The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease.

BACKGROUND: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m2. METHODS: In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m2 with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n = 125,392) were enrolled. A Cox proportional hazard model was used to assess the cardiorenal protective effects between the GLP-1RA and DDP-4i groups. RESULTS: A total of 8922 participants [mean (SD) age 68.4 (11.5) years; 4516 (50.6%) males; GLP-1RAs, n = 759; DPP-4is, n = 8163] were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively [hazard ratio (HR) 0.88, 95% confidence interval CI 0.68-1.13]. Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD compared with DPP-4is.

Analysis of Medication Rules of Traditional Chinese Medicine for Malaria Treatment Based on Data Mining.

Objective To analyze the medication rules of traditional Chinese medicine (TCM) for malaria treatment.Methods Statistical analysis was conducted on the basic attributes of TCM drugs with regard to property, therapeutic methods, flavor, and meridian tropism. A complex network of TCM drug associations was constructed. Cluster analysis was applied to obtain the core drugs for malaria treatment. The Apriori algorithm was applied to analyze the association rules of these core drugs.Results A total of 357 herbs were used 3,194 times in 461 prescriptions for malaria treatment. Radix Glycyrrhizae (), Rhizoma Pinelliae (), Radix Bupleuri (), and Radix Dichroae () were the frequently used herbs through supplementing, exterior-releasing, heat-clearing, qi-rectifying, and damp-resolving therapeutic methods. Such herbs had warm, natural, and cold herbal properties; pungent, bitter, and sweet flavors; and spleen, lung, and stomach meridian tropisms. Cluster analysis showed 61 core drugs, including Radix Glycyrrhizae, Rhizoma Pinelliae, Radix Bupleuri, and Radix Scutellariae (). Apriori association rule analysis yielded 12 binomial rules (herb pairs) and 6 trinomial rules (herb combinations). Radix Bupleuri plus Radix Scutellariae was the core herbal pair for treating malaria. This pair could be combined with Rhizoma Atractylodis Macrocephalae () for treating warm or cold malaria, combined with Pericarpium Citri Reticulatae () or Radix Dichroae () for treating miasmic malaria, or combined with turtle shells () for treating malaria with splenomegaly.Conclusions TCM can be used to classify and treat malaria in accordance with the different stages of development. As the core herbal pair, Radix Bupleuri and Radix Scutellariae can be combined with other drugs to treat malaria with different syndrome types.

Wuzi Yanzong pill attenuates MPTP-induced Parkinson's Disease via PI3K/Akt signaling pathway.

Wuzi Yanzong Pill (WYP) was found to play a protective role on nerve cells and neurological diseases, however the molecular mechanism is unclear. To understand the molecular mechanisms that underly the neuroprotective effect of WYP on dopaminergic neurons in Parkinson's disease (PD). PD mouse model was induced by the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Gait and hanging tests were used to assess motor behavioral function. Immunofluorescence assay was used to determine TH-positive neurons in substantia nigra (SN). Apoptosis, dopamine and neurotrophic factors as well as expression of PI3K/Akt pathway were detected by TUNEL staining, ELISA and western blotting, respectively. First, it was observed that WYP intervention improved abnormal motor function in MPTP-induced PD model, alleviated the loss of TH+ neurons in SN, and increased dopamine content in brain, revealing a potential protective effect. Second, network pharmacology was used to analyze the possible targets and pathways of WYP action in the treatment of PD. A total of 126 active components related to PD were screened in WYP, and the related core targets included ALB, GAPDH, Akt1, TP53, IL6 and TNF. Particularly, the effect of WYP on PD may be medicate through PI3K/Akt signaling pathway and apoptotic regulation. The WYP treated PD mice had higher expression of p-PI3K, p-Akt and Bcl-2 but lower expression of Bax and cleaved caspase-3 than the non-WYP treated PD mice. Secretion of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) were also increased in the treated mice. WYP may inhibit apoptosis and increase the secretion of neurotrophic factor via activating PI3K/ Akt signaling pathway, thus protecting the loss of dopamine neurons in MPTP-induced PD mice.

