Deep learning-assisted ultrasonic diagnosis of cervical lymph node metastasis of thyroid cancer: a retrospective study of 3059 patients.

Objective: This study aimed to develop a deep learning system to identify and differentiate the metastatic cervical lymph nodes (CLNs) of thyroid cancer. Methods: From January 2014 to December 2020, 3059 consecutive patients with suspected with metastatic CLNs of thyroid cancer were retrospectively enrolled in this study. All CLNs were confirmed by fine needle aspiration. The patients were randomly divided into the training (1228 benign and 1284 metastatic CLNs) and test (307 benign and 240 metastatic CLNs) groups. Grayscale ultrasonic images were used to develop and test the performance of the Y-Net deep learning model. We used the Y-Net network model to segment and differentiate the lymph nodes. The Dice coefficient was used to evaluate the segmentation efficiency. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the classification efficiency. Results: In the test set, the median Dice coefficient was 0.832. The sensitivity, specificity, accuracy, PPV, and NPV were 57.25%, 87.08%, 72.03%, 81.87%, and 66.67%, respectively. We also used the Y-Net classified branch to evaluate the classification efficiency of the LNs ultrasonic images. The classification branch model had sensitivity, specificity, accuracy, PPV, and NPV of 84.78%, 80.23%, 82.45%, 79.35%, and 85.61%, respectively. For the original ultrasonic reports, the sensitivity, specificity, accuracy, PPV, and NPV were 95.14%, 34.3%, 64.66%, 59.02%, 87.71%, respectively. The Y-Net model yielded better accuracy than the original ultrasonic reports. Conclusion: The Y-Net model can be useful in assisting sonographers to improve the accuracy of the classification of ultrasound images of metastatic CLNs.

Hemophagocytic lymphohistiocytosis with jaundice as first manifestation: A case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening condition. It is an immune-mediated disease that has a wide range of causes, elicits a hyperinflammatory response, and results in multiple organ damage. Clinical presentations vary, and in some cases, jaundice occurs as the first symptom. CASE SUMMARY: We report the case of a 71-year-old female patient who presented with jaundice. She was admitted to our hospital because of the occurrence of "jaundice for half a month", and upon examination, obstructive jaundice with choledocholithiasis and gallstones was suggested. Cholecystectomy and choledocholithotomy were performed. However, the jaundice did not improve after surgery. We found splenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated ferritin. Bone marrow biopsy revealed hemophagocytosis. Later, cardiac arrest occurred when she returned 3 wk after the surgery. We considered that HLH was triggered by septic shock. The patient's condition deteriorated rapidly, with multiple organ dysfunction and severe gastrointestinal bleeding. Corticosteroid therapy and symptomatic treatment failed to save her life. CONCLUSION: Jaundice rarely presents as the first symptom in HLH patients. The HLH in this case was triggered by septic shock with jaundice as the first symptom. Clinicians should try hard to reduce missed diagnoses and misdiagnoses.

Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis.

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.

Pomiferin targets SERCA, mTOR, and P-gp to induce autophagic cell death in apoptosis-resistant cancer cells, and reverses the MDR phenotype in cisplatin-resistant tumors in vivo.

Drug resistance in cancer has been classified as innate resistance or acquired resistance, which were characterized by apoptotic defects and ABC transporters overexpression respectively. Therefore, to preclude or reverse these resistance mechanisms could be a promising strategy to improve chemotherapeutic outcomes. In this study, a natural product from Osage Orange, pomiferin, was identified as a novel autophagy activator that circumvents innate resistance by triggering autophagic cell death via SERCA inhibition and activation of the CaMKKß-AMPK-mTOR signaling cascade. In addition, pomiferin also directly inhibited the P-gp (MDR1/ABCB1) efflux and reversed acquired resistance by potentiating the accumulation and efficacy of the chemotherapeutic agent, cisplatin. In vivo study demonstrated that pomiferin triggered calcium-mediated tumor suppression and exhibited an anti-metastatic effect in the LLC-1 lung cancer-bearing mouse model. Moreover, as an adjuvant, pomiferin potentiated the anti-tumor effect of the chemotherapeutic agent, cisplatin, in RM-1 drug-resistant prostate cancer-bearing mouse model by specially attenuating ABCB1-mediated drug efflux, but not ABCC5, thereby promoting the accumulation of cisplatin in tumors. Collectively, pomiferin may serve as a novel effective agent for circumventing drug resistance in clinical applications.

