Cooperative amplification of Prussian blue as a signal indicator and functionalized metal-organic framework-based electrochemical biosensor for an ultrasensitive HE4 assay.

Human epididymis protein 4 (HE4), a diagnostic biomarker of ovarian cancer, is crucial for monitoring the early stage of the disease. Hence, it is highly important to develop simple, inexpensive, and user-friendly biosensors for sensitive and quantitative HE4 assays. Herein, a new sandwich-type electrochemical immunosensor based on Prussian blue (PB) as a signal indicator and functionalized metal-organic framework nanocompositesas efficient signal amplifiers was fabricated for quantitative analysis of HE4. In principle, ketjen black (KB) and AuNPs modified on TiMOF (TiMOF-KB@AuNPs) could accelerate electron transfer on the electrode surface and act as a matrix for the immobilization of antibodies via cross-linking to improve the determination sensitivity. The PB that covalently binds to labeled antibodies endows the biosensors with intense electrochemical signals. Furthermore, the concentration of HE4 could be indirectly detected by monitoring the electroactivity of PB. Benefiting from the high signal amplification ability of the PB and MOF nanocomposites, this strategy displayed a wide linear range (0.1-80 ng mL-1) and a lower detection limit (0.02 ng mL-1). Hence, this study demonstrated great promise for application in clinical ovarian cancer diagnosis and treatment, and provided a new platform for detecting other cancer biomarkers.

A machine learning radiomics based on enhanced computed tomography to predict neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma.

Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.

Nomogram construction and validation of axial deviation in patients with tibial defects treated with the Ilizarov bone transport technique.

INTRODUCTION: The Ilizarov bone transport technique is widely recognised as an effective method for treating large segment bone defects in clinical practice. However, axial deviation is a common complication in the treatment of tibial large segment bone defects, which can have a serious impact on the clinical efficacy of bone transport. Our study aims to construct and validate a nomogram for predicting axial deviation of tibial bone transport. METHOD: This study retrospectively collected data from 363 patients who underwent the tibial Ilizarov technique for bone transport. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for axial deviation, which were later used to construct a nomogram. The nomogram was evaluated using the decision curve analysis (DCA), the calibration curve, and the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 363 patients who underwent Ilizarov tibial bone transport, 31.7% (115/363) experienced axial deviation. Multivariate logistic regression analysis showed that gender, height, defect site, and external fixation index were important risk factors for axial deviation. The AUC value of the nomogram model was 0.705. The calibration curve and the decision curve analysis showed a good consistency between the actual axial deviation and the predicted probability. CONCLUSION: The model assigns a quantitative risk score to each variable, which can be used to predict the risk of axial deviation during tibial bone transport.

Population pharmacokinetics and dose optimization of magnesium sulfate in Chinese preeclampsia population.

OBJECTIVE: To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO4)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE. METHODS: Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose. On the second day, only the maintenance dose was administration, and maternal blood samples were taken at 0, 4, 5, and 12 h after the second day's 10 g maintenance dose. The software Phoenix was used to estimate PPK parameters of MgSO4, such as clearance (CL) and volume of distribution (V), and to model PPK models with patient demographic, clinical, and laboratory covariates. RESULTS: A total of 199 blood samples were collected from 51 women with PE and PPK profiles were analyzed. The PPK of MgSO4 is consistent with to a one-compartment model. The base model adequately described the maternal serum magnesium concentrations after magnesium administration. The population parameter estimates were as follows: CL was 2.98 L/h, V was 25.07 L. The model predictions changed significantly with covariates (BMI, creatinine clearance, and furosemide). Furosemide statistically influences V. The creatinine clearance, BMI and furosemide jointly affects CL. Monte Carlo simulation results showed that a loading dose combined with a maintenance dose would need to be administered daily to achieve the therapeutic blood magnesium concentrations. For the non-furosemide group, the optimal dosing regimen was a 5 g loading dose combined with a 10 g maintenance dose of MgSO4. For the furosemide group, the optimal dosing regimen was a 2.5 g loading dose combined with a 10 g maintenance dose of MgSO4. CONCLUSIONS: The magnesium PPK model was successfully developed and evaluated in Chinese preeclampsia population, and the dose optimization of MgSO4 was completed through Monte Carlo simulation.

