Social determinants of health correlations and resource usefulness at a Milwaukee free clinic for uninsured individuals: A cross-sectional study.

Introduction: Addressing social determinants of health (SDOH) is fundamental to improving health outcomes. At a student-run free clinic, we developed a screening process to understand the SDOH needs and resource utilization of Milwaukee's uninsured population. Methods: In this cross-sectional study, we screened adult patients without health insurance (N = 238) for nine traditional SDOH needs as well as their access to dental and mental health care between October 2021 and October 2022. Patients were surveyed at intervals greater than or equal to 30 days. We assessed correlations between SDOH needs and trends in patient-reported resource usefulness. Results: Access to dental care (64.7%) and health insurance (51.3%) were the most frequently endorsed needs. We found significant correlations (P ≤ 0.05) between various SDOH needs. Notably, mental health access needs significantly correlated with dental (r = 0.41; 95% CI = 0.19, 0.63), medications (r = 0.51; 95% CI = 0.30, 0.72), utilities (r = 0.39; 95% CI = 0.17, 0.61), and food insecurity (r = 0.42; 95% CI = 0.19, 0.64). Food-housing (r = 0.55; 95% CI = 0.32, 0.78), housing-medications (r = 0.58; 95% CI = 0.35, 0.81), and medications-food (r = 0.53; 95% CI = 0.32, 0.74) were significantly correlated with each other. Longitudinal assessment of patient-reported usefulness informed changes in the resources offered. Conclusions: Understanding prominent SDOH needs can inform resource offerings and interventions, addressing root causes that burden under-resourced patients. In this study, patient-reported data about resource usefulness prompted the curation of new resources and volunteer roles. This proof-of-concept study shows how longitudinally tracking SDOH needs at low-resource clinics can inform psychosocial resources.

Maximum tolerated dose and toxicity evaluation of orally administered docetaxel granule in mice.

Oral delivery of chemotherapy drugs is the most favorable and preferred route of drug administration. However, because of poor solubility and/or permeability, most chemotherapy drugs are given by intravenous administration. Docetaxel (DTX) is a potent chemotherapy drug that inhibits microtubular depolymerization and is widely used to treat numerous cancers. DTX is highly lipophilic and insoluble in water; thus, 50% polysorbate 80, which may cause hypersensitivity reactions and reduce drug uptake by tumor tissue, is used in the commercial DTX injection to dissolve DTX. Maximum tolerated dose (MTD) and toxicity are important to determine parameters in preclinical studies and to predict human dose in clinical trials. However, MTD and toxicity of oral DTX formulations have not been studied although various oral DTX formulations have been reported. We have previously developed oral DTX granule and demonstrated its ability to inhibit tumor growth. In this study, we aimed to systemically measure MTD and tissue distribution and evaluate the toxicity of oral DTX granule in mice. Oral DTX granule showed sex differences in toxicity and absorption. The MTD of DTX granule was determined at 50 mg/kg for female mice and 25 mg/kg for male mice. However, female mice had higher tissue absorption than male mice. At a very high dose (400 mg/kg), oral DTX granule induced kidney damage but did not influence the liver and the lungs. The study provides the fundamental data for future preclinical studies and clinical application of oral DTX formulations for cancers.

Refining quinoa storage stability through microwave-induced structural alterations and activity suppression of key enzymes.

This study investigated the effects of microwave on preserving the quality of quinoa during storage. Quinoa treated with 9W/60s exhibited a significant decrease in fatty acid values compared to hot air treatment. Microwave effectively delayed lipid oxidation during quinoa storage by suppressing the increase in peroxide values. MDA gradually accumulated from peroxides during storage, reaching its peak at 0.423 µmol/L in the second week. Microwave disrupted the original hydrogen bonds in lipase, causing the unwinding of the α-helix and resulting in the loss of its regular structure. Microwave reduced the stability of the ß-sheet structure in lipoxygenase, breaking the natural secondary structure composition. The observed fluorescence and UV spectra features were similar, indicating that microwave alter the peptide chain of the enzyme's skeletal structure, increasing the exposure of hydrophobic chromophores. These results indicated the potential of microwave to enhance the stability of quinoa during storage.

Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma.