Integrated strategy of RNA-sequencing and network pharmacology for exploring the protective mechanism of Shen-Shi-Jiang-Zhuo formula in rat with non-alcoholic fatty liver disease.

CONTEXT: Shen-Shi-Jiang-Zhuo formula (SSJZF) exhibits a definite curative effect in the clinical treatment of non-alcoholic fatty liver disease (NAFLD). OBJECTIVE: To explore the therapeutic effect and mechanism of SSJZF on NAFLD. MATERIALS AND METHODS: Sprague Dawley rats were randomly divided into control, NAFLD, positive drug (12 mg/kg/day), SSJZF high-dose (200 mg/kg/day), SSJZF middle-dose (100 mg/kg/day), and SSJZF low-dose (50 mg/kg/day) groups. After daily intragastric administration of NAFLD rats for 8 weeks, lipid metabolism and hepatic fibrosis were evaluated by biochemical indices and histopathology. Then we uncovered the main active compounds and mechanism of SSJZF against NAFLD by integrating RNA-sequencing and network pharmacology, and PI3K/AKT pathway activity was verified by western blot. RESULTS: High dose SSJZF had the best inhibitory effect on hepatic lipid accumulation and fibrosis in rats with NAFLD, which significantly down-regulated total triglycerides (58%), cholesterol (62%), aspartate aminotransferase (57%), alanine aminotransferase (41%) andγ-glutamyl transpeptidase (36%), as well as the expression of ACC (5.3-fold), FAS (12.1-fold), SREBP1C (2.3-fold), and CD36 (4.4-fold), and significantly reduced collagen deposition (67%). Then we identified 23 compounds of SSJZF that acted on 25 key therapeutic targets of NAFLD by integrating RNA-sequencing and network pharmacology. Finally, we also confirmed that high dose SSJZF increased p-PI3K/PI3K (1.6-fold) and p-AKT/AKT (1.6-fold) in NAFLD rats. DISCUSSION AND CONCLUSION: We found for first time that SSJZF improved NAFLD in rats by activating the PI3K/Akt pathway. These findings provide scientific support for SSJZF in the clinical treatment of NAFLD and contribute to the development of new NAFLD drugs.

Telmisartan use and risk of dementia in type 2 diabetes patients with hypertension: A population-based cohort study.

BACKGROUND: Angiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)-modulating effects, has additional benefits compared to other ARBs remains unclear. METHODS AND FINDINGS: Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at p < 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97; p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data. CONCLUSIONS: The current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population.

Impact of Sodium-Glucose Co-Transporter 2 Inhibitors on Cardiac Protection.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been approved as a new class of anti-diabetic drugs for type 2 diabetes mellitus (T2DM). The SGLT2 inhibitors reduce glucose reabsorption through renal systems, thus improving glycemic control in all stages of diabetes mellitus, independent of insulin. This class of drugs has the advantages of no clinically relevant hypoglycemia and working in synergy when combined with currently available anti-diabetic drugs. While improving sugar level control in these patients, SGLT2 inhibitors also have the advantages of blood-pressure improvement and bodyweight reduction, with potential cardiac and renal protection. In randomized control trials for patients with diabetes, SGLT2 inhibitors not only improved cardiovascular and renal outcomes, but also hospitalization for heart failure, with this effect extending to those without diabetes mellitus. Recently, dynamic communication between autophagy and the innate immune system with Beclin 1-TLR9-SIRT3 complexes in response to SGLT2 inhibitors that may serve as a potential treatment strategy for heart failure was discovered. In this review, the background molecular pathways leading to the clinical benefits are examined in this new class of anti-diabetic drugs, the SGLT2 inhibitors.

Pioglitazone and PPAR-γ modulating treatment in hypertensive and type 2 diabetic patients after ischemic stroke: a national cohort study.

