Complement system is overactivated in patients with IgA nephropathy after COVID-19.

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.

Ebronucimab in Chinese patients with hypercholesterolemia---A randomized double-blind placebo-controlled phase 3 trial to evaluate the efficacy and safety of ebronucimab.

Randomized clinical trials (RCTs) of PCSK9 monoclonal antibody(mAb) specifically for Chinese patients have been limited. This multi-center RCT is to clarify the efficacy and safety of a novel mAb, Ebronucimab, in Chinese patients. Patients diagnosed with primary hypercholesterolemia, including Heterozygous Familial Hypercholesterolemia, or mixed dyslipidemia, were categorized by ASCVD risk and randomly assigned at a ratio of 2:1:2:1 to receive Ebronucimab 450 mg or matching placebo every 4 weeks (Q4W), or Ebronucimab 150 mg or matching placebo every 2 weeks (Q2W). The primary outcome was the percentage change of LDL-C from baseline to week 12 for all groups. The least squares mean reduction difference (95 %CI) in LDL-C from baseline to week 12 of Ebronucimab 450 mg Q4W and Ebronucimab 150 mg Q2W groups versus the placebo group was -59.13 (-64.103, -54.153) (Adjusted p<0.0001) and -60.43 (-65.450, -55.416) (Adjusted p<0.0001), respectively. Meanwhile, the Ebronucimab group exhibited notably high rates in reaching LDL-C goals of each cardiovascular risk stratification. In addition, Ebronucimab effectively improved other lipid panel. During the double-blind treatment period, relatively frequently reported adverse events (AEs) were injection site reactions (ISR), urinary tract infection, and hyperuricemia (Incidence rate are 6.9 %, 4.8 % and 3.5 %). Among treatment-associated AEs, only injection site reactions (ISR) occurred more in the dose groups. In conclusion, Ebronucimab, with either 450 mg Q4W or 150 mg Q2W doses, demonstrated significant efficacy in lowering serum LDL-C level with a favorable safety and immunogenicity profile among hypercholesterolemic patients.

Photoredox Synthesis of Silicon-Containing Isoindolin-1-ones and Deuterated Analogues Through Hydrosilylation and Deuterium-silylation.

An efficient, practical, and metal-free protocol for the synthesis of silicon-containing isoindolin-1-ones and deuterated analogues via the synergistic combination of an organic photoredox and hydrogen atom transfer process is described. This strategy features mild reaction conditions, high atom economy, and excellent functional group compatibility, delivering a myriad of structurally diverse and valuable products with good to excellent yields.

Photoredox-catalyzed C(sp2)-H trifluoromethylation of 3-methylene-isoindolin-1-ones under metal-free conditions.

A facile synthetic method for direct C(sp2)-H bond trifluoromethylation of 3-methylene-isoindolin-1-ones under visible-light-induced metal-free conditions is presented. This protocol features mild reaction conditions, broad substrate scope and excellent functional group tolerance, resulting in a range of structurally diverse trifluoromethylated products in good to excellent yields.

The Influence of Etiology and Stimulation Target on the Outcome of Deep Brain Stimulation for Chronic Neuropathic Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: Deep brain stimulation (DBS) to treat chronic neuropathic pain has shown variable outcomes. Variations in pain etiologies and DBS targets are considered the main contributing factors, which are, however, underexplored owing to a paucity of patient data in individual studies. An updated meta-analysis to quantitatively assess the influence of these factors on the outcome of DBS for chronic neuropathic pain is warranted, especially considering that the anterior cingulate cortex (ACC) has emerged recently as a new DBS target. MATERIALS AND METHODS: A comprehensive literature review was performed in PubMed, Embase, and Cochrane data bases to identify studies reporting quantitative outcomes of DBS for chronic neuropathic pain. Pain and quality of life (QoL) outcomes, grouped by etiology and DBS target, were extracted and analyzed (α = 0.05). RESULTS: Twenty-five studies were included for analysis. Patients with peripheral neuropathic pain (PNP) had a significantly greater initial stimulation success rate than did patients with central neuropathic pain (CNP). Both patients with CNP and patients with PNP with definitive implant, regardless of targets, gained significant follow-up pain reduction. Patients with PNP had greater long-term pain relief than did patients with CNP. Patients with CNP with ACC DBS gained less long-term pain relief than did those with conventional targets. Significant short-term QoL improvement was reported in selected patients with CNP after ACC DBS. However, selective reporting bias was expected, and the improvement decreased in the long term. CONCLUSIONS: Although DBS to treat chronic neuropathic pain is generally effective, patients with PNP are the preferred population over patients with CNP. Current data suggest that ACC DBS deserves further investigation as a potential way to treat the affective component of chronic neuropathic pain.

