Characteristics, hotspots, and prospects of short video research: A review of papers published in China from 2012 to 2022.

In recent years, due to the increase in their global popularity, short video applications have become an important topic of research. The number of users has now exceeded one billion in China; accordingly, Chinese researchers have conducted many studies on short videos. Their findings can serve as important references for both theoretical research on and the practical development of short videos worldwide. In this study, we used bibliometrics method and the CiteSpace application to analyze the content of 2163 representative research papers on short videos published in China from 2012 to 2022. The number of such papers is increasing annually in China; moreover, several core groups of authors and research institutions focusing on short video research have already been formed. Some popular topics of research on these videos include the main characteristics of short videos, phenomenon of media convergence based on short videos, and application scenarios of short videos. Over the years, research on the popular short video application Douyin has been increasing, as well. The research results indicate that issues such as the marketing of short knowledge videos, standardized management of short video platforms, and impact of these videos on the education of college students are expected to become popular subjects of scholarly research in the near future.

Pharmacokinetic and Safety Study of Single and Multiple Oral Doses of Safinamide in Healthy Chinese Volunteers.

This randomized, parallel-group study evaluated the plasma pharmacokinetic profile of safinamide in 24 healthy Chinese men and women, randomly assigned to receive 50 or 100 mg of safinamide as a single dose, followed, after a 7-day washout, by multiple doses once daily for 7 days. Plasma safinamide was determined up to 96 h after the first single dose (day 1) and the last multiple dose (day 14), and up to 24 h after the first multiple dose (day 8). Following single- and multiple-dose administration, peak concentrations were achieved at a median time of 1.5-2 h. Plasma exposure increased in a dose-proportional manner. After single dose, mean half-life was 23-24 h. Area under the concentration-time curve (AUC) from time zero extrapolated to infinity was only slightly higher than AUC from time zero to the last quantifiable concentration, corresponding for the 2 parameters, respectively, to 12,380 and 11,560 ng • h/mL for the 50 mg and to 22,030 and 20,790 ng • h/mL for the 100-mg dose. AUC in the dosing interval at steady state was 13,150 and 23,100 ng • h/mL for 50 and 100 mg of safinamide. Steady state was reached in 6 days, accumulation was approximately twofold, and the pharmacokinetics were time independent. The plasma safinamide pharmacokinetic profile observed in this study is in line with the published results in both Chinese and non-Asian populations.

A model for predicting degree of malignancy in patients with intraductal papillary mucinous neoplasm.

Background/Objectives: There is no predictive model available to address early stage malignant intraductal papillary mucinous neoplasm (IPMN) including high grade dysplasia (HGD) and pT1a (invasive component≤0.5 cm). The aim of this study was to establish an objective and sufficient model to predict the degree of malignancy in patients with IPMN, which can be easily applied in daily practice and adopted for any type of lesion. Methods: A retrospective cohort study of 309 patients who underwent surgical resection for IPMN was performed. Members of the cohort were randomly allocated to the training or testing set. A detection tree model and random forest model were used for a 3-class classification to distinguish low grade dysplasia (LGD), HGD/pT1a IPMN, and invasive intraductal papillary mucinous cancer (I-IPMC) beyond pT1a. Results: Of the 309 patients, 54 (17.4%) had early stage malignancy (19 HGD, 35 pT1a), 49 (15.9%) had I-IPMC beyond pT1a, and 206 (66.7%) had LGD IPMN. We proposed a 3-class classification model using a random forest algorithm, and the model had an accuracy of 99.5% with the training set, and displayed an accuracy of 96.0% with the testing set. We used SHAP for interpretation of the model and showed the top five factors (mural nodule size, main pancreatic duct diameter, CA19-9 levels, lesion edge and common bile duct dilation) were most likely to influence the 3-class classification results in terms of interpretation of the random forest model. Conclusions: This predictive model will help assess an individual's risk for different stages of IPMN malignancy and may help identify patients with IPMN who require surgery.

Dupilumab pharmacokinetics in Chinese healthy subjects and patients with atopic dermatitis: Results of two randomized, double-blind, placebo-controlled studies.