BACKGROUND AND AIM: Peroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have cardiovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS). However, whether there are additional benefits from intensive PPAR-γ modulating treatments in Asian patients with T2DM and hypertension (HTN) after IS remains unknown. METHODS: Between 2001 and 2013, patients admitted due to IS were identified from the National Health Insurance Research Database of Taiwan. Patients with T2DM and HTN using angiotensin receptor blockers were further included. Eligible patients were divided into two groups: (1) pioglitazone and (2) non-pioglitazone oral anti-diabetic agent groups. Propensity score matching (1:2) was used to balance the distribution of baseline characteristics, stroke severity and medications. The primary outcome was recurrent IS. Subgroup analysis for recurrent IS in pioglitazone and/or telmisartan users, the trend of IS risks across different PPAR-γ intensity treatments, and dose-dependent outcomes across different pioglitazone possession ratios were further studied. Statistical significance was set at p < 0.05 and p < 0.1 for clinical outcomes and interaction of subgroup analyses, respectively. RESULTS: There were 3190 and 32,645 patients in the pioglitazone and non-pioglitazone groups. Patients of the pioglitazone group had a lower risk of recurrent IS (subdistribution hazard ratio, 0.91; 95% confidence interval 0.84-0.99). Pioglitazone was also associated with reduced recurrent IS in patients who also used telmisartan (p for interaction = 0.071). A graded correlation was found a borderline significant trend between the intensity of PPAR-γ therapy and following IS (p = 0.076). The dose-dependent outcome also showed that a borderline significant trend that higher pioglitazone possession ratio was associated with a lower risk of recurrent IS (p = 0.068). CONCLUSIONS: The current study suggests that the use of pioglitazone in type 2 diabetic and hypertensive IS patients is associated with fewer recurrent IS events in an Asian population. Concurrent telmisartan use or a higher pioglitazone possession ratio may have a trend of increased pleiotropic effects, which could possibly be related to higher PPAR-γ effects. Future studies are warranted to confirm or refute the clinical effects and the possible mechanism of more intensive PPAR-γ-modulating treatments.

Sodium-glucose cotransporter 2 inhibitor versus metformin as first-line therapy in patients with type 2 diabetes mellitus: a multi-institution database study.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) has shown evidence of cardiovascular benefit in patients with type 2 diabetes mellitus (T2DM). Currently metformin is the guideline-recommended first-line treatment. We aimed to investigate the benefit of SGLT2i vs metformin as first-line therapy. METHODS: Electronic medical records from Chang Gung Research Database during 2016-2019 were retrieved for patients with T2DM. Patients aged < 20, not receiving anti-diabetic medication, first-line treatment neither metformin nor SGLT2i were excluded. Primary outcomes were heart failure hospitalization, acute coronary syndrome, ischemic stroke, and all-cause mortality. Patients were followed up for events or December 31, 2019, whichever comes first. RESULTS: After exclusion criteria, a total of 41,020 patients with T2DM were eligible for analysis. There were 1100 patients with SGLT2i as first-line and 39,920 patients with metformin as first-line treatment. IPTW was used for propensity score matching. During one year follow-up, the hazard ratio (HR) of patients on SGLT2i as first-line treatment to patients on metformin as first-line treatment were HR 0.47 (95% CI 0.41-0.54, p < 0.0001) in heart failure hospitalization, HR 0.50 (95% CI 0.41-0.61, p < 0.0001) in acute coronary syndrome, HR 1.21 (95% CI 1.10-1.32, p < 0.0001) in ischemic stroke, and HR 0.49 (95% CI 0.44-0.55, p < 0.0001) in all-cause mortality. CONCLUSIONS: In patients with T2DM, SGLT2i as first-line treatment may be associated with decreased events of heart failure hospitalization, acute coronary syndrome, and all-cause mortality, compared with metformin as first-line treatment. However, there may be an increased events of ischemic stroke using SGLT2i compared to metformin.