Population pharmacokinetics and pharmacogenetics of apatinib in adult cancer patients.

AIMS: Apatinib is widely used in Chinese cancer patients. As the in vivo drug disposition of apatinib has large individual differences, adverse events are prone to occur. Cytochrome P450 (CYP)3A5 and cancer types maybe the main factors affecting this individual differences. The objective of our study was to establish a population pharmacokinetics (PK) model of apatinib in adult cancer patients, and to explore optimal dosage regimens for individualized treatment. METHODS: Adult patients with various types of cancer treated with apatinib were enrolled. The concentration of apatinib in plasma was determined by high-performance liquid chromatography-tandem mass spectrometry. CYP3A5 genotype was determined using TaqMan allelic discrimination technique. The population PK model was developed by NONMEM V7.4. The dosing regimen was optimized based on Monte Carlo simulations. RESULTS: A population PK model of apatinib in adult cancer patient was established. CYP3A5 genotype and systemic cancer type (digestive system cancers, nondigestive system cancers) were the most significant covariates for PK parameters. Patients with CYP3A5*1 expressers (CYP3A5*1/*1 and CYP3A5*1/*3) had lower apparent clearance and apparent volume of distribution than patients who do not express CYP3A5*1 (CYP3A5*3/*3). Patients with nondigestive system cancer had higher apparent volume of distribution and absorption rate constant than digestive system cancer. The results of dose simulation suggest that the apatinib dose in patients who do not express CYP3A5*1 should be 33.33-50.00% higher than that in CYP3A5*1 expressers. CONCLUSIONS: A population PK model of apatinib in adult cancer patients was established. CYP3A5 genotype and systemic cancer type had concurrent effects on PK parameters. CYP3A5 patients who do not express CYP3A5*1 required higher doses.

Dynamic variables to predict fluid responsiveness in young children.

BACKGROUND: The evidence that dynamic variables predict fluid responsiveness in young children is limited by conflicting research results. METHODS: Sixty patients, 1-3 years of age, undergoing major neurosurgery, received 10 mL/kg of Ringer's solution over 10 min after anesthesia induction. Respiratory variation in aortic blood flow peak velocity (∆Vpeak), plethysmographic variability index (PVI), FloTrac/Vigileo-derived stroke volume variation (SVV), dynamic arterial elastance (Eadyn ), and pulse pressure variation (PPV) were measured before and following fluid loading. An increase in the cardiac index (CI) of ≥10% following fluid loading identified fluid "responders." RESULTS: Twenty-six patients (43.3%) were fluid responders. Baseline ∆Vpeak was an excellent predictor of a CI increase following fluid loading with an area under the receiver operating characteristic curve (AUROC) of 0.982 (p < 0.001). The PVI showed fair diagnostic accuracy for CI-fluid responsiveness (AUROC 0.775, p < 0.001). Baseline ∆Vpeak and PVI cutoff values were 9.6% and 15%, respectively. PPV, SVV, and Eadyn were not predictors or were poor predictors for CI-fluid responsiveness (AUROC 0.669, 0.653, and 0.533, respectively). CONCLUSION: Volume-based PVI and ∆Vpeak showed acceptable reliability for fluid responsiveness prediction in young children undergoing major neurosurgery, whereas pressure-based SVV using FloTrac/Vigileo, Eadyn , and PPV did not.

Addition of preoperative transversus abdominis plane block to multimodal analgesia in open gynecological surgery: a randomized controlled trial.