Photocatalytic synthesis of alkyl-alkyl sulfones via direct C(sp3)-H bond functionalization.

We report a highly efficient one-pot, three-component strategy for the construction of alkyl-alkyl sulfones through a photoinduced TBADT-catalyzed C(sp3)-H sulfonylation of unactivated hydrocarbon compounds. A wide range of commercially available hydrocarbon compounds and bioactive molecules can be successfully applied to the catalytic system, affording the corresponding alkyl-alkyl sulfones in good to excellent yields (>50 examples, up to 87% yield).

Photocatalytic Synthesis of Diarylmethyl Silanes via 1,6-Conjugate Addition of Silyl Radicals to p-Quinone Methides.

A novel photocatalytic method for the preparation of diarylmethyl silanes was reported through silyl radicals addition strategy to p-QMs (p-quinone methides). This protocol could tolerate a variety of functional groups affording the corresponding silylation products with moderate to excellent yields. The resulting silylation products could be easily converted into a series of bioactive GPR40 agonists and useful p-QMs precursors for the synthesis of compounds possessing both quaternary carbon centers and silicon substituents through simple operation. A plausible mechanism of silyl radicals to p-QMs was proposed on the basis of experimental results and previous literature.

Mild renal insufficiency and attributable risk of adverse In-hospital outcomes in patients with Acute Coronary Syndrome from the improving care for Cardiovascular Disease in China (CCC) project.

BACKGROUND: Renal insufficiency (RI) is a frequent comorbidity among patients with acute coronary syndrome (ACS). We aimed to evaluate the attributable risk associated with mild RI for the in-hospital outcomes in patients with ACS. METHODS: The Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) Project was a collaborative study of the American Heart Association and the Chinese Society of Cardiology. A total of 92,509 inpatients with a discharge diagnosis of ACS were included. The attributable risk was calculated to investigate the effect of mild RI (eGFR 60-89 ml / min · 1.73 m2) on major adverse cardiovascular events (MACEs) during hospitalization. RESULTS: The average age of these ACS patients was 63 years, and 73.9% were men. The proportion of patients with mild RI was 36.17%. After adjusting for other possible risk factors, mild RI was still an independent risk factor for MACEs in ACS patients. In the ACS patients, the attributable risk of eGFR 60-89ml/min·1.73m2 to MACEs was 7.78%, 4.69% of eGFR 45-59 ml/min·1.73m2, 4.46% of eGFR 30-44 ml/min·1.73m2, and 3.36% of eGFR<30 ml/min·1.73m2. CONCLUSION: Compared with moderate to severe RI, mild RI has higher attributable risk to MACEs during hospitalization in Chinese ACS population.

Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab, in Chinese Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, First-in-Human Phase 1 Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479, or LY-CoV016), in healthy adults. This paper describes a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose increased from 2.5 to 50 mg/kg. The elimination half-life (t1/2) value did not differ among different dose cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).

