Family Functioning and Intraindividual Reaction Time Variability Interactively Predict Children's Externalizing Problems.

Family functioning including family adaptability and family cohesion, and intraindividual reaction time variability (IIV) which serves as an index of attentional control has been found to relate to children's externalizing problems. However, it remains unknown whether family functioning interacts with children's IIV to predict their externalizing problems based on the diathesis-stress model. The present study examined this concern. Participants included 168 (Mage = 7.35 years, SD = 0.48; 48% boys) and 155 (Mage = 8.32 years, SD = 0.45; 49% boys) children at the first (T1) and second (after one year, T2) measurements, respectively. At T1, a flanker task was used to assess children's IIV. Mothers reported family functioning using the Chinese version of the Family Adaptability and Cohesion Scales, and children's externalizing problems using the Chinese version of the Child Behavior Checklist. At T2, mothers reported children's externalizing problems again. Results indicated that family functioning negatively and IIV positively correlated with children's externalizing problems. Furthermore, family functioning interacted with children's IIV to predict their externalizing problems concurrently and longitudinally. Specifically, low family functioning combined with greater IIV predicted prospective externalizing problems. Findings suggested that better attentional control (indexed by lower IIV) may buffer the negative effect of poor family functioning.

Study of nonsynchronous online teaching of regional anatomy for international students integrated with medical humanities and local culture during COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic imposed unexpected disruptions to anatomical educational practice, the teaching of regional anatomy for international students which has changed to an online format and faces various challenges. The challenges include creating online education homogeneous/equivalent to offline education, introducing local culture to international students, and educating students in medical humanities and ethics. METHODS: To address these problems, the teaching staff integrated medical humanities and local culture into nonsynchronous online teaching of regional anatomy. RESULTS: The nonsynchronous online teaching with interpreted videos of dissections does not significantly affect the experimental and total scores of regional anatomy courses for international students. Integrating medical humanities and local culture into this teaching model is appreciated by them and also has a good teaching effect. CONCLUSION: Students not only gained professional knowledge but also obtained enhanced exposure to local culture and professional spirit from this regional anatomy education.

RANK/RANKL Acts as a Protective Factor by Targeting Cholangiocytes in Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the highly selective autoimmune injury of small intrahepatic bile ducts. Studies reported that the cholangiocytes from PBC patients expressed significantly higher levels of both receptor activator of nuclear factor-kappa B (RANK) and its ligand RANKL. However, the accurate role of RANK/RANKL axis in PBC remains unclear. METHODS: Forty patients with PBC were enrolled according to the inclusion criteria. The biochemical parameters (alkaline phosphatase, ALP; gamma-glutamyltransferase, GGT; alanine aminotransferase, ALT; aspartate transaminase, AST; total bilirubin, TB) were collected at baseline and followed-up after 6 months of treatment with ursodeoxycholic acid (UDCA, 15 mg/kg d). Stages of PBC were diagnosed based on liver biopsy histopathology according to Nakanuma's criteria. RANK expression in hepatic tissues was detected by immunohistochemistry. The cellular immunofluorescence method was used to locate the distribution of RANK in the human intrahepatic biliary epithelial cells (HIBECs) cultured in vitro. HIBECs were treated with RANKL at a concentration of 100 ng/ml or transfected with RANK-overexpressing lentivirus (LV-RANK). CCK-8 assay and cell cycle assay were used to detect the cell proliferation. Real-time PCR was used to detect the expression of IL-6, E-cadherin, VCAM, ICAM-1, TNF-α, and CD80. RESULTS: RANK expression in liver biopsies from early PBC patients (stage I + stage II) was significantly lower than that from advanced PBC patients (stage III + stage IV) (1.7 ± 0.63 vs. 2.3 ± 0.45 scores, P < 0.05). High-RANK patients seemed to have better response to UDCA than low-RANK patients (88.9% vs. 40.9%, P < 0.05). The baseline biochemical parameters between the two groups were comparable. The decline percentages of ALP and GGT after UDCA treatment were more obvious in high-RANK patients than those in low-RANK patients (53.90% ± 9.82% vs. 23.93% ± 6.24%, P < 0.05; 74.11% ± 7.18% vs. 48.00% ± 8.17%, P < 0.05, respectively). HIBECs proliferation was significantly inhibited after treatment of RANKL or transfection with LV-RANK. Increased expression of IL-6 and E-cadherin was observed in HIBECs treated with RANKL or LV-RANK. CONCLUSION: The overall hepatic RANK expression was associated with disease severity and biochemical response in PBC patients. Activation of RANK/RANKL signaling pathway inhibited cholangiocytes proliferation in vitro. Our study suggested that RANK/RANKL pathway might be a potential target of immunotherapy of PBC based on its involvement in the occurrence and development of the disease.