BACKGROUND: Transversus abdominis plane (TAP) block can provide effective analgesia for abdominal surgery. However, it was questionable whether TAP had additional effect in the context of multimodal analgesia (MMA). Therefore, this study aimed to assess the additional analgesic effect of preoperative TAP block when added to MMA protocol in open gynecological surgery. METHODS: In this prospective, randomized-controlled trial, 64 patients scheduled for open gynecological surgery were randomized to receive preoperative TAP block (Study group, n = 32) or placebo (Control group, n = 32) in addition to MMA protocol comprising dexamethasone, acetaminophen, flurbiprofen and celecoxib, and rescued morphine analgesia. The primary outcome was rescued morphine within 24 h after surgery. Secondary outcomes included pain scores, adverse effects, quality of recovery measured by 40-item quality of recovery questionnaire score (QoR-40) at 24 h, and quality of life measured with short-form health survey (SF - 36) on postoperative day (POD) 30. RESULTS: The Study group had less rescued morphine than the control group within 24 h [5 (2-9) vs. 8.5 (5-12.8) mg, P = 0.013]. The Study group had lower pain scores at 1 h [3 (2-4) vs. 4 (3-5), P = 0.007], 2 h [3 (2-4) vs. 3.5 (3-5), P = 0.010] and 6 h [3 (2-3) vs. 3 (2.3-4), P = 0.028], lower incidence of nausea at 48 h (25.8% vs. 50%, P = 0.039), and higher satisfaction score [10 (10-10) vs. 10 (8-10), P = 0.041]. The SF-36 bodily pain score on POD 30 was higher in the Study group (59 ± 13 vs. 49 ± 16, P = 0.023). CONCLUSIONS: Preoperative TAP block had additional analgesic effect for open gynecological surgery when used as part of multimodal analgesia. Rescued morphine within 24 h was significantly reduced and the SF-36 bodily pain dimension at 30 days after surgery was significantly improved. TRIAL REGISTRATION: www.chictr.org.cn (ChiCTR2000040343, on Nov 28 2020).

[Characterization of greenhouse gas emissions and stable isotopic composition of ammonia during industrial composting process]. / å·¥åŽ‚åŒ–å †è‚¥æ¸©å®¤æ°”ä½“æŽ’æ”¾å’Œæ°¨æ°”åŒä½ç´ ç‰¹å¾.

Carbon dioxide (CO2), nitrous oxide (N2O), methane (CH4) and ammonia (NH3) emitted during the composting of livestock and poultry waste are important gaseous atmospheric pollutants. However, most previous studies on compost-related anthropogenic emissions of these gases were based on small reactor composting. Our understanding of their in situ emissions during industrial composting remains extremely limited. In order to explore the influence of gas produced by industrial composting on regional environment, we monitored CO2, CH4, N2O and NH3 emissions during industrial composting for 19 days and characterized the isotopic composition of emitted NH3. On average, the emission rates of CO2, CH4, N2O, and NH3 during the composting cycle were 86.8 g CO2-C·d-1·m-2, 9.8 g CH4-C·d-1·m-2, 3.7 mg N2O-N·d-1·m-2 and 736.6 mg NH3-N·d-1·m-2, respectively. The contribution of CH4 to daily global warming potential (GWP) was the highest (65%), followed by CO2, NH3(indirect), and N2O. Moreover, ammonia emitted from industrial compost had a mean δ15N value of -11.6‰±1.2‰ (range: -21.8‰--7.2‰). Overall, this study provided useful information for understanding greenhouse gas emission dynamics and characterizing atmospheric NH3 sources during composting process in livestock and poultry breeding areas.

Five-year clinical outcomes of rigid iris-fixated phakic intraocular lens in northern Chinese.

PURPOSE: To investigate the 5-year clinic outcomes of rigid iris-fixated pIOL on the visual performance, complications and intraocular light scattering in northern Chinese. METHODS: Thirty eyes implanted with iris-fixated phakic IOLs (pIOLs group) and 34 eyes with high myopia (myopia group) were involved in this study. At preoperatively, 6 months, 1, 3, and 5 years postoperatively, the uncorrected visual acuity (UCVA), best-spectacle corrected visual acuity (BSCVA), endothelial cell density (ECD), and intraocular pressure (IOP) were measured in pIOLs group. The objective scatter index (OSI), modulation transfer function cut off (MTF cut off), and Strehl ratio were measured by Optical Quality Analysis System and a pseudophakic dysphotopsia questionnaire (PDQ) was used to evaluate the subjects' satisfaction in pIOLs and myopia groups. RESULTS: At 5 years postoperatively, an UCVA of 20/20 or better was found in 43.33% of eyes in pIOLs group. At 6 months, 1, 3, and 5 years postoperatively, the mean ECD decrease were 1.29% ± 0.45%, 2.59% ± 1.30%, 6.67% ± 2.26%, and 10.80% ± 3.48%. The value of OSI in pIOLs group was significantly higher than that in myopia group (P < 0.001). The PDQ results showed that the subjects in myopia group complained less with intolerance of bright lights than those in pIOLs group. The values of Strehl ratio and MTF cut off in pIOLs group were significantly lower than that in myopia group (P < 0.001). CONCLUSIONS: Iris-fixated pIOL induce more intraocular light scattering. A significant decrease in ECD was observed at 5 years postoperatively. An annual evaluation of ECD is necessary for patients undergoing pIOL implantation.

