to atelectasis and bronchoscopy, bronchoscopy and interventional treatment were collected according to the inclusion and exclusion criteria. Patients were divided into two groups according to whether they had pulmonary atelectasis. Differences between the two groups were compared. Binary logistic regression was used to analyze the risk factors for pulmonary atelectasis. Results: The prevalence of pulmonary atelectasis was 14.7%, which was most common in the left upper lobe (26.3%). The median time from symptom onset to atelectasis was 130.50(29.75,358.50)d, and the median time from atelectasis to bronchoscopy was 5(3,7)d. The median age, the proportion of misdiagnosis of TBTB before admission, and the time from symptom onset to bronchoscopy in the atelectasis group were higher than those without atelectasis, and the proportion of receiving bronchoscopy examination and interventional therapy previously, and the proportion of pulmonary cavities were lower than those without atelectasis (all P<0.05). The proportions of cicatrices stricture type and lumen occlusion type in the atelectasis group were higher than those without atelectasis, while the proportions of inflammatory infiltration type and ulceration necrosis type were lower than those without atelectasis (all P<0.05). Older age (OR=1.036, 95%CI: 1.012-1.061), previous misdiagnosis(OR=2.759, 95%CI: 1.100-6.922), longer time from symptom onset to bronchoscopy examination (OR=1.002, 95%CI: 1.000-1.005) and cicatrices stricture type (OR=2.989, 95%CI: 1.279-6.985) were independent risk factors for pulmonary atelectasis in adults with TBTB (all P<0.05). Of the patients with atelectasis who underwent bronchoscopy interventional therapy, 86.7% had lung reexpansion or partial reexpansion. Conclusions: The prevalence of pulmonary atelectasis is 14.7% in adult patients with TBTB. The most common site of atelectasis is left upper lobe. The TBTB type of lumen occlusion is complicated by pulmonary atelectasis in 100% of cases. Being older, misdiagnosed as other diseases, longer time from onset of symptoms to bronchoscopy examination, and being the cicatrices stricture type are factors for developing pulmonary atelectasis. Early diagnosis and treatment are needed to reduce the incidence of pulmonary atelectasis and increase the rate of pulmonary reexpansion.

[Effects of extramedullary disease on patients with newly diagnosed multiple myeloma].

Objective: To summarize the characteristics of patients with newly diagnosed multiple myeloma (NDMM) admitted at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. We compared the clinical characteristics and prognoses among patients with non-extramedullary disease (EMD), bone-related extramedullary (EM-B) disease, and extraosseous extramedullary (EM-E) disease and further explored the effects of autologous hematopoietic stem cell transplantation (ASCT) for EMD. Methods: From January 2015 to January 2022, data of 114 patients (22%) with EMD out of 515 patients with NDMM were retrospectively analyzed; 91 (18%) and 23 (4%) patients comprised the EM-B and EM-E groups, respectively. The clinical characteristics of patients in all groups were compared with the Chi-square test. Progression-free survival (PFS) and overall survival (OS) of patients were analyzed by the Kaplan-Meier method. Independent prognostic factors were determined using multivariate Cox proportional hazard model. Results: There were no significant differences in age, gender, ISS stage, light chain, creatinine clearance, cytogenetic risk, 17p deletion, ASCT, and induction regimens among the three groups. Overall, 13% of EM-E patients had IgD-type M protein, which was significantly higher than that in EM-B patients (P=0.021). The median PFS of patients in the non-EMD, EM-B, and EM-E groups was 27.4, 23.1, and 14.0 months; the median OS was not reached, 76.8 months, and 25.6 months, respectively. The PFS (vs non-EMD, P=0.004; vs EM-B, P=0.036) and OS (vs non-EMD, P<0.001; vs EM-B, P=0.002) were significantly worse in patients with EM-E, while those were not significantly different between patients with EM-B and those with non-EMD. In the multivariate analysis, EM-E was an independent prognostic factor for OS in patients with NDMM (HR=8.779, P<0.001) and negatively impacted PFS (HR=1.874, P=0.050). In those who did not undergo ASCT, patients with EM-B had significantly worse OS than those with non-EMD (median 76.8 months vs. not reached, P=0.029). However, no significant difference was observed in the PFS and OS of patients with EM-B and those with non-EMD who underwent ASCT. Conclusions: Compared to patients with either non-EMD or EM-B, those with EM-E had the worst prognosis. EM-E was an independent risk factor for OS in patients with NDMM. ASCT can overcome the poor prognosis of EM-B.

