Opportunities and challenges for ChatGPT and large language models in biomedicine and health.

ChatGPT has drawn considerable attention from both the general public and domain experts with its remarkable text generation capabilities. This has subsequently led to the emergence of diverse applications in the field of biomedicine and health. In this work, we examine the diverse applications of large language models (LLMs), such as ChatGPT, in biomedicine and health. Specifically, we explore the areas of biomedical information retrieval, question answering, medical text summarization, information extraction and medical education and investigate whether LLMs possess the transformative power to revolutionize these tasks or whether the distinct complexities of biomedical domain presents unique challenges. Following an extensive literature survey, we find that significant advances have been made in the field of text generation tasks, surpassing the previous state-of-the-art methods. For other applications, the advances have been modest. Overall, LLMs have not yet revolutionized biomedicine, but recent rapid progress indicates that such methods hold great potential to provide valuable means for accelerating discovery and improving health. We also find that the use of LLMs, like ChatGPT, in the fields of biomedicine and health entails various risks and challenges, including fabricated information in its generated responses, as well as legal and privacy concerns associated with sensitive patient data. We believe this survey can provide a comprehensive and timely overview to biomedical researchers and healthcare practitioners on the opportunities and challenges associated with using ChatGPT and other LLMs for transforming biomedicine and health.

Enhancement of PRMT6 binding to a novel germline GATA1 mutation associated with congenital anemia.

Mutations in the master hematopoietic transcription factor GATA1 are often associated with functional defects in erythropoiesis and megakaryopoiesis. In this study, we identified a novel GATA1 germline mutation (c.1162delGG, p.Leu387Leufs*62) in a patient with congenital anemia and occasional thrombocytopenia. The C-terminal GATA1, a rarely studied mutational region, undergoes frameshifting translation as a consequence of this double-base deletion mutation. To investigate the specific function and pathogenic mechanism of this mutant, in vitro mutant models of stable re-expression cells were generated. The mutation was subsequently validated to cause diminished transcriptional activity of GATA1 and defective differentiation of erythroid and megakaryocytes. Using proximity labeling and mass spectrometry, we identified selective alterations in the proximal protein networks of the mutant, revealing decreased binding to a set of normal GATA1-interaction proteins, including the essential co-factor FOG1. Notably, our findings further demonstrated enhanced recruitment of the protein arginine methyltransferase PRMT6, which mediates histone modification at H3R2me2a and represses transcription activity. We also found an enhanced binding of this mutant GATA1/PRMT6 complex to the transcriptional regulatory elements of GATA1's target genes. Moreover, treatment of the PRMT6 inhibitor MS023 could partially rescue the inhibited transcriptional and impaired erythroid differentiation caused by the GATA1 mutation. Taken together, our results provide molecular insights into erythropoiesis in which mutation leads to partial loss of GATA1 function, and the role of PRMT6 and its inhibitor MS023 in congenital anemia, highlighting PRMT6 binding as a negative factor of GATA1 transcriptional activity in aberrant hematopoiesis.

Site effects in multisite fetal brain MRI: morphological insights into early brain development.

OBJECTIVE: To evaluate multisite effects on fetal brain MRI. Specifically, to identify crucial acquisition factors affecting fetal brain structural measurements and developmental patterns, while assessing the effectiveness of existing harmonization methods in mitigating site effects. MATERIALS AND METHODS: Between May 2017 and March 2022, T2-weighted fast spin-echo sequences in-utero MRI were performed on healthy fetuses from retrospectively recruited pregnant volunteers on four different scanners at four sites. A generalized additive model (GAM) was used to quantitatively assess site effects, including field strength (FS), manufacturer (M), in-plane resolution (R), and slice thickness (ST), on subcortical volume and cortical morphological measurements, including cortical thickness, curvature, and sulcal depth. Growth models were selected to elucidate the developmental trajectories of these morphological measurements. Welch's test was performed to evaluate the influence of site effects on developmental trajectories. The comBat-GAM harmonization method was applied to mitigate site-related biases. RESULTS: The final analytic sample consisted of 340 MRI scans from 218 fetuses (mean GA, 30.1 weeks ± 4.4 [range, 21.7-40 weeks]). GAM results showed that lower FS and lower spatial resolution led to overestimations in selected brain regions of subcortical volumes and cortical morphological measurements. Only the peak cortical thickness in developmental trajectories was significantly influenced by the effects of FS and R. Notably, ComBat-GAM harmonization effectively removed site effects while preserving developmental patterns. CONCLUSION: Our findings pinpointed the key acquisition factors in in-utero fetal brain MRI and underscored the necessity of data harmonization when pooling multisite data for fetal brain morphology investigations. KEY POINTS: Question How do specific site MRI acquisition factors affect fetal brain imaging? Finding Lower FS and spatial resolution overestimated subcortical volumes and cortical measurements. Cortical thickness in developmental trajectories was influenced by FS and in-plane resolution. Clinical relevance This study provides important guidelines for the fetal MRI community when scanning fetal brains and underscores the necessity of data harmonization of cross-center fetal studies.