BACKGROUND: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. METHODS: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. RESULTS: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. CONCLUSIONS: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577).

Soy isoflavones induces mitophagy to inhibit the progression of osteosarcoma by blocking the AKT/mTOR signaling pathway.

BACKGROUND: Soy isoflavones (SI) is a natural bioactive substance exhibiting beneficial effects on human health. This study aims to elucidate the therapeutic potential of SI in the treatment of osteosarcoma (OS) and to investigate the underlying mechanisms, particularly focusing on mitophagy. METHODS: The effects of SI on the proliferation, apoptosis, migration, and invasion of U2OS cells were analyzed. Mitophagy was assessed through multiple parameters: mitochondrial autophagosomes, mitochondrial membrane potential, autophagy-related proteins, reactive oxygen species (ROS), and oxygen consumption rate (OCR). Protein levels related to apoptosis, autophagy, and the AKT/mTOR pathway were analyzed using western blot. The therapeutic efficacy of SI was further identified using a mouse tumor xenograft model. Cell apoptosis and proliferation in tumor xenografts were detected by TUNEL staining and immunohistochemistry (IHC), respectively. RESULTS: SI dose-dependently suppressed the viability, colony formation, migration, and invasion of U2OS cells, and enhanced the apoptosis. SI also dose-dependently induced mitophagy in OS cells, evidenced by an increase in autophagosomes and ROS levels, a decrease in mitochondrial membrane potential and OCR, and concomitant changes in autophagy-related proteins. Mdivi-1, an inhibitor of mitophagy, reversed the anti-tumor effects of SI on U2OS cells. In addition, SI blocked the AKT/mTOR pathway in U2OS cells. SC-79, an AKT agonist, reversed the effect of SI on inducing mitophagy. Moreover, SI also promoted cell apoptosis and mitophagy in tumor xenografts in vivo. CONCLUSIONS: SI induces mitophagy in OS cells by blocking the AKT/mTOR pathway, contributing to the inhibition of OS.

Roles of rRNA N-methyladenosine modification in the function of ribosomes.

The N-methyladenosine (m6A) modification of ribosomal RNA (rRNA) plays critical roles in regulating the function of ribosomes, the essential molecular machines that translate genetic information from mRNA into proteins. Specifically, m6A modification affects ribosome biogenesis, stability, and function by regulating the processing and maturation of rRNA, the assembly and composition of ribosomes, and the accuracy and efficiency of translation. Furthermore, m6A modification allows for dynamic regulation of translation in response to environmental and cellular signals. Therefore, a deeper understanding of the mechanisms and functions of m6A modification in rRNA will advance our knowledge of ribosome-mediated gene expression and facilitate the development of new therapeutic strategies for ribosome-related diseases.

The Development of Lipid-Based Sorafenib Granules to Enhance the Oral Absorption of Sorafenib.

Sorafenib (SFN) is an anticancer multi-kinase inhibitor with great therapeutic potential. However, SFN has low aqueous solubility, which limits its oral absorption. Lipids and surfactants have the potential to improve the solubility of water-insoluble drugs. The aim of this study is thus to develop novel lipid-based SFN granules that can improve the oral absorption of SFN. SFN powder was coated with a stable binary lipid mixture and then absorbed on Aeroperl 300 to form dry SFN granules with 10% drug loading. SFN granules were stable at room temperature for at least three months. Compared to SFN powder, SFN granules significantly increased SFN release in simulated gastric fluid and simulated intestinal fluid with pancreatin. Pharmacokinetics and tissue distribution of SFN granules and SFN powder were measured following oral administration to Sprague Dawley rats. SFN granules significantly increased SFN absorption compared to SFN powder. Overall, the lipid-based SFN granules provide a promising approach to enhancing the oral absorption of SFN.

5-hydroxymethylcytosine sequencing in plasma cell-free DNA identifies unique epigenomic features in prostate cancer patients resistant to androgen deprivation therapy.