Natural Citrus flavanone 5-demethylnobiletin stimulates melanogenesis through the activation of cAMP/CREB pathway in B16F10 cells.

BACKGROUND: 5-demethylnobiletin is a natural polymethoxyflavone which is isolated from the extract of citrus fruits peels. It exhibits a broad spectrum of biological activities such as anti-cancer, anti-inflammatory, cardiovascular protective and neuroprotective effects, however, its effect in melanogenesis remains uninvestigated. PURPOSE: Melanin synthesis is a very important biological process in curing disease such as vitiligo with depigmentation on the skin. In the current work, we aim to confirm the bioactivity and mechanism of 5-demethylnobiletin in stimulating melanogenesis. STUDY DESIGN: To confirm the mechanistic role of 5-demethylnobiletin in enhancing melanogenesis, its effect on the activity of tyrosinase, together with the level of microphthalmia-associated transcription factor (MITF), Trp-1, Trp-2, melanocyte-specific marker protein PMEL17, Rab27a, Melanophilin and Myosin VA were studied in B16F10 melanoma cells. METHODS: Multiple biological assays on melanogenesis-associated proteins such as melanin content detection, tyrosinase activity colorimetric assay, qPCR, western blot analysis, dual-luciferase reporter assay, cAMP activity assay and Fontana-Masson ammoniacal silver staining were used to confirm the role of 5-demethylnobiletin in stimulating melanin synthesis and the transportation of melanosomes. RESULTS: As confirmed by multiple biological assays, 5-demethylnobiletin is found to stimulate dendrite structure formation in cells, melanin synthesis and the transportation of melanosomes, via inducing the phosphorylation of cAMP response element-binding protein (CREB) and increasing the intracellular levels of cAMP in vitro through the PKA-dependent pathway. CONCLUSION: The findings suggested that 5-demethylnobiletin may be considered as a potential natural product candidate for patients with pigment disorder.

Staphylococcus aureus bacteremia and infective endocarditis in a patient with epidermolytic hyperkeratosis: A case report.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) is among the leading causes of bacteraemia and infectious endocarditis. The frequency of infectious endocarditis (IE) among SAB patients ranges from 5% to 10%-12%. In adults, the characteristics of epidermolytic hyperkeratosis (EHK) include hyperkeratosis, erosions, and blisters. Patients with inflammatory skin diseases and some diseases involving the epidermis tend to exhibit a disturbed skin barrier and tend to have poor cell-mediated immunity. CASE SUMMARY: We describe a case of SAB and infective endocarditis in a 43-year-old male who presented with fever of unknown origin and skin diseases. After genetic tests, the skin disease was diagnosed as EHK. CONCLUSION: A breached skin barrier secondary to EHK, coupled with inadequate sanitation, likely provided the opportunity for bacterial seeding, leading to IE and deep-seated abscess or organ abscess. EHK may be associated with skin infection and multiple risk factors for extracutaneous infections. Patients with EHK should be treated early to minimize their consequences. If patients with EHK present with prolonged fever of unknown origin, IE and organ abscesses should be ruled out, including metastatic spreads.

Saponins isolated from Radix polygalae extent lifespan by modulating complement C3 and gut microbiota.

With the increase in human lifespan, population aging is one of the major problems worldwide. Aging is an irreversible progressive process that affects humans via multiple factors including genetic, immunity, cellular oxidation and inflammation. Progressive neuroinflammation contributes to aging, cognitive malfunction, and neurodegenerative diseases. However, precise mechanisms or drugs targeting age-related neuroinflammation and cognitive impairment remain un-elucidated. Traditional herbal plants have been prescribed in many Asian countries for anti-aging and the modulation of aging-related symptoms. In general, herbal plants' efficacy is attributed to their safety and polypharmacological potency via the systemic manipulation of the body system. Radix polygalae (RP) is a herbal plant prescribed for anti-aging and the relief of age-related symptoms; however, its active components and biological functions remained un-elucidated. In this study, an active methanol fraction of RP containing 17 RP saponins (RPS), was identified. RPS attenuates the elevated C3 complement protein in aged mice to a level comparable to the young control mice. The active RPS also restates the aging gut microbiota by enhancing beneficial bacteria and suppressing harmful bacteria. In addition, RPS treatment improve spatial reference memory in aged mice, with the attenuation of multiple molecular markers related to neuroinflammation and aging. Finally, the RPS improves the behavior and extends the lifespan of C. elegans, confirming the herbal plant's anti-aging ability. In conclusion, through the mouse and C. elegas models, we have identified the beneficial RPS that can modulate the aging process, gut microbiota diversity and rectify several aging-related phenotypes.