Two undescribed constituents from Salvia castanea Diels and evaluation of their cytotoxic activity.

One previously undescribed abietane diterpene alkaloid containing an oxazole ring (1), one unreported abietane diterpene (2), and nine known abietane diterpenes (3-11) were isolated from the roots and rhizomes of Salvia castanea Diels. Their structures and absolute configurations were elucidated by a combination of HRESIMS, 1D and 2D NMR, and ECD. All compounds were evaluated for their cytotoxic activity against several human cancer cell lines (HepG2, A549, H460, MCF7, PC3, and Hela). The results showed that 1 exhibited a moderate cytotoxic effect on HepG2 cells (IC50: 14.22 ± 1.05 µM) and was able to inhibit the cell growth of MCF7 and Hela cells by 35.08% and 47.26% respectively, at a concentration of 20 µM, while other compounds showed low cytotoxic activity.

Personal and work-related factors associated with post-traumatic growth in nurses: A mixed studies systematic review.

INTRODUCTION: Nurses, assuming a wide range of clinical and patient care responsibilities in a healthcare team, are highly susceptible to direct and indirect exposure to traumatic experiences. However, literature has shown that nurses with certain traits developed a new sense of personal strength in the face of adversity, known as post-traumatic growth (PTG). This review aimed to synthesize the best available evidence to evaluate personal and work-related factors associated with PTG among nurses. DESIGN: Mixed studies systematic review. METHODS: Studies examining factors influencing PTG on certified nurses from all healthcare facilities were included. Published and unpublished studies were identified by searching 12 databases from their inception until 4th February 2023. Two reviewers independently screened, appraised, piloted a data collection form, and extracted relevant data. Meta-summary, meta-synthesis, meta-analysis, as well as subgroup and sensitivity analyses were performed. Integration of results followed result-based convergent design. RESULTS: A total of 98 studies with 29,706 nurses from 18 countries were included. These included 49 quantitative, 42 qualitative, and seven mixed-methods studies. Forty-six influencing factors were meta-analyzed, whereas nine facilitating factors were meta-summarized. A PTG conceptual map was created. Four constructs emerged from the integration synthesis: (a) personal system, (b) work-related system, (c) event-related factors, and (d) cognitive transformation. CONCLUSION: The review findings highlighted areas healthcare organizations could do to facilitate PTG in nurses. Practical implications include developing intervention programs based on PTG facilitators. Further research should examine the trend of PTG and its dynamic response to different nursing factors. CLINICAL RELEVANCE: Research on trauma-focused therapies targeting nurses' mental health is lacking. Therefore, findings from this review could inform healthcare organizations on the PTG phenomenon and developing support measures for nurses through healthcare policies and clinical practice.

Serum procalcitonin as a marker of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD).

BACKGROUND: Neonatal Intrahepatic Cholestasis (NICCD), as the early-age stage of Citrin deficiency involving liver dysfunction, lacks efficient diagnostic markers. Procalcitonin (PCT) has been identified as a biomarker for infection as well as various organ damage. This study aimed to explore the potential of PCT as a biomarker for NICCD. METHODS: In a single-center retrospective case-control study. Serum PCT concentrations before and after treatment of 120 NICCD patients, as the study group, were compared to the same number of cholestatic hepatitis patients, as the control group. The potential value of PCT to discriminate NICCD from control disease was further explored using Receiver Operating Characteristic (ROC) curve analysis and compared to those of other inflammatory markers. RESULTS: There was a significantly higher level of PCT in NICCD patients than in the control group. PCT concentrations were only weakly correlated with neutrophil counts and CRP levels (p ˂ 0.05). At a cut-off value of 0.495 ng/mL, PCT exhibited a significantly higher diagnostic value compared to other inflammatory markers for discriminating NICCD from the control, with a sensitivity of 90.8 % and specificity of 98.3 %. CONCLUSION: PCT might be used as an initial biomarker to discriminate children with NICCD from another hepatitis disease.

[Clinical characteristics and genetic analysis of four children with Rotor syndrome].