Background: Currently there are no biomarkers to identify resistance to androgen-deprivation therapy (ADT) in men with hormone-naive prostate cancer. 5-hydroxymethylcytosines (5hmC) in the gene body are associated with gene activation and are critical for epigenomic regulation of cancer progression. Objective: To evaluate whether 5hmC signature in cell-free DNA (cfDNA) predicts early ADT resistance. Design Setting and Participants: Serial plasma samples from 55 prostate cancer patients receiving ADT were collected at three timepoints including baseline (prior to initiating ADT, N=55), 3-month (after initiating ADT, N=55), and disease progression (N=15) within 24 months or 24-month if no progression was detected (N=14). 20 of the 55 patients showed disease progression during the 24-month follow-up. The remaining 35 patients showed no progression in the same follow-up period. Outcome Measurements and Statistical Analysis: cfDNA (5-10ng) was used for selective chemical labeling (hMe-Seal) sequencing to map 5hmC abundance across the genome. Read counts in gene bodies were normalized with DESeq2. Differential methylation and gene set enrichment analyses were performed to identify the 5hmC-enriched genes and biological processes that were associated with disease progression. Kaplan-Meir analysis was utilized to determine the association of 5hmC signatures with progression-free survival. Results and Limitations: 5hmC-sequencing generated an average of 18.6 (range 6.03 to 42.43) million reads per sample with 98% (95-99%) mappable rate. Baseline sample comparisons identified significant 5hmC difference in 1,642 of 23,433 genes between 20 patients with progression and 35 patients without progression (false discovery rate, FDR<0.1). Patients with progression showed significant enrichments in multiple hallmark gene sets with androgen responses as the top enriched gene set (FDR=1.19E-13). Interestingly, this enrichment was driven by a subgroup of patients with disease progression featuring a significant 5hmC hypermethylation of the gene sets involving AR, FOXA1 and GRHL2. To quantify overall activities of these gene sets, we developed a gene set activity score algorithm using a mean value of log2 ratios of gene read counts in an entire gene set. We found that the activity scores in these gene sets were significantly higher in this subgroup of patients with progression than in the remaining patients regardless of the progression status. Furthermore, the high activity scores in these gene sets were associated with poor progression-free survival (p <0.05). Longitudinal analysis showed that activity scores in this subgroup with progression were significantly reduced after 3-month ADT but returned to high levels when the disease was progressed. Conclusions: 5hmC-sequencing in cfDNA identified a subgroup of prostate cancer patients with preexisting activation (5hmC hypermethylation) of gene sets involving AR, FOXA1 and GRHL2 before initiating ADT. Activity scores in these gene sets may serve as sensitive biomarkers to determine treatment resistance, monitor disease progression and potentially identify patients who would benefit from upfront treatment intensification. More studies are needed to validate this initial finding. Patient summary: There are no clinical tests to identify prostate cancer patients who will develop early resistance to androgen deprivation therapy within 24 months. In this study, we evaluated cell-free DNA epigenomic modification in blood and identified significant enrichment of 5-hydroxymethylation in androgen response genes in a subgroup of patients with treatment resistance. High level 5-hydroxylmethylation in these genes may serve as a discriminative biomarker to diagnose patients who are likely to experience early failure during androgen deprivation therapy.

High-speed counter-current chromatography assisted preparative isolation of phenolic compounds from the flowers of Chrysanthemum morifolium cv. Fubaiju.

Chrysanthemum morifolium cv. Fubaiju is rich in phenolic compounds with various benefits such as anti-inflammatory, antioxidant, and cardiovascular protection. In this study, 12 phenolic compounds, including five flavonoid glycosides and seven quinic acid derivatives, were successfully separated from the flowers of Chrysanthemum morifolium cv. Fubaiju by high-speed counter-current chromatography and preparative high-performance liquid chromatography. Ethyl acetate-n-butanol-acetonitrile-water-acetic acid (5:0.5:2.5:5:0.25, v/v/v/v/v) was selected as solvent system to separate six fractions from the flowers of Chrysanthemum morifolium cv. Fubaiju, and 20% aqueous acetonitrile (containing 0.1% formic acid) was chosen to be the elution solvent in preparative high-performance liquid chromatography for purifying the fractions above. Luteolin-7-O-ß-D-glucoside (1), luteolin-7-O-ß-D-glucuronide (2), apigenin-7-O-ß-D-glucoside (3), luteolin-7-O-ß-D-rutinoside (4), diosmetin-7-O-ß-D-glucoside (5), chlorogenic acid (6), 1,5-dicaffeoylquinic acid (7), 1,4-dicaffeoylquinic acid (8), 3,4-dicaffeoylquinic acid (9), 3,4-dicaffeoyl-epi-quinic acid (10), 3,5-dicaffeoylquinic acid (11), and 4,5-dicaffeoylquinic acid (12) were isolated with purities all above 95%, respectively. In addition, all isolates were evaluated for their protective effects on H2 O2 -induced oxidative damage in adult retinal pigment epithelial cells.

