Introduction:Traditional Chinese Medicine (TCM) Combined with Methimazole (MMI) versus MMI Alone for Thyroid Function and Autoantibodies in Graves' Disease(GD). Methods:A systematic literature search was performed in PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, VIP, CBM, and Wanfang databases up to June 2025 for RCTs comparing TCM plus MMI versus MMI alone. Study risk of bias was evaluated using the Cochrane tool. We assessed transitivity to ensure intervention comparability, verified consistency via node-splitting analysis, and planned sensitivity analysis according to risk-of-bias classification. A network meta-analysis was conducted in Stata 15.1 using a random-effects model. Results are reported as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI), and treatment efficacy was ranked using SUCRA values. Results:A network meta-analysis of 15 RCTs involving 1,317 GD patients and 14 TCM plus MMI regimens showed potential advantages over MMI alone in improving thyroid function indices and reducing selected autoantibodies, particularly TRAb and TPOAb. Adverse events were summarized descriptively because AE reporting was incomplete and heterogeneous across the included RCTs. Regarding SUCRA rankings, the Modified Huagan Decoction (MHD) + MMI ranked first for reducing FT3 (SUCRA = 93.4%), the Modified Xiaoyao Powder (MXYP) + MMI ranked first for reducing FT4 (SUCRA = 97.3%), and the Xiaoyao Powder (XYP) + MMI ranked first for regulating TSH (SUCRA = 96.3%). For decreasing TRAb, the MHD + MMI regimen ranked first (SUCRA = 88.2%), while for lowering TPOAb, the Huotan Jiangni Formula (HJF) + MMI showed the highest SUCRA ranking (SUCRA = 100%). Conclusion:TCM combined with MMI may have beneficial effects on thyroid function and selected autoantibody levels, particularly TRAb and TPOAb, in GD patients versus MMI alone. Among the evaluated regimens, MHD + MMI, MXYP + MMI, XYP + MMI, and HJF + MMI showed high SUCRA rankings for specific outcomes, including FT3, FT4, TSH, TRAb, and TPOAb. These findings suggest that TCM plus MMI may be a promising short-term adjunctive strategy for initial GD treatment, although safety evidence remains limited by incomplete and inconsistent AE reporting. Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier CRD420251151307.

Abstract Background Family caregivers of colorectal cancer (CRC) patients often experience significant distress, yet no validated instrument exists in China to screen for this distress. This study aimed to translate the CancerSupportSource™-Caregiver (CSS-Caregiver) scale into Chinese and evaluate its psychometric properties among CRC family caregivers. Methods A cross-sectional study was conducted with 340 family caregivers of CRC patients from three tertiary hospitals in Guangzhou. The Chinese CSS-Caregiver was translated and culturally adapted. Its psychometric properties were assessed using both Classical Test Theory and Rasch analysis. Reliability was evaluated via internal consistency and test-retest reliability. Validity was examined through confirmatory factor analysis (CFA), item-total correlations, and convergent validity. Measurement invariance was tested using multi-group CFA and Differential Item Functioning (DIF). The optimal cut-off score was determined via ROC analysis. Results The Chinese CSS-Caregiver demonstrated excellent internal consistency (Cronbach’s α = 0.902) and test-retest reliability (ICC = 0.935). CFA supported the original five-factor structure with good model fit (χ²/df = 2.064, CFI = 0.956, RMSEA = 0.073). Rasch analysis indicated generally satisfactory item fit and person separation. The scale exhibited strict measurement invariance across sex, age, and residence, with negligible DIF. Strong convergent validity was demonstrated by correlations with the criterion measures (r = 0.81 ~ 0.85). An optimal cut-off score of 18.5 was established. Conclusions The Chinese CSS-Caregiver is a valid and reliable instrument for assessing distress among family caregivers of CRC patients in China, facilitating early identification and timely psychosocial support.