Band Gap Engineering and Lattice Distortion for Synergetic Tuning Optical Properties of NaNbO3 toward Enhanced Piezo-photocatalytic Activity.

Piezo-photocatalytic efficiency is severely constrained by the wide band gap and bad piezoelectric properties. Herein, La(Mn0.5Ni0.5)O3 was successfully introduced into NaNbO3 lattices (referred to as 0LMN, 0.05LMN, 0.10LMN, and 0.15LMN) through a water-based sol-gel method. The piezo-photocatalytic degradation ratio for Rhodamine B (RhB) is enhanced from 59.7% (0LMN) to 89.7% (0.10LMN) within 100 min, and the kinetic rate constant (k) is increased from 0.009 to 0.022 min-1. The enhanced performance is attributed to (i) the narrowed band gap (from 3.40 to 2.84 eV), which is conducive to the generation of photogenerated electrons and holes, and (ii) the enhanced piezoelectric properties, which can strengthen the piezoelectric polarization, thereby accelerating the separation of the photogenerated electrons and holes. And we also found that the synergetic effect of photocatalysis and piezocatalysis was superior to that of photocatalysis and piezocatalysis alone. This study could provide new perspectives for the reasonable construction of an efficient catalyst in the piezo-photocatalytic field.

Nationwide Investigation on Organophosphate Flame Retardants in Tea from China: Migration from Packaging Materials and Implications for Global Risk Assessment.

In this study, we measured 15 common organophosphate flame retardants (OPFRs) in six categories of tea samples across China. OPFRs were found in all the tea samples, with the total concentrations of OPFRs (∑OPFRs) at 3.44-432 ng/g [geometric mean (GM): 17.6 ng/g]. Triphenyl phosphate (TPhP) was the dominant OPFR, accounting for 39.0-76.2% of ∑OPFRs across all tea categories. The potential factors influencing the residual OPFRs in tea were thoroughly examined, including the agricultural environment, fermentation, and packaging of teas. Tea packaging materials (TPMs) were then identified as the primary sources of OPFRs in teas. The migration test revealed that OPFRs with lower molecular weights and log Kow values exhibited a higher propensity for facilitating the migration of OPFRs from TPMs to teas. The estimated daily intakes of OPFRs from teas were relatively higher for the general populations in Mauritania, Gambia, Togo, Morocco, and Senegal (3.18-9.79 ng/kg bw/day) than China (3.12 ng/kg bw/day). The health risks arising from OPFRs in Chinese teas were minor. This study established a baseline concentration and demonstrated the contamination sources of OPFRs in Chinese tea for the first time, with an emphasis on enhancing the hygiene standards for TPMs.

Maternal-Fetal Exposure to Antibiotics: Levels, Mother-to-Child Transmission, and Potential Health Risks.

Due to its widespread applications in various fields, antibiotics are continuously released into the environment and ultimately enter the human body through diverse routes. Meanwhile, the unreasonable use of antibiotics can also lead to a series of adverse outcomes. Pregnant women and developing fetuses are more susceptible to the influence of external chemicals than adults. The evaluation of antibiotic exposure levels through questionnaire surveys or prescriptions in medical records and biomonitoring-based data shows that antibiotics are frequently prescribed and used by pregnant women around the world. Antibiotics may be transmitted from mothers to their offspring through different pathways, which then adversely affect the health of offspring. However, there has been no comprehensive review on antibiotic exposure and mother-to-child transmission in pregnant women so far. Herein, we summarized the exposure levels of antibiotics in pregnant women and fetuses, the exposure routes of antibiotics to pregnant women, and related influencing factors. In addition, we scrutinized the potential mechanisms and factors influencing the transfer of antibiotics from mother to fetus through placental transmission, and explored the adverse effects of maternal antibiotic exposure on fetal growth and development, neonatal gut microbiota, and subsequent childhood health. Given the widespread use of antibiotics and the health threats posed by their exposure, it is necessary to comprehensively track antibiotics in pregnant women and fetuses in the future, and more in-depth biological studies are needed to reveal and verify the mechanisms of mother-to-child transmission, which is crucial for accurately quantifying and evaluating fetal health status.