Pharmacokinetics and tissue distribution in rats of a novel anticancer platinum compound LLC-1903.

LLC-1903, a novel anticancer compound, was synthesized by optimizing the structure, which was derived from altering the leaving group of lobaplatin. It has an excellent in vitro anti-cancer activity, high water solubility, high stability in solution and low in vivo toxicity according to our former study.The plasma pharmacokinetics (PK) and tissue distribution of LLC-1903 and lobaplatin in rats were determined after intravenous administration of a single dose (0.06 mmol/kg body weight). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of platinum (Pt) in plasma and tissue samples.Most PK parameters of the Pt in LLC-1903 showed a significant difference from those of lobaplatin. The plasma level of LLC-1903 is only half of that of lobaplatin (p < 0.01) which could be the direct result of faster drug clearance. The tissue distribution showed that both LLC-1903 and lobaplatin were mainly found in the liver and kidney, and less in other organs. At four time points (0.083, 0.5, 1 and 4 h) after administration, the tissue concentrations of LLC-1903 were almost always significantly higher than those of lobaplatin (p < 0.05 or p < 0.01).

Ultrasound-Guided Percutaneous Microwave Ablation for Subserosal Uterine Myomas.

STUDY OBJECTIVE: To prospectively evaluate the clinical effectiveness and safety of ultrasound-guided percutaneous microwave ablation for symptomatic subserosal uterine myomas. DESIGN: Prospective observational study (Canadian Task Force classification II-1). SETTING: A teaching hospital (Department of Interventional Ultrasound, General Hospital of Chinese PLA, Beijing, China). PATIENTS: Sixty-nine patients with symptomatic subserosal uterine myomas treated with ultrasound-guided percutaneous microwave ablation. INTERVENTIONS: All 69 patients underwent ultrasound-guided percutaneous microwave ablation. The number of patients lost to follow-up at was 21 at 3 months, 34 at 6 months, and 35 at 12 months. MEASUREMENTS AND MAIN RESULTS: The efficacy of treatment was evaluated based the mean myoma volume shrinkage rate and changes in Uterine Fibroid Symptom and Quality of Life Questionnaire scores at 3, 6, and 12 months after therapy. Treatment safety was evaluated based on the Society of Interventional Radiology practice guidelines. The mean patient age was 40.3 ± 4.9 years (range, 26-49 years). The mean myoma volume was 221.74 ± 153.18 cm3 before ablation, decreasing to 87.24 ± 45.93 cm3 at 3 months after ablation (p < .001), 46.68 ± 24.7 cm3 at 6 months after ablation (p < .001), and 38.05 ± 24.93 cm3 at 12 months after ablation (p <.001), respectively. Between pretreatment and 3-month follow-up, the mean symptom severity score decreased from 34.53 ± 3.83 to 12.74 ± 3.07 (p < .001), and the mean health-related quality of life score increased from 45.25 ± 10.97 to 78.48 ± 11.39 (p < .001). Both scores remained stable at the 6- and 12-month follow-up time points. No permanent injury or fatal complications were seen in this series. CONCLUSION: Ultrasound-guided percutaneous microwave ablation of subserosal uterine myomas is a promising treatment method. Further studies with larger sample sizes and a control group are needed.