Thyroid cancer (TC) represents the most prevalent malignancy within the endocrine system. In recent years, there has been a marked global increase in the incidence of thyroid cancer, garnering substantial scientific interest. Comprehensive investigations into the pathogenesis of TC have identified a significant association with ferroptosis, a newly characterized form of cell death mediated by iron ions. Distinct from apoptosis, necrosis, and autophagy, ferroptosis is characterized by the accumulation of lipid peroxides and reactive oxygen species, culminating in cellular damage and death.Recent research has elucidated a connection between ferroptosis and the initiation, progression, and treatment of thyroid cancer. These findings underscore the significance of ferroptosis in thyroid cancer and offer valuable insights into the development of novel therapeutic strategies and precise predictive markers. The unique mechanisms of ferroptosis present opportunities for targeting treatment-resistant thyroid cancers. Consequently, the regulation of ferroptosis may emerge as a novel therapeutic target, potentially addressing the limitations of current treatments. Moreover, elucidating the molecular mechanisms underpinning ferroptosis in thyroid cancer may facilitate the identification of novel biomarkers for early detection and prognostication. This review endeavors to synthesize the extant knowledge regarding the role of ferroptosis in thyroid cancer, examine potential therapeutic implications, and propose future research trajectories to enhance the understanding and clinical application of ferroptosis.

Resistance to the BRAF inhibitor vemurafenib (PLX4032) limits its efficacy in thyroid cancer. Ubiquitin-specific peptidase 7 (USP7), a key regulator of oncogenic signaling, and USP7 inhibitor may help overcome drug resistance. This study investigated the combined efficacy of PLX4032 and the USP7 inhibitor P5091 in BRAFV600E-mutant thyroid cancer. Bioinformatics showed that USP7 and integrin subunit beta 3 (ITGB3), a MAPK/PI3K pathway gene, may jointly mediate resistance. In thyroid cancer cell lines, the combination treatment significantly reduced viability, proliferation, colony formation, migration, and invasion versus monotherapy. Moreover, the combination treatment can reduce viability and induce cell death in thyroid cancer organoids. Given USP7's role in oxidative stress and ferroptosis, we examined its involvement and found that P5091 induced ferroptosis via reactive oxygen species (ROS) elevation, glutathione peroxidase 4 (GPX4) downregulation, and elevated lipid peroxidation. These findings demonstrate that USP7 inhibition by P5091 enhances PLX4032 efficacy by promoting tumor suppression and ferroptosis in BRAFV600E-mutant thyroid cancer, offering a promising strategy to overcome resistance.

Background: The current research aims to elucidate the interplay between the anatomical distribution of spinal metastases, MRI features, and the intensity of bone pain in patients with breast cancer. Methods: A retrospective analysis was used on a cohort of 45 breast cancer patients with verified spinal metastases, examining the relationship between metastatic locations, MRI-derived metrics, and bone pain scores. The Visual Analogue Scale (VAS) was conducted to measure the severity of bone pain. Results: The results revealed a significant association between lumbar spine metastases and elevated pain scores, outpacing those observed in thoracic and cervical regions. Furthermore, a strong correlation was found between the multiplicity of metastatic sites and the ratio of high-intensity areas on MRI, both of which were predictive of increased pain severity. Conclusions: The study's outcomes indicate that distinct MRI profiles, including the number and location of spinal metastases, can serve as prognostic indicators of bone pain intensity in breast cancer patients. Our data highlighted the need for personalized pain management strategies and targeted interventions tailored to specific imaging characteristics. Ultimately, this research underscores the dual role of MRI in both detecting spinal metastases and informing symptom management, with the potential to augment the overall well-being of breast cancer patients with spinal involvement.

