Dual-mode sensing strategy based on carbon dots for sensitive and selective detection of molybdate ions.

Two kinds of carbon dots with the maximum fluorescence peak of 492 nm (named as G-CDs) and 607 nm (named as R-CDs) were synthesized. In the presence of MoO42- ions, the fluorescence of R-CDs at 607 nm can be quenched, which can probably be assigned to their aggregation caused by MoO42-, while that of G-CDs at 492 nm remained unchanged. For the first time, a ratiometric fluorescence probe was developed for MoO42- ions detection. In the range 0.25 ~ 100 µM, the fluorescence ratio (F492/F607) of the probe was linearly related to MoO42- concentration, and the detection limit was 61.5 nM, which fully meets the minimum detection requirements of MoO42- ions in drinking water. On the other hand, when MoO42- was introduced, a significant fading phenomenon of R-CDs can be observed with the naked eye; thereby, the colorimetric method can also be proposed. Based on above, the ratiometric fluorometric/colorimetric dual-mode sensing method was established for MoO42- anion quantification. Compared with the traditional analysis methods, the results obtained by multimodal sensing can be mutually verified, which effectively improves the accuracy and reliability. The dual-mode assay proposed in this work provides an alternative scheme to meet the need of sensing target compounds in complex matrices.

Quality assessment indictors and benchmarks for pancreatic surgery / 中华外科杂志

Pancreatic surgery is the most complex type of abdominal surgery,with high technical requirements and long learning curve,and the quality of surgery is directly related to the prognosis of the patients. In recent years,more and more indicators have been used to evaluate the quality of pancreatic surgery,such as operation time,intraoperative blood loss,morbidity,mortality, prognosis and so on,and different evaluation systems have been established,including benchmarking,auditing,outcome evaluation based on risk factor adjustment and textbook outcomes. Among them,the benchmark is the most widely used to evaluate surgical quality and is expected to become the standard for comparison among peers. This article reviews existing quality evaluation indicators and benchmarks for pancreatic surgery and anticipates its future application prospects.

[Time-dependent injury of mouse cerebral cortex and hippocampus by acute hypoxia].

The aim of this study was to investigate the harmful effects of acute hypoxia on mouse cerebral cortex and hippocampus and the underlying mechanism. Mouse model of acute hypoxia was constructed by using a sealed glass jar. Laser speckle contrast imaging was used to detect the changes of cerebral blood flow after different time duration of hypoxia. Total superoxide dismutase (T-SOD) and malondialdehyde (MDA) assay kits were used to detect oxidative stress in cerebral cortex and hippocampus. Immunofluorescent staining was used to detect neuroinflammatory response of microglia in the cerebral cortex and hippocampus. One-step TUNEL method was used to detect neuronal apoptosis. The results showed that, compared with non-hypoxia (0 min hypoxia) group, 30 min hypoxia group exhibited decreased cerebral blood flow, higher percentage of CD68+/Iba1+ microglia, and increased neural apoptosis in the cerebral cortex and hippocampus. Compared with 30 min group, 60 min hypoxia group showed significantly decreased cerebral blood flow, increased MDA content in the cortex, as well as greater percentage of CD68+/Iba1+ microglia and neuronal apoptosis in the cerebral cortex and hippocampus. These results suggest that acute hypoxia damages brain tissue in a time-dependent manner and the oxidative stress and neuroinflammation are important mechanisms.

SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves.

BACKGROUND: The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice. RESULTS: Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds. CONCLUSIONS: These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.

Yttrium vanadates based ratiometric fluorescence probe for alkaline phosphatase activity sensing.