BACKGROUND: Dupilumab, a fully human monoclonal antibody targeting IL-4Rα, has demonstrated rapid and sustained improvements in clinical outcomes in patients with atopic dermatitis (AD), asthma, and chronic rhinosinusitis with nasal polyps. METHODS: In a phase 1, double-blind, ascending-dose study, 30 healthy Chinese adults were randomized to single subcutaneous doses of dupilumab 200, 300, 600 mg, or placebo. In a phase 3, double-blind study, 165 Chinese adults with AD were randomized to dupilumab 300 mg or placebo every 2 weeks. RESULTS: Following single doses of dupilumab 200, 300, and 600 mg in the phase 1 study, mean serum maximum concentrations (Cmax) were 25.4 ± 4.0, 37.2 ± 14.5, and 77.3 ± 19.0 mg/L, respectively. For a 1.5-fold increase in dupilumab dose, 1.31-, 1.73-, and 1.66-fold increases in Cmax, area under the curve to real time (AUClast), and extrapolated to infinity (AUC) were observed, respectively, while a 2-fold dose increase resulted in 2.17-, 2.81-, and 2.80-fold increases, respectively. In the phase 3 study, mean dupilumab trough concentrations were 78.8 ± 32.0 and 86.4 ± 33.6 mg/L at weeks 12 and 16, respectively. CONCLUSIONS: Cmax increased approximately proportionally to dose, while AUC and AUClast increased greater than proportionally. Dupilumab pharmacokinetics were generally comparable between Chinese and non-Asian healthy subjects (single dose) and between Chinese and non-Asian AD patients (repeated doses), with differences accounted for by body weight. As differences in exposure by weight are unlikely to be clinically relevant based on late-stage study results, no dose adjustment by ethnic origin or weight is required.

Direct visualization of drug behaviors in the upper GI tract via magnetically controlled capsule endoscopy.

BACKGROUND AND AIMS: Actual behaviors of drugs in the upper GI tract are not well elucidated. We assess the feasibility of magnetically controlled capsule endoscopy (MCE) in direct and real-time visualization of oral drug behaviors in the stomach. METHODS: From November 2019 to December 2019, 9 patients with a recent history of upper GI symptoms and 10 healthy volunteers were enrolled in this study. Participants swallowed magnetically controlled capsules to examine the whole stomach. After baseline examination, participants ingested dyed sucralfate gel, and MCE recorded the adhesion time, retention time, and distribution area of sucralfate gel. Outcomes included behaviors of sucralfate gel, safety, and satisfaction assessment of the procedures. RESULTS: Adhesion time of sucralfate gel in the abdominal symptoms group was significantly shorter than in the healthy control group (23.76 ± 1.37 minutes vs 31.96 ± 3.09 minutes; P = .032), whereas retention time was longer (98.85 ± 13.94 minutes vs 63.93 ± 8.57 minutes; P = .043). The distribution area of sucralfate gel in the abdominal symptoms group was significantly larger than in healthy control group in cardia (24.29 ± 7.39 vs 9.18 ± 4.06; P < .0001), fundus (18.90 ± 7.08 vs 8.49 ± 4.10; P = .0015), and pylorus (4.64 ± 2.72 vs 0.94 ± 0.90; P = .0019). No adverse events were observed. All participants had a high degree of satisfaction. CONCLUSIONS: MCE is a feasible and noninvasive tool for direct and real-time visualization of drug behaviors (eg, sucralfate gel) in the stomach. (ClinicalTrials.gov. ID: NCT04327869.).

[Corrigendum] SiRNA­mediated PIAS1 silencing promotes inflammatory response and leads to injury of cerulein­stimulated pancreatic acinar cells via regulation of the P38MAPK signaling pathway.