Effect of XlogP and Hansen Solubility Parameters on Small Molecule Modified Paclitaxel Anticancer Drug Conjugates Self-Assembled into Nanoparticles.

Small molecule modified anticancer drug conjugates (SMMDCs) can self-assemble into nanoparticles (NPs) as therapeutic NP platforms for cancer treatment. Here we demonstrate that the XlogP and Hansen solubility parameters of paclitaxel (PTX) SMMDCs is essential for SMMDCs self-assembling into NPs. The amorphous state of PTX SMMDCs will also affect SMMDCs self-assembling into NPs. However, the antitumor activity of these PTX SMMDCs NPs decreased along with their XlogP values, indicating that a suitable XlogP value for designing the SMMDCs is important for self-assembling into NPs and for possessing antitumor activity. For higher level XlogP SMMDCs, a degradable linker should be considered in the design of SMMDCs to overcome the problem of lower antitumor activity. It is preferable that the hydrophilic groups in the SMMDCs should be present on the surface of self-assembling NPs.

Reversal of Ovarian Cancer Multidrug Resistance by a Combination of LAH4-L1-siMDR1 Nanocomplexes with Chemotherapeutics.

The mortality of ovarian cancer stably ranks first in gynecological malignancies due to the lack of specific symptoms and diagnostic methods at an early stage. For most patients, the cancer cells had metastasized before they were diagnosed. As a result, 90% of them died of multidrug resistance (MDR) to chemotherapeutics. In our study, RNAi technology was introduced and applied to overcome this big problem. LAH4-L1, an amphipathic cationic polypeptide, was reported to have high transfection efficiency and was first selected by us to deliver siMDR1 for overcoming ovarian cancer cells MDR. In this research, LAH4-L1-siRNA nanocomplexes (LSCs) delivery system was designed via electrostatic interactions. The nanocomplexes could realize 87.3% MDR1 gene silence and 85% P-gp down-regulation on SKOV-3 cells. What's more, with the combination of chemotherapeutics, SKOV-3 cells growth inhibition can reach to 82.9%. We have also found that there was about 50% reduction on cells migration when MDR1 gene was down-regulated. Besides what have been mentioned above, physicochemical characteristics, cytotoxicity, pH responsivity, cells cycle, cellular uptake, and endosomal escape abilities were also studied in this research. In conclusion, lower cytotoxicity, higher down-regulation of targeted gene, and great cell inhibition, when combined with chemotherapeutics, all show the great potential of LSCs for the reversal of multidrug resistance on SKOV-3 cells in the future.

Effect of sertraline on breathing in depressed patients without moderate-to-severe sleep-related breathing disorders.

