Preclinical characterization of a novel investigational monoclonal antibody CM313 with potent CD38-positive cell killing activity.

Introduction: CM313 is currently under clinical investigation for treatments of multiple myeloma, systemic lupus erythematosus, and immune thrombocytopenia. We aimed to report the preclinical profile of the novel therapeutic anti-CD38 monoclonal antibody (mAb) CM313, with an emphasis on the difference with other CD38-targeting mAb. Methods: The binding of CM313 to CD38 recombinant protein across species was assessed using ELISA. The binding of CM313 to CD38-positive (CD38+) cells was detected using flow cytometry assays. CM313-induced complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and apoptosis on different CD38+ cells were assessed by LDH release assays or flow cytometry assays. The effect of CM313 on CD38 enzymatic activity was measured using fluorescence spectroscopy. CM313 immunotoxicity in human blood was assessed using flow cytometry assays, ELISA, and LDH release assays. Anti-tumor activity of CM313 was assessed in multiple mouse xenograft models. Safety profile of CM313 were evaluated in cynomolgus monkeys and human CD38 transgenic (B-hCD38) mice. Results: There exist unique sequences at complementarity-determining regions (CDR) of CM313, which facilitates its affinity to CD38 is consistently higher across a spectrum of CD38+ cell lines than daratumumab. In vitro studies showed that CM313 induces comparable killing activity than daratumumab, including ADCC, CDC, ADCP, apoptosis induced by Fc-mediated cross-linking, and effectively inhibited the enzymatic activity of CD38. However, CM313 showed more potent CDC than isatuximab. In vivo, CM313 dose-dependently inhibited xenograft tumor growth, both as a monotherapy and in combination with dexamethasone or lenalidomide. Furthermore, CM313 was well tolerated with no drug-related clinical signs or off-target risks, as evidenced by 4-week repeat-dose toxicology studies in cynomolgus monkeys and B-hCD38 mice, with the later study showing no observed adverse effect level (NOAEL) of 300mg/kg once weekly. Discussion: CM313 is a novel investigational humanized mAb with a distinct CDR sequence, showing comparable killing effects with daratumumab and stronger CDC activity than isatuximab, which supports its clinical development.

Quality assessment of clinical practice guidelines for adult obstructive sleep apnea: A systematic review.

OBJECTIVE: Clinical Practice Guidelines (CPGs) are crucial in standardizing the management of obstructive sleep apnea (OSA) in adults. However, there has been insufficient evaluation of the overall quality of CPGs for adult OSA. This review aimed to comprehensively assess the overall quality of CPGs in the field of adult OSA. METHODS: A systematic search was conducted on various literature databases, guideline-related databases, and academic websites from January 2013 to December 2023 to select CPGs relevant to adult OSA. The methodological and reporting quality of the eligible CPGs were thoroughly appraised by three reviewers using the AGREE II instrument and RIGHT checklist, respectively. RESULTS: This review included 44 CPGs, consisting of 42 CPGs in English and 2 CPGs in Chinese. The assessment of methodological quality revealed that four domains attained an average standardized score above 60%. Among the domains, "clarity of presentation" received the highest standardized score of 85.10%, while the lowest standardized score was observed in the "rigor of development" domain with the value of 56.77%. The evaluation of reporting quality indicated an overall reporting rate of 51.30% for the eligible CPGs, with only three domains achieving an average reporting rate higher than 50%. The domain with the highest reporting rate was "basic information" at 60.61%, while the domain with the lowest reporting rate was "review and quality assurance" at 15.91%. Furthermore, a significantly positive correlation was found between the AGREE II standardized scores and the RIGHT reporting rates (r = 0.808, P < 0.001). CONCLUSIONS: The overall quality of the currently available guidelines for adult OSA demonstrated considerable variability. Researchers should prioritize the utilization of evidence-based methods and adhere to the items listed in the RIGHT checklist when developing CPGs to enhance efficient clinical decision-making and promote the translation of evidence into practice.

FPR1: A critical gatekeeper of the heart and brain.