Phthalate alternatives and their monoesters in indoor dust from several regions, China and implications for human exposure.

Household products, in response to regulations, increasingly incorporate phthalate (PAE) alternatives instead of traditional PAEs. However, limited information exists regarding the fate and exposure risk of these PAE alternatives and their monoesters in indoor environments. The contamination levels of PAE alternatives and their monoesters in indoor dust might vary across regions due to climate, population density, industrial activities, and interior decoration practices. By analyzing indoor dust samples from six geographical regions across China, this study aims to shed light on concentrations, profiles, and human exposure to 12 PAE alternatives and 9 their monoesters. Bis(2-ethylhexyl) benzene-1,4-dicarboxylate (DEHTP), tributyl 2-acetyloxypropane-1,2,3-tricarboxylate (ATBC), and tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate (TOTM) were the main PAE alternatives in dust across all regions. The total concentrations of 12 PAE alternatives ranged from 0.125 to 4160 µg/g in indoor dust. High molecular weight PAE alternatives had significantly correlated concentrations (p < 0.05) based on Spearman analysis, suggesting their co-use in heat-resistant plastic products. A collective of nine monoesters were identified in most samples, with total concentrations ranging from 0.048 to 29.6 µg/g. The median concentrations of PAE alternatives were highest in North China (66.8 µg/g), while those of monoesters were highest in Southwest China (6.93 µg/g). A significant correlation (p < 0.05) between the concentrations of DEHTP and its monoester suggested that degradation could be a potential source of monoesters. Although hazard quotients (HQs) have been calculated to suggest that the current exposure is unlikely to pose a significant health risk, the lack of toxicity threshold data and the existence of additional exposure pathways necessitate a further confirmation.

Ecological risk of synthetic phenolic antioxidants: A study based on their spatial distribution in water, sediment, and soil from the Yangtze River Delta, China.

Environmental occurrence and risks of novel synthetic phenolic antioxidants (SPAs) remain largely unclear. By using a typical algae (Chlorella pyrenoidosa) as model organism, we evaluated the ecological risks of both traditional and novel SPAs, based on their concentrations in water, sediment, and soil collected from the Yangtze River Delta, China. Detection frequencies (DFs) of 10 novel SPAs were 25-100% in water, 3-100% in sediment, and 0-100% in soil, with geometric means (GMs) of 2700 ng/L, 1270 ng/g, and 2440 ng/g, respectively. For 8 traditional SPAs, DFs were 50-100% (GM: 680 ng/L), 3-100% (534 ng/g), and 47-100% (2240 ng/g) in water, sediment, and soil, respectively. AO3114 was the main pollutant in water, while AO1010 dominated in sediment and soil. Notably, low-molecular-weight SPAs showed migration behavior from sediment to water. Four SPAs (AO626, AO1035, AO1098, and AO1076) showed dose- and time-dependent toxicity on Chlorella pyrenoidosa. As time progressed, sediment-released SPAs became more toxic than those in water. Two SPAs (AO1135 and BHT-Q) posed high risks (RQW > 1) to green algae, daphnia, and fish. The SPA mixture exhibited high risks (RQmix > 1) to these organisms, increasing with the trophic level. This research holds valuable guidance for further SPA risk assessments.

Cognition of diet quality and dietary management in elderly patients with coronary and other atherosclerotic vascular disease in western China, a qualitative research study.