OBJECTIVE: To explore the characteristics of SLCO1B1/SLCO1B3 gene variants among children with Rotor syndrome (RS). METHODS: Four children who were admitted to the Department of Hepatology of Hunan Children's Hospital between January 2019 and January 2022 were selected as the study subjects. Trio-whole exome sequencing was carried out for the four families, and gel electrophoresis was used to verify an insertional variant of long-interspersed element-1 (LINE-1). RESULTS: Genetic testing has identified three variants of the SLCO1B1 gene, including c.1738C>T (p.R580*), c.757C>T (p.R253*) and c.1622A>C (p.Q541P), and two variants of the SLCO1B3 gene, including c.481+22insLINE-1 and c.1747+1G>A among the children. Three of them were found to harbor homozygous variants of the SLCO1B1/SLCO1B3 genes, and one has harbored compound heterozygous variants. Sanger sequencing confirmed the existence of all variants, and gel electrophoresis has confirmed the existence of the LINE-1 insertional variant of about 6 kb within intron 6 of the SLCO1B3 gene in all children. CONCLUSION: The pathogenesis of the RS among the four children may be attributed to the variants of the SLCO1B1/SLCO1B3 genes. The LINE-1 insertion variant of the SLCO1B3 gene may be common among Chinese RS patients.

Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B.

This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.

SCB-YOLOv5: a lightweight intelligent detection model for athletes' normative movements.

Intelligent detection of athlete behavior is beneficial for guiding sports instruction. Existing mature target detection algorithms provide significant support for this task. However, large-scale target detection algorithms often encounter more challenges in practical application scenarios. We propose SCB-YOLOv5, to detect standardized movements of gymnasts. First, the movements of aerobics athletes were captured, labeled using the labelImg software, and utilized to establish the athlete normative behavior dataset, which was then enhanced by the dataset augmentation using Mosaic9. Then, we improved the YOLOv5 by (1) incorporating the structures of ShuffleNet V2 and convolutional block attention module to reconstruct the Backbone, effectively reducing the parameter size while maintaining network feature extraction capability; (2) adding a weighted bidirectional feature pyramid network into the multiscale feature fusion, to acquire precise channel and positional information through the global receptive field of feature maps. Finally, SCB-YOLOv5 was lighter by 56.9% than YOLOv5. The detection precision is 93.7%, with a recall of 99% and mAP value of 94.23%. This represents a 3.53% improvement compared to the original algorithm. Extensive experiments have verified that our method. SCB-YOLOv5 can meet the requirements for on-site athlete action detection. Our code and models are available at https://github.com/qingDu1/SCB-YOLOv5 .

Diterpenoid glucosides with anti-inflammatory activity from Sigesbeckia glabrescens.

Six previously undescribed diterpenoid glucosides, along with four known compounds, were isolated from the aerial parts of Sigesbeckia glabrescens. The structures and absolute configurations of undescribed compounds were elucidated using extensive spectroscopic techniques, ECD calculations and chemical methods. Compounds 1 and 8 exhibited anti-inflammatory activity against LPS-induced NO production in RAW 264.7 macrophages, with compound 8 demonstrating significant inhibitory activity compared to positive control minocycline, boasting an IC50 value at 14.20 µM.

Correction to "Engineering of CuMOF-SWCNTs@AuNPs-Based Electrochemical Sensors for Ultrasensitive and Selective Monitoring of Imatinib in Human Serum".

[This corrects the article DOI: 10.1021/acsomega.3c08002.].

A design of a nature-like fishway to solve the fractured river connectivity caused by small hydropower based on hydrodynamics and fish behaviors.

Achieving a harmonious alignment between the biological characteristics of fish and hydrodynamics patterns is crucial for ensuring the efficacy of fish passage facilities. In this study, based on the hydrodynamic characteristics of the river and the biological characteristics of fish, we evaluated the internal flow field in the nature-like fishway of Congen II hydropower station located along the Chabao river and explored methods to improve the operation efficiency. Based on comprehensive considerations of the flow field, turbulent kinetic energy, and the migration pathways of fish, it is found that the implementation of a continuous oblique bottom slope represents a more cost-effective and operationally convenient solution. The influence of different permutation of bulkheads in the nature-like fishway on operational efficiency was further examined. Our investigation revealed that the nature-like fishway with the continuous slope of 2% and the arrangement of three bulkheads in each row (model 3) exhibited a relatively simple velocity distribution and linear flow line, which poses challenges for fish in locating resting areas. In addition, the distribution of low turbulence kinetic energy area in the mainstream made it less favorable for fish to transition from the mainstream to the rest area within the fishway. The nature-like fishway with the continuous slope of 2% and the arrangement of two or three bulkheads in staggered rows (model 4) demonstrated better performance. Several potential fish migration routes for both model 3 and model 4 were proposed based on the numerical simulation results. In model 3, fish exhibited a continuous sprint through the concentrated high-speed area, which was less favorable for fish to rest and forage. In contrast, model 4 exhibited a diversified flow velocity distribution, enabling fish to make timely changes in their direction during migration. This feather proved to be advantageous in enhancing fish migration within the passage. The design of nature-like fishway in this study provides an important reference and technical support for the construction and optimization of the nature-like fishway for low dams, and is of great significance for restoring river connectivity destroyed by small hydropower construction and improving fish migration.