Parathyroid carcinoma (PC) is a rare and aggressive malignancy, characterized by severe hypercalcemia and elevated parathyroid hormone (PTH) levels, making it particularly challenging to diagnose. In this case report, the patient’s PC was not diagnosed during the initial surgery. The diagnosis was delayed until two years later, when metastatic lesions appeared in the lungs, leading to repeat surgery and a retrospective review of the patient’s medical history. This case emphasizes the diagnostic difficulty of PC, particularly during the initial evaluation. Close postoperative follow-up is crucial for suspected cases. Upon biochemical evidence of recurrence, comprehensive systemic screening should be conducted, not only focusing on the neck but also on common metastatic sites such as the lungs, bones, and liver.

Endocrine cancers are a heterogeneous group of malignancies that originate from cells capable of secreting hormones. Examples include but are not limited to thyroid cancer, adrenocortical carcinoma, prostate cancer, and pancreatic cancer. Our limited understanding of endocrine cancers is partially due to constraints related to model systems, which cannot accurately replicate the pathogenesis of these tumors. Patient-derived organoids (PDOs) are clusters of multiple cell types that grow in a three-dimensional environment. They have become innovative models that faithfully reproduce genotype and phenotype of the tissues from which they originated, facilitating the prediction of patient treatment responses and guiding the development of precision medicine. This article provides a comprehensive review of the establishment of endocrine cancer PDOs and their applications in cancer research, drug screening, and personalized therapy. These excellent preclinical models have the potential to advance our understanding of endocrine cancers in basic research and clinical practice. In addition, we discuss the challenges related to current organoid technologies and provide future perspectives on the applications of organoids in precision medicine to improve the management of endocrine cancers.

Backgrounds Papillary thyroid cancer (PTC), which is often driven by acquired somatic mutations in BRAF genes, is the most common pathologic type of thyroid cancer. PTC has an excellent prognosis after treatment with conventional therapies such as surgical resection, thyroid hormone therapy and adjuvant radioactive iodine therapy. Unfortunately, about 20% of patients develop regional recurrence or distant metastasis, making targeted therapeutics an important treatment option. Current in vitro PTC models are limited in representing the cellular and mutational characteristics of parental tumors. A clinically relevant tool that predicts the efficacy of therapy for individuals is urgently needed. Methods Surgically removed PTC tissue samples were dissociated, plated into Matrigel, and cultured to generate organoids. PTC organoids were subsequently subjected to histological analysis, DNA sequencing, and drug sensitivity assays, respectively. Results We established 9 patient-derived PTC organoid models, 5 of which harbor BRAF V600E mutation. These organoids have been cultured stably for more than 3 months and closely recapitulated the histological architectures as well as mutational landscapes of the respective primary tumors. Drug sensitivity assays of PTC organoid cultures demonstrated the intra- and inter-patient specific drug responses. BRAF V600E inhibitors, vemurafenib and dabrafenib monotherapy was mildly effective in treating BRAF V600E -mutant PTC organoids. Nevertheless, BRAF inhibitors in combination with MEK inhibitors, RTK inhibitors, or chemotherapeutic agents demonstrated improved efficacy compared to BRAF inhibition alone. Conclusions These data indicate that patient-derived PTC organoids may be a powerful research tool to investigate tumor biology and drug responsiveness, thus being useful to validate or discover targeted drug combinations.

Thyroid cancer (TC) is one of the most common malignancies involving the head and neck, and its incidences are increasing every year. Small G protein signaling modulators 2 (SGSM2) belongs to a newly identified protein group that contributes to numerous cancer progression. However, its role in TC remains unknown. The aim of this study was to explore the functions and underlying molecular mechanism of SGSM2 in the progression of thyroid tumorigenesis. Here, we demonstrated that SGSM2 expression was markedly decreased in TC, and that lower SGSM2 expression was potentially related to worse patient prognosis. Meanwhile, the SGSM2 levels were not directly correlated with BRAF or RAS mutations in TC. Based on our functional analysis, ectopic SGSM2 expression strongly prevented cell proliferation, migration, invasion, and tumorigenic activity in TC cells that harbored wild type RAS. Mechanistically, we demonstrated that SGSM2 interacted with Small G protein Ras-associated protein 1(RAP1) and augmented its activity. Activated RAP1 then competitively suppressed RAS activation and thereby downregulated output of MAPK/ERK and PI3K/Akt networks, which are primary contributors of TC. In summary, the present study reports a tumor suppressive role of SGSM2 in TC. Moreover, we revealed the underlying molecular mechanism, thus providing a potential therapeutic target for TCs that harbor wild type RAS.