[Effect of Mycobacterium tuberculosis protein Rv0309 on intracellular survival of Mycobacterium smegmatis by inhibiting macrophage autophagy via protein STUB1].

Objective: To investigate the molecular regulatory mechanism of Mycobacterium tuberculosis (MTB) protein Rv0309 to promote the survival of Mycobacterium smegmatis (Ms) in macrophages. Methods: Using Ms as a model to study Mycobacterium tuberculosis, recombinant Ms transfected with pMV261 and PMV261-RV0309 in the control group and RAW264.7 cells were constructed. The effect of Rv0309 protein on intracellular survival of Ms was investigated by counting colony forming units (CFUs). Mass spectrometry was used to screen proteins interacting with host protein Rv0309, and immunocoprecipitate (Co-IP) was used to verify that host protein STUB1 could interact with host protein Rv0309. STUB1 gene knock-out RAW264.7 cells were infected with Ms, and CFUs were counted to explore the effect of protein Rv0309 on intracellular survival of Ms after STUB1 gene knock-out. STUB1 gene knock-out RAW264.7 cells were infected with Ms, and after obtaining samples, Western blotting assay was performed to explore the effect of protein Rv0309 on autophagy function of macrophages after STUB1 gene knock-out. Statistical analysis was performed using GraphPad Prism 8 software. T-test was selected for analysis in this experiment, with P<0.05 was considered statistically significant. Results: Western blotting showed that Rv0309 was expressed in M. smegmatis and secreted extracellularly. The CFUs of the Ms-Rv0309 group was higher than that of Ms-pMV261 group at 24 h after THP-1 macrophage infection, and the difference was statistically significant (P<0.05). The trend of infected RAW264.7 macrophages was the same as that of infected THP-1 macrophages. The Co-IP results showed that the corresponding Flag and HA bands appeared in the results of immunoprecipitation (IP):Flag and IP: HA. The level of CFUs in the experimental group with STUB1 deletion was significantly higher than that in the control group without STUB1 deletion. Compared with Ms-pMV261, the CFUs in the Ms-Rv0309 group was significantly higher than that in the Ms-pMV261 group. The gray scale of LC3Ⅱ bands of Ms-Rv0309 in experimental group was lighter than that of Ms-pMV261 in the control group at the corresponding time point, and the result was most significant at 8 h (LC3Ⅱ/ß-actin: 0.76±0.05 vs 0.47±0.07), the difference being statistically significant (P<0.05). After STUB1 genome knock-out, the gray level of LC3Ⅱ bands at the corresponding time was lighter than that without STUB1 genome knock-out. Comparison of the results of Ms-pMV261 and Ms-Rv0309 strains revealed that LC3Ⅱ band gray Rv0309 group was lighter at the corresponding time compared with pMV261 group. Conclusions: MTB protein Rv0309 can be successfully expressed in M. smegmatis and secreted extracellularly, which can inhibit the autophagy process of macrophages. Protein Rv0309 interacts with host protein STUB1 to inhibit macrophage autophagy and promote intracellular survival of Ms.

A radiomics model development via the associations with genomics features in predicting axillary lymph node metastasis of breast cancer: a study based on a public database and single-centre verification.

