Protein Profiles and Novel Molecular Biomarkers of Schizophrenia Based on 4D-DIA Proteomics.

Schizophrenia is a severe psychological disorder. The current diagnosis mainly relies on clinical symptoms and lacks laboratory evidence, which makes it very difficult to make an accurate diagnosis especially at an early stage. Plasma protein profiles of schizophrenia patients were obtained and compared with healthy controls using 4D-DIA proteomics technology. Furthermore, 79 DEPs were identified between schizophrenia and healthy controls. GO functional analysis indicated that DEPs were predominantly associated with responses to toxic substances and platelet aggregation, suggesting the presence of metabolic and immune dysregulation in patients with schizophrenia. KEGG pathway enrichment analysis revealed that DEPs were primarily enriched in the chemokine signaling pathway and cytokine receptor interactions. A diagnostic model was ultimately established, comprising three proteins, namely, PFN1, GAPDH and ACTBL2. This model demonstrated an AUC value of 0.972, indicating its effectiveness in accurately identifying schizophrenia. PFN1, GAPDH and ACTBL2 exhibit potential as biomarkers for the early detection of schizophrenia. The findings of our studies provide novel insights into the laboratory-based diagnosis of schizophrenia.

Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients: A retrospective cohort study.

BACKGROUND: Early systemic anticoagulation (SAC) is a common practice in acute necrotizing pancreatitis (ANP), and its impact on in-hospital clinical outcomes had been assessed. However, whether it affects long-term outcomes is unknown. This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients. METHODS: During January 2013 and December 2018, ANP patients admitted within 7 days from the onset of abdominal pain were screened. The primary outcome was 90-day readmission after discharge. Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission. RESULTS: A total of 241 ANP patients were enrolled, of whom 143 received early SAC during their hospitalization and 98 did not. Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis (SVT) [risk ratio (RR) = 0.40, 95% CI: 0.26-0.60, P < 0.01] and lower 90-day readmission with an RR of 0.61 (95% CI: 0.41-0.91, P = 0.02) than those who did not. For the quality of life, patients who received early SAC had a significantly higher score in the subscale of vitality (P = 0.03) while the other subscales were all comparable between the two groups. Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57 (95% CI: 0.34-0.96, P = 0.04). Mediation analysis showed that SVT mediated 37.0% of the early SAC-90-day readmission causality. CONCLUSIONS: The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients, and reduced SVT incidence might be the primary contributor.

Auricular Vagal Nerve Stimulation Inhibited Central Nerve Growth Factor/Tropomyosin Receptor Kinase A/Phospholipase C-Gamma Signaling Pathway in Functional Dyspepsia Model Rats With Gastric Hypersensitivity.

OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.

Risk factor analysis for adverse prognosis of the fetal ventricular septal defect (VSD).

BACKGROUND: Ventricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses. METHODS: Fetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated. RESULTS: Chromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome. CONCLUSIONS: The current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence.

[Clinical Outcome and Risk Factors of Treatment Failure of Peritoneal Dialysis Associated Peritonitis Caused by Klebsiella Pneumoniae:A Multicenter Study].

Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.

A Fibrosis-Independent Hepatic Transcriptomic Signature Identifies Drivers of Disease Progression in Primary Sclerosing Cholangitis.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a heterogeneous cholangiopathy characterized by progressive biliary fibrosis. RNA sequencing of liver tissue from patients with PSC (n = 74) enrolled in a 96-week clinical trial was performed to identify associations between biological pathways that were independent of fibrosis and clinical events. APPROACH AND RESULTS: The effect of fibrosis was subtracted from gene expression using a computational approach. The fibrosis-adjusted gene expression patterns were associated with time to first PSC-related clinical event (e.g., cholangitis, hepatic decompensation), and differential expression based on risk groups and Ingenuity Pathway Analysis were performed. Baseline demographic data were representative of PSC: median age 48 years, 71% male, 49% with inflammatory bowel disease, and 44% with bridging fibrosis or cirrhosis. The first principle component (PC1) of RNA-sequencing data accounted for 18% of variance and correlated with fibrosis stage (ρ = -0.80; P < 0.001). After removing the effect of fibrosis-related genes, the first principle component was not associated with fibrosis (ρ = -0.19; P = 0.11), and a semisupervised clustering approach identified two distinct patient clusters with differential risk of time to first PSC-related event (P < 0.0001). The two groups had similar fibrosis stage, hepatic collagen content, and α-smooth muscle actin expression by morphometry, Enhanced Liver Fibrosis score, and serum liver biochemistry, bile acids, and IL-8 (all P > 0.05). The top pathways identified by Ingenuity Pathway Analysis were eukaryotic translation inhibition factor 2 (eIF2) signaling and regulation of eIF4/p70S6K signaling. Genes involved in the unfolded protein response, activating transcription factor 6 (ATF6) and eIF2, were differentially expressed between the PSC clusters (down-regulated in the high-risk group by log-fold changes of -0.18 [P = 0.02] and -0.16 [P = 0.02], respectively). Clinical events were enriched in the high-risk versus low-risk group (38% [12/32] vs. 2.4% [1/42], P < 0.0001). CONCLUSIONS: Removing the contribution of fibrosis-related pathways uncovered alterations in the unfolded protein response, which were associated with liver-related complications in PSC.