Background and purpose: The Chest Pain Center accreditation project was launched in 2011 in China as a nationwide effort to improve clinical management of acute chest pain patients. In this study, we summarize the clinical characteristics and in-hospital outcomes of patients undergoing treatment for acute coronary syndrome (ACS) in Chest Pain Centers in China. Methods: Data were based on the Chinese Cardiovascular Association (CCA) Database-Chest Pain Center of 1,745,118 ACS patients admitted at 2,096 accredited Chest Pain Center between January 1, 2016, and December 31, 2021. Patient characteristics, time delays, treatment, and outcomes were analyzed using descriptive analysis. Results: The final analysis included a total of 1,745,118 patients, 699,476 patients (40.1%) with ST segment elevation myocardial infarction (STEMI), 349,572 (20.0%) with non-ST segment elevation myocardial infarction (NSTEMI), and 696,070 (39.9%) with unstable angina (UA). Electrocardiogram (ECG) was conducted in 89.4% of the patients within 10 min after first medical contact. For STEMI patients, the median door-to-wire crossing time was 72.1 (53.1 to 91.9) min and the median first medical contact-to-needle time was 32.3 (23.8 to 58.6) min. In-hospital mortality was 2.0% in the overall analysis, 3.6% for STEMI, 2.1% for NSTEMI, and 0.3% for UA. Primary percutaneous coronary intervention (PCI) was conducted in 62.8% of STEMI patients, with increasing rate in grade I and II hospitals over the 6-year study period. Patients treated with thrombolysis had significantly higher mortality than those treated with PCI and thrombolysis combined with PCI. The development of Chest Pain Centers varied substantially across geographic regions. Conclusions: Based on CCA Database-Chest Pain Center, the current study provided an overall description of the clinical characteristics of ACS patients in China. The results on management pattern and in-hospital outcomes of STEMI patients identified important areas for further improvement in ACS patient management in China.

Background and purpose: In the past 30 to 40 years, percutaneous coronary intervention (PCI) in China has greatly improved. The State Ministry of Health established a quality control (QC) system in 2009, and all medical centers were required to report their PCI cases. We analyzed the data from the QC system to describe the current status and development of PCI in China. Methods: PCI case data during a period from 2010 to 2018 were extracted from the online QC system. Data quality was audited by QC centers at the provincial level. Statistical analysis was mainly descriptive. Trend analysis was conducted by recoding the year as a continuous variable in linear regression or logistic regression. Results: The number of medical centers reporting PCI cases was 941 in 2010, and increased to 1,788 in 2018. Total number of PCI cases reported online to the QC system was 236,717 in 2010, and increased to 705,970 in 2018. Estimate of the actual case number that included those reported offline only (based on offline audit by provincial QC centers) was 284,936 in 2010, and increased to 915,256 in 2018. The most common indication for PCI was unstable angina (52.9%–59.1%), followed by ST elevation myocardial infarction (STEMI; 25.0%–27.4%). Majority of the PCI procedures were performed via the radial artery (65.4% in 2010 and 90.7% in 2018). Angiography detected a left main lesion in 5%, single-vessel disease in 38.7% to 44.4%, two-vessel disease in 22.3% to 27.5%, and three-vessel disease in 27.0% to 28.7% of the patients. The rate of primary PCI for STEMI in all STEMI cases was 28.0% in 2010, and increased to 45.9% in 2018. The average number of stents implanted per case was 1.63 in 2010, and decreased to 1.46 in 2018. There was a trend for decreasing mortality (0.31% in 2010; 0.26% in 2018). Conclusions: The number of PCI cases in China increased steadily during a period from 2010 to 2018, with stable mortality rate. Transradial access is the dominant PCI route. The rate of primary PCI for STEMI increased substantially, but remained relatively low.