AIM: To evaluate the predictive performance of the radiomics model in predicting axillary lymph node (ALN) metastasis through the associations between radiomics features and genomic features in patients with breast cancer. MATERIALS AND METHODS: Patients with breast cancer were enrolled retrospectively from a public database (111 patients as training group) and one hospital (15 patients as external validation group). The genomics features from transcriptome data and radiomics features from dynamic contrast-enhanced magnetic resonance imaging (MRI) were collected. Firstly, overlapping genes were identified using the Kyoto Encyclopedia of Genes and Genomes and differentially expressed gene analysis, while radiomics features were reduced using a data-driven method. Then, the associations between overlapping genes and retained radiomics features were assessed to obtain key pairs of radiomics-genomics features. Furthermore, the least absolute shrinkage and selection operator (LASSO) algorithm was used to detect the key-pairs features. Finally, radiomics and genomics models were constructed to predict ALN metastasis. RESULTS: After using the hybrid data- and gene-driven selection method, key pairs of features were detected, which consisted of six radiomic features associated with four genomic features. The radiomics model exhibited comparable performance to the genomics model in predicting ALN metastasis (radiomic model: area under the curve [AUC] = 0.71, sensitivity = 77%, specificity = 56%; genomic model: AUC = 0.72, sensitivity = 85%, specificity = 74%). The four genomic features were enriched in six pathways and related to metabolism and human diseases. CONCLUSION: The radiomics model established using the gene-driven hybrid selection method could predict ALN metastasis in breast cancer, which showed comparable performance to the genomics model.

[Effects of colpotomic approaches on prognosis and recurrence sites of stage â a2-â ¡a2 cervical cancer after laparoscopic radical hysterectomy].

Objective: To investigate the factors affecting the prognosis of stage Ⅰa2-Ⅱa2 cervical cancer after laparoscopic radical hysterectomy (LRH), and to compare the prognosis and recurrence sites of patients with different colpotomy paths. Methods: The clinical data of 965 patients with stage Ⅰa2-Ⅱa2 cervical cancer who underwent LRH in the First Affiliated Hospital of Army Medical University from January 2015 to December 2018 were collected. The median age was 47.0 years of all patients with a median follow-up of 62 months (48-74 months). Cox regression was used to perform the univariate and multivariate analysis of the clinicopathological factors associated with the prognosis that included disease-free survival (DFS) and overall survival (OS). Patients were categorized into LRH through vaginal colpotomy (VC group, n=475) and LRH through intracorporeal colpotomy (IC group, n=490) according to the colpotomic approaches. The prognosis and recurrence sites of patients in each group were compared. Results: (1) During the follow-up period, 137 cases recurred (14.2%, 137/965) and 98 cases died (10.2%, 98/965). The 5-year DFS and OS were 85.8% and 89.9%, respectively. In univariate analysis, positive vaginal margin (PVM) was significantly affected the 5-year OS of patients with cervical cancer (P=0.023), while clinical stage, maximum diameter of tumor, degree of pathological differentiation, lymph node metastasis (LNM), depth of cervical stromal invasion, parametrium involvement, and uterine corpus invasion (UCI) were significantly associated with 5-year DFS and OS in patients with cervical cancer (all P<0.05). In multivariate analysis, clinical stage (HR=1.882, 95%CI: 1.305-2.716), LNM (HR=2.178, 95%CI: 1.483-3.200) and UCI (HR=3.650, 95%CI: 1.906-6.988) were independent risk factors of 5-year DFS (all P<0.001). Clinical stage (HR=2.500, 95%CI: 1.580-3.956), LNM (HR=2.053, 95%CI: 1.309-3.218), UCI (HR=3.984, 95%CI: 1.917-8.280), PVM (HR=3.235, 95%CI: 1.021-10.244) were independent risk factors of 5-year OS (all P<0.05). (2) Different colpotomy paths did not significantly affect the 5-year DFS and OS of patients with stage Ⅰa2-Ⅱa2 cervical cancer. The 5-year DFS in VC group and IC group were 85.9% and 85.6% (P=0.794), and the 5-year OS were 90.8% and 89.3% (P=0.966), respectively. Recurrence patterns consisted of intraperitoneal recurrence, pelvic recurrence, vaginal stump recurrence, and lymph node and distant metastasis. The intraperitoneal recurrence rate of VC group was significantly lower than that of IC group [0.6%(3/468) vs 2.3% (11/485), P=0.037], while the rates of pelvic recurrence, vaginal stump recurrence, lymph node and distant metastasis and overall recurrence were not significantly different between two groups (all P>0.05). Subgroup analysis of patients with different clinical stages, LNM and UCI showed that statistical differences of the intraperitoneal recurrence rates between two groups were only in patients without LNM (0.5% vs 2.3%, P=0.030) or without UCI (0.7% vs 2.3%, P=0.037). Conclusions: Clinical stage, LNM, PVM and UCI are independent risk factors for the prognosis of patients with stage Ⅰa2-Ⅱa2 cervical cancer. For patients without LNM or UCI, LRH through VC could reduce the intraperitoneal recurrence rate, while it is not enough to improve 5-year DFS and OS of patients. Low proportion of intraperitoneal recurrence, intra-operative tumor cells spillage to vagina stump and pelvic cavity might be the explanation.