Following the publication of the above article, an interested reader drew to the authors' attention that the data shown in Fig. 2D representing the P53 and Bax data were strikingly similar. After having re­examined their raw data, the authors have realized that this error arose inadvertently; the data shown for Bax in the original figure were selected incorrectly. In the article, the expression levels of the apoptosis­regulatory factors P53 and Bax were investigated by western blot analysis and reverse transcription­quantitative PCR analysis. The authors were also able to confirm that this error regarding the image placement did not influence the statistical analysis shown for the effect of PIAS1 gene silencing on pancreatic acinar cell apoptosis. The corrected version of Fig. 2, containing the correct data for Bax protein expression in Fig. 2D, is shown below. The authors are grateful to the Editor of International Journal of Molecular Medicine for granting them the opportunity to publish this Corrigendum, and stress that this error did not significantly influence either the results or the conclusions of the paper. Furthermore, the authors apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 26: 919-926, 2010; DOI: 10.3892/ijmm_00000507].

Knockdown of the DJ-1 (PARK7) gene sensitizes pancreatic cancer to erlotinib inhibition.

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib, in combination with gemcitabine, has been shown to be a promising therapy in the treatment of pancreatic cancer. Our previous study showed that DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/extracellular signal-regulated kinase (ERK)/uPA. The aim of this study was to evaluate whether knockdown of DJ-1 expression can sensitize pancreatic cancer cells to erlotinib treatment. Knockdown of DJ-1 expression accelerated erlotinib-induced cell apoptosis and improved the inhibitory effect of erlotinib on pancreatic cancer cell proliferation (for the BxPC-3, PANC-1, and MiaPACa-2 cell lines, regardless of KRAS mutation status) in vitro and in xenograft tumor growth in vivo. Knockdown of DJ-1 decreased K-RAS expression, membrane translocation, and activity in BxPC-3 cells. Knockdown of DJ-1 also decreased K-RAS, H-RAS, and N-RAS expression in PANC-1 and MiaPACa-2 cells. Knockdown of DJ-1 synergistically inhibited AKT and ERK1/2 phosphorylation with erlotinib in pancreatic cancer cells. These findings indicate that DJ-1 may activate the RAS pathway, reinforcing erlotinib drug resistance. Therefore, blocking DJ-1 in combination with the EGFR tyrosine kinase inhibitor erlotinib may be an attractive therapeutic target in pancreatic cancer.

TRPV4 Overexpression Promotes Metastasis Through Epithelial-Mesenchymal Transition in Gastric Cancer and Correlates with Poor Prognosis.

PURPOSE: Transient receptor potential vanilloid 4 (TRPV4) has been reported to be involved in the progression of several human tumors. Nevertheless, clinical significance and molecular mechanism of TRPV4 in gastric cancer (GC) remain poorly defined. PATIENTS AND METHODS: Immunohistochemistry assays were used to investigate the correlation between the expression of TRPV4 and epithelial-mesenchymal transition (EMT) markers in human GC tissues. The correlations between TRPV4 expression and clinicopathological features and between TRPV4 expression and survival rates were also examined. TRPV4 knockdown was performed by using small interfering RNAs. In vitro, Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and transwell assay were employed to further explore the biological functions of TRPV4, and Western blotting was used to evaluate the changes in the expression of TRPV4 protein and EMT-related proteins in HGC-27 and MGC-803 human GC cell lines. RESULTS: TRPV4 expression was upregulated in GC tissues and cell lines. TRPV4 overexpression was associated with greater depth of tumor invasion, lymph node metastasis, higher TNM stage, poor overall survival, and worse disease-free survival. TRPV4 expression was inversely correlated with E-cadherin expression and positively correlated with vimentin expression. In vitro, knockdown of TRPV4 inhibited GC cell proliferation, colony formation, and invasion. Furthermore, the knockdown of TRPV4 modulated EMT by upregulating E-cadherin expression and downregulating the expression of N-cadherin and vimentin. In addition, the EMT-related transcription factor Snail was downregulated, whereas the expression levels of other transcription factors such as Slug and Twist did not change. CONCLUSION: TRPV4 was upregulated in human GC and the overexpression of TRPV4 could promote GC progression, partially through Snail-mediated EMT.

IgA, albumin, and eosinopenia as early indicators of cytomegalovirus infection in patients with acute ulcerative colitis.

BACKGROUND: Cytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients. METHODS: A total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses. RESULTS: A total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49-73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05-119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively. CONCLUSIONS: High-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.

