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.

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 Published and unpublished studies were identified by searching 12 databases from their inception until 4th February 2023.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.

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.

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 .

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.

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.].

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.

(±)-Salvicatone A: A Pair of C27-Meroterpenoid Enantiomers with Skeletons from the Roots and Rhizomes of Salvia castanea Diels f. tomentosa Stib.

(±)-Salvicatone A (1), a C27-meroterpenoid featuring a unique 6/6/6/6/6-pentacyclic carbon skeleton with a 7,8,8a,9,10,10a-hexahydropyren-1 (6H)-one motif, was isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Its structure was characterized by comprehensive spectroscopic analyses along with computer-assisted structure elucidation, including ACD/structure elucidator and quantum chemical calculations with 1H/13C NMR and electronic circular dichroism. Biogenetically, compound 1 was constructed from decarboxylation following [4 + 2] Diels-Alder cycloaddition reaction between caffeic acid and miltirone analogue. Bioassays showed that (-)-1 and (+)-1 inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophage cells with an IC50 value of 6.48 ± 1.25 and 15.76 ± 5.55 µM, respectively. The structure-based virtual screening based on the pharmacophores in ePharmaLib, as well as the molecular docking and molecular dynamics simulations study, implied that (-)-1 and (+)-1 may potentially bind to retinoic acid receptor-related orphan receptor C to exert anti-inflammatory activities.

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.

Advantages of Total Hip Arthroplasty Using the Posterolateral Approach Combined with Phased Rehabilitation Management for Patients with Femoral Neck Fractures.

Background: Total hip arthroplasty (THA) has emerged as a pivotal approach for addressing femoral neck fractures (FNFs), a prevalent type of fracture in older people. Restoring joint functionality following surgery significantly contributes to patients' overall well-being. Therefore, the implementation of rational and effective rehabilitation exercises is crucial. Objective: This study aims to investigate the impact of phased rehabilitation management on patients with FNFs who have undergone THA. Methods: In this prospective comparative study, a total of 89 patients were enrolled. Among them, 49 patients underwent phased rehabilitation management, while 40 patients received conventional postoperative rehabilitation. The evaluation encompassed a range of assessments, including the Harris Hip Score (HHS) for the evaluation of hip joint function, the Five-Times-Sit-to-Stand Test (FTSST) to quantify lower limb muscle strength, the Barthel Index to assess activities of daily living, and the Visual Analog Scale (VAS) to measure pain intensity. Furthermore, preoperative and postoperative serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were diligently measured to provide a comprehensive understanding of the patient's inflammatory responses. Results: Overall, the study group exhibited a significantly higher average HHS after surgery compared to the control group. Notably, the VAS scores at 1 day and 3 days post-surgery in both groups demonstrated a reduced trend compared to preoperative values. This trend was more significant in the study group compared to the control group. The time taken for the FTSST in patients undergoing phased rehabilitation management was less compared to the control group. Furthermore, phased rehabilitation management was associated with more significant improvements in activities of daily living. Notably, IL-6 levels were higher in both the study and control groups at 1 day postoperatively than before surgery, while they decreased at 3 days postoperatively compared to the 1-day mark. The study group exhibited significantly lower levels of CRP (mg/L) and ESR (mm/h) compared to the control group. Conclusions: Implementing phased rehabilitation management for patients with FNFs following THA improves hip joint function, lower limb muscle strength, daily living activities, pain intensity, and inflammatory response.

A real-world cost-effectiveness study of vancomycin versus linezolid for the treatment of late-onset neonatal sepsis in the NICU in China.