The association between atrial fibrillation and in-hospital outcomes in chronic kidney disease patients with acute coronary syndrome: findings from the improving care for cardiovascular disease in China-acute coronary syndrome (CCC-ACS) project.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia in patients with chronic kidney disease (CKD) and acute coronary syndrome (ACS). This study aimed to explore the frequency and impact of AF on clinical outcomes in CKD patients with ACS. METHODS: CKD inpatients with ACS between November 2014 and December 2018 were included based on the improving care for cardiovascular disease in China-ACS (CCC-ACS) project. Included patients were divided into an AF group and a non-AF group according to the discharge diagnosis. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: A total of 16,533 CKD patients with ACS were included. A total of 1418 (8.6%) patients had clinically recognized AF during hospitalization, 654 of whom had an eGFR of 45 to < 60 ml/min/1.73 m2, and 764 had an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2. Compared with the non-AF group, the AF group had a higher risk of in-hospital mortality [OR 1.250; 95% CI (1.001-1.560), P = 0.049] and major adverse cardiovascular events (MACEs) [OR 1.361; 95% CI (1.197-1.547), P < 0.001]. We also found that compared with patients with eGFR 45 to < 60 ml/min/1.73 m2, patients with eGFR < 45 ml/min/1.73 m2 had a 1.512-fold increased risk of mortality and a 1.435-fold increased risk of MACEs. CONCLUSIONS: AF was a risk factor affecting the short-term prognosis of ACS patients in the CKD population. Furthermore, the lower the eGFR, the higher the risk of in-hospital mortality and MACEs in CKD patients with ACS. TRIAL REGISTRY: Clinicaltrial.gov, NCT02306616. Registered 29 November 2014, https://clinicaltrials.gov/ct2/show/NCT02306616?term=NCT02306616&draw=2&rank=1.

LncRNA MEG3 promotes endoplasmic reticulum stress and suppresses proliferation and invasion of colorectal carcinoma cells through the MEG3/miR-103a-3p/PDHB ceRNA pathway.

LncRNA maternally expressed gene 3 (MEG3) is a potential prognostic and diagnostic biomarker in colorectal carcinoma (CC). However, its cellular functions and mechanism remain not fully uncovered. Relative expression of MEG3, miRNA (miR)-103a-3p, and pyruvate dehydrogenase E1 subunit beta (PDHB) was detected by RT-qPCR and western blotting. Cell proliferation was measured by CCK-8 assay, colony formation assay, and flow cytometry, as well as xenograft tumor assay. Transwell assay examined cell invasion. Endoplasmic reticulum (ER) stress was evaluated by western blotting. Dual-luciferase reporter assay and RNA immunoprecipitation determined the relationship between miR-103a-3p and MEG3 or PDHB. Expression of MEG3 was downregulated in human CC tumor tissues and cells (SW620 and HCT116), accompanied by higher miR-103a-3p and lower PDHB. Restoring MEG3 suppressed cell viability, colony formation ability, and invasion, arrested cell cycle, and induced apoptosis rate in SW620 and HCT116 cells, as well as promoted expression of ER stress-related proteins (GRP78, ATF6, CHOP, caspase-3, and caspase-9). Furthermore, MEG3 overexpression hindered tumor growth and facilitated ER stress in vivo. Molecularly, miR-103a-3p was a target of MEG3, and further targeted PDHB. Similarly, in function, blocking miR-103a-3p suppressed CC in vitro by affecting proliferation, invasion, and ER stress; in addition, restoring miR-103a-3p partially counteracted the suppressive role of MEG3 in CC cells. MEG3 sponged miR-103a-3p to suppress CC malignancy by inducing ER stress and inhibiting cell proliferation and invasion via upregulating PDHB, suggesting a novel MEG3/miR-103a-3p/PDHB ceRNA pathway.

Two kinds of rare light chain cast nephropathy caused by multiple myeloma: case reports and literature review.