Comparison of urethral parameters in females presenting cystoceles with and without stress urinary incontinence based on dynamic magnetic resonance imaging: are they different?

PURPOSE: To compare urethral parameters between cystocele patients with and without stress urinary incontinence (SUI) and explore factors influencing SUI in cystocele patients via dynamic MRI. METHODS: The two-dimensional parameters evaluated included the paravaginal defects, levator ani muscle defects, urethral length, urethral funnel shape, bladder neck funnel width, bladder neck funnel depth, urethral angle, posterior vesicourethral angle, and anterior bladder protrusion. The three-dimensional parameters included the proximal urethra rotation angle, the distal urethra rotation angle, bladder neck mobility, urethral midpoint mobility, and external urethral meatus mobility. The independent samples t test was used for continuous variables, and the chi-square test was used for categorical variables. Binary logistic regression was used to identify factors independently associated with SUI in cystocele patients. RESULTS: The baseline parameters were similar between the 2 groups. Cystocele patients with SUI had a significantly higher point Aa (1.63 ± 1.06 cm vs. 0.81 ± 1.51 cm, p = 0.008); more anterior bladder protrusion (33.3% vs. 11.4%, p = 0.017); greater bladder neck mobility (36.38 ± 11.46 mm vs. 28.81 ± 11.72 mm, p = 0.005); mid-urethral mobility (22.94 ± 6.50 mm vs. 19.23 ± 6.65 mm, p = 0.014); and external urethral meatus mobility (22.42 ± 8.16 mm vs. 18.03 ± 8.51 mm, p = 0.022) than did cystocele patients without SUI. The other urethral parameters were similar in the groups (p > 0.05). Binary logistic regression showed that bladder neck mobility was independently associated with SUI in females with cystoceles (odds ratio, 1.06; 95% CI 1.015-1.107; p = 0.009). CONCLUSION: Cystocele patients with SUI have a higher point Aa, more anterior bladder protrusion, and greater urethral mobility than those without SUI. Bladder neck mobility is independently associated with SUI in females with cystoceles. REGISTRATION NUMBER: NCT03146195.

LncRNA HOTTIP regulates TLR4 promoter methylation by recruiting H3K4 methyltransferase MLL1 to affect apoptosis and inflammatory response of fibroblast-like synoviocyte in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and the role of HOXA transcript at the distal tip (HOTTIP) in its pathogenesis remains underexplored. This study investigates the mechanism by which HOTTIP influences apoptosis and the inflammatory response of fibroblast-like synoviocytes (FLS). An RA mouse model was established, and clinical scores were analyzed. Pathological changes in synovial tissues, bone mineral density (BMD) of the paws, serum tartrate-resistant acid phosphatase (TRAP) activity, and TNF-α and IL-1ß levels were assessed. FLS were transfected, and cell proliferation and apoptosis were examined. The RNA-pull-down assay determined HOTTIP's interaction with mixed-lineage leukemia 1 (MLL1), while RNA immunoprecipitation assay measured HOTTIP expression pulled down by MLL1. The levels of MLL1 and toll-like receptor 4 (TLR4) after MLL1 overexpression based on HOTTIP silencing were determined. Chromatin immunoprecipitation (ChIP) was performed with H3K4me3 as an antibody, followed by the evaluation of TLR4 expression. HOTTIP expression was elevated in RA mouse synovial tissues. Inhibition of HOTTIP led to reduced clinical scores, inflammatory infiltration, synovial hyperplasia, TRAP activity, and TNF-α and IL-1ß levels, along with increased BMD. In vitro Interference with HOTTIP suppressed RA-FLS apoptosis and inflammation. HOTTIP upregulated TLR4 expression by recruiting MLL1 to facilitate TLR4 promoter methylation. MLL1 overexpression reversed HOTTIP silencing-mediated repression of RA-FLS apoptosis. Activation of H3K4 methylation counteracted HOTTIP knockout, ameliorating the inflammatory response. HOTTIP regulates TLR4 expression by recruiting MLL1, leading to TLR4 promoter methylation, thereby suppressing RA-FLS proliferation and inducing cell apoptosis and inflammatory response in RA.