G protein-coupled receptors (GPCRs) are currently the most widely focused drug targets in the clinic, exerting their biological functions by binding to chemicals and activating a series of intracellular signaling pathways. Formyl-peptide receptor 1 (FPR1) has a typical seven-transmembrane structure of GPCRs and can be stimulated by a large number of endogenous or exogenous ligands with different chemical properties, the first of which was identified as formyl-methionine-leucyl-phenylalanine (fMLF). Through receptor-ligand interactions, FPR1 is involved in inflammatory response, immune cell recruitment, and cellular signaling regulation in key cell types, including neutrophils, neural stem cells (NSCs), and microglia. This review outlines the critical roles of FPR1 in a variety of heart and brain diseases, including myocardial infarction (MI), ischemia/reperfusion (I/R) injury, neurodegenerative diseases, and neurological tumors, with particular emphasis on the milestones of FPR1 agonists and antagonists. Therefore, an in-depth study of FPR1 contributes to the research of innovative biomarkers, therapeutic targets for heart and brain diseases, and clinical applications.

Oncologic and reproductive outcomes after fertility-sparing surgery for bilateral borderline ovarian tumors: A retrospective study.

OBJECTIVES: To investigate the oncological safety and fertility outcomes of different fertility-sparing surgery procedures for bilateral borderline ovarian tumors (BOTs) and to identify the safest and most effective approach to help patients conceive with minimal risk. STUDY DESIGN: A retrospective study of 144 patients (≤40 years) with pathologically confirmed bilateral BOTs were included in the study.The effects of surgery type on fertility outcome and recurrence were compared. Cox regression analysis was employed to determine potential prognostic factors. Survival analysis utilized the Kaplan-Meier method. RESULTS: Three therapeutic modalities were applied in our study, including bilateral ovarian cystectomy (BOC; n = 29), unilateral adnexectomy + contralateral cystectomy (UAC; n = 4) and radical surgery (n = 61). Totally 33 cases (22.9 %) relapsed during the follow-up period. In 37 % of cases administered conservative surgery, relapses were diagnosed in the first 2 years. Only conservative surgery and adjuvant chemotherapy were risk factors for recurrence. Meanwhile, a pregnancy rate of 55.4 % was obtained in patients with bilateral BOTs. The pregnancy rate was slightly higher but no significant (P = 0.539) difference in patients treated with BOC (n = 17, 63 %) compared with UAC (n = 29, 55.8 %) group. GnRHa treatment significantly improved the clinical pregnancy rate in this study(P = 0.029). CONCLUSIONS: Satisfactory pregnancy rate can be achieved after conservative surgery in patients with bilateral BOTs. BOC is worth recommending for bilateral borderline ovarian tumors and a critical factor in fertility is the preservation of maximum healthy ovarian tissue. Patients should make a pregnancy plan in 2 years after the first surgery. GnRHa increase the rate of successful clinical pregnancies.

Influence of ambient temperature on the CO2 emitted of light-duty vehicle.

Because of global warming, people have paid more attention to greenhouse gas emitted by vehicles. To quantify the impact of temperature on vehicle CO2 emissions, this study was conducted using the world light vehicle test cycle on two light-duty E10 gasoline vehicles at ambient temperatures of -10, 0, 23, and 40℃, and found that CO2 emission factors of Vehicle 1 in the low-speed phase were 22.07% and 20.22% higher than those of Vehicle 2 at cold start and hot start under -10℃. The reason was vehicle 1 had a larger displacement and more friction pairs than vehicle 2. There was the highest CO2 emission at the low-speed phase due to low average speed, frequent acceleration, and deceleration. The CO2 temperature factor and the ambient temperature had a strong linear correlation (R2 = 0.99). According to CO2 temperature factors and their relationships, CO2 emission factors of other ambient temperatures could be calculated when the CO2 emission factor of 23℃ was obtained, and the method also could be used to obtain the CO2 temperature factors of different vehicles. To separate the effect of load setting and temperature variation on CO2 emission quantitatively, a method was proposed. And results showed that the load setting was dominant for the CO2 emission variation. Compared with 23℃, the CO2 emission for vehicle 1 caused by load setting variation were 62.83 and 47.42 g/km, respectively at -10 and 0℃, while those for vehicle 2 were 45.01 and 35.63 g/km, respectively.

Efficacy of fertility-sparing treatment with LNG-IUS is associated with different ProMisE subtypes of endometrial carcinoma or atypical endometrial hyperplasia.