BACKGROUND: Previous studies have reported that selective serotonin reuptake inhibitors (SSRIs) might improve sleep-related breathing disorders (SRBDs). However, the effects of SSRIs on breathing are not evaluated in subjects without moderate-to-severe SRBDs. Further, many symptoms of depression and SRBDs overlap, and so, it is interesting whether there are interactions between breathing and psychopathologic symptoms during SSRI treatment for depression. METHODS: Data were taken from an open-label 8-week trial of sertraline in depressed patients with insomnia (n = 31). The depressed patients were administered 50 mg sertraline at 8 AM on the first day, and the dosage was subsequently titrated up to a maximum of 200 mg/day during the 8-week trial. All the patients were tested by repeated polysomnography (PSG) (baseline, 1st day, 14th day, 28th day, and 56th day). Sleep-disordered breathing events were categorized as apneas, hypopneas, and respiratory event-related arousals (RERAs). RESULTS: The clinical responses and PSG characteristics improved continuously during the 8-week trial. From the 14th day on, the RERA index during all-night and non-rapid eye movement (NREM) sleep became stable and significantly higher than baseline and the first day (RERA index 7.3 ± 2.2 at baseline, 7.3 ± 2.5 on the 1st day, 4.4 ± 1.9 on the 14th day, 3.9 ± 1.3 on the 28th day, 4.2 ± 2.0 on the 56th day, F = 5.71, P = 0.02; NREM-RERA index 6.2 ± 2.0 at baseline, 6.3 ± 2.3 on the 1st day, 3.2 ± 1.5 on the 14th day, 3.5 ± 0.9 on the 28th day, 3.2 ± 1.7 on the 56th day, F = 4.92, P = 0.03). Additionally, the NREM-apnea index showed a similar pattern to that of the RERA index and reached a significant difference between baseline (1.0 ± 0.5) and the 14th day (0.5 ± 0.4) (KW = 4.28, P = 0.047). Compared to the no-improvement group, the improvement group with a decreasing score rate of the respiratory disturbance index (RDI) greater than or equal to -50 % had a more positive decreasing score rate of slow wave sleep (SWS) (439.0 ± 78.2 vs 373.2 ± 77.9 %, T = 3.46, P = 0.04) and a more negative decreasing score rate on the arousal index (-43.7 ± 16.7 vs -26.6 ± 9.7 %, T = 9.16, P = 0.01), Pittsburgh Sleep Quality Index (PSQI) scores (-65.1 ± 33.7 vs -49.6 ± 21.4 %, T = 4.74, P = 0.05), and Epworth Sleepiness Scale (ESS) scores (-55.7 ± 21.3 vs -36.4 ± 17.5 %, T = 6.44, P = 0.02). DISCUSSION: This research indicates that SRBDs could be improved to some extent by sertraline treatment, which might be more common in patients with relatively more severe sleep-disordered breathing (e.g., RDI ≥ 10 in the current study). Although the sertraline-induced SRBD improvement seems not to have a significant clinical effect, the SRBD improvement group with decreasing score rate of RDI greater than or equal to -50 % has better subjective and objective sleep aspects than the no-improvement group. Thus, the fact that the SRBDs' improvement was related to SSRIs might have a potential clinical benefit in the antidepressant treatment.

Ultrasound-guided percutaneous microwave ablation for submucosal uterine fibroids.

STUDY OBJECTIVE: To prospectively evaluate the efficiency and safety of ultrasound-guided percutaneous microwave ablation (PMWA) in treating symptomatic submucosal uterine myomas. DESIGN: Self-controlled study (Canadian Task Force classification II-1). SETTING: Single center. PATIENTS: Twenty-two premenopausal women with 22 symptomatic submucosal uterine myomas. INTERVENTION: All patients underwent ultrasound-guided PMWA. MEASUREMENTS AND MAIN RESULTS: PMWA was performed in 22 premenopausal women with 22 symptomatic submucosal uterine myomas. Mean (SD) patient age was 42 (4.60) years (95% confidence interval [CI], 39.96-44.04). Five symptomatic submucosal uterine myomas were identified as type 0, 7 as type 1, and 10 as type 2. Contrast-enhanced ultrasound and magnetic resonance imaging were performed before and after surgery. Myoma volume, hemoglobin concentration, and scores on the UFS-QOL (Uterine Fibroid Symptom and Quality of Life) questionnaire were recorded before and at 3 and 12 months after ablation. Complications were also recorded. In all patients, therapy was completed with a single ablation. The baseline diameter of the symptomatic submucosal uterine myomas was 4.90 (1.60) cm. Mean myoma volume reduction rate was 81.46% (16.33%) (95% CI, 73.06%-89.86%) at 3 months (p < .001) and reached 90.00% (9.79%) (95% CI, 85.07-95.13) at 12 months (p < .001). At 3 months after ablation, hemoglobin concentration increased from 88.64 (21.87) g/L (95% CI, 78.94-98.34) to 123.21 (15.77) g/L (95% CI, 115.10-131.32) (p < .001), and remained stable at 12 months, with a value of 125.92 (14.90) g/L (95% CI, 117.98-133.86). Scores on the UFS-QOL were comparable, with normal levels observed at 1 year. No major complications were observed. Nine patients were discharged with necrotic masses. CONCLUSION: PMWA seems to be effective and safe for treatment of submucosal myomas.