Engineering of CuMOF-SWCNTs@AuNPs-Based Electrochemical Sensors for Ultrasensitive and Selective Monitoring of Imatinib in Human Serum.

Imatinib (IMA) is a common chemotherapy drug for the treatment of leukemia and can potentially lead to drug resistance and toxicity during the course of treatment. Monitoring IMA concentrations in body fluids is necessary to optimize therapeutic schedules and avoid overdosage. In this paper, a novel ultrasensitive electrochemical sensor based on CuMOF and SWCNTs@AuNPs was developed to determine this antileukemic drug. Herein, AuNPs were supported on carboxylic single-walled carbon nanotubes (SWCNT-COOH), and then poly(diallyldimethylammonium chloride) (PDDA) was used as a dispersant to overcome the internal van der Waals interactions among the CNTs, further increasing the AuNP loading. Moreover, the morphology, structure, composition, and electrochemical properties of the CuMOF-SWCNTs@AuNPs composite film were characterized using SEM, TEM, FT-IR, UV-vis, XRD, XPS, CV, and EIS. Due to the advantage of the superior electrocatalytic and conductive properties of SWCNTs@AuNPs and their preferable adsorptivity and affinity to IMA of CuMOF, the fabricated glassy carbon electrode significantly improved the determination performance via their synergetic amplified effect. Under optimal conditions, a wide linear response was exhibited in the range from 0.05 to 20.0 µM and the low detection limit of 5.2 nM. In addition, our prepared sensor has been applied to the analysis of IMA in blood serum samples with acceptable results. Therefore, our CuMOF-SWCNTs@AuNPs-based electrochemical sensor possessed prominent sensing responses for IMA, which could be used as a prospective approach in clinical application.

circ_0029463 promotes osteoclast differentiation by mediating miR-134-5p/Rab27a axis.

OBJECTIVE: Osteoporosis is the imbalance in bone homeostasis between osteoblasts and osteoclasts. In this study, we investigated the effects of the circ_0029463/miR-134-5p/Rab27a axis on RANKL-induced osteoclast differentiation. METHODS: RT-qPCR and western blotting were used to detect the expression of circ_0029463, miR-134-5p, and Rab27a in tissues from patients with osteoporosis and in RANKL-induced osteoclasts. Osteoclast differentiation was verified by TRAP staining. Osteoclast biomarkers, including NFATc1, TRAP, and CTSK, were measured. The target and regulatory relationships between circ_0029463, miR-134-5p, and the Rab27a axis were verified using RIP, dual-luciferase reporter gene, and RNA pull-down assays. RESULTS: Elevated expression of circ_0029463 and Rab27a and decreased miR-134-5p expression were observed in the tissues of patients with osteoporosis, and a similar expression pattern was observed in RANKL-induced osteoclasts. Suppression of circ_0029463 expression or miR-134-5p overexpression curbed RANKL-induced osteoclast differentiation, whereas such an effect was abolished by Rab27 overexpression. circ_0029463 sponges miR-134-5p to induce Rab27a expression. CONCLUSION: circ_0029463 sponges miR-134-5p to abolish its suppressive effect of miR-134-5p on Rab27a expression, thereby promoting osteoclast differentiation.

Salvirrane A-F, six undescribed nordrimane sesquiterpene derivatives from Salvia castanea Diels f. tomentosa Stib and their cytotoxic activities.