BACKGROUND: Healthy eating is one of the most important nonpharmacologic treatments for patients with atherosclerosis(AS). However, it is unclear how elderly AS patients in western China perceive their dietary status and which type of nutritional assistance they would be willing to receive. Therefore, the primary purpose of this study was to understand the level of knowledge about current dietary habits and healthy eating habits among elderly AS patients in western China, and the secondary purpose was to identify acceptable nutritional assistance measures or pathways for those patients to help them manage disease progression. METHODS: An implementation study approach was used to recruit elderly patients with AS-related diseases in western China for semistructured interviews. RESULTS: 14 participants were included in the study, and the following three themes were identified from the interviews:(1) the diet with regional characteristics; (2) low nutrition-related health literacy; (3) complex attitudes towards nutritional assistance. Most participants had misconceptions about healthy eating, and the sources of their knowledge might not be trustworthy. Participants expressed a preference for personalized nutritional assistance, especially that provided by medical-nursing combined institutions. CONCLUSION: Patients in western China need nutritional assistance for their regional dietary habits; therefore, healthy dietary patterns consistent with the regional culture are proposed to improve the prevailing lack of knowledge about healthy diets, improve the dietary structure of patients, and control the development of the disease.

Closed-Loop Control of Melt Pool Temperature during Laser Metal Deposition.

Laser metal deposition (LMD) is a technology for the production of near-net-shape components. It is necessary to control the manufacturing process to obtain good geometrical accuracy and metallurgical properties. In the present study, a closed-loop control method of melt pool temperature for the deposition of small Ti6Al4V blocks in open environment was proposed. Based on the developed melt pool temperature sensor and deposition height sensor, a closed-loop control system and proportional-integral (PI) controller were developed and tested. The results show that with a PI temperature controller, the melt pool temperature tends to the desired value and remains stable. Compared to the deposition block without the controller, a flatter surface and no oxidation phenomenon are obtained with the controller.

D-1553: A novel KRASG12C inhibitor with potent and selective cellular and in vivo antitumor activity.

D-1553 is a small molecule inhibitor selectively targeting KRASG12C and currently in phase II clinical trials. Here, we report the preclinical data demonstrating antitumor activity of D-1553. Potency and specificity of D-1553 in inhibiting GDP-bound KRASG12C mutation were determined by thermal shift assay and KRASG12C -coupled nucleotide exchange assay. In vitro and in vivo antitumor activity of D-1553 alone or in combination with other therapies were evaluated in KRASG12C mutated cancer cells and xenograft models. D-1553 showed selective and potent activity against mutated GDP-bound KRASG12C protein. D-1553 selectively inhibited ERK phosphorylation in NCI-H358 cells harboring KRASG12C mutation. Compared to the KRAS WT and KRASG12D cell lines, D-1553 selectively inhibited cell viability in multiple KRASG12C cell lines, and the potency was slightly superior to sotorasib and adagrasib. In a panel of xenograft tumor models, D-1553, given orally, showed partial or complete tumor regression. The combination of D-1553 with chemotherapy, MEK inhibitor, or SHP2 inhibitor showed stronger potency on tumor growth inhibition or regression compared to D-1553 alone. These findings support the clinical evaluation of D-1553 as an efficacious drug candidate, both as a single agent or in combination, for patients with solid tumors harboring KRASG12C mutation.

Inhibition of checkpoint kinase prevents human oocyte apoptosis induced by chemotherapy and allows enhanced tumour chemotherapeutic efficacy.