BACKGROUND AND OBJECTIVE: Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceed the national average drug resistance level, and vancomycin and linezolid are the primary antibacterial drugs used for these resistant bacteria according to the results of etiological examinations. However, a comprehensive evaluation of their costs and benefits in late-onset neonatal sepsis in a neonatal intensive care unit (NICU) has not been conducted. This study aimed to compare the cost and effectiveness of vancomycin and linezolid in treating neonatal sepsis in the NICU. METHODS: A cost-effectiveness analysis of real-world data was carried out by retrospective study in our hospital, and the cost and effectiveness of vancomycin and linezolid were compared by establishing a decision tree model. The drug doses in the model were 0.6 g for linezolid and 0.5 g for vancomycin. The cost break down included cost of medical ward, NICU stay, intravenous infusion of vancomycin or linezolid, all monitoring tests, culture tests and drugs. The unit costs were sourced from hospital information systems. The effectiveness rates were obtained by cumulative probability analysis. One-way sensitivity analysis was used to analyze uncertain influencing factors. RESULTS: The effectiveness rates of vancomycin and linezolid in treating neonatal sepsis in the NICU were 89.74% and 90.14%, respectively, with no significant difference. The average cost in the vancomycin group was ¥12261.43, and the average cost in the linezolid group was ¥17227.96. The incremental cost effectiveness was ¥12416.33 cost per additional neonate with treatment success in the linezolid group compared to vancomycin group at discharge. Factors that had the greatest influence on the sensitivity of the incremental cost-effectiveness ratio were the price of linezolid and the effectiveness rates. CONCLUSIONS: The cost for treatment success of one neonate in linezolid group was ¥5449.17 more than that in vancomycin group, indicating that vancomycin was more cost-effective. Therefore, these results can provide a reference for a cost effectiveness treatment scheme for neonatal sepsis in the NICU.

Dose optimisation of linezolid in critically ill patients based on a population pharmacokinetic model: A two-centre prospective interventional study.

OBJECTIVES: This study evaluated the intervention effect of clinical pharmacist-mediated optimisation of a linezolid regimen using a population pharmacokinetic (PPK) model. METHODS: Patients treated with linezolid in two medical centres from January 2020 to June 2021 were retrospectively included in the control group; those treated from July 2021 to June 2022 were prospectively enrolled in the intervention group. Clinical pharmacists optimised the dosage regimen according to a published linezolid PPK model in the intervention group. An interrupted times series approach was used to analyse the data. The incidence of linezolid-induced thrombocytopenia (LIT), target attainment of pharmacokinetic/pharmacodynamic parameters and other adverse drug reactions (ADRs) were compared between the two groups. RESULTS: In total, 77 and 103 patients were enrolled in the control and intervention groups, respectively. The intervention group had a lower incidence of LIT and other ADRs than the control group (10.7% vs. 23.4%, P = 0.002; 1.0% vs. 7.8%, P = 0.027). The intervention group exhibited a considerably lower trough concentration (Cmin) and area under the concentration-time curve/MIC ratio (AUC24/MIC) (P = 0.001 and P < 0.001). Cmin and AUC24/MIC rates within the target range were substantially higher in the intervention group (49.6% vs. 20.0%, adjusted P < 0.05; 48.1% vs. 25.6%, adjusted P < 0.05). CONCLUSION: Interventions by clinical pharmacists reduced the incidence of LIT and other ADRs. Implementation of model-informed precision dosing (MIPD) for linezolid markedly increased the Cmin and AUC24/MIC rates within the target range. We recommend MIPD-guided linezolid dose reduction for patients with renal impairment.

Risk factors associated with attendance at postpartum blood pressure follow-up visit in discharged patients with hypertensive disorders of pregnancy.

BACKGROUND: This study aims to investigate the risk factors for not returning to postpartum blood pressure (BP) follow-up visit at different time points in postpartum discharged hypertensive disorders of pregnancy (HDP) patients. Likewise, females with HDP in China should have a BP evaluation continuously for at least 42 days postpartum and have BP, urine routine, and lipid and glucose screening for 3 months postpartum. METHODS: This study is a prospective cohort study of postpartum discharged HDP patients. Telephone follow-up was conducted at 6 weeks and 12 weeks postpartum, the maternal demographic characteristics, details of labor and delivery, laboratory test results of patients at admission, and adherence to BP follow-up visits postpartum were collected. While logistic regression analysis was used to analyze the factors associated with not returning to postpartum BP follow-up visit at 6 weeks and 12 weeks after delivery, the receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value for predicting not returning to postpartum BP visit at each follow-up time point. RESULTS: In this study, 272 females met the inclusion criteria. 66 (24.26%) and 137 (50.37%) patients did not return for postpartum BP visit at 6 and 12 weeks after delivery. A multivariate logistic regression analysis identified education level of high school or below (OR = 3.71; 95% CI = 2.01-6.85; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.97; 95% CI = 0.94-0.99; p = 0.0230)and delivery gestational age (OR = 1.12; 95% CI = 1.005-1.244; p = 0.040)as independent risk factors in predicting not returning to postpartum BP follow-up visit at 6 weeks postpartum, and education level of high school or below (OR = 3.20; 95% CI = 1.805-5.67; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.95; 95% CI = 0.92-0.97; p = 0.000), delivery gestational age (OR = 1.13; 95% CI = 1.04-1.24; p = 0.006) and parity (OR = 1.63; 95% CI = 1.06-2.51; p = 0.026) as risk factors for not returning to postpartum BP follow-up visit at 12 weeks postpartum. The ROC curve analysis indicated that the logistic regression models had a significant predictive value for identify not returning to BP follow-up visit at 6 and 12 weeks postpartum with the area under the curve (AUC) 0.746 and 0.761, respectively. CONCLUSION: Attendance at postpartum BP follow-up visit declined with time for postpartum HDP patients after discharge. Education at or below high school, maximum diastolic BP during pregnancy and gestational age at delivery were the common risk factors for not returning for BP follow-up visit at 6 and 12 weeks postpartum in postpartum HDP patients.