Comparison of the efficacy of febuxostat vs. benzbromarone in the treatment of gout: a meta-analysis in Chinese gout patients.

OBJECTIVE: Febuxostat and benzbromarone are two common drugs for the treatment of gout, but the clinical efficacy of these two drugs is controversial. This meta-analysis aimed to compare the efficacy of febuxostat and benzbromarone in the treatment of gout. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for articles related to febuxostat and benzbromarone in the treatment of gout from inception to January 7, 2023. Titles and abstracts were reviewed in accordance with predesigned inclusion and exclusion criteria, and data were extracted independently. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies, and the continuous variables were expressed as the standard mean square error (SMD) by STATA 16 (Stata Corp., College Station, TX, USA). The sensitivity analysis was conducted by randomly removing a study, and the heterogeneity was analyzed by funnel plots and Egger's test. RESULTS: According to the search strategy, a total of 1,043 publications were retrieved from the three aforementioned databases, of which 45 publications were excluded due to duplication. Fourteen studies remained after screening titles and abstracts, and a total of 7 studies met the inclusion criteria after a comprehensive evaluation of the 14 studies. Meta-analysis showed that the uric acid (UA)-reducing effect of febuxostat is better than that of benzbromarone, while febuxostat showed a better ability to improve the estimated glomerular filtration rate (eGFR) and reduce Cr and blood urea nitrogen (BUN). In terms of hepatotoxicity, benzbromarone was not as potent as febuxostat in increasing alanine transaminase (ALT) and aspartate transaminase (AST), suggesting that benzbromarone has less hepatotoxicity. Moreover, there was no significant difference in the effect on blood lipid levels between the two drugs. CONCLUSIONS: The beneficial effect of febuxostat on renal function-related indexes such as the eGFR, Cr and BUN is significant, while benzbromarone is more effective in reducing UA and has relatively less hepatotoxicity. The specific efficacy of the two drugs needs to be confirmed by further research.

A Southeast Asian collaborative Delphi consensus on surveying risk factors for head and neck cancer screening and prevention.

The objective of this study was to determine high value questions for early detection and prevention of head and neck cancer by querying content experts on patient risk factors relevant to local communities in Southeast Asia (i.e., Vietnam, Laos, China, and Singapore). The Delphi method was employed using three rounds of asynchronous surveying which included participants among five different collaborating medical centers. 60 total survey items were assessed for consensus defined by a priori measures on the relative level of value of these questions for use in head and neck cancer screening. 77% of items reached a consensus and no items were concluded to be of low value despite differences in conclusions regarding relative importance. Survey items focused on patient demographic information and physical examination were examined across variables such as expert department affiliation, academic designation, and years of experience and found to be without statistically significant differences. However, with consensus items related to social risk factors, it was determined that participants who had 15 or more years of experience or identified as otolaryngologists rated these items at a relatively lower value than their peers with less experience (p < 0.0001, p = 0.0017) or outside the field of otolaryngology (p = 0.0101). This study explicitly identifies patient variables to consider in head and neck cancer screening that have not previously been comprehensively or methodically assessed in current literature. Increasing awareness of these risk factors may benefit the design and implementation of future head and neck cancer early detection and prevention programs in Southeast Asia and beyond as well as positively impact head and neck cancer outcomes.