[Follow-ups of mid-term and long-term outcomes for uterine intramural myomas after percutaneous microwave ablation therapy].

OBJECTIVE: To evaluate the mid-term and long-term clinical outcomes for symptomatic intramural uterine myoma after ultrasound-guided percutaneous microwave ablation therapy (PMAT). METHODS: A total of 123 women with intramural uterine myoma underwent PMAT. Prospective studies were conducted to compare the dominant fibroid volume (FV), hemoglobin (HGB) and Uterine Fibroid Symptoms and Quality of Life Questionnaire (UFS-QOL) at baseline and 1, 2, 3 and 4 years of follow-up RESULTS: Comparing with the baseline, the shrinkage rate of FV at 1 year follow-up was 74.5%. HGB of anemic patients pre-PMAT increased from 91 ± 11 to 114 ± 20 g/L. Two parts of UFS-QOL symptoms severity scores (SSS) and health-related quality of life (HRQL) changed from 43 ± 10 to 18 ± 16 and 41 ± 21 to 90 ± 16 respectively at 1year follow-up. All four items stayed nearly the same at 2, 3 and 4 years post-therapy. CONCLUSION: Ultrasound-guided PMAT of uterine fibroids can effectively ameliorate the mid-term and long-term clinical syndromes and improve quality of life by shrinking fibroids effectively or even disappearing completely.

Ursolic acid promotes cancer cell death by inducing Atg5-dependent autophagy.

Ursolic acid (UA) has been reported to possess anticancer activities. Although some of the anticancer activities of UA have been explained by its apoptosis-inducing properties, the mechanisms underlying its anticancer actions are largely unknown. We have found that UA-activated autophagy induced cytotoxicity and reduced tumor growth of cervical cancer cells TC-1 in a concentration-dependent manner. UA did not induce apoptosis of TC-1 cells in vitro as determined by annexin V/propidium iodide staining, DNA fragmentation, and Western blot analysis of the apoptosis-related proteins. We found that UA increased punctate staining of light chain 3 (LC3), which is an autophagy marker. LC3II, the processed form of LC3I which is formed during the formation of double membranes, was induced by UA treatment. These results were further confirmed by transmission electron microscopy. Wortmannin, an inhibitor of autophagy, and a small interfering RNA (siRNA) for autophagy-related genes (Atg5) reduced LC3II and simultaneously increased the survival of TC-1 cells treated with UA. We also found that LC3II was significantly reduced and that survival was increased in Atg5-/- mouse embryonic fibroblast (MEF) cells compared to Atg5+/+ MEF cells under UA treatment. However, silencing BECN1 by siRNA affected neither the expression of LC3II nor the survival of TC-1 cells under UA treatment. These results suggest that autophagy is a major mechanism by which UA kills TC-1 cells. It is Atg5 rather than BECN1 that plays a crucial role in UA-induced autophagic cell death in TC-1 cells. The activation of autophagy by UA may become a potential cancer therapeutic strategy complementing the apoptosis-based therapies. Furthermore, regulation of Atg5 may improve the efficacy of UA in cancer treatment.

Chemical constituents from Solidago canadensis with hypolipidemic effects in HFD-fed hamsters.

Two new compounds, 8-dehydroxymethylvisanol (1) and 9-O-[3-O-acetyl-ß-d-glucopyranosyl]-4-hydroxy-cinnamic acid (4), together with two known lignans, visanol (2) and 9-aldehydevibsanol (3), were isolated from the 80% EtOH extract of Solidago canadensis. The structures of the two new compounds were elucidated on the basis of 1D, 2D NMR, and mass spectral analysis. All the lignans exhibited moderate hypolipidemic activity in high-fat diet-fed hamsters.

Effect of the Holistic Nursing Model of Responsibility System on the Mental State of Elderly Patients with Limb Fractures Fixed by Splints in the Emergency Department.