Alkaline phosphatase (ALP) is an important biomarker for diagnosis, and the abnormal level of serum ALP is closely related to a variety of diseases. In present work, a ratiometric fluorescence probe based on hybrid nanoparticles CDs@YVO4: Dy3+ nanoparticle is introduced for alkaline phosphatase (ALP) activity determination. The CDs@YVO4: Dy3+ probe is constructed by the carbon dots (CDs) and YVO4: Dy3+ through a simple mixing method, in which the blue emission of CDs at 405 nm acts as the calibrated signal, the green emission of YVO4: Dy3+ at 574 nm decreased with the increasing targets ALP, and used as the output signal. In addition, the Cu2+ and pyrophosphate (PPi) were also employed in this strategy to utilize the excellent fluorescnece quenching efficiency of Cu2+ to the Dy3+ ions emission of CDs@YVO4: Dy3+, as well as the strong affinity of PPi for Cu2+. In the presence of analyts ALP, ALP catalyzes the hydrolysis of PPi, causing the release of Cu2+, resulting in the Dy3+ ions emission quenched, while the CDs emission at 405 nm retained unchanged, based on this, we designed the off-on-off ratiometric fluorescence platform for ALP sensing. The experiment result shows that the ratio of F574/F405 is linear to the concentration of ALP in arange of 0.05∼3000 U/L with a detection limit of 0.04 U/L, which is comparable or better than those reported fluorescence probe, especially the calibrated signal introduction of CDs can eliminate the background interference, improve the accuracy of proposed probe greatly. Furthermore, the discrimination of ALP enzyme inhibitor with the IC50 of 26 µM, and ALP concentration in real human serum sample has also demonstrated the applicability of CDs@YVO4: Dy3+ fluorescence sensor well.

Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage.

Novel fatty acid-bile acid conjugates (1a-1k) were designed and synthesized by coupling of the fatty acids to the 3-OH of bile acids using lysine for linkage. In the conjugates, the 24-COOH of the bile acids was kept intact to preserve liver-specific recognition. The ability of the newly synthesized conjugates (at 100 mg/kg dosage) to reduce total cholesterol (TC) and triglyceride (TG) levels in mice fed with high-fat diet (HFD) was evaluated. Conjugates of stearic acid with cholic acid and palmitic acid with ursodeoxycholic acid (at dosages of 50, 100, and 200 mg/kg) were further evaluated to determine their ability to reduce aspartate aminotransferase (AST), alanine aminotransferase (ALT), TC, and TG levels in mice fed with HFD. All conjugates showed potent hypolipidemic activity. Further investigation revealed that compounds 1c and 1 g not only dose-dependently reduced serum levels of TC and TG, but also inhibited the elevation of serum AST and ALT levels in mice fed with HFD. Thus, compounds 1c and 1 g are promising hypolipidemic agents with hepatocyte protective effects against HFD-induced liver damage.

RLA8-A New and Highly Effective Quadruple PPAR-α/γ/δ and GPR40 Agonist to Reverse Nonalcoholic Steatohepatitis and Fibrosis.

Nonalcoholic fatty liver disease (NAFLD) is a very common chronic hepatic disease, with nonalcoholic steatohepatitis (NASH) as a major and severe subcategory that can lead to cirrhosis and hepatocellular carcinoma, and thereby to a high mortality rate. Currently, there has been no approved drug to treat NAFLD or NASH. The current study has presented RLA8, a novel and balanced quadruple agonist for hepatic lipid metabolism and inflammation-related peroxisome proliferator-activated receptors (PPARs)-α/γ/δ and G protein-coupled receptor 40 (GPR40), as a NASH drug candidate. The efficacy of RLA8 to treat NASH was evaluated in vivo using two mouse models induced by methionine/choline-deficient diet or by high-fat diet, respectively. RLA8 was shown to improve serum alanine aminotransferase and high-density lipoprotein cholesterol levels, reduce hepatic free fatty acid and triglyceride levels, and alleviate insulin resistance. Cytokine and lipoperoxide analysis revealed that RLA8 could reduce oxidative stress and inflammation. Histochemical and morphologic examination of mouse livers showed that RLA8 could improve pathologic changes such as steatosis, ballooning, collagen fiber, and inflammation. Polymerase chain reaction and Western blot analyses proved that RLA8 could result in PPARs and GPR40 activation, accompanied by upregulation of the 5'AMP-activated protein kinase-acetyl-CoA carboxylase pathway and inhibition of the expression of lipogenic genes and proteins, which provided more insights into its action mechanisms. In summary, RLA8 has significantly better efficacy to improve NASH-induced liver damage such as steatosis, inflammation, and fibrosis, and, consequently, it represents a new and highly promising NASH drug candidate that is worthy of further investigation and development.

Value and controversy of lymphadenectomy for pancreatic neuroendocrine neoplasms / 中国实用外科杂志

In recent years,with the progress of imaging and diagnostic technology,the detection rate of pancreatic neuroendocrine neoplasms has increased rapidly.However,its clinical manifestations are diverse,the rate of misdiagnosis is high,the therapeutic treatments are complex,and the guidelines for diagnosis and treatment are relatively imperfect,which has caused great trouble in clinical practice.Especially in surgical treatment,it is difficult to choose between preservation of pancreatic function and standard radical resection,especially for tumors less than 2 cm.At the same time,whether lymph node resection should be performed is another open question.Because it is difficult to carry out randomized controlled studies,most of the studies on this issue are long-span retrospective studies based on public databases,which are greatly influenced by factors such as time,medical level in different regions and different surgeons.It is the confounding factors that lead to inconsistent results.