Establishment and validation of a risk prediction model incorporating concentrations of linezolid and its metabolite PNU142300 for linezolid-induced thrombocytopenia.

BACKGROUND: Linezolid-induced thrombocytopenia is the main factor restricting the clinical application of linezolid. OBJECTIVES: To investigate the relationship between PNU-14230 concentration and linezolid-induced thrombocytopenia and further develop and validate a risk model for predicting linezolid-induced thrombocytopenia. METHODS: A regression model was constructed to predict the occurrence of linezolid-induced thrombocytopenia, and further externally validated. The predictive performance was evaluated by receiver operating characteristic curve and Hosmer-Lemeshow test. Linezolid Cmin and PNU-142300 concentrations were compared for different kidney function groups. The Kaplan-Meier method was used to estimate the difference in cumulative incidence of linezolid-induced thrombocytopenia among different kidney function patients. RESULTS: In the derivation (n = 221) and validation (n = 158) cohorts, 28.5% and 24.1% of critically ill patients developed linezolid-induced thrombocytopenia. Logistic regression analysis indicated that the independent risk factors were linezolid Cmin, PNU-142300 concentration, baseline platelet count, renal insufficiency (RI) and continuous venovenous haemofiltration (CVVH). The AUC for the risk model was 0.901, and the model was good (P = 0.633). The model also showed good discrimination (AUC 0.870) and calibration (P = 0.282) in the external validation cohort. Compared with normal kidney function patients, patients with RI and CVVH had higher linezolid Cmin and PNU-142300 concentrations (P < 0.001) and higher cumulative incidence of linezolid-induced thrombocytopenia (P < 0.001). CONCLUSIONS: PNU142300 concentration, as well as linezolid Cmin, might identify patients at risk of linezolid-induced thrombocytopenia. The risk prediction model had good predictive performance for linezolid-induced thrombocytopenia development. Concentrations of linezolid and PNU-142300 accumulated in patients with RI and CVVH.

In vitro and in vivo evaluation of a modified porcine acellular dermal matrix for soft tissue augmentation.

OBJECTIVES: To evaluate the effects of a modified porcine acellular dermal matrix (P-ADM), subepithelial connective tissue graft (SCTG) and other commercial bovine acellular dermal matrix membrane materials (B-ADM) on gingival soft tissue augmentation in the oral esthetic zone. MATERIAL AND METHODS: The characteristics of P-ADM were observed by scanning electron microscope (SEM), Hematoxylin and eosin (H&E) and Masson's trichrome staining (Masson staining). The biocompatibility of P-ADM was verified by CCK8, phalloidin and living/dead cell staining. Beagle dog models were constructed and the thickness of gingiva was analyzed by the intraoral scanner. The morphology was observed by H&E and Masson staining. RESULTS: Scanning electron microscopy, H&E and Masson staining showed that the P-ADM was mainly composed of collagen fibers, with no component of nuclear. The results of CCK8, phalloidin and living/dead cell staining indicated that the P-ADM had good cytocompatibility and no cytotoxicity. Human gingival fibroblasts were able to adhere and stretch on the surface of the material with pseudopodia. The SCTG group outperformed the B-ADM and P-ADM groups in terms of effectiveness, according to the analysis of digital oral scanning data at various time points following incremental soft tissue surgery. Compared with the B-ADM group, the effect of soft tissue increment was better in the P-ADM group. CONCLUSIONS: P-ADM, as a biocompatible biomaterial, can be used as an alternative biomaterial for oral soft tissue thickening. However, the results of this study need to be verified by more clinical trials.