Six undescribed nordrimane sesquiterpene derivatives, salvirrane A-F (1-6), were isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Comprehensive spectral analysis and a quantum chemical calculation strategy were employed to determine their structures. These compounds represent four previously unreported nordrimane carbon skeletal types in Salvia genus, including 15-nor-drimane, 11,15-di-nor-drimane, 14,15-di-nor-drimane, and 11,14,15-tri-nor-drimane sesquiterpenes. All compounds were evaluated for their cytotoxic activities against several human cancer cell lines (A549, H460, Hep3B, MCF7, PC3, and HeLa). The results showed that 3 exhibited low activity against MCF7 cells (IC50,72.72 ± 6.95 µM) and moderate activity against HeLa cells (IC50, 9.80 ± 0.64 µM). Moreover, the EdU (5-ethynyl-2'-deoxyuridine) assay demonstrates that 3 displays dose-dependent efficacy in suppressing the proliferation of HeLa cells. Network pharmacology and molecular docking technology implied that 3 may potentially bind to Src (proto-oncogene tyrosine-protein kinase) to exert anti-proliferative activity.

Epidemiology, site-specific characteristics and survival of carcinosarcoma: a retrospective study based on SEER database.

OBJECTIVES: Carcinosarcoma (CS) is a rare and biphasic malignancy characterised by a highly invasive biological nature and poor prognosis. This study explored the epidemiology, site-specific characteristics and survival outcome of CS. DESIGN: We conducted a retrospective study in the Surveillance, Epidemiology and End Results (SEER) database (1975-2018) for primary CS. SETTING AND PARTICIPANTS: SEER database includes publicly available information from regional and state cancer registries in the US centres. A total of 5042 CS patients were identified. We selected the top five anatomic CS (uterus, double adnexa, lung, bladder and breast) patients for further analysis. PRIMARY OUTCOME MEASURES: Incidence was estimated by geographical region, age, sex, race, stage and primary site. Trends were calculated using joinpoint regression. The cancer-specific survival (CSS) rate and initial treatment were summarised. RESULTS: Nearly 80% of CS occurred in the uterus and double adnexa, followed by lung, bladder and breast. The elderly and black population presented the highest age-adjusted rate of CS. The rates of distant metastasis in CS progressively increased from 1989 to 2018. Atlanta was the area with the highest incidence at 0.7 per 100 000. Pulmonary and bladder CS more frequently occurred in men and were diagnosed with regional stage. Distant metastasis was mostly found in ovary/fallopian tube CS. Radiotherapy was more commonly applied in uterine CS, while adnexa CS cases were more likely to receive chemotherapy. Multiple treatments were more used in breast CS. Pulmonary CS seemed to suffer worse CSS (median: 9.92 months), for which radiotherapy might not provide survival benefits (HR 0.60, 95% CI 0.42 to 0.86). Compared with the common histological types in each site, CS had the shortest survival. CONCLUSIONS: CS has unique clinical features in each primary site. Substantial prognosis variances exist based on tumour locations. The aggressive course is the common feature in CS at all sites.

Pharmacogenomics-based individualized treatment of hypertension in preterm infants: A case report and review of the literature.

BACKGROUND: Neonatal hypertension is a rare but potentially serious condition that requires careful monitoring and treatment. Pharmacogenomics can help guide individualized drug therapy and improve outcomes. CASE SUMMARY: We report a case of a preterm infant with multiple complications, including bronchopulmonary dysplasia (BPD), sepsis, intracranial hemorrhage, and hypertension. The infant was treated with various drugs, including dexamethasone and amlodipine. The infant was diagnosed with neonatal hypertension based on blood pressure measurements exceeding the 95th percentile for his age and sex. The possible causes of hypertension included dexamethasone, hydrochlorothiazide, spironolactone, and BPD. The infant was treated with oral amlodipine to lower his blood pressure. A pharmacogenomic test was performed to evaluate the genetic polymorphisms of ABCB1 and CYP3A5, which are involved in the metabolism and transport of dexamethasone and amlodipine. The infant's blood pressure was well controlled after the dose of amlodipine was reduced according to the pharmacogenomic results. The infant had a stable general condition and was discharged on the 100th d after birth. CONCLUSION: This case illustrates the importance of regular blood pressure monitoring and etiological investigation in preterm infants with hypertension. Pharmacogenomics can provide useful information for individualized drug therapy and safety in this population.