An approach combining bioinformatics and machine learning to identify eight autophagy-related biomarkers and construct molecular mechanisms underlying COVID-19 and major depressive disorders.

OBJECTIVE: A lack of objective biomarkers is preventing the screening and diagnosis of COVID-19 combined with major depression disorder (COVID-19-MDD). The purpose of this study was to identify diagnostic biomarkers and gene regulatory mechanisms associated with autophagy; a crucial process significantly involved in the pathogenesis of COVID-19-MDD. MATERIALS AND METHODS: In this study, differentially expressed genes (DEGs) were screened using GSE98793 from the GEO2R analysis (GEO) database, and intersected with the COVID-19-related gene (CRGs) and autophagy-related genes (ARGs) to obtain common genes involved in. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these common genes were performed. Subsequently, the transcription factor (TF)-gene regulatory network and comorbidity network were constructed. In addition, 10 drug candidates were screened using the DSigDB database. To identify diagnostic markers, we used LASSO regression. RESULTS: In total, 13 common genes were screened, which were primarily enriched in lysosomes, endoplasmic reticulum membranes, and other endomembrane systems also associated with autophagy. Additionally, these genes were involved in neurological cell signaling and have a functional role in pathways related to vascular endothelial growth factor, tyrosine kinase, autophagy, inflammation, immunity, and carcinogenesis. Tumors and psychiatric disorders were the most highly linked diseases to COVID-19. Finally, ten drug candidates and eight diagnostic markers (STX17, NRG1, RRAGD, XPO1, HERC1, HSP90AB1, EPHB2, and S1PR3) were screened. CONCLUSIONS: This is the first study to screen eight diagnostic markers and construct a gene regulatory network for COVID-19-MDD from the perspective of autophagy. The findings of our study provide novel insights into the diagnosis and treatment of COVID-19-MDD.

TRPM7 Elicits Proliferation and Differentiation of Human Lens Epithelial Cells through the TGF-ß/Smad Pathways.

Epithelial-mesenchymal transition (EMT) plays a crucial role in the development of cataract. This study aimed to explore the effects of TRPM7 on the proliferation and differentiation of human lens epithelial cells. TRPM7 was over-expressed in LECs treated with TGF-ß2. Down-regulation of TRPM7 attenuated the increase in cell viability and cell proliferation induced by TGF-ß2. The LEC migration induced by TGF-ß2 was also repressed by down-regulation of TRPM7. Epithelial-specific protein E-cadherin was up-regulated through knock-down of TRPM7. EMT-specific proteins, α-SMA, fibronectin and vimentin, were down-regulated through knockdown of TRPM7. Moreover, phosphorylation of Smad2 and Smad3 was also prevented by inhibition of TRPM7. Therefore, TRPM7 elicited LEC proliferation and EMT through enhancing activation of the TGF-ß/Smad pathways, implying a new therapeutic target for cataract.

Burden of brain and central nervous system cancers in China from 1990 to 2019.