STUDY QUESTION: Could inhibition of the checkpoint kinase (CHEK) pathway protect human oocytes and even enhance the anti-tumour effects, during chemotherapy? SUMMARY ANSWER: CHEK inhibitors prevented apoptosis of human oocytes induced by chemotherapy and even enhanced the anti-tumour effects. WHAT IS KNOWN ALREADY: CHEK inhibitors showed ovarian protective effects in mice during chemotherapy, while their role in human oocytes is unclear. STUDY DESIGN, SIZE, DURATION: This experimental study evaluated the ovarian reserve of young patients (120 patients) with cancer, exposed or not exposed to taxane and platinum (TP)-combined chemotherapy. Single RNA-sequencing analysis of human primordial oocytes from 10 patients was performed to explore the mechanism of oocyte apoptosis induced by TP chemotherapy. The damaging effects of paclitaxel (PTX) and cisplatin on human oocytes were also evaluated by culturing human ovaries in vitro. A new mouse model that combines human ovarian xenotransplantation and patient-derived tumour xenografts was developed to explore adjuvant therapies for ovarian protection. The mice were randomly allocated to four groups (10 mice for each group): control, cisplatin, cisplatin + CK1 (CHEK1 inhibitor, SCH 900776), and cisplatin + CK2 (CHEK2 inhibitor, BML277). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the prospective cohort study, human ovarian follicles were counted and serum AMH levels were evaluated. RNA-sequencing analysis was conducted, and staining for follicular damage (phosphorylated H2AX histone; γH2AX), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) assays and assessments of apoptotic biomarkers (western blot and immunofluorescence) were conducted in human ovaries. After the treatments, histological analysis was performed on human ovarian samples to investigate follicular populations, and oocyte damage was measured by γH2AX staining, BAX staining, and TUNEL assays. At the same time, the tumours were evaluated for volume, weight, and apoptosis levels. MAIN RESULTS AND THE ROLE OF CHANCE: Patients who received TP chemotherapy showed decreased ovarian reserves. Single RNA-sequencing analysis of human primordial oocytes indicated that TP chemotherapy induced apoptosis of human primordial oocytes by causing CHEK-mediated TAp63α phosphorylation. In vitro culture of human ovaries showed greater damaging effects on oocytes after cisplatin treatment compared with that after PTX treatment. Using the new animal model, CHEK1/2 inhibitors prevented the apoptosis of human oocytes induced by cisplatin and even enhanced its anti-tumour effects. This protective effect appeared to be mediated by inhibiting DNA damage via the CHEK-TAp63α pathway and by generation of anti-apoptotic signals in the oocytes. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This was a preclinical study performed with human ovarian samples, and clinical research is required for validation. WIDER IMPLICATIONS OF THE FINDINGS: These findings highlight the therapeutic potential of CHEK1/2 inhibitors as a complementary strategy for preserving fertility in female cancer patients. STUDY FUNDING/COMPETING INTEREST(S): This work was financially supported by the National Natural Science Foundation of China (nos. 82001514 and 81902669) and the Fundamental Research Funds for the Central Universities (2021yjsCXCY087). The authors declare no conflict of interest.

DDX04+ Stem Cells in the Ovaries of Postmenopausal Women: Existence and Differentiation Potential.

Ovarian aging is a pacemaker with multiple organ dysfunction. Recently, stem cells with the ability to generate new oocytes have been identified, which provides the possibility of stem cell therapy for ovarian aging. Several studies have revealed the existence of stem cells in the human postmenopausal ovary. In this study, we describe a new method using magnetic-activated cell sorting combined with differential adhesion to isolate DDX4+ stem cells from ovaries of postmenopausal women and show that the cells exhibit similar gene expression profiles and growth characteristics with primitive germ cells. Furthermore, the DDX4+ stem cells could enter the meiosis stage and differentiation into oocytes. The RNA-seq data of the differentiated oocytes shows that mitochondrial metabolism may play an important role in the oogenesis process of the DDX4+ stem cells. Through using the human ovarian cortical fragments transplantation model, we indicated that the GFP-DDX4+ stem cells differentiated into some GFP positive oocyte-like structure in vivo. Our study provided a new method for the isolation of DDX4+ stem cells from the ovaries of postmenopausal women and confirmed the ability of these stem cells to differentiate into oocytes.

Cumulative Exposure to Phthalates and Their Alternatives and Associated Female Reproductive Health: Body Burdens, Adverse Outcomes, and Underlying Mechanisms.

The global birth rate has recently shown a decreasing trend, and exposure to environmental pollutants has been identified as a potential factor affecting female reproductive health. Phthalates have been widely used as plasticizers in plastic containers, children's toys, and medical devices, and their ubiquitous presence and endocrine-disrupting potential have already raised particular concerns. Phthalate exposure has been linked to various adverse health outcomes, including reproductive diseases. Given that many phthalates are gradually being banned, a growing number of phthalate alternatives are becoming popular, such as di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) adipate (DEHA), and di(2-ethylhexyl) terephthalate (DEHTP), and they are beginning to have a wide range of environmental effects. Studies have shown that many phthalate alternatives may disrupt female reproductive function by altering the estrous cycle, causing ovarian follicular atresia, and prolonging the gestational cycle, which raises growing concerns about their potential health risks. Herein, we summarize the effects of phthalates and their common alternatives in different female models, the exposure levels that influence the reproductive system, and the effects on female reproductive impairment, adverse pregnancy outcomes, and offspring development. Additionally, we scrutinize the effects of phthalates and their alternatives on hormone signaling, oxidative stress, and intracellular signaling to explore the underlying mechanisms of action on female reproductive health, because these chemicals may affect reproductive tissues directly or indirectly through endocrine disruption. Given the declining global trends of female reproductive capacity and the potential ability of phthalates and their alternatives to negatively impact female reproductive health, a more comprehensive study is needed to understand their effects on the human body and their underlying mechanisms. These findings may have an important role in improving female reproductive health and in turn decreasing the number of complications during pregnancy.