OBJECTIVE: To determine whether proactive molecular risk classifier for endometrial cancer (ProMisE) could be used to assess the prognosis of patients with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC) treated with levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: A retrospective cohort study was conducted among 93 AEH or early-stage EC patients who received LNG-IUS to preserve fertility . By immunohistochemistry and gene sequencing, 4 subtypes of ProMisE were identified (p53 wild type [p53 wt], mismatch repair-deficient [MMRd], p53-abnormal, and POLE-mutated). The primary outcome was the time to complete response (CR) after LNG-IUS therapy. Secondary outcomes included the recurrence rate after CR and success rate of conception. RESULTS: Among the 93 patients, 15 (16.1%) were classified as MMRd, 6 (6.5%) as POLE-mutated, 5 (5.4%) as p53-abnormal, and 67 (72.0%) as p53 wt. Comparison of serum cancer antigen 125, family history of tumor, and positive rates of programmed cell death 1 ligand 1 protein and Ki67 protein in 4 groups showed statistically significant differences (p<0.05). Patients with the p53-abnormal subtype had the lowest overall CR rate (40%) and the highest recurrence rate (2/2). Patients with POLE-mutated subtype had the best prognosis, and all 6 patients achieved CR. When patients achieved complete remission, assisted reproductive technology was more likely to help them conceive than natural conception (p<0.05). CONCLUSION: Patients with early-stage EC or AEH who are more likely to benefit from fertility-sparing treatment can be identified using ProMisE classifier. Patients with POLE-mutated are suitable for fertility-sparing treatment with LNG-IUS.

Text Dialogue Analysis for Primary Screening of Mild Cognitive Impairment: Development and Validation Study.

BACKGROUND: Artificial intelligence models tailored to diagnose cognitive impairment have shown excellent results. However, it is unclear whether large linguistic models can rival specialized models by text alone. OBJECTIVE: In this study, we explored the performance of ChatGPT for primary screening of mild cognitive impairment (MCI) and standardized the design steps and components of the prompts. METHODS: We gathered a total of 174 participants from the DementiaBank screening and classified 70% of them into the training set and 30% of them into the test set. Only text dialogues were kept. Sentences were cleaned using a macro code, followed by a manual check. The prompt consisted of 5 main parts, including character setting, scoring system setting, indicator setting, output setting, and explanatory information setting. Three dimensions of variables from published studies were included: vocabulary (ie, word frequency and word ratio, phrase frequency and phrase ratio, and lexical complexity), syntax and grammar (ie, syntactic complexity and grammatical components), and semantics (ie, semantic density and semantic coherence). We used R 4.3.0. for the analysis of variables and diagnostic indicators. RESULTS: Three additional indicators related to the severity of MCI were incorporated into the final prompt for the model. These indicators were effective in discriminating between MCI and cognitively normal participants: tip-of-the-tongue phenomenon (P<.001), difficulty with complex ideas (P<.001), and memory issues (P<.001). The final GPT-4 model achieved a sensitivity of 0.8636, a specificity of 0.9487, and an area under the curve of 0.9062 on the training set; on the test set, the sensitivity, specificity, and area under the curve reached 0.7727, 0.8333, and 0.8030, respectively. CONCLUSIONS: ChatGPT was effective in the primary screening of participants with possible MCI. Improved standardization of prompts by clinicians would also improve the performance of the model. It is important to note that ChatGPT is not a substitute for a clinician making a diagnosis.

Macroscopic handedness inversion of terbium coordination polymers achieved by doping homochiral ligand analogues.

Inspired by natural biological systems, chiral or handedness inversion by altering external and internal conditions to influence intermolecular interactions is an attractive topic for regulating chiral self-assembled materials. For coordination polymers, the regulation of their helical handedness remains little reported compared to polymers and supramolecules. In this work, we choose the chiral ligands R-pempH2 (pempH2 = (1-phenylethylamino)methylphosphonic acid) and R-XpempH2 (X = F, Cl, Br) as the second ligand, which can introduce C-H⋯π and C-H⋯X interactions, doped into the reaction system of the Tb(R-cyampH)3·3H2O (cyampH2 = (1-cyclohexylethylamino)methylphosphonic acid) coordination polymer, which itself can form a right-handed superhelix by van der Waals forces, and a series of superhelices R-1H-x, R-2F-x, R-3Cl-x, and R-4Br-x with different doping ratios x were obtained, whose handedness is related to the second ligand and its doping ratio, indicating the decisive role of interchain interactions of different strengths in the helical handedness. This study could provide a new pathway for the design and self-assembly of chiral materials with controllable handedness and help the further understanding of the mechanism of self-assembly of coordination polymers forming macroscopic helical systems.