OBJECTIVE: Primary central nervous system (CNS) cancer is a predominant source of mortality and morbidity globally. This study aims to analyze the burden and variation trends of CNS cancer in China from 1990 to 2019. MATERIALS AND METHODS: In this cross-sectional study, we analyzed people of all ages with CNS cancer in China from January 1, 1990, to December 31, 2019. We collected the data including incidence, deaths, and disability-adjusted life-years (DALYs) from the Global Burden of Disease (GBD) study 2019. The age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and DALYs rate were compared by age and sex. RESULTS: In 2019, there were more than 94 (95% uncertainty intervals [CI]: 73-114) thousand incident cases, 63 (47-76) thousand deaths and 2.0 (1.5-2.5) million DALYs due to CNS cancer in China in 2019. From 1990 to 2019, the absolute number of incident cases, deaths, and DALYs increased by 107.0% (39.0 to 169.0), 67.0% (12.0 to 117.0), and 16.0% (-23.0 to 63.0). The ASIR increased by 28.0% (-16.0 to 64.0). ASDR and age-standardized DALYs rate decreased by -10.0% (-40.0 to 15.0) and -22.0% (-50.0 to 10.0), respectively. CONCLUSIONS: The overall burden due to CNS cancer in China remains high, as evidenced by the sharp increase in the incident cases, deaths, and DALYs from 1990 to 2019. Elderly patients and neonates show relatively high burden. Sex-specific differences in the incidence of CNS cancer in China are observed.

[Recommendations of EASL clinical practice guidelines on haemochromatosis].

Haemochromatosis is characterised by elevated transferrin saturation (TSAT) and progressive iron loading that mainly affects the liver. Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy and other complications. In patients homozygous for p.Cys282Tyr in HFE, provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 µg/L in females and TSAT >50% and ferritin >300 µg/L in males and postmenopausal women) is sufficient to diagnose haemochromatosis. In patients with high TSAT and elevated ferritin but other HFE genotypes, diagnosis requires the presence of hepatic iron overload on MRI or liver biopsy. The stage of liver fibrosis and other end-organ damage should be carefully assessed at diagnosis because they determine disease management. Patients with advanced fibrosis should be included in a screening programme for hepatocellular carcinoma. Treatment targets for phlebotomy are ferritin <50 µg/L during the induction phase and <100 µg/L during the maintenance phase.

[IL-1ß inhibitor sensitizes to olaparib in homologous recombination deficiency proficient ovarian cancer cells].