Prevalence and clinico-genomic characteristics of patients with TRK fusion cancer in China.

Neurotrophic tyrosine kinase (NTRK) fusions involving NTRK1, NTRK2, and NTRK3 were found in a broad range of solid tumors as driver gene variants. However, the prevalence of NTRK fusions in Chinese solid tumor patients is rarely reported. Based on the next-generation sequencing data from 10,194 Chinese solid tumor patients, we identified approximately 0.4% (40/10,194) of Chinese solid tumor patients with NTRK fusion. NTRK fusions were most frequently detected in soft tissue sarcoma (3.0%), especially in the fibrosarcoma subtype (12.7%). A total of 29 NTRK fusion patterns were identified, of which 11 were rarely reported. NTRK fusion mostly co-occurred with TP53 (38%), CDKN2A (23%), and ACVR2A (18%) and rarely with NTRK amplification (5.0%) and single nucleotide variants (2.5%). DNA-based NTRK fusion sequencing exhibited a higher detection rate than pan-TRK immunohistochemistry (100% vs. 87.5%). Two patients with NTRK fusions showed clinical responses to larotrectinib, supporting the effective response of NTRK fusion patients to TRK inhibitors.

Who should be first? How and when AI-human order influences procedural justice in a multistage decision-making process.

Artificial intelligence (AI) has fundamentally changed the way people live and has largely reshaped organizational decision-making processes. Particularly, AI decision making has become involved in almost every aspect of human resource management, including recruiting, selecting, motivating, and retaining employees. However, existing research only considers single-stage decision-making processes and overlooks more common multistage decision-making processes. Drawing upon person-environment fit theory and the algorithm reductionism perceptive, we explore how and when the order of decision makers (i.e., AI-human order vs. human-AI order) affects procedural justice in a multistage decision-making process involving AI and humans. We propose and found that individuals perceived a decision-making process arranged in human-AI order as having less AI ability-power fit (i.e., the fit between the abilities of AI and the power it is granted) than when the process was arranged in AI-human order, which led to less procedural justice. Furthermore, perceived AI ability buffered the indirect effect of the order of decision makers (i.e., AI-human order vs. human-AI order) on procedural justice via AI ability-power fit. Together, our findings suggest that the position of AI in collaborations with humans has profound impacts on individuals' justice perceptions regarding their decision making.

Microplastics in polystyrene-made food containers from China: abundance, shape, size, and human intake.

Polystyrene-made food containers (PMFCs) have been widely used as takeout containers in China. However, the pollution of microplastics (MPs) in PMFCs used in Chinese restaurants remains not well known. For the first time, this study analyzed MPs in PMFC samples (n = 354) collected from different restaurants in 28 Chinese cities. MPs were detected in all PMFC samples, with an abundance of 5-173 items/container. PMFC samples from Taiyuan (mean of 86 items/container) contained the highest mean abundance of MPs. A relatively lower abundance of MPs was found in PMFCs from Urumqi (mean of 19 items/container) and Fuzhou (18 items/container). Fiber was the predominant shape of MPs in most of the PMFC samples. The abundance of MPs in PMFCs was positively correlated with the proportion of fiber. The major polymer composition of MPs was polystyrene, accounting for a mean of 45-90% of total polymers for MPs in PMFCs from different cities. The abundance of MPs in PMFC samples was negatively correlated with the proportion of polystyrene. The mean estimated oral exposure of MPs for the general population in different Chinese cities was 0.24-1.4 items/kg bw/day. Such data is important for human MP exposure risk assessment and also for elucidating the sources of human exposure to MPs.