A nicotine-induced positive feedback loop between HIF1A and YAP1 contributes to epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma.

BACKGROUND: Nicotine, an active ingredient in tobacco, can promote epithelial-to-mesenchymal transition (EMT) processes that enhance the aggressiveness of a number of human cancers. In the present study, we investigated whether cigarette smoke/nicotine drives EMT in pancreatic ductal adenocarcinoma (PDAC). METHODS: Quantitative real-time PCR, western blot, immunohistochemistry, and immunofluorescence assays were used to evaluate Yes-associated protein 1 (YAP1) expression associated with cigarette smoking in human PDAC tissue samples and with nicotine exposure in PDAC cell lines. Bioinformatics, loss- and gain- of- function experiments, luciferase reporter assays, chromatin immunoprecipitation (ChIP), and murine tumor xenograft models were performed to examine the function of YAP1 in PDAC and to identify potential mechanisms of action. RESULTS: Exposure to smoking or nicotine promoted EMT and tumor growth in PDAC cells and in xenograft tumors. Functional studies revealed that YAP1 might drive nicotine-stimulated EMT and oncogenic activity in vitro and in vivo. In human PDAC tissues, upregulation of YAP1 was associated with "ever smoking" status and poor overall survival. In term of mechanism, hypoxia inducible factor (HIF)1A promoted YAP1 nuclear localization and YAP1 transactivation by directly binding to the hypoxia responsive elements of the YAP1 promoter upon nicotine treatment. Nicotine stimulated HIF1A and YAP1 expression by activating cholinergic receptor nicotinic alpha7 (CHRNA7). In addition, YAP1 increased and sustained the protein stability of HIF1A. CONCLUSIONS: These data demonstrate that YAP1 enhances nicotine-stimulated EMT and tumor progression of PDAC through a HIF1A/YAP1 positive feedback loop. Developing inhibitors that specifically target YAP1 may provide a novel therapeutic approach to suppress PDAC growth, especially in PDAC patients who have a history of smoking.

Nicotine promotes tumor progression and epithelial-mesenchymal transition by regulating the miR-155-5p/NDFIP1 axis in pancreatic ductal adenocarcinoma.

BACKGROUND: Nicotine, the major component of cigarette smoke, has been reported to promote pancreatic ductal adenocarcinoma (PDAC) growth and invasion. Deregulation of microRNA (miRNA) expression is found in many cancers, including PDAC. The effects of nicotine on miRNAs change in PDAC progression remain unknown. METHODS: The effects of cigarette smoking/nicotine exposure on PDAC cell lines and tissues were evaluated. Quantitative real-time PCR and in situ hybridization assays were used to determine miR-155-5p expression in human PDAC tissue and cell lines upon cigarette smoking/nicotine exposure. Bioinformatics, loss-of-function experiments, luciferase reporter assay were performed to validate Nedd4 family interacting protein 1 (NDFIP1) as a direct target of miR-155-5p. The potentials of systemic miR-155-5p inhibitor-based therapy in overcoming nicotine exposure were evaluated in tumor xenograft model. RESULTS: Nicotine promoted PDAC cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a dose-response manner. MiR-155-5p was found to be highly expressed in PDAC cell lines and tissues upon cigarette smoking/nicotine exposure. Functional studies showed that miR-155-5p knockdown could override the enhancement of oncogenic activity due to nicotine exposure in vitro and in vivo by directly interacting with the 3' untranslated regions (UTRs) of NDFIP1. CONCLUSIONS: These data demonstrate that nicotine-regulated miR-155-5p/NDFIP1 promotes tumor progression and EMT of PDAC.

Cigarette Smoking and Mortality in Patients With Pancreatic Cancer: A Systematic Review and Meta-analysis.