Circ_0000190 suppresses gastric cancer progression potentially via inhibiting miR-1252/PAK3 pathway.

BACKGROUND: Gastric cancer is a serious malignant tumor associated with aberrant circular RNAs (circRNAs) expression. In this study, we aim to investigate the role and the underlying mechanism of circ_0000190, a circRNA in gastric cancer. METHODS: Circ_0000190 expression in vivo was examined in gastric cancer and adjacent normal tissues by RT-PCR. Circ_0000190 expression in gastric cancer cell lines was detected by FISH and RT-PCR. The role of the circRNA in gastric cancer cells was assessed by the analysis of cell viability, apoptosis, proliferation, cell cycle and migration. The potential effector of circ_0000190 was predicted by computational screen and validated by luciferase reporter assay. Furthermore, Mice model of human gastric cancer was established to observe the underlying mechanisms of circ_0000190. RESULTS: Circ_0000190 was down-regulated in gastric cancer tissues and cells, with a major location in cytoplasm. Circ_0000190 inhibited gastric cancer cell viability, proliferation and migration, and induced apoptosis and cell cycle arrest by regulating the expression of capase-3, p27 and cyclin D. In addition, the circRNA was validated as a sponge of miR-1252, which directly targeted PAK3. The effects of circ_0000190 on the cellular processes were blocked by miR-1252 mimics, which could be rescued after further overexpression of PAK3. CONCLUSIONS: Circ_0000190 suppresses gastric cancer progression potentially via inhibiting miR-1252/PAK3 pathway, employing circ_0000190 might be a promising therapeutic strategy for the treatment of gastric cancer.

BIX-01294 enhanced chemotherapy effect in gastric cancer by inducing GSDME-mediated pyroptosis.

Adjuvant chemotherapy in combination with surgery is expected to be a curative strategy for gastric cancer. However, drug resistance remains an obstacle in effective chemotherapy. Therefore, understanding the potential mechanisms of chemotherapy induced gastric cancer cell death is of great importance. We demonstrated that BIX-01294 (BIX) at low concentration could induce autophagic flux by converting LC3B-I to LC3B-II and directly activate autophagy associated cell death in gastric cancer cell lines at high concentration. BIX at low concentration could help obtain sensitivity of gastric cancer cells to chemotherapy with significantly reduced cell viability. Interestingly, BIX combined Cis (BIX + Cis) treated SGC-7901 cells display pyroptosis related cell death with large bubbles blown around the membrane, significantly decreased cell viability, elevated lactate dehydrogenase release and increased percentage of propidium iodide and Annexin-V double positive cells. Furthermore, the cleavage of gasdermin E (GSDME) and caspase-3 but not GSDMD was detected by immunoblotting and the knockout of GSDME switched pyroptosis into apoptosis in the BIX + Cis combined treated group. Furthermore, the deficiency of Beclin-1 to inhibit BIX induced autophagic flux completely blocked BIX + Cis combined treated induced cell pyroptosis related cell death. Additionally, BIX + Cis in vivo treatment could inhibit tumor growth, which could be reversed by the deficiency of Beclin-1 and be delayed by the deficiency of GSDME. In conclusion, our data was the first to reveal that BIX enhanced the anticancer chemotherapy effect by induced GSDME-mediated pyroptosis through the activation of autophagic flux in gastric cancer cells.

Similar Cardiovascular Outcomes Between Insulin Detemir and Insulin Glargine In Type 2 Diabetic Patients With Extremely Atherosclerotic Cardiovascular Disease Risks.