Risk factors for mortality among lung cancer patients with covid-19 infection: A systematic review and meta-analysis.

BACKGROUND: Lung cancer patients with coronavirus disease 2019 (COVID-19) infection experience high mortality rates. The study aims to determine the risk factors for mortality in lung cancer patients with COVID-19 infection. MATERIALS AND METHODS: Followed the PRISMA reporting guidelines, PubMed, Embase, and Web of Science were systematically searched to February 20, 2023, for studies of lung cancer patients with COVID-19 infection. The main outcome of interest was the risk factor for mortality. We also compared the mortality rate of those patients among different continents. A pooled risk ratio (RR) with 95% CI was presented as the result of this meta-analysis. RESULTS: Meta-analysis of 33 studies involving 5018 patients showed that pooled mortality rate of lung cancer in COVID-19 patients was 0.31 (95% CI: 0.25-0.36). Subgroup analysis based on the continents showed significant difference of the mortality rate was observed between Asia and the rest of world (χ2 = 98.96, P < 0.01). Older age (SMD: 0.24, 95% CI: 0.09-0.40, P < 0.01), advanced lung cancer (RR: 1.14, 95% CI: 1.04-1.26, P < 0.01), coexisting comorbidities such as hypertension (RR: 1.17, 95% CI: 1.01-1.35, P = 0.04) and cardiovascular disease (RR: 1.40, 95% CI: 1.03-1.91, P = 0.03) were associated with higher risk of mortality rate in those patients. CONCLUSIONS: Findings of this meta-analysis confirms an increased risk of mortality in lung cancer patients with COVID-19 infection, whose risk factors for these patients appear to be exacerbated by older age, advanced-stage lung cancer, and comorbidities such as hypertension and cardiovascular disease.

Ethical Considerations of Using ChatGPT in Health Care.

ChatGPT has promising applications in health care, but potential ethical issues need to be addressed proactively to prevent harm. ChatGPT presents potential ethical challenges from legal, humanistic, algorithmic, and informational perspectives. Legal ethics concerns arise from the unclear allocation of responsibility when patient harm occurs and from potential breaches of patient privacy due to data collection. Clear rules and legal boundaries are needed to properly allocate liability and protect users. Humanistic ethics concerns arise from the potential disruption of the physician-patient relationship, humanistic care, and issues of integrity. Overreliance on artificial intelligence (AI) can undermine compassion and erode trust. Transparency and disclosure of AI-generated content are critical to maintaining integrity. Algorithmic ethics raise concerns about algorithmic bias, responsibility, transparency and explainability, as well as validation and evaluation. Information ethics include data bias, validity, and effectiveness. Biased training data can lead to biased output, and overreliance on ChatGPT can reduce patient adherence and encourage self-diagnosis. Ensuring the accuracy, reliability, and validity of ChatGPT-generated content requires rigorous validation and ongoing updates based on clinical practice. To navigate the evolving ethical landscape of AI, AI in health care must adhere to the strictest ethical standards. Through comprehensive ethical guidelines, health care professionals can ensure the responsible use of ChatGPT, promote accurate and reliable information exchange, protect patient privacy, and empower patients to make informed decisions about their health care.

Serum cell division cycle 42 reflects the treatment response and survival in patients with advanced cervical cancer who receive immune checkpoint inhibitor treatment.

Cell division cycle 42 (CDC42) regulates immune escape, which predicts immune checkpoint inhibitor (ICI) treatment response in several types of cancer. The present study aimed to evaluate the potential of serum CDC42 in predicting the ICI treatment outcome in patients with advanced cervical cancer. A total of 46 patients with advanced cervical cancer who received ICI treatment with or without antiangiogenic agents were enrolled. Serum CDC42 was detected in all patients before treatment (baseline) and following two treatment cycles by enzyme-linked immunosorbent assay. CDC42 at baseline was elevated in patients with target lesion size ≥5 cm (P=0.020), pelvis metastasis (P=0.031) and lung metastasis (P=0.043). Following treatment, the objective response rate (ORR) and disease control rate (DCR) were 30.4 and 78.3%, respectively. Meanwhile, the median progression-free survival (PFS) and overall survival (OS) were 5.8 and 13.1 months. CDC42 at baseline was decreased in patients achieving ORR (P=0.042) but not DCR (P=0.055). PFS (P=0.006) and OS (P=0.019) were decreased in patients with baseline CDC42 ≥600 pg/ml. After two treatment cycles, CDC42 was generally reduced (P<0.001). CDC42 following two treatment cycles was more significantly decreased in patients with ORR (P=0.032) and DCR (P=0.019). Multivariate Cox's regression analysis showed that CDC42 ≥600 pg/ml following two treatment cycles was associated with the shorter PFS (P=0.022, hazard ratio=2.469) and OS (P=0.013, hazard ratio=4.166). Serum CDC42 was reduced after treatment; high expression following treatment reflected a lower possibility of achieving treatment response and poorer survival in patients with advanced cervical cancer.