Cordycepin is an extract from the Cordyceps genus of ascomycete fungi. In the present study, the anticancer potential of cordycepin against nasopharyngeal carcinoma (NPC), and the potential underlying mechanisms, were investigated. Using Cell Counting Kit 8, wound-healing and Transwell assays, cordycepin was found to reduce the viability and inhibit the migration of C666-1 cells in a dose-dependent manner. In addition, in colony formation assays, co-treatment with cordycepin and cisplatin inhibited the proliferation of C666-1 cells. Furthermore, RNA sequencing analysis identified 72 significantly differentially expressed genes and different signaling pathways that may be regulated by cordycepin. After treatment with cordycepin, the expression levels of ERK1/2, phosphorylated ERK1/2 and β-catenin were significantly downregulated. Therefore, cordycepin may be a novel candidate for NPC treatment or a co-treatment candidate with cisplatin in chemotherapy.

Objective: Differentiated thyroid carcinoma (DTC) is the most common type of thyroid cancer (TC), accounting for 70% to 80% of all TC cases. However, 10% to 15% of DTC patients experience neoplasm metastasis and recurrence. Plumbagin is a bioactive molecule that inhibits the formation of neoplastic cells by inactivating signal pathways. Methods: We investigated the antitumor activity of plumbagin in DTC and its molecular mechanisms based on network pharmacology, molecular biological techniques and animal experiments. The underlying processes of plumbagin were investigated using gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: Plumbagin reduced the growth of DTC cells and increased the cells' apoptotic rate in vitro. Tumor volumes were significantly lessened after administration of plumbagin (P<0.05) as compared to tumor dimensions in the control group. In total, 1,225 cancer target genes and 89 putative plumbagin target genes were distinguished. As revealed in bioinformatics data, 12 predominant targets of plumbagin for treating DTC were obtained, and western blotting further confirmed that TP53, AKT1, CASP3, and PTEN were the most important biomolecules in the effects exerted by plumbagin. Conclusion: These findings show that plumbagin induced DTC cell apoptosis and suppressed tumor growth via TP53, AKT1, CASP3, and PTEN mediated pathways in human DTC cells. GO and KEGG enrichment analysis of differentially expressed genes (DEGs) related to plumbagin activation indicated pathways involved in cell survival, apoptosis, and metabolism, that were all significantly enriched.

The coronavirus disease 2019 (COVID-19) global pandemic evoked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a major public health problem with significant morbidity and mortality. Understanding the pathogenesis and molecular mechanisms underlying this novel virus is crucial for both fundamental research and clinical trials in order to devise effective therapies and vaccination regimens. Basic research on SARS-CoV-2 largely depends on ex vivo models that allow viral invasion and replication. Organoid models are now emerging as a valuable tool to investigate viral biology and disease progression, serving as an efficient platform to investigate potential therapies for COVID-19. Here, we summarize various human stem cell-derived organoid types employed in SARS-CoV-2 studies. We highlight key findings from these models, including cell tropisms and molecular mechanisms in viral infection. We also describe their use in identifying potential therapeutic agents against SARS-CoV-2. As more and more advanced organoids emerge, they will facilitate the understanding of disease pathogenesis for drug development in this dreaded pandemic.