BACKGROUND: Light chain cast nephropathy (LCCN) is the most common renal disease caused by multiple myeloma (MM). In addition to ordinary light chain protein casts, there are a few rare casts with unique shapes, including light chain amyloid casts (LCAC) and light chain crystal casts (LCCC). CASE PRESENTATIONS: Here, we report two patients. Patient 1 is a 72-year-old man who was clinically diagnosed with MM and acute kidney injury (AKI). Pathological examination of a renal biopsy revealed that there were many amyloid casts in the distal tubules that had a lightly-stained central area and a deeply-stained burr-like edge. The marginal zone of the cast was positive for Congo red staining and contained numerous amyloid fibers, as observed by electron microscopy. No systemic amyloidosis was found. The patient received 4 courses of bortezomib-based chemotherapy, and then, his MM achieved partial remission. Patient 2 is a 57-year-old man who was also clinically diagnosed with MM and AKI. Pathological examination of a renal biopsy showed that there were many crystalline casts in the distal tubules that were fully or partially composed of crystals with different shapes, including rhomboid, needle, triangle, rectangle and other geometric shapes. Congo red staining was negative. Crystals were also detected in the urine of this patient. After 9 courses of treatment with a bortezomib-based regimen, his MM obtained complete remission and his renal function returned to normal. CONCLUSIONS: LCAC and LCCC nephropathy caused by MM are two rare types of LCCN, and both have their own unique morphological manifestations. LCAC nephropathy may not be accompanied by systemic amyloidosis. The diagnosis of these two unique LCCNs must rely on renal biopsy pathology, and the discovery of urine crystals is of great significance for indicating LCCC nephropathy.

Risk factors of acute kidney injury in patients with Stanford type B aortic dissection involving the renal artery who underwent thoracic endovascular aortic repair.

BACKGROUND: Acute kidney injury (AKI) is one of the most common and serious complications in patients with type B aortic dissection (TBAD). This study aimed at investigating the incidence and risk factors of in-hospital AKI in TBAD patients involving the renal artery who underwent thoracic endovascular aortic repair (TEVAR) only. METHODS: A total of 256 patients who were diagnosed as TBAD combined with renal artery involvement were included in this retrospective study. All patients were divided into the AKI group and the non-AKI group according to the KDIGO criteria. The risk factors for AKI were identified using a multivariate logistic regression model. RESULTS: A total of 256 patients were included in this study, and the incidence of AKI was 18% (46/256). Patients in the AKI group were more likely to have a higher proportion of the youth, a higher level of body mass index, and a shorter time from onset to admission. Multivariate logistic regression analysis revealed that the youth (age ≤40 years) (OR: 2.853, 95%CI: 1.061-7.668, p = .038) were prone to AKI, and lower estimated glomerular filtration rate (eGFR) (OR: 1.526, per 15-ml/min/1.73 m2 decrease, 95%CI: 1.114-2.092; p = .009), higher diastolic blood pressure (DBP) (OR: 1.418, per 10-mmHg increase; 95%CI: 1.070-1.879; p = .015), and fasting blood glucose (FBG) ≥7 mmol/L on admission (OR: 2.592; 95%CI: 1.299-5.174; p = .007) were independent risk factors for AKI. CONCLUSIONS: Higher incidence of AKI had been perceived in this study, most of them were young and middle-aged patients. Renopreventive measures should be considered in those high-risk patients with younger age, lower eGFR, higher DBP, and higher FBG on admission.

In-hospital acute kidney injury and atrial fibrillation: incidence, risk factors, and outcome.