A novel hypoxia-stimulated lncRNA HIF1A-AS3 binds with YBX1 to promote ovarian cancer tumorigenesis by suppressing p21 and AJAP1 transcription.

Hypoxia is characteristic of the ovarian tumor (OC) microenvironment and profoundly affects tumorigenesis and therapeutic response. Long noncoding RNAs (lncRNAs) play various roles in tumor progression; however, the characteristics of lncRNAs in pathological responses of the OC microenvironment are not entirely understood. Through high-throughput sequencing, lncRNA expression in hypoxia (1% O2 ) and normoxia (21% O2 ) SKOV3 cells was explored and analyzed. The 5'- and 3'-rapid amplification of complementary DNA ends was used to detect the full length of the novel HIF1A-AS3 transcript. Real-time quantitative polymerase chain reaction was used to assess HIF1A-AS3 expression in OC cells and tissues. In vitro and in vivo evaluations of the biological functions of hypoxic HIF1A-AS3 were conducted. To clarify the underlying mechanisms of HIF1A-AS3 in hypoxic OC, a dual-luciferase assay, chromatin immunoprecipitation, RNA pull-down, RNA immunoprecipitation, and RNA-sequencing were used. We used high-throughput sequencing to investigate a novel lncRNA, HIF1A-AS3, as a hypoxic candidate significantly elevated in OC cells/tissues. HIF1A-AS3 was predominantly localized in the nucleus and promoted in vitro and in vivo OC growth and tumorigenesis. Hypoxia-inducible factor 1α bound to hypoxia response elements in the HIF1A-AS3 promoter region and stimulated its expression in hypoxia. Under hypoxia, HIF1A-AS3 directly integrated with Y-Box binding protein 1 and inhibited its ability to bind to the promoters of p21 and AJAP1 to repress their transcriptional activity, thereby promoting hypoxic OC progression. Our results revealed the crucial role and mechanism of the novel hypoxic HIF1A-AS3 in the oncogenesis of OC. The novel HIF1A-AS3 could be a crucial biomarker and therapeutic target for future OC treatments.

Low expression of acyl-CoA thioesterase 13 is associated with poor prognosis in ovarian serous cystadenocarcinoma.

Objective: Acyl-CoA thioesterase 13 (ACOT13) encodes a member of the thioesterase superfamily. It has not been reported in ovarian cancer. This research aimed at evaluating the expression and prognostic value of ACOT13 in ovarian serous cystadenocarcinoma (OSC). Methods: We extracted and analyzed TCGA, GEPIA, THPA, GTEx, miRWalk, and GDSC databases to investigate the potential carcinogenic mechanism of ACOT13 in OSC, including the correlation of ACOT13 with prognosis, immune checkpoint, tumor mutational burden (TMB), and 50% inhibition concentration (IC50) score. The incidence of endpoint events was compared with Kaplan-Meier survival analysis. Independent prognostic factors for OSC were evaluated with univariate and multivariate Cox regression analyses, and a nomogram was established. Results: The expression of ACOT13 was increased in OSC and correlated with tumor stage, with higher expression in stages I and II than in stages III and IV. Besides, it was observed that low expression of ACOT13 is correlated with poor overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) in patients with OSC. There was a positive correlation between ACOT13 expression and immune checkpoint sialic acid-binding Ig-like lectin (SIGLEC) 15 and TMB. Patients with low ACOT13 expression had higher cisplatin IC50 scores. Conclusion: ACOT13 is an independent prognostic factor and a promising clinical target for OSC. In the future, the carcinogenic mechanism and clinical application value of ACOT13 in ovarian cancer need to be further studied.