Regression of Left Ventricular Hypertrophy in Patients Combined with Peritoneal Dialysis and Hemodialysis.

Methods: This retrospective study enrolled 58 patients at The Second Affiliated Hospital of Soochow University who switched from PD to PHD. Clinical data and echocardiographic examination results were collected. Data from the two groups with a normal distribution were compared with the paired t-test. A pvalue <0.05 (two-tailed) was considered statistically significant. Results: A total of 58 subjects were enrolled, including 46 males and 12 females, with a median age of 50.2 ± 11.1 (47-68) years. The mean duration of peritoneal dialysis was 67.2 ± 33.6 months. Before and after PHD, the ultrafiltration volume (p = 0.021) and hemoglobin (p = 0.001) were increased, while SBP (p = 0.002), DBP (p = 0.002), phosphorus (p < 0.001), and ESA dosage (p < 0.001) were decreased. Before and after combined dialysis (PHD), the incidence of LVH was 76.4% and 61.8%, respectively (p = 0.013), and LVMI decreased from 173.8 ± 86.2 g/m2 to 160.6 ± 78.5 g/m2 (p < 0.001). Conclusion: Compared with PD alone, the combination of PD and HD resulted in regression of LVH and reduced LVMI.

Management of colonic fistulas in patients with infected pancreatic necrosis being treated with a step-up approach.

BACKGROUND: Colonic fistula is a potentially fatal complication in acute necrotizing pancreatitis (ANP), especially in patients with infected pancreatic necrosis (IPN). The aim of this study was to evaluate the feasibility of a step-up approach including percutaneous catheter drainage (PCD) and continuous negative pressure irrigation (CNPI) in a group of patients with colonic fistula. METHODS: A retrospective review of a prospectively collected data was performed. Data were extracted for patients complicated by colonic fistula from January 2010 to January 2017. RESULTS: A total of 1750 patients were admitted with ANP during the study period. Of these patients, 711 (41%) developed IPN and colonic fistula was present in 132 (19%). A step-up approach was adopted for all patients, with 47% avoiding surgery. The mortality in patients requiring surgery (37%) was higher than that in patients managed non-surgically (19%) constituting an overall mortality rate of 29%. In patients managed conservatively, 92% had spontaneous closure of the fistula. CONCLUSION: Colonic fistula is not a rare complication in ANP occurring in 19% of patients with IPN in the current study. A step-up approach was effective and safe in managing colonic fistula and surgery could be obviated in nearly half of the patients.

[Study on quality standard of fried Vaccariae Semen standard decoction].

According to the preparation principle of standard decoction of Chinese herbal medicines, fourteen batches of fried Vaccariae Semen decoction were prepared in this study and the quality research was carried out to establish a quality evaluation method for the standard decoction of fried Vaccariae Semen. The contents of vaccarin were determined, and its transfer rate from decoction piece to standard decoction was calculated. The extract rate and pH value were measured, and HPLC fingerprint method was established for analysis. The results of the 14 batches of samples revealed that the transfer rates of vaccarin were between 58.98%-93.94%; the extract rates were between 8.67%-17.83%, and the pH values were between 5.55-6.44. Moreover, 9 common chromatographic peaks were identified in fingerprints analysis. The similarities of the 14 batches of samples were analyzed and compared, and the results showed that the similarities were all higher than 0.96. In this study, the preparation process for fried Vaccariae Semen standard decoction was standard, with high similarities in fingerprint. A convenient and reliable method of comprehensive quality evaluation was established in this study, with a high precision, stability and repeatability, which can provide a reference for the quality control of fried Vaccariae Semen standard decoction, dispensing granule and related Chinese classical formulas(decoction).