Prinsepia utilis Royle leaf extract: Ameliorative effects on allergic inflammation and skin lesions in allergic contact dermatitis and polyphenolic profiling through UPLC-MS/MS coupled to chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic contact dermatitis (ACD) is a common allergic inflammatory disease that is concomitant with skin swelling, redness, dry itching, and relapses. Prinsepia utilis Royle, a Chinese and Indian folk medicine, is rich in polyphenols with potential anti-inflammatory and skin-protective activities. However, the underlying mechanism of P. utilis leaf (PUL) in the treatment of ACD and its functional basis remains unclear. AIM OF THE STUDY: This study is aimed to explore and reveal the active substances and mechanism of PUL against ACD. MATERIALS AND METHODS: Hyaluronidase inhibitory assay and fluorescein isothiocyanate (FITC)-induced ACD mouse model were performed to assess the antiallergic effects of PUL in vitro and in vivo. Different solvents were applied to obtain multiple PUL extracts. The extracts were further tested for total phenolic content (TPC) and total flavonoid content (TFC) by using spectrophotometric assays. Polyphenolic profiles were analyzed by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), and a simultaneous quantification method was established using UPLC-QTrap-MS/MS through multiple reaction monitoring (MRM) and applied to analyze the pharmacokinetics of the multiple major polyphenols of PUL in mice. RESULTS: The water extract of PUL with the highest TPC/TFC exhibited the strongest antihyaluronidase effect (IC50 = 231.93 µg/mL). In vivo assays indicated that the oral administration of PUL water extract dose-dependently attenuated ACD-like symptoms by decreased interleukin (IL)-4, IL-5, IL-13, IL-33, thymic stromal lymphopoietin, and IgE production, suppressed eosinophil and basophil secretion, and increasing the expression of tight junction (TJ) proteins (claudin-1 [CLDN-1] and occludin). Concomitantly, UPLC-QTOF-MS/MS analysis enabled the identification of 60 polyphenols and the pharmacokinetic parameters of seven quantified constituents of PUL were characterized. Four compounds, trans-p-coumaric acid 4-O-ß-D-glucopyranoside (11), vicenin-2 (21), isoschaftoside (31), and kaempferol 3-O-(2″,6″-di-O-α-L-rhamnopyransoyl)-ß-D-glucopyranoside (38) which displayed satisfactory pharmacokinetic features, were considered as potential effective substances in PUL. CONCLUSIONS: PUL water extract ameliorated the allergic inflammation of ACD by repairing the epithelial barrier and alleviating Th2-type allergic inflammation. The anti-allergic effect of PUL is closely related to its phenolic substances, and compounds 11, 21, 31, and 38 were the active substances of PUL. It revealed that P. utilis could be developed as a new source of antiallergic agents for ACD therapy.

Polyhalogenated carbazoles in indoor dust from Hangzhou, China.

Carbazoles (CZ) and polyhalogenated carbazoles (PHCZs), showing dioxin-like toxicity, have gained increasing attention in recent years as novel persistent organic pollutants. However, the occurrence of these chemicals in indoor dust from China remains not well known. In this study, CZ and 11 chloro/bromo CZs were analyzed in indoor dust samples collected from residential houses in rural (n = 51) and urban (n = 55) regions of Hangzhou, China. CZ was detected in all indoor dust samples, with the concentrations of 0.81-18 ng/g (mean 5.4 ng/g). All 11 measured PHCZs were detected in indoor dust samples, showing the detection frequency of 7.3-96 %. This means that general populations had wide exposure to CZ and PHCZs through indoor dust ingestion. 3,6-dichlorocarbzole (36-CCZ) and 3,6-dibromocarbazole (36-BCZ) were the predominant PHCZs in indoor dust, having comparable mean concentrations of 1.2 ng/g, followed by 3-monobromocarbazole (3-BCZ; mean 0.66 ng/g, range < LOD-2.1 ng/g) and 1,3,6-tribromocarbazole (136-BCZ; 0.36 ng/g, < LOD-1.0 ng/g). Indoor dust concentrations of 3-BCZ, 36-BCZ, and 1,3,6,8-tetrabromocarbazole in urban regions were significantly (p ≤ 0.01-0.035) higher than that in rural regions. Daily intakes (DIs) of CZ and PHCZs through indoor dust ingestion were estimated for general Chinese population. Among PHCZs, 36-CCZ and 36-BCZ (mean 1.4-3.4 pg/kg bw/day) had the highest mean DIs, followed by 3-BCZ (0.77-1.9 pg/kg bw/day) and 136-BCZ (0.42-1.0 pg/kg/day). To our knowledge, this is the first study reporting the concentrations of CZ and PHCZs in indoor dust from China, which contributes to the better understanding of the sources of human exposure to CZ and PHCZs.