OBJECTIVE: The cardiovascular outcomes of insulin detemir in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-life cohort study was to evaluate the cardiovascular outcomes of insulin detemir (IDet) versus insulin glargine (IGlar) in T2DM patients after ACS or AIS. METHODS: A retrospective cohort study was conducted between June 1, 2005, and December 31, 2013, utilizing the Taiwan National Health Insurance Research Database. A total of 3,129 ACS or AIS patients were eligible for the analysis. Clinical outcomes were evaluated by comparing 1,043 subjects receiving IDet with 2,086 propensity score-matched subjects who received IGlar. The primary composite outcome included cardiovascular (CV) death, nonfatal myocardial infarction (MI) and nonfatal stroke. RESULTS: The primary composite outcome occurred in 322 patients (30.9%) in the IDet group and 604 patients (29.0%) in the IGlar group (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.95 to 1.32) with a mean follow-up of 2.4 years. No significant differences were observed for CV death (HR, 1.09; 95% CI, 0.86 to 1.38), nonfatal MI (HR, 0.88; 95% CI, 0.66 to 1.19), and nonfatal stroke (HR, 1.15; 95% CI, 0.97 to 1.35). There were similar risks of all-cause mortality, hospitalization for heart failure and revascularization between the IDet group and the IGlar group (P = .647, .115, and .390 respectively). CONCLUSION: Compared with IGlar, in T2DM patients after ACS or AIS, IDet was not associated with increased risks of CV death, nonfatal MI, or nonfatal stroke. ABBREVIATIONS: ACS = acute coronary syndrome; AIS = acute ischemic stroke; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; DKA = diabetic ketoacidosis; HHF = hospitalization for heart failure; HHS = hyperosmolar hyperglycemic state; HR = hazard ratio; IDet = insulin detemir; IGlar = insulin glargine; MI = myocardial infarction; NHIRD = National Health Insurance Research Database; PCI = percutaneous coronary intervention; PSM = propensity score matching; T2DM = type 2 diabetes mellitus.

Risk factors of synchronous multifocal necrotizing fasciitis: a case control study in comparison with monofocal necrotizing fasciitis in Taiwan.

BACKGROUND: Monofocal necrotizing fasciitis (MONF) involves a single site in a rapidly progressing infection and necrosis of the fascia and surrounding soft tissue. Synchronous multifocal necrotizing fasciitis (SMNF), the simultaneous development of NF in multiple noncontiguous sites, is rarely reported. This study aimed to compare the clinical characteristics and outcomes between patients with SMNF and MONF, and to determine the risk factors of SMNF. METHODS: Our retrospective case-control study compared the clinical characteristics and outcomes, between January 2006 and January 2013, of patients with SMNF and of patients with MONF of the extremities. RESULTS: We enrolled 144 patients with NF of the extremities: 19 with SMNF and 125 with MONF. The duration of symptoms before admission was significantly shorter for the former than for the latter (1.7 days vs. 3.3 days, p = 0.001); the prevalence of shock at the initial visit significantly higher (73.7% vs. 36%, p = 0.002); and the total-case postoperative mortality rate significantly higher (68.4% vs. 14.4%, p <  0.001). In further analysis of the total-case mortality, 9 in 13 SMNF deaths (69.2%) within 7 days after fasciotomy were in the majority while 13 with 28-day mortality (72.2%) was the majority of MONF deaths (p <  0.001). SMNF was significantly more likely to involve bacteremia (89.5% vs. 36%, p <  0.001). Independent risk factors for SMNF were liver cirrhosis (LC) (odds ratio [OR] 6.0, p = 0.001) and end-stage renal disease (ESRD) (OR 7.1, p = 0.035). Gram-negative bacteria were most common in SMNF, and Gram-positive bacteria in MONF (83.3% vs. 53.3%, p = 0.005). Vibrio species were the most common single microbial cause (35.4%) of all NF patients and were the overwhelming cause (73.7%) of SMNF. Staphylococcus aureus and group A ß-hemolytic streptococcus (45.6%) were the other predominant causes of MONF while both (10.5%) rarely caused multifocal NF. CONCLUSIONS: SMNF was more fulminant than was MONF. SMNF was attributable primarily to marine Gram-negative bacteria. Physicians should be aware of SMNF because of its extremely high mortality rate.

Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke.