MicroRNA-329 upregulation impairs the HMGB2/ß-catenin pathway and regulates cell biological behaviors in melanoma.

Melanoma is responsible for the majority of deaths caused by skin cancer. Antitumor activity of microRNA-329 (miR-329) has been seen in several human cancers. In this study, we identify whether miR-329 serves as a candidate regulator in melanoma. Melanoma-related differentially expressed genes were screened with its potential molecular mechanism predicted. Melanoma tissues and pigmented nevus tissues were collected, where the levels of miR-329 and high-mobility group box 2 (HMGB2) were determined. To characterize the regulatory role of miR-329 on HMGB2 and the ß-catenin pathway in melanoma cell activities, miR-329 mimics, miR-329 inhibitors, and siRNA-HMGB2 were transfected into melanoma cells. Cell viability, migration, invasion, cell cycle, and apoptosis were assessed. miR-329 was predicted to influence melanoma by targeting HMGB2 via the ß-catenin pathway. High level of HMGB2 and low miR-329 expression were observed in melanoma tissues. HMGB2 was targeted and negatively regulated by miR-329. In melanoma cells transfected with miR-329 mimics or siRNA-HMGB2, cell proliferation, migration, and invasion were impeded, yet cell cycle arrest and apoptosis were promoted, corresponding to decreased levels of ß-catenin, cyclin D1, and vimentin and increased levels of GSK3ß and E-cadherin. Collectively, our results show that miR-329 can suppress the melanoma progression by downregulating HMGB2 via the ß-catenin pathway.

Pollinator effectiveness and importance between female and male mining bee (Andrena).

Bees are often considered to be effective pollinators in both agricultural and natural ecosystems but could be ineffective pollinators in that they collect large quantities of pollen for food provision but deliver little to stigmas. Male bees do not collect pollen to feed larvae, and their pollination role has been underappreciated. Here we compare pollination effectiveness, visit frequency and pollen foraging behaviour between female and male individuals of a mining bee, Andrena emeishanica, visiting a nectariferous spring flower (Epimedium pubescens). Female bees were observed to forage for both pollen and nectar, but male bees foraged only for nectar. Female bees had large hairy hind tibiae with conspicuous scopae, and nearly 90% of the pollen grains they collected went onto the hind legs. Male bees removed less pollen from anthers than female bees but deposited more pollen on stigmas per visit. The higher pollen transfer efficiency of male bees was due to 48.4% of pollen grains remaining ungroomed on the thorax and abdomen, available for stigma contact, but their visitation rate to flowers was much lower. Our results indicate that male solitary bees could transfer more pollen on the stigma per visit but were less important (transferred less pollen in total, because they made fewer visits per unit time) than females.

[Data-mining characteristics of adverse drug reactions and pharmacovi-gilance of Chinese patent drugs including Aconitum herbs].

The common Aconitum herbs in clinical application mainly include Aconiti Radix(Chuanwu), Aconiti Kusnezoffii Radix(Caowu) and Aconiti Lateralis Radix Praeparaia(Fuzi), all of which have toxicity. Therefore, the safety of using Chinese patent drugs including Aconitum herbs has become an hot topic in clinical controversy. Based on the data-mining methods, this study explored the characteristics and causes of adverse drug reactions/events (ADR/ADE) of the Chinese patent drugs including Aconitum, in order to provide pharmacovigilance and rational drug use suggestions for clinical application. The detailed ADR/ADE reports about the Chinese patent drugs including Aconitum herbs were retrieved in the domestic literature databases since 1984 to now. The information extraction and data-mining were conducted based on the platforms of Microsoft office Excel 2016, Clementine 12.0 and Cytoscape 3.3.0. Finally, 78 detailed ADR/ADE reports involving a total of 30 varieties were included. 92.31% ADR/ADE were surely or likely led by the Chinese patent drugs including Aconitum, mostly involving multiple system/organ damages with good prognosis, and even 1 case of death. The incidence of included ADRs/ADEs was associated with various factors such as the patient idiosyncratic, drug toxicity, as well as clinical medication. The patient age was most closely related to ADR/ADEs, and those aged from 60 to 69 were more easily suffered from the ADRs/ADEs of Chinese patent drugs including Aconitum. The probability of ADR/ADEs for the drugs including Chuanwu or Caowu was greater than that of Fuzi, and the using beyond the instructions dose was the most important potential safety hazard in the clinical medication process. For the regular and characteristics of ADR/ADEs led by Chinese patent drugs including Aconitum, special attention shall be paid to the elder patients or with the patients with allergies; strictly control the dosage and course of treatment, strengthen the safety medication education to public, and avoid misuse or abuse to ensure rational drug use.