Diagnostic Test Accuracy of Deep Learning Prediction Models on COVID-19 Severity: Systematic Review and Meta-Analysis.

BACKGROUND: Deep learning (DL) prediction models hold great promise in the triage of COVID-19. OBJECTIVE: We aimed to evaluate the diagnostic test accuracy of DL prediction models for assessing and predicting the severity of COVID-19. METHODS: We searched PubMed, Scopus, LitCovid, Embase, Ovid, and the Cochrane Library for studies published from December 1, 2019, to April 30, 2022. Studies that used DL prediction models to assess or predict COVID-19 severity were included, while those without diagnostic test accuracy analysis or severity dichotomies were excluded. QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2), PROBAST (Prediction Model Risk of Bias Assessment Tool), and funnel plots were used to estimate the bias and applicability. RESULTS: A total of 12 retrospective studies involving 2006 patients reported the cross-sectionally assessed value of DL on COVID-19 severity. The pooled sensitivity and area under the curve were 0.92 (95% CI 0.89-0.94; I2=0.00%) and 0.95 (95% CI 0.92-0.96), respectively. A total of 13 retrospective studies involving 3951 patients reported the longitudinal predictive value of DL for disease severity. The pooled sensitivity and area under the curve were 0.76 (95% CI 0.74-0.79; I2=0.00%) and 0.80 (95% CI 0.76-0.83), respectively. CONCLUSIONS: DL prediction models can help clinicians identify potentially severe cases for early triage. However, high-quality research is lacking. TRIAL REGISTRATION: PROSPERO CRD42022329252; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD 42022329252.

Is There Re-staging Surgery Necessity for Borderline Ovarian Tumors.

OBJECTIVE: This study assessed the necessity of surgical re-staging in women with borderline ovarian tumors (BOTs) and evaluated the impact of complete surgical staging, lymphadenectomy, and omentectomy on disease recurrence and survival. METHODS: We retrospectively reviewed the medical records of patients with BOTs. A total of 901 patients were eligible for inclusion in the study, and we evaluated some of the variables and clinical/surgical characteristics of the cases. The effects of the type of surgical procedure, surgical staging, and complete or incomplete staging on recurrence were calculated. The rates of disease-free survival, overall survival, and recurrence were compared according to complete surgical staging. A Cox regression analysis was performed to identify potential prognostic factors, and survival curves were constructed using the Kaplan-Meier method. RESULTS: The overall recurrence rate was 13.9%, and recurrence was comparable between the complete surgical staging group and the incomplete groups (P>0.05). The performance of complete surgical staging did not show an effect on long-term survival, and complete surgical staging, omentectomy, and lymphadenectomy had no effect on recurrence. In multivariate analyses, only radical surgery and adjuvant chemotherapy were risk factors for the recurrence of BOTs. Furthermore, we found that omentectomy led to a relatively low recurrence rate in patients with International Federation of Gynecology and Obstetrics (FIGO) stage > I (P=0.022). CONCLUSION: Our results suggest that complete surgical staging should be considered a standard treatment for patients with advanced stage BOTs but not for those at FIGO stage I. It might be safe to reduce the scope of surgical procedures in patients with early-stage BOTs. However, it is not necessary to perform re-staging operations for BOTs with a macroscopically normal extra-ovarian appearance.

Utility of ChatGPT in Clinical Practice.

ChatGPT is receiving increasing attention and has a variety of application scenarios in clinical practice. In clinical decision support, ChatGPT has been used to generate accurate differential diagnosis lists, support clinical decision-making, optimize clinical decision support, and provide insights for cancer screening decisions. In addition, ChatGPT has been used for intelligent question-answering to provide reliable information about diseases and medical queries. In terms of medical documentation, ChatGPT has proven effective in generating patient clinical letters, radiology reports, medical notes, and discharge summaries, improving efficiency and accuracy for health care providers. Future research directions include real-time monitoring and predictive analytics, precision medicine and personalized treatment, the role of ChatGPT in telemedicine and remote health care, and integration with existing health care systems. Overall, ChatGPT is a valuable tool that complements the expertise of health care providers and improves clinical decision-making and patient care. However, ChatGPT is a double-edged sword. We need to carefully consider and study the benefits and potential dangers of ChatGPT. In this viewpoint, we discuss recent advances in ChatGPT research in clinical practice and suggest possible risks and challenges of using ChatGPT in clinical practice. It will help guide and support future artificial intelligence research similar to ChatGPT in health.