BACKGROUND: The cardiovascular safety and efficacy of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-world cohort study was to evaluate the cardiovascular outcomes of linagliptin in patients with T2DM after ACS or AIS. METHODS: An open observational noncrossover retrospective cohort study was conducted between June 1, 2012 and December 31, 2013 utilizing Taiwan National Health Insurance Research Database. A total of 1203 patients with T2DM after ACS or AIS were selected as the study cohort. Cardiovascular safety and efficacy of linagliptin were evaluated by comparing outcomes of 401 subjects receiving linagliptin after ACS or AIS to 802 matched control subjects not receiving any incretin-based therapy after ACS or AIS. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke. RESULTS: The primary composite outcome after 15-month follow-up was 7% (28 patients) in the linagliptin group compared with 6.1% (49 patients) in the control group [hazard ratio (HR) 1.06; 95% confidence interval (CI) .66-1.68]. The linagliptin group also had similar risks of all-cause mortality, hospitalization for heart failure, percutaneous coronary intervention and coronary artery bypass grafting compared to the control group in terms of the secondary outcomes. CONCLUSIONS: In T2DM patients after ACS or AIS, treatment with linagliptin was not associated with increased risks of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke.

Dynamic evolution of a vesicle formed by comb-like block copolymer-tethered nanoparticles: a dissipative particle dynamics simulation study.

Vesicles are well-sealed capsules that can store or transport substances. Their dynamic evolution mechanisms are important to fulfill specific functions. In the present study, dissipative particle dynamics (DPD) simulation was employed to study the formation, fusion, and fission pathways of vesicles. Our results show that comb-like block copolymer-tethered nanoparticles can self-assemble into stable vesicles, which may be a good candidate for drug entrapment and controlled release of drug. The spontaneous fusion of this type of vesicles has been studied, whose mechanism is different from that of the vesicles formed from comb-like block copolymers. However, the fission mechanisms of the two types of vesicles are similar. To summarize, the introduction of nanoparticles alters the fusion mechanism, but causes no difference in the fission pathway of vesicles. The reason may be attributed to the nature of nanoparticles. The fusion and fission processes always experience the congregation of nanoparticles. The large and rigid nanoparticles inevitably result in changes of surface tension of the vesicle that is a key factor influencing the membrane dynamics.

Cascade bicyclization of triethylammonium thiolates with hydrazines: efficient access to pyrazolo[3,4-c]quinolines.

A new bicyclization strategy has been established, allowing a flexible and practical approach to 33 examples of pyrazolo[3,4-c]quinolines from low-cost and readily accessible triethylammonium thiolates with hydrazines. Notably, the features of this work include broad functional group compatibility, mild reaction conditions and good reaction yields.

Risk factors of distant metastasis in the follicular variant of papillary thyroid carcinoma.

BACKGROUND/PURPOSE: The follicular variant of papillary thyroid carcinoma (FVPTC) is the most common variant of papillary thyroid carcinoma (PTC). A previous population-based study revealed its clinical behavior as a mix of classic papillary thyroid carcinoma (C-PTC) and follicular thyroid carcinoma. Whereas locoregional extension was lower in FVPTC than in C-PTC, the distant metastasis rate was higher in FVPTC than in C-PTC. The aim of this study was to evaluate the risk factors of distant metastasis in FVPTC postoperatively. METHODS: A retrospective review of 359 patients with final pathological diagnosis of FVPTC treated at Chang Gung Memorial Hospital between January 2000 and January 2014 was performed. After excluding patients who had inadequate pathological data for analysis or did not attend regular follow up for >1 year, 346 patients were included in this study. Univariate and multivariate statistical analyses were performed to determine the significance of various factors. RESULTS: Of the 346 patients with FVPTC, 19 (5.5%) had lymph node metastases and 32 (9.2%) had distant metastases. Two positive and one negative risk factors were predictive for distant metastasis using multivariate analysis: angiolymphatic invasion [odds ratio (OR), 3.085; 95% confidence interval (CI), 1.008-9.442], extrathyroidal extension (OR, 3.929; 95% CI, 1.330-11.602), and encapsulation (OR, 0.361; 95% CI, 0.154-0.850). CONCLUSION: The presence of angiolymphatic invasion, extrathyroidal extension, or nonencapsulation was associated with distant metastasis in FVPTC in this study. In FVPTC patients, postoperative investigation for distant metastasis may be warranted by the presence of these two positive risk factors or the absence of the one negative risk factor.