Current evidence on cigarette smoking associated with pancreatic cancer mortality is limited. We searched MEDLINE, Web of Science, and Embase databases to identify relevant studies published through January 31, 2018. A random-effects model was used to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 20 studies were retrieved, involving 2,517,623 participants. Of these, more than 15,341 patients with pancreatic cancer died. Compared with never smokers, current (summary HR, 1.56; 95% CI, 1.34-1.83) and former (summary HR, 1.15; 95% CI, 1.06-1.26) smokers had elevated risk of total mortality in patients diagnosed with pancreatic cancer. This effect of cigarette smoking is observed both in the Western regions and the Asia-Pacific regions. This effect of smoking is independent of alcohol use, body mass index, and history of diabetes but is modified by tumor stage and study settings. Dose-response associations between smoking and pancreatic cancer mortality were revealed for smoking intensity, cumulative amount of cigarettes smoked, and duration of smoking. Cigarette smoking was associated with an increase in total mortality for patients with pancreatic cancer. Future studies should further clarify the role of smoking as an effect modifier in treatment trials of pancreatic cancer.

[Corrigendum] High expression of RELM-α correlates with poor prognosis and promotes angiogenesis in gastric cancer.

Following the publication of the above article, the authors have drawn to our attention that, in Fig. 6 on p. 83, the 'Ad5/F­35 vector' and 'Control' experiment data panels for the MKN45 cell line were inadvertently derived from the same original source. The Ad5/F35­vector and Control groups were both negative controls; Ad5/F35­vector was the empty vector condition, whereas 'Control' represented the 'no vector' experiment. A representative image belonging to the Control MKN45 experiment was inadvertently used to show the 'Ad5­F35­vector' experiment. An examination of the original data files confirmed that the data shown in the histogram for Fig. 6 were correct; therefore, this error in terms of figure placement did not influence the statistical analysis shown for the invasive ability of the cells. A corrected version of Fig. 6, containing correct representative data for the 'Ad5­F35­vector' experiment, is shown opposite. This error did not affect the results or the conclusions reported in this study. The authors sincerely apologize for this mistake, and regret any inconvenience this mistake has caused. [the original article was published in Oncology Reports 34: 77­86, 2015; DOI: 10.3892/or.2015.3943].

Study of disease phenotype and its association with prognosis of paediatric inflammatory bowel disease in China.

BACKGROUND: To investigate the unique features of inflammatory bowel disease (IBD) in children, we wanted to identify whether there might be a strong correlation between the disease phenotype and its prognosis at various ages in paediatric patients. METHODS: We collected data from patients diagnosed with IBD (ulcerative colitis (UC) or Crohn's disease (CD)) from 2002 to 2016. The diagnosis was made according to the Porto criteria and Paris Classification. Patient characteristics, clinical manifestations and treatments were collected. Risk factors for surgery, mortality and relapse were analysed by Cox proportional hazard models. RESULTS: Of the 143 patients, 113 had CD, and 30 had UC; there were 89 males and 54 females with a median age of 9 years (y). Thirteen patients in the 0-2 y group were identified as having mutations in IL-10 receptor A, and this mutation was significantly more common in this age group than in 3-9 and 10-16 y patients. The risk factor for surgery was the B3 phenotype; risk factors for death were age 0-2 y and B3 phenotype; 0-2 y, B3 phenotype and steroid dependency were risk factors for early relapse. CONCLUSIONS: Clinical manifestations of the onset of IBD in infants and toddlers were extensive and aggressive and were closely associated with early relapse and death. It is of particular interest that some of these patients developed IBD due to monogenic disorders; thus, introduction of genetic testing is essential for these patients.

Effect of p53 on pancreatic cancer-glucose tolerance abnormalities by regulating transglutaminase 2 in resistance to glucose metabolic stress.