Comparison of Ultrasound Features of Primary Metastatic Papillary Thyroid Carcinoma and Recurrent/Persistent Metastatic Cervical Lymph Nodes.

Objective To explore the ultrasound features and levels of cervical lymph node metastases in primary and recurrent/persistent papillary thyroid cancer (PTC).Methods We retrospectively analyzed the clinical data of 2181 patients who underwent cervical lymph nodes dissection for PTC from January 1st 2015 to January 1st 2016.Totally 418 PTC patients (with 622 lymph nodes) who met the inclusion criteria entered the final analysis.Patients who had not received any prior thyroid treatment (surgery with or without radioactive iodine) were categorized as the primary group (352 patients with 527 metastatic lymph nodes),and patients who had received prior treatment (thyroidectomy with or without radioactive iodine) for PTC were categorized as recurrent/persistent group (66 patients with 95 metastatic lymph nodes).Pathological results from lymph node dissections were used as the gold standards by means of level-to-level analysis.Results The mean of the minimum axis diameter of the lymph nodes in the primary group was (6.7±3.6)mm,and that of the recurrent/persistent group was (6.6±3.1)mm (U=0.180,P=0.857).The proportion of metastasis in the central area of primary group was 40.0%,which was significantly higher than that in the recurrent/persistent group (12.6%);the proportion of metastasis in the lateral area was 60.6% in the primary group,which was significantly lower than that in the recurrent/persistent group (87.4%)(χ2=26.288,P<0.001).In lateral metastatic lymph nodes,Ⅲ level was the most common place in both groups.Level Ⅴ metastatic lymph was rare in both primary group and recurrent/persistent group.Calcifications (63.1% vs. 48.2%;χ2=7.207,P=0.007) and peripheral vascularity (81.1% vs. 59.4%;χ2= 16.147, P<0.001) were more common in the recurrent/persistent group.The round shape,absence of an echogenic hilum,hyperechogenicity,and cystic aspects were not significantly different between these two groups (all P>0.05).Conclusions Primary metastatic lymph nodes often occur in the central area of lymph nodes,while lateral metastatic lymph nodes are more common in recurrent/persistent PTC.For metastatic lymph nodes,calcifications and peripheral vascularity are more common in recurrent/persistent PTC.

[Identification of biomarkers in urine of rats with spleen Qi deficiency and biological significance].

To identify biomarkers for spleen Qi deficiency by analyzing small molecule metabolites in urine, in order to expound the relationship between biomarkers and metabolic pathways. The spleen Qi deficiency model was established through dietary restriction and overstrain. All of the rats received D-xylose absorption experiment and blood routine test. Urine samples were collected in the next day. The urine samples were analyzed using UPLC-Q-TOF-MS to obtain the dataset of urine metabolic group. Principal component analysis (PCA), orthogonal partialleast squares-discriminant analysis (OPLS-DA) and other multivariate statistical methods were employed to evaluate the quality of the dataset and screen out potential biomarkers of spleen Qi deficiency. The results of D-xylose absorption and blood routine demonstrated that the spleen Qi deficiency model was successfully established. In positive ion mode and negative ion mode, PCA and OPLS-DA score plots could clearly distinguish model group and blank group. According to S-plot of OPLS-DA, VIP value, t-test and area under receiver operating characteristic curve (ROC), 24 biomarkers, including phenylalanine, succinic acid, aconitic acid, isocitrate acid, betaine, kynurenine, indole, creatine, creatinine, orotic acid, xanthine, and xanthurenic acid, were identified as associated with the spleen Qi deficiency, mainly involving energy metabolism, amino acid metabolism, tryptophan metabolism, purine metabolism and pyrimidine metabolism. Urine metabolomics method combined with online software package for data processing and analysis metabolic pathway can provide new methods and ideas for studies for spleen Qi deficiency and other traditional Chinese medicine symptoms.

[Research on fast detecting tomato seedlings nitrogen content based on NIR characteristic spectrum selection].