Design and fabrication of multifunctional holographic optical elements in laser Doppler velocimeter.

Replacing the bulky traditional optical elements in the optical system with a holographic optical element (HOE) is conducive to the functional integration and volume miniaturization. However, when the HOE is used in the infrared system, the mismatch between the recording wavelength and the working wavelength will lead to the reduction of diffraction efficiency and the introduction of aberration, which will seriously affect the performance of the optical system. This paper proposes a design and fabrication method of multifunctional infrared HOEs that can be used in laser Doppler velocimeter (LDV), which can reduce the effect of wavelength mismatch on HOE performance while integrating the functions of the optical system. The restriction relationship and selection method of parameters in typical LDV are summarized; the decrease of diffraction efficiency due to the mismatch between recording and working wavelengths is compensated by designing the angle of signal and reference wave of the HOE; and the aberration caused by wavelength mismatch is compensated by cylindrical lens. The optical experiment shows that the HOE can produce two groups of fringes with opposite gradient, which proves the feasibility of the proposed method. Moreover, this method has a certain degree of universality, and it is expected to design and fabricate HOEs for any working wavelength in the near-infrared band.

Activation of NR1H3 attenuates the severity of septic myocardial injury by inhibiting NLRP3 inflammasome.

Most sepsis deaths are due to the development of multiple organ failure, in which heart failure is a recognized manifestation of sepsis. To date, the role of liver X receptors α (NR1H3) in sepsis is still uncertain. Here, we hypothesized that NR1H3 mediates multiple essential sepsis-related signalings to attenuate septic heart failure. Adult male C57BL/6 or Balbc mice and HL-1 myocardial cell line were performed for in vivo and in vitro experiments, respectively. NR1H3 knockout mice or NR1H3 agonist T0901317 was applied to evaluate the impact of NR1H3 on septic heart failure. We found decreased myocardial expression levels of NR1H3-related molecules while increased NLRP3 level in septic mice. NR1H3 knockout worsensed cardiac dysfunction and injury in mice subjected to cecal ligation and puncture (CLP), in association with exacerbated NLRP3-mediated inflammation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis-related markers. The administration of T0901317 reduced systemic infection and improve cardiac dysfunction in septic mice. Moreover, Co-IP assays, luciferase reporter assays, and chromatin immunoprecipitation analysis, confirmed that NR1H3 directly repressed NLRP3 activity. Finally, RNA-seq detection further clarified an overview of the roles of NR1H3 in sepsis. In general, our findings indicate that NR1H3 had a significant protective effect against sepsis and sepsis-induced heart failure.

Abscisic acid alleviates mercury toxicity in wheat (Triticum aestivum L.) by promoting cell wall formation.

Mercury (Hg) is a heavy metal (HM) that affects crop growth and productivity. In a previous study, we found that application of exogenous abscisic acid (ABA) alleviated growth inhibition in Hg-stressed wheat seedlings. However, the physiological and molecular mechanisms underlying ABA-mediated Hg detoxification remained unclear. In this study, Hg exposure reduced the plant fresh and dry weights and root numbers. Exogenous ABA treatment significantly resumed the plant growth, increased the plant height and weight, and enriched the roots numbers and biomass. The application of ABA enhanced Hg absorption and raised the Hg levels in the roots. In addition, exogenous ABA decreased Hg-induced oxidative damage and significantly brought down the activities of antioxidant enzymes, such as SOD, POD and CAT. Global gene expression patterns in the roots and leaves exposed to HgCl2 and ABA treatments were examined via RNA-Seq. The data showed that genes related to ABA-mediated Hg detoxification were enriched in functions related to cell wall formation. Weighted gene co-expression network analysis (WGCNA) further indicated that the genes implicated in Hg detoxification were related to cell wall synthesis. Under Hg stress, ABA significantly induced expression of the genes encoding cell wall synthesis enzymes, regulated the activity of hydrolase, and increased the concentrations of cellulose and hemicellulose, hence promoting cell wall synthesis. Taken together, these results suggest that exogenous ABA could alleviate Hg toxicity in wheat by promoting cell wall formation and suppressing translocation of Hg from roots to shoots.

Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates.

PURPOSE: Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. PATIENTS AND METHODS: Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non-small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti-PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. RESULTS: Anti-PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti-PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells ≥ 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment. CONCLUSION: Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.