Organophosphate Flame Retardants in Pregnant Women: Sources, Occurrence, and Potential Risks to Pregnancy Outcomes.

Organophosphate flame retardants (OPFRs) are found in various environmental matrixes and human samples. Exposure to OPFRs during gestation may interfere with pregnancy, for example, inducing maternal oxidative stress and maternal hypertension during pregnancy, interfering maternal and fetal thyroid hormone secretion and fetal neurodevelopment, and causing fetal metabolic abnormalities. However, the consequences of OPFR exposure on pregnant women, impact on mother-to-child transmission of OPFRs, and harmful effects on fetal and pregnancy outcomes have not been evaluated. This review describes the exposure to OPFRs in pregnant women worldwide, based on metabolites of OPFRs (mOPs) in urine for prenatal exposure and OPFRs in breast milk for postnatal exposure. Predictors of maternal exposure to OPFRs and variability of mOPs in urine have been discussed. Mother-to-child transmission pathways of OPFRs have been scrutinized, considering the levels of OPFRs and their metabolites in amniotic fluid, placenta, deciduae, chorionic villi, and cord blood. The results showed that bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP) were the two predominant mOPs in urine, with detection frequencies of >90%. The estimated daily intake (EDIM) indicates low risk when infants are exposed to OPFRs from breast milk. Furthermore, higher exposure levels of OPFRs in pregnant women may increase the risk of adverse pregnancy outcomes and influence the developmental behavior of infants. This review summarizes the knowledge gaps of OPFRs in pregnant women and highlights the crucial steps for assessing health risks in susceptible populations, such as pregnant women and fetuses.

Nanoscale Zinc-Based Metal-Organic Frameworks Induce Neurotoxicity by Disturbing the Metabolism of Catecholamine Neurotransmitters.

As a group of new nanomaterials, nanoscale metal-organic frameworks (MOFs) are widely applied in the biomedical field, exerting unknown risks to the human body, especially the central nervous system. Herein, the impacts of MOF-74-Zn nanoparticles on neurological behaviors and neurotransmitter metabolism are explored in both in vivo and in vitro assays modeled by C57BL/6 mice and PC12 cells, respectively. The mice exhibit increased negative-like behaviors, as demonstrated by the observed decrease in exploring behaviors and increase in despair-like behaviors in the open field test and forced swimming test after exposure to low doses of MOF-74-Zn nanoparticles. Disorders in the catecholamine neurotransmitter metabolism may be responsible for the MOF-74-Zn-induced abnormal behaviors. Part of the reason for this is the inhibition of neurotransmitter synthesis caused by restrained neurite extension. In addition, MOF-74-Zn promotes the translocation of more calcium into the cytoplasm, accelerating the release and uptake and finally resulting in an imbalance between synthesis and catabolism. Taken together, the results from this study indicate the human toxicity risks of nanoscale low-toxicity metal-based MOFs and provide valuable insight into the rational and safe use of MOF nanomaterials.

Anlotinib dramatically improved pulmonary hypertension and hypoxia caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) associated with gastric carcinoma: a case report.

BACKGROUND: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, demonstrating rapid progression of pulmonary hypertension (PH) and respiratory failure. Although a number of treatments have been attempted for patients diagnosed with or suspected of having PTTM, successful-treated cases of PTTM were mainly from imatinib therapy, which was a PDGF receptor inhibitor. Anlotinib was a novel tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR, and c-kit. CASE PRESENTATION: We reported a patient of PTTM associated with gastric carcinoma, whom were treated with anlotinib, thereby exhibiting significant improvement of PH and respiratory dysfunction. CONCLUSION: Our case provides a new understanding of therapy to PTTM, with implications for defining anlotinib as candidate drug for PTTM. Clinical diagnosis and prompt initiation of anlotinib might be one of the strategies in patients with unstable PTTM.