Objective: To explore the effect of the overall nursing mode of responsibility system on the psychological state of elderly patients with limb fractures fixed by splints. Methods: This study selected 150 elderly patients who received emergency treatment of a limb fracture fixed by a traditional Chinese medicine splint in our hospital from May 2018 to June 2021 as the research subjects. They were divided into a control group and an observation group, with 75 cases in each group. The control group was intervened by traditional nursing mode, and the research group was intervened by responsible overall nursing mode. The quality of nursing work was observed and compared with the nursing staff's work quality and satisfaction, patients' psychological states and satisfaction, and the risk of clinical adverse events. Results: After management, the quality of nursing work in the two groups was significantly improved. Compared with before management, the scores of basic nursing measures, nursing of critical patients, ward environment management, disinfection and isolation, rescue drugs and instruments, and nursing document management in the observation group were significantly higher than those in the control group (P < 0.05). After management, the work quality and satisfaction of nurses in the two groups were significantly higher than those before management. The SERVQUAL scale score and satisfaction score in the observation group were significantly higher than those in the control group (P < 0.05). The scores of HAMA and HAMD in the observation group were significantly lower than those in the control group (P < 0.05). The overall satisfaction of nursing in the observation group was 96.00%, which was significantly higher than the 80.00% in the control group (P < 0.05). The incidence of adverse events in the observation group was 8.00%, which was significantly lower than 17.33% in the control group (P < 0.05). Conclusion: Giving elderly patients with limb fracture emergencies treated with splint fixation using traditional Chinese medicine the overall nursing mode management and responsibility system can give the elderly patients comprehensive and systematic clinical nursing, increase their trust and compliance with nursing work, improve the patient's psychological state, improve clinical satisfaction, and achieve the ideal doctor-patient relationship, which is worthy of clinical application.

Synthesis and biological evaluation of cholic acid-conjugated oxaliplatin as a new prodrug for liver cancer.

A cholic acid-conjugated oxaliplatin, LLC-202, is developed as a novel prodrug for liver cancer. The conjugate is obtained by using 3-NH2-cyclobutane-1,1-dicarboxylate as a linker between the oxaliplatin analogue and cholic acid moiety and cholic acid is strongly bonded to the linker via an amide bond. Pharmacokinetic experiment shows that LLC-202 is mainly distributed and accumulated in the liver after intravenous administration to Sprague-Dawley rats, revealing the liver-targeting profile. Compared to oxaliplatin, LLC-202 is more easily taken up by human liver cancer cells than normal human liver cells. LLC-202 exhibits higher in vitro anticancer activity and higher efficacy comparable to oxaliplatin in treating primary hepatocellular carcinoma in C57BL/6 mice. It can significantly prolong the survival time of tumor-bearing mice by inducing apoptosis and inhibiting proliferation of cancer cells. In addition, LLC-202 shows less cytotoxicity toward normal human liver cells than oxaliplatin. Its acute toxicity in healthy Kunming (KM) mice after i.v. administration is comparable to oxaliplatin. Histopathological examination reveals that the main toxicity of LLC-202 in mice is the depression of bone marrow hematopoietic cells. The results suggest that LLC-202 has great potential for further development as a new prodrug specific for liver cancer.

A Nomogram Based on Conventional and Contrast-Enhanced Ultrasound for Pre-operative Prediction of Nipple-Areola Complex Involvement in Breast Cancer: A Prospective Study.