Background: Peripheral blood mononuclear cells (PBMCs) play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). However, the specific roles of PBMCs in the development and progression of idiopathic PAH (IPAH) have not been fully understood. Methods: Here, differentially expressed genes (DEGs) of PBMCs or lung tissues between IPAH patients and healthy controls were identified via bioinformatics analysis of Gene Expression Omnibus (GEO) datasets and , respectively. Subsequently, extensive target prediction and network analysis were performed to assess protein-protein interaction (PPI) networks, Gene Ontology (GO) terms, and pathway enrichment for DEGs. Co-expressed DEGs between PBMCs and lung tissues coupled with corresponding predicted miRNAs involved in PAH were also assessed. We identified 251 DEGs in PBMCs and 151 DEGs in lung tissue samples from IPAH. PDK4, RBPMS2, and PDE5A expression were altered in both PBMCs and lung tissues from IPAH patients compared to healthy control. Results: CXCL8, JUN, TLR8, IL1B, and TLR7 could be implicated as the hub genes in PBMCs, whereas ENO1, STAT1, CXCL10, GPI, and IRF1 in lung tissues. Finally, co-expressed DEGs of PDK4, RBPMS2, and PDE5A coupled with corresponding predicted miRNAs, especially miR-103a-3p, miR-185-5p, and miR-515-5p, are significantly associated with IPAH. Conclusion: Our findings collectively suggest that the expression levels of PDK4, RBPMS2, and PDE5A in PBMCs are associated with the expression of these genes in lung tissues. Thus, these molecules may serve as potential circulating biomarkers and/or possible therapeutic targets for IPAH.

Small nucleolar RNA SNORD50A and SNORD50B (SNORD50A/B) has been reported to be recurrently deleted and function as a putative tumor suppressor in different types of cancer by binding to and suppressing the activity of the KRAS oncoproteins. Its deletion correlates with poorer patient survival. However, in this study, we surprisingly found that SNORD50A/B loss predicted a better survival in breast cancer patients carrying wild-type p53. Functional studies showed that SNORD50A/B deletion strongly inhibited the proliferation, migration, invasion and tumorigenic potential, and induced cell cycle arrest and apoptosis in p53 wild-type breast cancer cells, while exerted the opposite effects in p53 mutated breast cancer cells. This was also supported by ectopically expressing SNORD50A/B in both p53 wild-type and mutated breast cancer cells. Mechanistically, SNORD50A/B clearly enhances the interaction between E3 ubiquitin ligase TRIM21 and its substrate GMPS by forming a complex among them, thereby promoting GMPS ubiquitination and its subsequent cytoplasmic sequestration. SNORD50A/B deletion in p53 wild-type breast cancer cells will release GMPS and induce the translocation of GMPS into the nucleus, where GMPS can recruit USP7 and form a complex with p53, thereby decreasing p53 ubiquitination, stabilizing p53 proteins, and inhibiting malignant phenotypes of cancer cells. Altogether, the present study first reports that SNORD50A/B plays an oncogenic role in p53 wild-type breast cancers by mediating TRIM21-GMPS interaction.

Background BRAFV600E mutation is the most common mutation in thyroid cancer. It strongly activates MAPK/ERK pathway and indicates an invasive subtype of thyroid cancer. PLX4032 is a selective oral inhibitor of the BRAFV600 kinase although with limited effect in treating this panel of thyroid cancer, due to the feedback activation of MAPK/ERK as well as PI3K/AKT pathways. It was investigated that Vitamin C plays a positive role in inhibiting these pathways in thyroid cancer. However, whether Vitamin C could enhance the antitumor effect of PLX4032 remains largely unclear. Methods The antitumor efficacy of combination therapy with PLX4032 and Vitamin C on BRAF MT thyroid cancer cell was assessed by the MTT assay, EdU assay and colony formation, Chou-Talalay way was employed to analyze the synergistic effect. Flow cytometry were employed to assess cells’ apoptosis and cell cycle arrest in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Western blot and IHC were applied to investigate the mechanism underlying synergistic effect. Results PLX4032 or Vitamin C monotherapy was mildly effective in treating BRAF MT thyroid cancer cell and xenografts model. The combination therapy significantly inhibited cancer cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest compared to either monotherapy. PLX4032 monotherapy induced feedback activation of MAPK/ERK as well as PI3K/AKT pathway; while combination therapy significantly relieved this feedback. Conclusion Vitamin C promotes the antitumor effect of PLX4032 in BRAF MT thyroid cancer cell and xenografts model via relieving the feedback activation of MAPK/ERK as well as PI3K/AKT pathway. PLX4032/Vitamin C combination may be a potential therapeutic approach to treat BRAF MT thyroid cancer.