Klebsiella pneumoniae infection secondary to spontaneous renal rupture that presents only as fever: A case report.

BACKGROUND: Spontaneous renal rupture is a rare disease in the clinic. The causes of spontaneous renal rupture include extrarenal factors, intrarenal factors, and idiopathic factors. Reports on infection secondary to spontaneous renal rupture and the complications of spontaneous renal rupture are scarce. Furthermore, there are few patients with spontaneous renal rupture who present only with fever. CASE SUMMARY: We present the case of a 52-year-old female patient who was admitted to our hospital. She presented only with fever, and the cause of the disease was unclear. She underwent a contrast-enhanced computed tomography (CT) scan, which showed that the left renal capsule had a crescent-shaped, low-density shadow; the perirenal fat was blurred, and exudation was visible with no sign of calculi, malignancies, instrumentation, or trauma. Under ultrasound guidance, a pigtail catheter was inserted into the hematoma, and fluid was drained and used for the bacterial test, which proved the presence of Klebsiella pneumoniae. Two months later, abdominal CT showed that the hematoma was absorbed, so the drainage tube was removed. The abdominal CT was normal after 4 mo. CONCLUSION: Spontaneous renal rupture due to intrarenal factors causes a higher proportion of shock and is more likely to cause anemia.

Ultrasound-guided erector spinae plane block versus thoracic paravertebral block on postoperative analgesia after laparoscopic nephroureterectomy: study protocol of a randomized, double-blinded, non-inferiority design trial.

INTRODUCTION: Erector spinae plane block (ESPB) is a novel inter-fascial plane block, which is applied more and more in postoperative pain control, especially in chest surgery. Regional block is advocated in order to decrease opioid consumption and improve analgesia in urological surgery. Therefore, we aimed to explore whether ESPB would have similar analgesia compared with thoracic paravertebral block (TPVB) in laparoscopic nephroureterectomy. METHODS AND ANALYSIS: This prospective, randomized, double-blinded, non-inferiority trial will enroll 166 patients undergoing laparoscopic nephroureterectomy. Participants will be randomly assigned 1:1 into receiving ESPB or TPVB before surgery. Both ultrasound-guided ESPB and TPVB will be performed with an injection of 0.375% ropivacaine 0.4 ml/kg before anesthesia induction. Standardized patients controlled intravenous analgesia (PCIA) will be applied for each patient. The primary endpoint is the joint of cumulative 24 h opioid (sufentanil) consumption and average pain score via numeric rating scale (NRS) at 24 h after surgery. Secondary endpoints include rescued analgesic demand, cumulative opioid consumption, and pain NRS scores at different preset timepoints within 48 h after surgery. Other predefined outcomes include clinical features of blockage, quality of recovery, subjective sleep quality, time to ambulation and diet, and adverse events, as well as length of stay in hospital and anesthesia cost. DISCUSSION: Previous studies investigating the analgesic efficacy of ESPB only concentrated on a single endpoint for postoperative pain evaluation, while studies focusing on the direct comparison between ESPB and TPVB in urological surgery are still lacking. Our study is the first trial in non-inferiority design of comparing ESPB and TPVB in patient undergoing laparoscopic nephroureterectomy, and the primary outcome is the joint endpoint of opioid consumption and pain NRS score. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR 2000031916 . Registered on 14 April 2020.

[Concurrent Collection of Ammonia Gas and Aerosol Ammonium in Urban Beijing During National Celebration Days Utilizing an Acid-Coated Honeycomb Denuder in Combination with a Filter System].