The adequate number of lymph node dissection in pancreatic cancer radical surgery based on nodal staging score(with four-center cohort validation) / 中国实用外科杂志

OBJECTIVE: To estimate the number of lymph nodes(LNs)needed to be examined for adequate LN staging via nodal staging score(NSS).METHODS: A model was fitted based on 3989 pN + patients with resected primary pancreatic adenocarcinoma in the Surveillance,Epidemiology and End RESULTS:(SEER)database.The number of nodes to examine to achieve an N SS of 90% was used as the optimal number.The results were validated in node negative patients from the SEER cohort(2583 patients)and a local multicenter cohort(93 patients).RESULTS: Tumor size is a determinant for the extent of lymphadenectomy.According to the tumor size<2 cm and ≥2 cm,15 and 20 LNs would need to be examined to achieve90% confidence in a pN0 patient.As a result of missing node-positive case,the prevalence of nodepositive was adjusted from 60.7% to 71.0%.In the survival analysis,more LNs examined was shown to be correlated with better prognosis in patients with tumor ≥2 cm.CONCLUSION: The minimum number of LNs for adequate staging depends on the tumor size.The estimation provides a practical standard for evaluating the extent of LN yield for surgeons.

Fast and Selective Detection of Cr(III) in Environmental Water Samples Using Phosphovanadate Y(V0.2P0.8O4):Eu3+ Fluorescence Nanorods.

Phosphovanadate Y(V0.2P0.8O4):Eu3+ nanorods have been created via a simple hydrothermal method and used for the highly sensitive and selective fluorescence detection of Cr3+ over other common heavy metal ions within a 10 min period. It was found that the fluorescence intensity of Y(V0.2P0.8O4):Eu3+ linearly decreases with Cr3+ concentrations ranging from 1 × 10-9 to 1.2 × 10-6 M. The sensing mechanism for Cr3+ is ascribed to the aggregation of Y(V0.2P0.8O4):Eu3+ nanorods triggered by Cr3+ ions owing to the high affinity of phosphate groups to metal ions. The excellent chemical stability, photostability over a wide pH range of 3-12, and high salt-tolerance performance with ionic strength from 1× 10-3 to 12 M of Y(V0.2P0.8O4):Eu3+ allow these nanorods to successfully overcome the photobleaching and pH-dependent fluorescence property of traditional organic fluorescence probes. These characteristics ensure their applicability to environmental monitoring of Cr3+. The sensitive determination of Cr3+ in different environmental water samples demonstrated the potential application of Y(V0.2P0.8O4):Eu3+ as a practical environmental probe. With the help of a UV lamp (254 nm), the visual Cr3+ values for dynamic monitoring in industrial wastewater further verified that this method can even exhibit on-site visible features in daytime and night easily. This allows for the direct monitoring of environmental Cr3+.

Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06.

Camptothecin (CPT) is a cytotoxic quinoline alkaloid that is used clinically as an anticancer drug. However, the clinical application of CPT is limited due to its low solubility as well as serious and unfathomable side-effects. In the present study, we created a novel 10-hydroxy CPT prodrug, ZBH-ZM­06. Its cellular cytotoxic activity was analyzed in terms of cellular viability, acetylcholinesterase (AchE) inhibition, DNA relaxation, cellular cycling and apoptosis properties. Our results showed that the AchE inhibition rate of 10 µmol/l ZBH-ZM-06 was 12.5%, compared to 96.5% for carbonyl-oxycamptothecin (CPT-11). In a chemical stability assay, only 4.9% of ZBH-ZM-06 remained after 4 h at pH 7.4. In addition, 10 µmol/l ZBH-ZM-06 significantly inhibited the tumor cell viability of nine tumor cell lines, compared to CPT-11 and the CPT active ingredient, 7-ethyl-10-hydroxy-camptothecin (SN38) (p<0.01-0.05). In the apoptosis assay, ZBH-ZM-06 increased the ratio of annexin V+/propidium iodide (PI)-/+ cells by flow cytometric analysis (p<0.05). Moreover, ZBH-ZM-06 activated caspase-3 and poly(ADP-ribose)polymerase (PARP) expression by immunoblotting. Furthermore, ZBH-ZM-06 induced a greater G2/M phase arrest ratio, compared to CPT-11 and SN38. These results indicated that ZBH-ZM-06 had higher antitumor activity than CPT-11 and SN38, which was shown by its: i) release of the effective ingredient; ii) growth inhibition of a broad spectrum of tumor cells; iii) inhibition of DNA topoisomerase (Topo-1); and iv) promotion of apoptosis through an intrinsic signaling pathway. Thus, ZBH-ZM-06 may be applied in the preclinic study for cancer treatment.