OBJECTIVE: Accurately predicting nipple-areola complex (NAC) involvement in breast cancer is essential for identifying eligible patients for a nipple-sparing mastectomy. This study was aimed at developing a pre-operative nomogram for NAC involvement in breast cancer using conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). METHODS: All patients with primary breast cancer confirmed by pre-operative biopsy underwent US and CEUS examinations. Post-operative pathology was used as the gold standard in assessing NAC involvement. Lasso regression was used to select the predictors most associated with NAC involvement. A nomogram was constructed to calculate the diagnostic efficacy. The data were internally verified with 500 bootstrapped replications, and a calibration curve was generated to validate the predictive capability. RESULTS: Seventy-six patients with primary breast cancer were included in this study, which included 16 patients (21.1%) with NAC involvement and 60 patients (78.9%) without NAC involvement. Among the 23 features of US and CEUS, Lasso regression selected one US feature and two CEUS features, namely, ductal echo extending from the lesion, ductal enhancement extending to the nipple and focal nipple enhancement. A nomogram was constructed, and the results revealed that the area under the curve, sensitivity, specificity and accuracy were 0.891, 81.3%, 86.7% and 85.5%, respectively. The calibration curve exhibited good consistency between the predicted probability and the actual probability. CONCLUSION: The nomogram developed based on US and CEUS had good performance in predicting NAC involvement in breast cancer before surgery, which may facilitate the selection of suitable patients for NAC preservation with greater oncological safety.

Enhance the dissolution rate and oral bioavailability of pranlukast by preparing nanosuspensions with high-pressure homogenizing method.

PURPOSE: Pranlukast, one of the potential therapeutic tools in the treatment of asthma, has limited clinical applications due to its poor water solubility. The study is aimed to provide a platform for better utilizing pranlukast with enhancement of the dissolution rate and, thus, the oral bioavailability of pranluka'st by preparing nanosuspensions through high-pressure homogenization method. METHOD: Poloxamer407 and PEG200 were chosen as stabilizer and surfactant. The formulation was investigated systematically with the dissolution tests as predominant method. Nanosuspensions were prepared by programmed high-pressure homogenization method. The product was characterized by particle size analysis, TEM and XRD are evaluated by in vitro dissolution tests and in vivo absorption examination. In addition, nanosuspensions with only pranlukast were prepared and compared with formulated nanosuspensions. RESULTS: The optimal values of formulation were 0.5% (w/v) pranlukast with 0.375% (w/v) Poloxamer407, 0.375% (w/v) PEG200 and the screened programming homogenizing procedure parameters were 680 bar for the first 15 circles, 1048 bar for the next 9 circles and 1500 bar for the last 9 circles. Nanosuspensions of 318.2 ± 7.3 nm, -29.3 ± 0.8 mV were obtained. The XRD analysis indicated no change of crystalline occurred in the process of homogenization. The in vitro dissolution behavior of nanosuspensions exhibited complete release in 30 min with a remarkable fast dissolution rate. The in vivo bioavailability of formulated pranlukast nanosuspensions demonstrated its enhancement of fast onset of therapeutic drug effects with 4.38-fold improved compared to that of raw crystals. CONCLUSION: The study provides a feasible, practical thinking of industry development in the clinical use of pranlukast.

Self-assembled human serum albumin-coated complexes for gene delivery with improved transfection.

The efficiency and safety of gene delivery vectors were important factors for gene therapy. To enhance gene transfection efficiency and to incorporate biocompatible components to the polyamidoamine (PAMAM) dendrimer mediated gene delivery systems, human serum albumin (HSA) was introduced to dendriplexes of PAMAM dendrimer and DNA via electrostatic interactions to form self-assembled PAMAM/DNA/HSA complexes (HSA-dendriplexes). The self-assembled complexes were characterized by gel retardation assay and particle size and zeta potential analysis. Meanwhile, the toxicity of HSA-dendriplexes was evaluated by the MTT assay and haemolysis test, which indicated that the complexes exhibited decreased cytotoxicity with the incorporation of HSA. As compared to dendriplexes, the ternary HSA-dendriplexes increased the enhanced green fluorescent protein gene (EGFP) expression in vitro by 1.7-fold. In addition, HSA-dendriplexes showed a significantly higher luciferase gene expression than dendriplexes or naked DNA in the liver, kidney, lungs and spleen of mice. Our results demonstrated that HSA-dendriplexes increases PAMAM mediated gene transfection efficiency and decreases the cytotoxicity and haemolysis, which made the ternary complexes a promising targeting gene delivery system.