BACKGROUND: The incidence and the risk factors of in-hospitalized acute kidney injury (AKI) in patients hospitalized for atrial fibrillation (AF) were unclear. METHODS: The Improving Care for Cardiovascular Disease in China-AF (CCC-AF) project is an ongoing registry and quality improvement project, with 240 hospitals recruited across China. We selected 4527 patients hospitalized for AF registered in the CCC-AF from January 2015 to January 2019. Patients were divided into the AKI and non-AKI groups according to the changes in serum creatinine levels during hospitalization. RESULTS: Among the 4527 patients, the incidence of AKI was 8.0% (361/4527). Multivariate logistic analysis results indicated that the incidence of in-hospital AKI in patients with AF on admission was 2.6 times higher than that in patients with sinus rhythm (OR 2.60, 95% CI 1.77-3.81). Age (per 10-year increase, OR 1.22, 95% CI 1.07-1.38), atrial flutter/atrial tachycardia on admission (OR 2.16, 95% CI 1.12-4.15), diuretics therapy before admission (OR 1.48, 95% CI 1.07-2.04) and baseline hemoglobin (per 20 g/L decrease, OR 1.21, 95% CI 1.10-1.32) were independent risk factors for in-hospital AKI. ß blockers therapy given before admission (OR 0.67, 95% CI 0.51-0.87) and non-warfarin therapy during hospitalization (OR 0.71, 95% CI 0.53-0.96) were associated with a decreased risk of in-hospital AKI. After adjustment for confounders, in-hospital AKI was associated with a 34% increase in risk of major adverse cardiovascular (OR 1.34, 95% CI 1.02-1.90, p = 0.023). CONCLUSIONS: Clinicians should pay attention to the monitoring and prevention of in-hospital AKI to improve the prognosis of patients with AF.

Admission fasting plasma glucose is associated with in-hospital outcomes in patients with acute coronary syndrome and diabetes: findings from the improving Care for Cardiovascular Disease in China - Acute Coronary Syndrome (CCC-ACS) project.

BACKGROUND: The discrepancy between glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) in clinical practice may be related to factors such as acute stress, renal dysfunction, and anemia, and its relationship with in-hospital outcomes is uncertain. The aim of this study was to investigate the association between the type of discrepancy between HbA1c and FPG and in-hospital outcomes in patients with acute coronary syndrome (ACS) and diabetes. METHODS: The Improving Care for Cardiovascular Disease in China - Acute Coronary Syndrome (CCC-ACS) project is a national, hospital-based quality improvement project with an ongoing database. Patients with ACS, diabetes and complete HbA1c and FPG values at admission were included. The consistent group included patients with HbA1c < 6.5% and FPG < 7.0 mmol/L or HbA1c ≥ 6.5% and FPG ≥ 7.0 mmol/L. The discrepancy group included patients with HbA1c ≥ 6.5% and FPG < 7.0 mmol/L (increased HbA1c group) or HbA1c < 6.5% and FPG ≥ 7.0 mmol/L (increased FBG group). RESULTS: A total of 7762 patients were included in this study. The numbers of patients in the consistent and discrepancy groups were 5490 and 2272 respectively. In the discrepancy group, increased HbA1c accounted for 77.5% of discrepancies, and increased FPG accounted for 22.5% of discrepancies. After adjusting for confounders, patients in the increased FPG group had a 1.6-fold increased risk of heart failure (OR, 1.62; 95% CI, 1.08-2.44), a 1.6-fold increased risk of composite cardiovascular death and heart failure (OR, 1.63; 95% CI, 1.09-2.43), and a 1.6-fold increased risk of composite major adverse cardiovascular and cerebrovascular events (MACCEs) and heart failure (OR, 1.56; 95% CI, 1.08-2.24) compared to patients in the increased HbA1c group. CONCLUSIONS: Patients with an increased FPG but normal HbA1c had a higher risk of in-hospital adverse outcomes than those with increased HbA1c but normal FPG. This result may indicate that when HbA1c and FPG are inconsistent in patients with ACS and diabetes, the increased FPG that may be caused by stress hyperglycemia may have a more substantial adverse effect than increased HbA1c, which may be caused by chronic hyperglycemia. These high-risk patients should be given more attention and closer monitoring in clinical practice. TRIAL REGISTRY: Clinicaltrial.gov , NCT02306616 . Registered 29 November 2014.

[Preventing Infection Measures of COVID-19 Patients during Mechanical Ventilation].