Objective: To investigate the inhibitory effect of combined strategy of poly adenosine diphosphate ribose polymerase (PARP) inhibitor and interleukin-1ß (IL-1ß) inhibitor on homologous recombination deficiency (HRD)-proficient ovarian cancer cells. Methods: (1) HRD-proficient ovarian cancer cell lines OVCAR3 and CAOV3 were treated with PARP inhibitor olaparib. Screening by RNA sequencing analysis, the expression level of IL-1ß was validated by enzyme-linked immunosorbent assay (ELISA) and western blot. (2) The dose-response curves of IL-1ß inhibitor diacerein were evaluated by cell counting kit-8 (CCK-8) assays in OVCAR3 and CAOV3 cells. CCK-8 assays were further applied to determine the viabilities of OVCAR3 and CAOV3 cells. (3) To evaluate the synergistic effects of olaparib and IL-1ß inhibitor in vivo, the transplanted ovarian cancer model was constructed. BALB/c-nude mice (n=16) were injected intraperitoneally with 1×107 OVACR3 cells labelled with luciferase (OVCAR3-Luc). Immunohistochemistry (IHC) assay was performed to determine nuclear antigen associated with cell proliferation (Ki-67) expression. (4) Blood routine tests, kidney and liver function tests were performed to analyze the toxic reaction of different drug treatments. The potential drug-induced injuries of vital organs including heart, liver, spleen, lungs and kidneys of nude mice were determined by hematoxylin-eosin (HE) staining. Results: (1) The RNA sequencing results showed that the mRNA level of IL-1ß was the most significantly increased among the 25 differentially expressed genes in OVCAR3 cells treated with olaparib, compared to the negative control group. Olaparib treatment significantly promoted the secretion and expression of IL-1ß protein in both OVACR3 and CAOV3 cells by ELISA [(36.2±3.5) and (49.5±3.5) pg/ml, respectively; all P<0.001] and western bolt (2.87±0.37 and 2.05±0.08, respectively; all P<0.01). (2) The half maximal inhibitory concentration (IC50) value of IL-1ß inhibitor was determined as follows: 75 µmol/L for OVACR3 cells and 100 µmol/L for CAOV3 cells. The treatments were divided into four groups including control group, olaparib monotherapy group, IL-1ß inhibitor monotherapy group and the combination therapy group. The cell viabilities of each group in OVCAR3 and CAOV3 were determined by CCK-8 assay. The data in each group were showed as follows for OVCAR3 and CAOV3 cells: (100.0±0.4)% and (100.0±3.5)% in control group; (63.1±6.2)% and (63.3±3.8)% in olaparib monotherapy group; (61.6±4.7)% and (63.8±3.5)% in IL-1ß inhibitor monotherapy group; and (32.9±5.2)% and (30.0±1.3)% in the combination therapy group. The viability assay showed that the combined strategy exhibited a significant inhibition effect on OVACR3 and CAOV3 cells, compared to the monotherapy group and the control group (all P<0.01). (3) All mice with transplanted tumors of HRD-proficient ovarian cancer cells were randomly divided into four groups, and treated with four different treatments as mentioned above, respectively. After 4 weeks (on day 29), the vivo fluorescence imaging were determined. The results showed that the amount of fluorescence of transplanted tumors was mostly decreased in the combination therapy group [(0.5±0.4)×1010 p/s], compared to the control group [(4.2±1.0)×1010 p/s] or the groups treated with any single drug [(3.1±0.9)×1010, (2.2±0.9)×1010 p/s; all P<0.05]. Mice were then sacrificed under anesthesia, and all transplanted tumors detached and weighed for further investigation. The weight of transplanted tumors was significantly decreased in the combination therapy group [(0.09±0.03) g], compared to that in control group [(0.25±0.05) g] or groups treated with any single drug [(0.17±0.03), (0.19±0.04) g; all P<0.05]. The measurement of the expression of Ki-67 showed that it was significantly decreased in the combination therapy group (0.33±0.10), compared to that in the control group (1.00±0.20) or monotherapy groups (0.76±0.07, 0.77±0.12; all P<0.05). (4) There were no significant differences of body weights, blood routine test, renal and liver function tests among mice with different treatments (all P>0.05). Moreover, no significant injuries were observed in the vital organs among the four groups. Conclusions: The combination of olaparib and IL-1ß inhibitor synergistically exhibits significant cytotoxicity in HRD-proficient ovarian cancer cells. Moreover, the blood routine and blood biochemistry results confirmed the biosafety of the combination of olaparib and IL-1ß inhibitor.

Comparison study of three laparoscopic ligation procedures for pediatric inguinal hernia: a multicenter cohort of 5523 cases.

PURPOSE: Single-site laparoscopic percutaneous extraperitoneal ligation (SLPEL) for pediatric inguinal hernia has gained popularity worldwide. However, complications associated with extraperitoneal knotting are not rare. This study evaluated the effectiveness of a modified SLPEL (M-SLPEL) to decrease adverse events associated with ligation knotting by comparing it with two other methods: classical SLPEL (C-SLPEL) and intracorporeal purse-string suturing (IPS). METHODS: A multicenter retrospective comparative study was conducted among 5523 pediatric inguinal hernia patients. Cases were divided into three groups according to the surgical procedure: the M-SLPEL, C-SLPEL, and IPS groups. Data describing the clinical characteristics, operative time, and complications were collected. RESULTS: All procedures were performed uneventfully. There were no significant differences in the age at operation (mean 2.62 ± 1.38 years). The operative time was shorter in the M-SLPEL group both for unilateral hernias (12.5 ± 1.8 min in C-SLPEL, 11.7 ± 1.3 min in M-SLPEL, and 17.6 ± 2.9 min in IPS) and for bilateral hernias (15.1 ± 2.1 min, 14.6 ± 1.7 min, and 23.9 ± 2.3 min, respectively). The overall incidence of adverse events in the inguinal region was 0% for M-SLPEL, 2.2% for C-SLPEL, and 0.5% for IPS. All patients were followed up for 12-93 months (mean 54 months). Recurrence occurred in 8 cases in the C-SLPEL group, 1 case in the M-SLPEL group, and 8 cases in the IPS group, with no significance between groups. No scrotal hematoma, testicular atrophy, or iatrogenic cryptorchidism occurred in any group. CONCLUSION: The M-SLPEL procedure has time-consumption efficiency equivalent to that of C-SLPEL and even fewer adverse events in the inguinal region than IPS and C-SLPEL.

Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research.

Endometriosis is a chronic systemic disease that can cause pain, infertility and reduced quality of life. Diagnosing endometriosis remains challenging, which yields diagnostic delays for patients. Research on diagnostic test accuracy in endometriosis can be difficult due to verification bias, as not all patients with endometriosis undergo definitive diagnostic testing. The purpose of this State-of-the-Art Review is to provide a comprehensive update on the strengths and limitations of the diagnostic modalities used in endometriosis and discuss the relevance of diagnostic test accuracy research pertaining to each. We performed a comprehensive literature review of the following methods: clinical assessment including history and physical examination, biomarkers, diagnostic imaging, surgical diagnosis and histopathology. Our review suggests that, although non-invasive diagnostic methods, such as clinical assessment, ultrasound and magnetic resonance imaging, do not yet qualify formally as replacement tests for surgery in diagnosing all subtypes of endometriosis, they are likely to be appropriate for advanced stages of endometriosis. We also demonstrate in our review that all methods have strengths and limitations, leading to our conclusion that there should not be a single gold-standard diagnostic method for endometriosis, but rather, multiple accepted diagnostic methods appropriate for different circumstances. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Effects of essential oil/palygorskite composite on performance, egg quality, plasma biochemistry, oxidation status, immune response and intestinal morphology of laying hens.

The current study aimed to assess the effects of different levels of essential oil/palygorskite composite (EO-PGS) supplementation on performance, egg quality, oxidative status, immunity and intestinal morphology of laying hens. A total of 480 laying hens aged 65 wk were randomly assigned into 4 groups (6 replicates of 20 hens each). Hens were fed the basal diet supplemented with 0 (control diet), 0.5, 0.75 or 1.0 g/kg EO-PGS for 56 d. Data were analyzed by One-way ANOVA. Results showed that birds fed with diet supplemented with EO-PGS had increased the egg production (P < 0.05) more than birds fed with control diet. The yolk index and shell thickness were increased in 0.75 and 1.0 g/kg EO-PGS groups at d56 (P < 0.05). There was no significant difference in plasma biochemical parameters among all groups. Compared with the control group, supplementation of EO-PGS increased the immunoglobulin-G and interleukin-2 levels in plasma (P < 0.05). The total antioxidant capacity in plasma and liver, the plasma catalase concentration, the activity of total superoxide dismutase in the liver and the activity of glutathione peroxidase in the spleen were increased in the EO-PGS groups (P < 0.05). The concentration of malondialdehyde in the liver was decreased with the increasing level of EO-PGS (P < 0.05). The crypt depth of ileum and duodenum of birds fed with EO-PGS supplemented diet had a tendency to decrease (0.05

External control arms in oncology: current use and future directions.

Although randomized control trials allow for a comparison of treatment arms with minimal concern for confounding by known and unknown factors, a randomized study is not feasible in certain disease settings. When a randomized design is not possible, incorporating external control data into the study design can be an effective way to expand the interpretability of the results of an experimental arm by introducing the ability to carry out a formal or an informal comparative analysis. This paper provides an introduction to the concepts of external controls in oncology trials, followed by a review of relevant and current research on this topic. The paper also focuses on general considerations for designing a trial that may incorporate external control data, followed by case studies of the marketing applications submitted to the Food and Drug Administration that included external control data.