Pancreatic ductal adenocarcinoma (PanCa) is an extremely lethal disease characterized by mutations of p53 in up to 70% of cases. Our previous studies have confirmed that hyperglycemia may be the first clinical manifestation for the early diagnosis of PanCa. In this article, we showed that targeted knockdown of TG2 or p53 in tumor cells led to decreased cell survival in response to glucose deprivation, while this phenomenon was abolished by combined inhibition of TG2 and p53. We observed that inhibition of TG2 or p53 sensitized glucose deprivation resistance through an intracellular reactive oxygen species (ROS) pathway and the induction of Bcl-2. Moreover, to understand whether pancreatic cancer cells with TG2 and p53 combined interference had possible effects on pancreatic ß cells, we performed studies comparing pancreatic cancer cells with TG2 and p53 combined interference and pancreatic ß cells. We discovered that the supernatant of pancreatic cancer cells withTG2 and p53 combined interference decreased cell survival in pancreatic ß cells. Following the creation of an orthotopic pancreatic cancer mouse model, we revealed glucose tolerance abnormalities in the pancreatic cancer mouse model with TG2 and p53 combined interference, indicating a possible mechanism for damage of ßcells in pancreatic cancer. Taken together, our findings establish roles for TG2 and p53 in response to glucose deprivation in pancreatic cancer cells. The relationship between TG2 and p53 suggests a possible mechanism for glucose tolerance abnormalities-associated pancreatic cancer and could have therapeutic potential for cancer treatment and diagnosis.

Association between ABO blood types and sporadic pancreatic neuroendocrine tumors in the Chinese Han population.

BACKGROUND: Although the relationship between non-O blood types and the risk of exocrine pancreatic cancer has been demonstrated, the association between ABO blood types and sporadic pancreatic neuroendocrine tumor (PNET) has not been reported thus far. METHODS: This hospital-based, case-control study included 387 patients with PNET and 542 age- and sex-matched controls. Unconditional multivariable logistic regression analysis was performed to estimate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs). The relationship between ABO blood types and clinicopathologic features was also analyzed. RESULTS: After adjusting for age, sex, smoking status, alcohol drinking, and first-degree family history of any cancer, the AORs (95% CI) of functional PNET were 0.87 (0.59-1.28) for blood type A, 0.86 (0.58-1.28) for blood type B, and 0.71 (0.39-1.26) for blood type AB compared with subjects with blood type O. A similar ABO blood-type distribution was observed among cases with non-functional PNETs compared with controls. On comparing blood type B with non-B blood type, cases with non-functional PNETs had marginally higher rates of lymph node invasion (P = 0.047), distant metastasis (P = 0.044), and advanced European Neuroendocrine Tumor Society Stage (P = 0.040). CONCLUSIONS: There is no association between the ABO blood group and the development of functional and non-functional PNETs. The ABO blood types are not associated with the clinicopathologic features in patients with functional and non-functional PNETs.

Serum metabolomics differentiating pancreatic cancer from new-onset diabetes.

To establish a screening strategy for pancreatic cancer (PC) based on new-onset diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the metabolic pathways associated with PC related DM were performed. Serum samples from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM were examined by liquid chromatography-mass spectrometry. Data were analyzed using principal components analysis (PCA) and orthogonal projection to latent structures (OPLS) of the most significant metabolites. The diagnostic model was constructed using logistic regression analysis. Metabolic pathways were analyzed using the web-based tool MetPA. PC patients with NO-DM were older and had a lower BMI and shorter duration of DM than those with NO-DM. The metabolomic profiles of patients with PC and NO-DM were significantly different from those of patients with NO-DM in the PCA and OPLS models. Sixty two differential metabolites were identified by the OPLS model. The logistic regression model using a panel of two metabolites including N_Succinyl_L_diaminopimelic_acid and PE (18:2) had high sensitivity (93.3%) and specificity (93.1%) for PC. The top three metabolic pathways associated with PC related DM were valine, leucine and isoleucine biosynthesis and degradation, primary bile acid biosynthesis, and sphingolipid metabolism. In conclusion, screening for PC based on NO-DM using serum metabolomics in combination with clinic characteristics and CA19-9 is a potential useful strategy. Several metabolic pathways differed between PC related DM and type 2 DM.

Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVE: Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects. METHODS: In this open-label, randomised, parallel-group study, following screening and baseline evaluation, eligible healthy subjects received single oral doses of LCZ696 50, 100, 200 or 400 mg. The pharmacokinetics, safety and tolerability of LCZ696 were assessed up to 72 h after dosing. A total of 40 healthy male subjects were enrolled, and all completed the study. RESULTS: Following oral administration, LCZ696 delivered systemic exposure to sacubitril, LBQ657 and valsartan with a median time to reach maximum plasma concentration (T max) ranging from 0.50 to 1.25, 2.00 to 3.00 and 1.50 to 2.50 h, respectively, over the investigated dose range. The mean terminal elimination half-life (T 1/2) ranged from 0.89 to 1.35, 8.57 to 9.24 and 5.33 to 7.91 h for sacubitril, LBQ657 and valsartan, respectively. The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and maximum plasma concentration (C max) for LBQ657 increased dose proportionally over the entire dose range. Dose linear increase in the exposure was observed across the dose range for sacubitril and valsartan. LCZ696 was safe and well tolerated at all doses in this study. Adverse events of only mild intensity, which required no treatment, were reported in 6 (15 %) subjects. CONCLUSION: The pharmacokinetic profiles of LCZ696 analytes in Chinese subjects are similar to those reported previously in Caucasian subjects.

Adsorptive Granulocyte and Monocyte Apheresis in the Treatment of Ulcerative Colitis: The First Multicenter Study in China.

BACKGROUND/AIMS: Patients with active ulcerative colitis (UC) have elevated levels of activated myeloid-derived leukocytes as a source of inflammatory cytokines. The selective depletion of these leukocytes by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn should alleviate inflammation, promote remission and enhance drug efficacy. However, studies have reported contrasting efficacy outcomes based on patients' baseline demographic variables. This study was undertaken to understand the demographic features of GMA responders and nonresponders. METHODS: This was a multicenter study in China involving four institutions and 34 patients with active UC. Baseline conventional medications were continued without changing the dosage. The treatment efficacy was evaluated based on the endoscopic activity index and the Mayo score. RESULTS: Thirty of the 34 patients completed all 10 GMA treatment sessions. The overall efficacy rate was 70.59%. The receiver operating characteristic analysis showed that the area under the curve was approximately 0.766 for a Mayo score of ≤5.5 with 0.273 specificity and 0.857 sensitivity (Youden index, 0.584) for GMA responders. No GMA-related serious adverse events were observed. CONCLUSIONS: The overall efficacy of GMA in patients with active UC who were taking first-line medications or were corticosteroid refractory was encouraging. Additionally, GMA was well tolerated and had a good safety profile.

Assessment of Drug-Drug Interaction Potential Between Atorvastatin and LCZ696, A Novel Angiotensin Receptor Neprilysin Inhibitor, in Healthy Chinese Male Subjects.

BACKGROUND AND OBJECTIVE: LCZ696 (sacubitril/valsartan), a novel angiotensin receptor neprilysin inhibitor has been recently approved for the treatment of patients with heart failure (HF) and reduced ejection fraction. As several HF patients are likely to use statins as co-medications, the potential for a pharmacokinetic drug-drug interaction between atorvastatin and LCZ696 was evaluated. METHODS: This was an open-label, three-period, single-sequence study in 28 healthy Chinese male subjects wherein LCZ696 200 mg was administered twice daily for 5 days in period 1. Following a washout period, atorvastatin 80 mg was administered once daily for 4 days (period 2) and subsequently co-administered with LCZ696 200 mg for 5 days (period 3). Serial plasma samples were collected to determine pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan) and atorvastatin and its metabolites. RESULTS: Atorvastatin co-administration had no effect on the pharmacokinetics of LBQ657, while the AUCτ,ss and C max,ss of sacubitril increased by 30 and 19 %, respectively, and the corresponding values for valsartan decreased by 19 and 9 %, respectively. Co-administration with LCZ696 increased C max,ss of atorvastatin, o-hydroxyatorvastatin, and p-hydroxyatorvastatin by 74, 68, and 108 %, respectively, and the AUCτ,ss of corresponding analytes increased by 34, 22, and 26 %, respectively. CONCLUSIONS: While atorvastatin had no significant impact on the pharmacokinetics of LCZ696 analytes upon co-administration, the C max of atorvastatin and its metabolites increased twofold, with a marginal increase in AUC (<1.3-fold). Multiple-dose administration of LCZ696 200 mg twice daily and atorvastatin 80 mg once daily either alone or in combination was generally safe and well tolerated in healthy subjects.