In order to improve the accuracy and robustness of detecting tomato seedlings nitrogen content based on near-infrared spectroscopy (NIR), 4 kinds of characteristic spectrum selecting methods were studied in the present paper, i. e. competitive adaptive reweighted sampling (CARS), Monte Carlo uninformative variables elimination (MCUVE), backward interval partial least squares (BiPLS) and synergy interval partial least squares (SiPLS). There were totally 60 tomato seedlings cultivated at 10 different nitrogen-treatment levels (urea concentration from 0 to 120 mg . L-1), with 6 samples at each nitrogen-treatment level. They are in different degrees of over nitrogen, moderate nitrogen, lack of nitrogen and no nitrogen status. Each sample leaves were collected to scan near-infrared spectroscopy from 12 500 to 3 600 cm-1. The quantitative models based on the above 4 methods were established. According to the experimental result, the calibration model based on CARS and MCUVE selecting methods show better performance than those based on BiPLS and SiPLS selecting methods, but their prediction ability is much lower than that of the latter. Among them, the model built by BiPLS has the best prediction performance. The correlation coefficient (r), root mean square error of prediction (RMSEP) and ratio of performance to standard derivate (RPD) is 0. 952 7, 0. 118 3 and 3. 291, respectively. Therefore, NIR technology combined with characteristic spectrum selecting methods can improve the model performance. But the characteristic spectrum selecting methods are not universal. For the built model based or single wavelength variables selection is more sensitive, it is more suitable for the uniform object. While the anti-interference ability of the model built based on wavelength interval selection is much stronger, it is more suitable for the uneven and poor reproducibility object. Therefore, the characteristic spectrum selection will only play a better role in building model, combined with the consideration of sample state and the model indexes.

In vivo study of the effect of combining endostatin gene therapy with 32P-colloid on hepatocarcinoma and its functioning mechanism.

PURPOSE: To investigate the therapeutic effect of combining 32P colloid radiotherapy with endostatin anti-angiogenesis therapy on hepatocellular carcinoma (HCC) cells. METHODS: HCC mouse models were prepared using H22 cells and randomly divided into four groups. The mice were administered phosphate buffered saline (PBS), (32)Pcolloid, secretory endostatin encoding plasmid and combination of 32P and endostatin, respectively. Seven, 14 and 21 days after treatment the mice were sacrificed. Expression of endostatin was confirmed using western blot. Tumor growth rate, microvessel density (MVD) in the solid tumor and apoptotic index (AI) of tumor cells was analyzed using immunohistochemistry and TUNEL methods. RESULTS: (1): From the western blot results, 1400 bp endostatin specific protein bands were observed in the samples from groups 3 and 4, but not in the other two groups; (2): The tumor growth rate of groups 2, 3 and 4 was significantly decreased compared to group 1 and that of group 4 was significantly lower than group 2 and 3 (3): The MVD of group 1 was greatly higher than in the other groups (4): The AI of group 4 was dramatically higher than in the other groups. CONCLUSIONS: (32)Pcolloid radiotherapy or endostatin anti-angiogenesis therapy were able to inhibit the growth of HCC cells in vivo, while the combination of (32)P and endostatin showed much better therapeutic effect in HCC treatment.

Survey and analysis of the current state of residency training in medical-school-affiliated hospitals in China.

BACKGROUND: Since the global standards for postgraduate medical education (PGME) were published in January 2003, they have gained worldwide attention. The current state of residency training programs in medical-school-affiliated hospitals throughout China was assessed in this study. METHODS: Based on the internationally recognized global standards for PGME, residents undergoing residency training at that time and the relevant residency training instructors and management personnel from 15 medical-school-affiliated hospitals throughout China were recruited and surveyed regarding the current state of residency training programs. A total of 938 questionnaire surveys were distributed between June 30, 2006 and July 30, 2006; of 892 surveys collected, 841 were valid. RESULTS: For six items, the total proportions of "basically meets standards" and "completely meets standards" were <70% for the basic standards. These items were identified in the fields of "training settings and educational resources", "evaluation of training process", and "trainees". In all fields other than "continuous updates", the average scores of the western regions were significantly lower than those of the eastern regions for both the basic and target standards. Specifically, the average scores for the basic standards on as many as 25 of the 38 items in the nine fields were significantly lower in the western regions. There were significant differences in the basic standards scores on 13 of the 38 items among trainees, instructors, and managers. CONCLUSIONS: The residency training programs have achieved satisfactory outcomes in the hospitals affiliated with various medical schools in China. However, overall, the programs remain inadequate in certain areas. For the governments, organizations, and institutions responsible for PGME, such global standards for PGME are a very useful self-assessment tool and can help identify problems, promote reform, and ultimately standardize PGME.