BACKGROUND:Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving pandemic, hypertension is one of the most common co-existing chronic conditions and a risk factor for mortality. Nearly one-third of the adult population is hypertensive worldwide, it is urgent to identify the factors that determine the clinical course and outcomes of COVID-19 patients with hypertension.METHODS AND RESULTS:148 COVID-19 patients with pre-existing hypertension with clarified outcomes (discharge or deceased) from a national cohort in China were included in this study, of whom 103 were discharged and 45 died in hospital. Multivariate regression showed higher odds of in-hospital death associated with high-sensitivity cardiac troponin (hs-cTn) > 28 pg/ml (hazard ratio [HR]: 3.27, 95% confidence interval [CI]: 1.55-6.91) and interleukin-6 (IL-6) > 7 pg/ml (HR: 3.63, 95% CI:1.54-8.55) at admission. Patients with uncontrolled blood pressure (BP) (n = 52) which were defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg for more than once (≥2 times) during hospitalization, were more likely to have ICU admission (p = 0.037), invasive mechanical ventilation (p = 0.028), and renal injury (p = 0.005). A stricter BP control with the threshold of 130/80 mm Hg was associated with lower mortality. Treatment with renin-angiotensin-aldosterone system (RAAS) suppressors, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and spironolactone, was associated with a lower rate of ICU admission compared to other types of anti-hypertensive medications (8 (22.9%) vs. 25 (43.1%), p = 0.048).CONCLUSION:Among COVID-19 patients with pre-existing hypertension, elevated hs-cTn and IL-6 could help clinicians to identify patients with fatal outcomes at an early stage, blood pressure control is associated with better clinical outcomes, and RAAS suppressors do not increase mortality and may decrease the need for ICU admission.

BRAF V600E is the most common genetic alteration and has become a major therapeutic target in thyroid cancers; however, intrinsic feedback mechanism limited clinical use of BRAF V600E specific inhibitors. Synthetic lethal is a kind of interaction between two genes, where only simultaneously perturbing both of the genes can lead to lethality. Here, we identified CYP2S1 as a synthetic lethal partner of BRAF V600E in thyroid cancers. First, we found that CYP2S1 was highly expressed in papillary thyroid cancers (PTCs) compared to normal thyroid tissues, particularly in conventional PTCs (CPTCs) and tall-cell PTCs (TCPTCs), and its expression was positively associated with BRAF V600E mutation. CYP2S1 knockdown selectively inhibited cell proliferation, migration, invasion and tumorigenic potential in nude mice, and promoted cell apoptosis in BRAF V600E mutated thyroid cancer cells, but not in BRAF wild-type ones. Mechanistically, BRAF V600E -mediated MAPK/ERK cascade upregulated CYP2S1 expression by an AHR-dependent pathway, while CYP2S1 in turn enhanced transcriptional activity of AHR through its metabolites. This AHR/CYP2S1 feedback loop strongly amplified oncogenic role of BRAF V600E in thyroid cancer cells, thereby causing synthetic lethal interaction between CYP2S1 and BRAF V600E . Finally, we demonstrated CYP2S1 as a potential therapeutic target in both BRAF V600E -drived xenograft and transgenic mouse models by targetedly delivering CYP2S1-specific siRNA. Altogether, our data demonstrate CYP2S1 as a synthetic lethal partner of BRAF V600E in thyroid cancers, and indicate that targeting CYP2S1 will provide a new therapeutic strategy for BRAF V600E mutated thyroid cancers.