Regulation of epithelial cell differentiation by the Ubiquitous expressed transcript isoform 1 in ulcerative colitis.

BACKGROUND AND AIM: Mucosal healing has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Healing of mucosal wounds involves epithelial cell proliferation and differentiation, and Y-box transcription factor ZONAB has recently been identified as the key modulator of intestinal epithelial restitution. METHODS: We studied the characteristics of UXT-V1 expression in UC patients using immunohistochemistry and qPCR. The functional role of UXT-V1 in the colonic epithelium was investigated using lentivirus-mediated shRNA in vitro and ex vivo. Through endogenous Co-immunoprecipitation and LC-MS/MS, we identified ZONAB as a UXT-V1-interactive protein. RESULTS: Herein, we report that UXT-V1 promotes differentiation of intestinal epithelial cells by regulating the nuclear translocation of ZONAB. UXT-V1 was upregulated in the intestinal epithelia of UC patients compared with that of healthy controls. Knocking down UXT-V1 in NCM-460 cells led to the enrichment of pathways associated with proliferation and differentiation. Furthermore, the absence of UXT-V1 in cultured intestinal epithelial cells and colonic organoids inhibited differentiation to the goblet cell phenotype. Mechanistically, the loss of UXT-V1 in the intestinal epithelial cells allowed nuclear translocation of ZONAB, wherein it regulated the transcription of differentiation-related genes, including AML1 and KLF4. CONCLUSION: Taken together, our study reveals a potential role of UXT-V1 in regulating epithelial cell differentiation, proving a molecular basis for mucosal healing in UC.

A scoping review on multimodal deep learning in biomedical images and texts.

OBJECTIVE: Computer-assisted diagnostic and prognostic systems of the future should be capable of simultaneously processing multimodal data. Multimodal deep learning (MDL), which involves the integration of multiple sources of data, such as images and text, has the potential to revolutionize the analysis and interpretation of biomedical data. However, it only caught researchers' attention recently. To this end, there is a critical need to conduct a systematic review on this topic, identify the limitations of current work, and explore future directions. METHODS: In this scoping review, we aim to provide a comprehensive overview of the current state of the field and identify key concepts, types of studies, and research gaps with a focus on biomedical images and texts joint learning, mainly because these two were the most commonly available data types in MDL research. RESULT: This study reviewed the current uses of multimodal deep learning on five tasks: (1) Report generation, (2) Visual question answering, (3) Cross-modal retrieval, (4) Computer-aided diagnosis, and (5) Semantic segmentation. CONCLUSION: Our results highlight the diverse applications and potential of MDL and suggest directions for future research in the field. We hope our review will facilitate the collaboration of natural language processing (NLP) and medical imaging communities and support the next generation of decision-making and computer-assisted diagnostic system development.

Negative association between triglyceride glucose index and BMI-adjusted skeletal muscle mass index in hypertensive adults.

BACKGROUND: The triglyceride glucose (TyG) index, an indicator of insulin resistance, is often associated with adverse outcomes in various cardiovascular diseases, while hypertension is associated with an increased risk of cardiovascular diseases. As the loss of muscle mass in people with hypertension is poorly understood, the current study aimed to explore the relationship between TyG index and muscle mass in hypertensive population. METHODS: We analyzed data from hypertensive adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. The TyG index and body mass index (BMI)-adjusted skeletal muscle mass index (SMI) were calculated and the relationship between the two was evaluated using multivariable linear regression and restricted cubic spline (RCS) regression models. RESULTS: A total of 1633 participants in the dataset were included for the final analysis. In the multivariable regression analysis, the adjusted ß of SMI with a 95% confidence interval (CI) for the highest TyG index quartile was - 5.27 (- 9.79 to - 0.75), compared with the lowest quartile. A negative linear relationship between TyG index and SMI was plotted by RCS regression (nonlinear P = 0.128). Stratified models of non-smoking women of different ages also demonstrated that SMI decreased as TyG index increased (all P for trend < 0.05). CONCLUSION: This linear and negative correlation between TyG index and SMI in hypertensive patients suggests that insulin resistance adversely affects muscle mass.