Deep learning-enabled pelvic ultrasound images for accurate diagnosis of ovarian cancer in China: a retrospective, multicentre, diagnostic study.

BACKGROUND: Ultrasound is a critical non-invasive test for preoperative diagnosis of ovarian cancer. Deep learning is making advances in image-recognition tasks; therefore, we aimed to develop a deep convolutional neural network (DCNN) model that automates evaluation of ultrasound images and to facilitate a more accurate diagnosis of ovarian cancer than existing methods. METHODS: In this retrospective, multicentre, diagnostic study, we collected pelvic ultrasound images from ten hospitals across China between September 2003, and May 2019. We included consecutive adult patients (aged ≥18 years) with adnexal lesions in ultrasonography and healthy controls and excluded duplicated cases and patients without adnexa or pathological diagnosis. For DCNN model development, patients were assigned to the training dataset (34 488 images of 3755 patients with ovarian cancer, 541 442 images of 101 777 controls). For model validation, patients were assigned to the internal validation dataset (3031 images of 266 patients with ovarian cancer, 5385 images of 602 with benign adnexal lesions), external validation datasets 1 (486 images of 67 with ovarian cancer, 933 images of 268 with benign adnexal lesions), and 2 (1253 images of 166 with ovarian cancer, 5257 images of 723 benign adnexal lesions). Using these datasets, we assessed the diagnostic value of DCNN, compared DCNN with 35 radiologists, and explored whether DCNN could augment the diagnostic accuracy of six radiologists. Pathological diagnosis was the reference standard. FINDINGS: For DCNN to detect ovarian cancer, AUC was 0·911 (95% CI 0·886-0·936) in the internal dataset, 0·870 (95% CI 0·822-0·918) in external validation dataset 1, and 0·831 (95% CI 0·793-0·869) in external validation dataset 2. The DCNN model was more accurate than radiologists at detecting ovarian cancer in the internal dataset (88·8% vs 85·7%) and external validation dataset 1 (86·9% vs 81·1%). Accuracy and sensitivity of diagnosis increased more after DCNN-assisted diagnosis than assessment by radiologists alone (87·6% [85·0-90·2] vs 78·3% [72·1-84·5], p<0·0001; 82·7% [78·5-86·9] vs 70·4% [59·1-81·7], p<0·0001). The average accuracy of DCNN-assisted evaluations for six radiologists reached 0·876 and were significantly augmented when they were DCNN-assisted (p<0·05). INTERPRETATION: The performance of DCNN-enabled ultrasound exceeded the average diagnostic level of radiologists matched the level of expert ultrasound image readers, and augmented radiologists' accuracy. However, these observations warrant further investigations in prospective studies or randomised clinical trials. FUNDING: National Key Basic Research Program of China, National Sci-Tech Support Projects, and National Natural Science Foundation of China.

Antitumor Activity of α-Linolenic Acid-Paclitaxel Conjugate Nanoparticles: In vitro and in vivo.

PURPOSE: Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo. METHODS: We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated. RESULTS: The size of ALA-PTX NPs was approximately 110.7±1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5-2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models. CONCLUSION: ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity.

[Study on the anti-tumor effect of paclitaxel mixed micelle by using in vivo optical imaging technique].

In vivo tumor imaging technique method based on bioluminescence principle was established to evaluate the anti-tumor effect of paclitaxel mixed micelle (PMM). MDA-MB-231 tumor cells with luciferase reporter vectors were firstly implanted into nude mice, and subsequently the luciferase substrate was regularly injected during intraperitoneal administration of PMM. Then the tumor size, growth and the intensity of light signals were monitored with in vivo imaging technique. The method of luciferase tumor in vivo imaging could be real-time, reliable and exact in labeling and reflecting the growth of tumors, and the observed results were consistent with that by conventional method, so it would be a feasible approach to study anti-tumor effect of drugs. The anti-tumor effect of paclitaxel mixed micelle was observed by this method, and the results showed that this formulation could inhibit growth of tumor, and the anti-tumor rate of it was about 85%.