Discovery of xanthine oxidase inhibitors and/or α-glucosidase inhibitors by carboxyalkyl derivatization based on the flavonoid of apigenin.

Three series of apigenin derivatives have been prepared by coupling the carboxyl alkyl group to 4'-, 5- or 7-hydroxyl groups of apigenin respectively. Preliminary biological evaluation in vitro revealed that xanthine oxidase inhibitory activity was improved by modifications at 4'-position and decreased by similar modifications at 5-, 7-positions while α-glucosidase inhibitory activity was maintained by modifications at 5-, 7-positions but lost by modifications at 4'-position. Administration (ip) of 7e markedly lowered serum uric acid levels in potassium oxonate induced hyperuricemic mouse model and administration (p.o.) of 11d or 11e effectively suppressed the elevation of serum glucose in the oral sucrose tolerance test in mice, while apigenin were not significantly effective in both tests.

Novel phenoxyalkylcarboxylic acid derivatives as hypolipidaemic agents.

Novel phenoxyalkylcarboxylic acid derivatives based on the natural scaffolds, flavonoids, or resveratrol were designed, synthesized, and evaluated for hypolipidaemic activity. Among the compounds, 30b lowered the triglycerides by 48.5% (P < 0.05) and total cholesterol by 44.2% (P < 0.05), respectively, and was more effective than the reference drug fenofibric acid in a Triton WR-1339-induced hyperlipidaemic mice model orally (300 mg/kg body weight). 30b also showed 59.4% triglycerides lowering in an alloxan-induced diabetic mice model orally (150 mg/kg body weight). Receptor docking studies revealed that compound 30b could interact with the amino acid residues in the ligand-binding domain essential for the activation of the PPARα. The results indicate that resveratrol should be a better scaffold to derive a new class of hypolipidaemic agents in comparison with a flavonoid scaffold.

[The current progress in the development of HIV-1 fusion inhibitors].

HIV-1 fusion inhibitors are a new class of anti-HIV compounds, which block the entry of HIV into target cells through preventing the fusion between viral and cell plasma membrane and thus interrupt the initial steps of viral replication. T-20 (enfuvirtide), which has been clinically approved as the first fusion inhibitor of HIV-1 by U.S. FDA in 2003, can suppress replication of HIV variants with multi-drug resistance to reverse transcriptase and protease inhibitors. Peptides and small molecules display potent anti-HIV fusion activities by targeting gp41 thus inhibit its fusogenic function. In recent years, with the development of studies on the molecular mechanism of HIV membrane fusion process and the function of gp41, many new fusion inhibitors are found and some have been in advanced clinical trials. This review discusses recent progress in the development of HIV-1 fusion inhibitors targeting the gp41.

[The preliminary analysis of the recognition epitopes of anti-HEV monoclonal antibodies on HEV ORF2].

Western blot, capture-PCR, blocking ELISA and synthetic polypeptides were used to systematically study the recognition epitopes on HEV ORF2 of 23 anti-HEV monoclonal antibodies(McAbs) which were previously generated in our laboratory directed against HEV ORF2. Results showed that seven McAbs recognized linear epitopes that located at aa408-458 of HEV ORF2 and 16 conformation-dependent McAbs, most of which recognized the surface epitopes of native HEV, located at aa459-606 of HEV ORF2. The systematical study of the recognition epitopes of anti-HEV McAbs on HEV ORF2 provides important information for the investigation of virus receptor and HEV infection mechanism, as well as its vaccine and diagnostics development.

[Isolation and purification of 10-hydroxycamptothecin and vincoside-lactam from Camptotheca acuminata seed by polyamide].