Family structure and depressive symptoms among older adults in China: A marginal structural model analysis.

BACKGROUND: Mental well-being in the aging population is inevitably linked to families due to the reliance of older adults on family members. This study investigates the causal relationship between family structure and depressive symptoms among Chinese older adults in general and between gender and residential areas. METHODS: We used China Health and Retirement Longitudinal Study (CHARLS) panel data, covering four data collection rounds over seven years. Family structure was classified into single-member, couple, nuclear family, and extended family. Taking into account time-varying confounding, we estimated the causal effects of family structure on depressive symptoms using marginal structural models. RESULTS: Older people with cumulative exposure to single-member family type had an increased odds of depressive symptoms by an average of 33 % (95 % CI: 1.22-1.44) than their counterparts who lived in the couple family. Additionally, older people living in extended families also had 6 % higher odds of experiencing depressive symptoms (95 % CI: 1.00, 1.11). The longitudinal associations were consistent across gender groups and residential areas (p-value for interaction is 0.6638 for gender and 0.7043 for the residential area). LIMITATION: The time-varying confounders (e.g., chronic health conditions) included in the analysis are based on self-reported data, which may be subject to measurement errors. CONCLUSION: The risk of depressive symptoms is greater for older individuals living alone and in extended families. Screening for depression in the older population, particularly those living in "at-risk" households, is recommended.

Chinese expert consensus on the diagnosis and treatment of HER2-altered non-small cell lung cancer.

Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non-small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2-altered NSCLC, including conventional chemotherapy, programmed death 1 (PD-1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T-DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2-mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2-targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2-altered NSCLC, focusing on the diagnosis and treatment strategies.

Landscape of somatic alterations in large-scale solid tumors from an Asian population.

Extending the benefits of tumor molecular profiling for all cancer patients requires a comprehensive analysis of tumor genomes across distinct patient populations worldwide. In this study, we perform deep next-generation DNA sequencing (NGS) from tumor tissues and matched blood specimens from over 10,000 patients in China by using a 450-gene comprehensive assay, developed and implemented under international clinical regulations. We perform a comprehensive comparison of somatically altered genes, the distribution of tumor mutational burden (TMB), gene fusion patterns, and the spectrum of various somatic alterations between Chinese and American patient populations. Here, we show 64% of cancers from Chinese patients in this study have clinically actionable genomic alterations, which may affect clinical decisions related to targeted therapy or immunotherapy. These findings describe the similarities and differences between tumors from Chinese and American patients, providing valuable information for personalized medicine.

The relationship between serum uric acid levels and glomerular ischemic lesions in patients with Immunoglobin A nephropathy-a analytical cross-sectional study.

BACKGROUND: To investigate the relationship between serum uric acid levels and glomerular ischemic lesions in patients with immunoglobulin A nephropathy (IgAN) and the relevant risk factors. METHODS: A total of 86 patients with IgAN and normal renal functions were divided into a hyperuricemia group and a normal serum uric acid group (control group). These patients were further divided into a glomerular ischemic lesions group and a non-glomerular ischemic lesions group (control group) based on the renal biopsy results. The relationship between serum uric acid levels and glomerular ischemic lesions was analysed. RESULTS: In patients with IgAN, the prevalence or occurrence of glomerular ischemic lesions was significantly higher in the hyperuricemia group compared with the normal serum uric acid group. Elevated serum uric acid levels are independently associated with glomerular ischemic disease. CONCLUSION: Hyperuricemia in patients with IgAN may lead to glomerular ischemic lesions, and lowering serum uric acid levels may delay the progression of IgAN.