OBJECTIVE: To explore the preventing infection measures of new coronavirus disease 2019(COVID-19) patients during mechanical ventilation, and to provide reference for the safe application of mechanical ventilation. METHODS: Retrieved from PubMed, Ovid and other databases, and combined with the application experience of mechanical ventilation were collected to explore the preventing infection measures of COVID-19 patients during mechanical ventilation. RESULTS: This paper put forward the preventing infection measures of external circuit, internal circuit, outer surface, filter and special parts in ventilator. The preventing infection measures of sputum suction and nebulization were summarized. CONCLUSIONS: The preventing infection measures of COVID-19 patients during mechanical ventilation are successfully completed, which can provide suggestions for the application and maintenance of mechanical ventilation.

Antineutrophil cytoplasmic antibody and/or antiglomerular basement membrane antibody associated crescentic glomerulonephritis in combination with IgG4-related tubulointerstitial nephritis.

OBJECTIVES: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder and is characterised by elevated serum IgG4 concentrations and dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells. IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common manifestation of IgG4-related kidney disease (IgG4-RKD). We report four cases of kidney injury with concurrent IgG4-TIN and crescentic glomerulonephritis confirmed by renal pathology. METHODS: The medical charts of four patients were reviewed to collect clinical and laboratory data at the time of diagnosis, treatment and outcomes after 6-36 months. Two of them are cases of IgG4-TIN with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and the other two cases are rare IgG4-TIN with antiglomerular basement membrane (anti-GBM) glomerulonephritis coexistent with ANCA-positive serum. RESULTS: Compared with IgG4-TIN, IgG4-TIN combined with AAV or anti-GBM glomerulonephritis is less associated with other organ injuries, and the clinical manifestations, treatment effects and prognosis were consistent with that of crescentic glomerulonephritis. CONCLUSIONS: IgG4-TIN concurrent with anti-GBM glomerulonephritis and positivity in serum has more severe clinical features and a worse renal prognosis than IgG4-TIN coexistent with AVV.

Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel solution with larotaxel-loaded folate receptor-targeting amphiphilic copolymer-modified liposomes.

1. The aim of this study was to compare the pharmacokinetics (PKs) and tissue distribution of larotaxel (LTX) solution with a newly developed formulation called LTX-loaded folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL)-modified liposomes in rats. 2. An ultra-performance liquid chromatography-tandem mass spectrometry method has been developed and validated for the determination of LTX in rat plasma and tissues to investigate the influence of FA-PEG-PCHL-modified lipid carrier on LTX PKs and tissue distribution. 3. The PK study result showed significantly higher area under the concentration-time curve (97.2%, **p < 0.01), slower clearance (49.2%, **p < 0.01) and lower volume of distribution (42.5%, **p < 0.01) in rats following intravenous administration of modified liposomes. The biodistribution results exhibited significantly lower uptake of LTX-loaded modified liposomes in heart (20.4%, **p < 0.01), lung (8.33%, **p < 0.01), muscle (13.4%, *p < 0.05) and spleen (15.0%, **p < 0.01) among all sampled tissues, indicating that the modified lipid carriers may avoid the trapping by the reticuloendothelial system and the modified liposomes may reduce toxicity in cardiovascular system compared to LTX solution. Moreover, markedly higher concentrations of LTX in the kidney (100%, **p < 0.01) were found in LTX-loaded modified liposome treated rats and could be explained by the high folate receptor level in kidney. 4. These results indicated that the FA-PEG-PCHL-modified liposome could be an effective parenteral carrier for the delivery of LTX in cancer treatment.

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial.

OBJECTIVES: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 µg ethinylestradiol [EE] and 120 µg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 µg EE and 3 mg drospirenone in healthy Chinese women aged 18-40 years. METHODS: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study. RESULTS: Participants were randomised either to the NuvaRing (n = 732) or to the COC (n = 214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result. CONCLUSIONS: Once-monthly NuvaRing is efficacious and safe for use in Chinese women.