[Data Integration and Information Sharing of Parasite Resources in Fujian Province].

Objective: To establish parasite library and database in Fujian Province by integrating information on human-animal coinfecting parasites, vectors and　intermediates, in the aim of resource sharing. Methods: According to the Standards and Technical Regulation for Preservation of Parasitic Germplasm Resources set by the Resource Sharing Platform for Parasitic and Tropical Diseases(referred to as Germplasm Resource Sharing Platform), the preserved and newly discovered parasitic germplasm resources in Fujian Center for Disease Control and Prevention were categorized, information described, preserved and displayed, and the information sharing was made through the Germplasm Resource Sharing Platform. Results: The library and database on parasites, medical vectors, and hosts were established. The library was comprised of 1 020 parasite specimens, vectors and hosts, including 100 （9.8%） adult worm specimens, 120（11.7%） eggs and larvae, and 800（78.4%） vectors and hosts. Information digitalization was achieved for 61 resources, including 9 species of nematodes, 16 species of trematodes, 7 species of tapeworms, 16 different medical mollusks, and 13 different medical arthropods, resulting in 3 150 pieces of information and 6 300 images. The database was integrated into the Germplasm Resource Sharing Platform for resource sharing. Conclusion: The library and database on parasite gemplasm resources in Fujian Province has been established. Information sharing is made available through the Germplasm Resource Sharing Platform.

Two new compounds from Aconitum tanguticum.

A phytochemical investigation on the whole plant of Aconitum tanguticum (Ranunculaceae) resulted in the isolation and characterization of two new phenylpropanoid glycosides (1 and 2). Their structures were elucidated as 4-hydroxyphenethoxy-8-O-ß-d-[6-O-(4-O-ß-d-glucopyranosyl)-sinapoyl]-glucopyranoside (1) and 3,4-dimethoxy-trans-cinnamic acid-9-O-ß-d-allopyranoside (2) on the basis of spectroscopic data (1D NMR, 2D NMR, and MS) and comparison with the literature data.

[Chemical constituents from whole plants of Aconitum tanguticum (III)].

Nineteen compounds were isolated from the whole plants of Aconitum tanguticum by various of chromatographic techniques and their structures were determined through spectral analysis (1D, 2D-NMR and MS) and comparison with the literature data. These compounds were identified as 5-hydroxymethy furfural (1), 5-acetoxymethyl furfural (2), pyrrolezanthine [5-hydroxymethyl-1-[2-(4-hydroxyphenyl) -ethyl] -1H-pyrrole-2-carbaldehyde] (3), lichiol B (4), phthalic acid dibutyl ester (5), 3, 4-dihydroxy phenylethanol (6), 3, 4-dihydroxy phenylethanol glucoside (7), salidroside (8), p-hydroxy phenylethanol (9), p-hydroxybenzoie acid glucoside (10), p-hydroxybenzoic acid (11), gastrodin (12), 1-(3, 4-dimethoxyphenyl) -1, 2-ethanediol (13), p-hydroxy benzaldehyde (14), p-hydroxy acetophenone (15), 3, 4-dihydroxy phenyl ethyl acetate (16), syringic aldehyde (17), ethyl beta-D-fructopyranoside (18), and p-hydroxybenzoic acid methyl ester (19). Compounds 3 and 4 were isolated from the Ranunculaceae family for the first time, and compounds 2, 6 and 9-19 were isolated from the Aconitum genus for the first time, and compounds 1 and 5 were isolated from the species for the first time.