Since 2013, the Chinese government implemented the Air Pollution Prevention and Control Action Plan. As a result, the atmospheric concentrations of sulfate reduced significantly, whereas the nitrate concentrations remain relatively high due to the excess of ammonia (NH3). To date, there is no official observation network monitoring NH3 concentrations in China. Previous studies have focused on NH3 or ammonium (NH4+) separately. These limitations hinder a complete understanding of their dynamic changes due to the rapid gas-to-particle conversion. In this study, the concentrations of NH3 and NH4+ were measured concurrently in urban Beijing during autumn 2019 utilizing an acid-coated denuder-filter combination with a time resolution from 2 h (PM2.5>35 µg·m-3) to 5 h (PM2.5<35 µg·m-3). The mean concentrations of NH3 and NH4+ during the study were (4.1±2.9)µg·m-3 and (1.7±1.4) µg·m-3, respectively. The temporal patterns of NH3 or NH4+ coincided with that of PM2.5, CO, and NO2 throughout the sampling period. The diurnal distributions of NH3 were bimodal, both on polluted (PM2.5>75 µg·m-3) and non-polluted (PM2.5<75 µg·m-3) days, peaking at 21:30-05:30 and 05:30-08:30, respectively. The NH3 concentrations on polluted days were relatively lower during 17:30-21:30, which may be related to higher wind speeds. In contrast to NH3, NH4+ had an obvious peak during 17:30-21:30 due to the formation of ammonium nitrate. The meteorological conditions favor the gas-to-particle conversion on polluted days, resulting in a lower NH3/NH4+ ratio of 0.8. However, this value may reach 2.8 on non-polluted days. The concentrations of NH3, CO, NO2, SO2, and PM2.5 in the emission control period showed a significant increase greater than or comparable to those in the non-control period by 54.2%, 40.4%, 33.3%, 0%, and 49.4%, respectively. This result shows that the stagnant conditions offset the benefit of emission control actions implemented during and before the National Celebration Day.

Oral drugs used to treat persistent pulmonary hypertension of the newborn.

Introduction:Persistent Pulmonary Hypertension of the Newborn (PPHN) is a life-threatening neonatal condition, mostly treated with inhaled nitric oxide (iNO), intravenous prostaglandins, oral bosentan, sildenafil and tadalafil. However, the utility of non-oral agents is limited in PPHN for their side effects and inconvenient deliveries. Therefore, oral agents such as bosentan, sildenafil and tadalafil are becoming appealing for their satisfactory efficacy, easy mode of administration and acceptable side effects. Areas covered: We conducted a comprehensive search on Pubmed, Scopus, Web of Sciences concerning the use of bosentan, sildenafil and tadalafil to treat PPHN and summarized their efficacy, safety and pharmacokinetics. Expert opinion: Current randomized controlled trials (RCTs) have demonstrated the favorable responses and tolerable side effects of bosentan and sildenafil. Nevertheless, those RCTs are small and only one study has described the pharmacokinetics of sildenafil in neonates. Accordingly, bosentan, sildenafil and tadalafil remain off-label in clinical use. More well-designed RCTs with large samples and long-term follow-up and pharmacometrics studies are needed to demonstrate the efficacy, safety and pharmacokinetics of bosentan, sildenafil and tadalafil in PPHN.

Off-label use of tacrolimus in children with glomerular disease: Effectiveness, safety and pharmacokinetics.

Glomerular diseases are leading causes of end-stage renal disease in children. Tacrolimus is frequently used off-label in the treatment of glomerular diseases. The effectiveness, safety and pharmacokinetic data of tacrolimus in the treatment of glomerular diseases in children are reviewed in this paper to provide evidence to support its rational use in clinical practice. The remission rates in previously published studies were different. In 19 clinical trials on children with nephrotic syndrome, the overall remission rate was 52.6-97.6%. In four clinical trials on children with lupus nephritis, the overall remission rate was 81.8-89.5%. In a pilot study with paediatric Henoch-Schönlein purpura nephritis patients, the overall remission rate was 100.0%. Infection, nephrotoxicity, gastrointestinal symptoms and hypertension are the most common adverse events. Body weight, age, CYP3A5 genotype, cystatin-C and daily dose of tacrolimus may have significant effects on the pharmacokinetics of tacrolimus in children with glomerular disease. More prospective controlled trials with long follow-up are needed to demonstrate definitely the effectiveness, safety and pharmacokinetics of tacrolimus in children with glomerular diseases.

Long noncoding RNA LEF1-AS1 silencing suppresses the initiation and development of prostate cancer by acting as a molecular sponge of miR-330-5p via LEF1 repression.