To investigate the technological parameters of the isolation and purification of 10-hydroxycamptothecin and vincoside-lactam from Camptotheca acuminata seed by polyamide. The static arid dynamic adsorption characteristics of 10-hydroxycamptothecin and vincoside-lactam on polyamide were studied, and the contents were determined by HPLC. The optimum parameters for adsorption were as follows: the contents of 10-hydroxycamptothecin and vincoside-lactam in the extracts were 0.189 g x L(-1) and 0.334 g x L(-1), respectively, pH 6, flow rate was 1.0 mL x min(-1), processing volume was 3 BV; for desorption: ethanol-water (60:40), flow rate was 1.0 mL x min(-1), 5 BV as an eluent. After treated with polyamide, the contents of 10-hydroxycamptothecin and vincoside-lactam were 17.52% and 32.87%, respectively, the recovery yields were 66.05% and 75.86%, respectively. Results showed that polyamide revealed a good ability to separate 10-hydroxycamptothecin and vincoside-lactam. Therefore, we concluded that results in this study may provide scientific references for the large-scale production of 10-hydroxycamptothecin and vincoside-lactam extracted from C. acuminata seed.

[The molecular differences between genotype 1 and genotype 4 of HEV in their neutralization region].

HEV is classified into H (human) group and Z (zoonosis) group according to its compatible host. H group contains genotype 1 and genotype 2 HEV isolates which infect human only; Z group contains genotype 3 and genotype 4 HEV isolates which infect both human and animals. After analysis of amino acid sequences between ORF2 aa368 and aa606, four group-conserved sites that were all located in the neutralization region of ORF2 were identified. They are aa483, aa492, aa497 and aa599. Mutation analysis and capture PCR were then performed on these sites with a group of monoclonal antibodies. Results showed that the difference of the aa497 between H and Z groups was responsible for the maintenance of their group-specific immunodominant epitopes, probably through confirmation-dependent epitope changes. Thus, aa497 and its related change on the surface structure of HEV may play important roles in host selection by H and Z groups of HEV.

[Color Doppler in differential diagnosis of scrotal mass].

OBJECTIVE: To evaluate the differential diagnosis of scrotal mass with color Doppler ultrasound. METHODS: Retrospective analysis was made of 21 cases of scrotal mass confirmed both surgically and pathologically in our hospital. RESULTS: Eight of the total number were malignancy of the testis origin, accounting for 38.1% of whole study group and 13 were benign, accounting for 61.9%. Of the 13 benign cases, only 2 were of the testis origin (15.4%) while the other 11 (84.6%) were not. CONCLUSION: Color Doppler ultrasound plays an increasingly important role in the differential diagnosis of scrotal mass.

[Study on interventing effect of puerarin on insulin resistance in patients with coronary heart disease].

OBJECTIVE: To explore the effect of puerarin in improving the insulin resistance (IR) and its closely related abnormal lipid and fibrinolytic activity in patients with coronary heart disease (CHD). METHODS: Seventy-six patients with CHD were randomly divided into two groups, 40 in the puerarin group and 36 in the routine treated group. Puerarin 500 mg was given to the former in addition to routine therapy by adding to 250 ml of normal saline for intravenous dripping once a day with a therapeutic course of 3 weeks. The changes of fasting blood glucose (FBG), fasting plasma insulin (FINS), plasma total cholesterol (TC), triglyceride (TG), low and high density lipoprotein cholesterol (LDL-C & HDL-C) and plasminogen activator inhibitor-1 (PAI-1) activity were measured before and after treatment, and the insulin sensitivity index (ISI) calculated. At the same time, tissue plasminogen activator (tPA) activity before and during venous occlusion test (VOT) was tested. Besides, 30 healthy subjects were taken as control. RESULTS: In CHD patients, FINS, TC, TG, LDL-C and PAI-1 levels were higher and ISI, HDL-C and tPA before and during VOT were lower than those in the healthy controls. FINS and ISI correlated well with lipids and fibrinolytic abnormality. After puerarin treatment, FINS level lowered and ISI increased significantly (P < 0.01), while comparing with the routine group, TC, TG, LDL-C and PAI-1 were lower but HDL-C and tPA activity before and during VOT were higher in the puerarin group (P < 0.05, P < 0.01). Correlation analysis showed that FINS was positively correlated with TC, TG, LDL-C and PAI-1 and negatively correlated with HDL-C, tPA before and during VOT; ISI was negatively correlated with TC, TG, LDL-C and PAI-1 and positively correlated with HDL-C and tPA before and during VOT in the puerarin group. CONCLUSION: Puerarin could improve the IR, IR related lipid and fibrinolytic activity abnormality in CHD patients.