Prostate cancer (PCa) is one of the major cancers affecting males with high mortality around the world. Recent studies have found that some long noncoding RNAs play a critical part in the cellular processes of PCa. In our study, aberrant expressed lymphoid enhancer-binding factor-1 antisense RNA 1 (LEF1-AS1), microRNA-330-5p (miR-330-5p), and lymphoid enhancer-binding factor-1 (LEF1) were screened out from a microarray database, the role of the novel noncoding RNA regulatory circuitry in the initiation and development of PCa was investigated. LEF1-AS1 and LEF1 were highly expressed while miR-330-5p was poorly expressed in PCa. Following that, the PCa PC-3 cell line was adopted for subsequently experiments, in which the expression of LEF1-AS1 and miR-330-5p was subsequently altered by means of exogenous transfection. After that, the effects of up- or downregulation of LEF1-AS1 and miR-330-5p on epithelial-mesenchymal transition (EMT) and the cell ability for proliferation, invasion, migration in vitro, and tumorigenesis and lymph node metastasis (LNM) in vivo were evaluated. RNA crosstalk revealed that LEF1-AS1 bound to miR-330-5p and LEF1 was the target gene of miR-330-5p. Silenced LEF1-AS1 or elevated miR-330-5p exhibited inhibited EMT processes, reduced ability of proliferation, invasion and migration, coupling with decreased tumorigenesis and LNM in nude mice. The key findings of this study collectively propose downregulation of LEF1-AS1 competing with miR-330-5p to inhibit EMT, invasion and migration of PCa by LEF1 repression.

Adiponectin protects against lung ischemia-reperfusion injury in rats with type 2 diabetes mellitus.

Adiponectin (APN) has been associated with the pathogenesis of acute brain, liver and heart injury. However, the role of APN in lung ischemia-reperfusion injury (LIRI) in diabetes mellitus remains unclear. To investigate this, the present study evaluated the effects of APN on lung dysfunction and pathological alterations in rats with type 2 diabetes mellitus via lung ischemia/reperfusion (I/R). The lung­protective effects of APN globular domain (gAPN) in rats with type 2 diabetes mellitus were also investigated by measuring the oxygenation index, inflammatory cytokines, lung edema, histopathology, oxidative stress, apoptosis and the protein expression levels of phosphorylated 5'adenosine monophosphate­activated protein kinase (p­AMPK), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). The results of the present study demonstrated that the diabetes mellitus rats + I/R (DIR) group exhibited greater concentrations of tumor necrosis factor­α and interleukin­6, and increases in the wet­weight to dry­weight ratio, lung injury score, oxidative stress and cellular apoptosis. These effects were accompanied by lower pulmonary oxygenation compared with the normal rat + I/R (NIR) group (P<0.05). Additionally, all of these alterations were attenuated in the NIR + gAPN and DIR + gAPN groups compared with in the NIR and DIR groups, respectively. In the DIR group, the expression levels of p­AMPK/AMPK and eNOS were significantly downregulated, and the levels of iNOS were upregulated, compared with those of the NIR group. Treatment with APN activated AMPK, increased eNOS expression and attenuated iNOS expression. The results of the present study demonstrated that APN exerted protective effects against LIRI via its anti­inflammatory, antioxidative stress and anti­apoptotic activities. These protective effects of APN were eliminated in rats with type 2 diabetes mellitus, in which LIRI was exacerbated. The present study indicated that APN may be a potential therapeutic agent for LIRI in type 2 diabetes mellitus.

[Outcomes of treatment of 32 cases of advanced or relapsed post-surgery pulmonary sarcomatoid carcinoma].

OBJECTIVE: To determine the efficacy of the third generation chemotherapy agents on relapsed post-surgery and advanced pulmonary sarcomatoid carcinoma (PSC). METHODS: We reviewed the medical records of 32 PSC patients. Their treatment modalities and survival rate, as well as risk factors associated with the survival rate including gender, age, location and size of tumor, relapse, initial diagnosis of stage, pathologic subtypes and smoking history were analysed. RESULTS: All of the 32 PSC patients received chemotherapy with gemcitabine combined with cisplatin (GP) or paclitaxel combined with cisplatin (TP). They had a median of 14 months overall survive (OS) and 5 months progress-free survive (PFS). The remission rate was 21.9%. An initial stage IV diagnosis and a larger than 6 cm tumor in diameter were independent factors associated with poor prognosis. CONCLUSION: The efficacy of TP and GP chemotherapy on patients with relapsed post-surgery and advanced PSC is comparable with that reported by other researchers. An initial stage IV diagnosis and a larger than 6 cm tumor in diameter are predictors of poor prognosis.