Analyzing S100A6 expression in endoscopic ultrasonography-guided fine-needle aspiration specimens: a promising diagnostic method of pancreatic cancer.

BACKGROUND AND GOALS: Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) cytology in combination with other tests is necessary to improve diagnostic accuracy. We evaluated the diagnostic utility of S100A6 expression in EUS-FNA tissue samples in pancreatic ductal adenocarcinoma (PDA). METHODS: RNA was extracted from 36 PDA and 44 nontumor pancreatic tissues obtained during surgery. S100A6 expression was quantified by real-time reverse transcription-polymerase chain reaction, and receiver operating characteristic analysis was performed to determine the cutoff value for PDA. We preoperatively performed EUS-FNA in 52 patients with pancreatic masses, then prospectively evaluated the diagnostic value of S100A6 expression of EUS-FNA samples in pancreatic cancer diagnosis. S100A6 immunohistology was conducted to validate the S100A6 expression data in PDA samples. RESULTS: Of the 52 EUS-FNA patients with pancreatic masses, RNA was successfully extracted from 44, which comprised 34 pancreatic cancer patients and 10 patients with benign pancreatic diseases. Cytology results were malignant in 23 cases, benign in 9, and atypical or abnormal in 12. The sensitivity, specificity, and accuracy of cytology for diagnosis of pancreatic cancer were 67.65%, 100%, and 75%, respectively. When an S100A6 expression >0.005248 was defined as positive for malignancy, the sensitivity, specificity, and accuracy of S100A6 expression of EUS-FNA for diagnosis of pancreatic cancer were 88.24%, 90.00%, and 88.64%, respectively. CONCLUSIONS: Quantification of S100A6 expression in EUS-FNA samples had a high sensitivity and specificity for the diagnosis of PDA.

[Effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase and S-100ß and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head].

OBJECTIVE: To explore the effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase (NSE) and S-100ß and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head. METHODS: After the approval of institutional review board and the provision of informed consent, 80 patients over 70 years old, undergoing acute replacement of femoral head under combined spinal and epidural anesthesia and midazolam sedation at Qingdao Municipal Hospital and Qingdao Hiser Medical Center from January 2011 to May 2012, were randomly assigned into control group (group C, n = 40) and parecoxib group (group P, n = 40). In group P, parecoxib sodium 20/40 mg (based on weight 50 kg) was administered via an intravenous injection after admission with 12 hours intervals for six times. In group C, morphine 2/4 mg was given initially. Additional morphine 2 mg was given to maintain the pain visual analog scale (VAS) of 3 points or less in both groups. Primary observation indices: (1) postoperative time and additional amount of morphine; (2) rate of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) at 3 days, 1 week, 3 months and 6 months postoperation (T1-T4); (3) se rum levels of NSE and S-100ß were measured at the timepoints of before analgesia (t0), before anesthesia (t1), end of surgery (t2) and 6 hours, 24 hours, 48 hours postoperation (t3-t5); (4) other serious complications. RESULTS: Compared with group C, the additional amount of morphine, postoperative time, rate of POD and POCD at T1-T4, the level of NSE at t2-t5 and S-100ß at t1-t5 were lower in group P (P < 0.05). No other serious complications were observed. CONCLUSIONS: Parecoxib sodium analgesia reduces the rate of POD and POCD in elderly patients with neuroprotective effects.

Activating transcription factor 4 drives the progression of diabetic cardiac fibrosis.

AIMS: Diabetic cardiomyopathy (DC) is one of serious complications of diabetic patients. This study investigated the biological function of activating transcription factor 4 (ATF4) in DC. METHODS AND RESULTS: Streptozotocin-treated mice and high glucose (HG)-exposed HL-1 cells were used as the in vivo and in vitro models of DC. Myocardial infarction (MI) was induced by left coronary artery ligation in mice. Cardiac functional parameters were detected by echocardiography. Target molecule expression was determined by real time quantitative PCR and western blotting. Cardiac fibrosis was observed by haematoxylin and eosin and Masson's staining. Cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labelling. Activities of superoxide dismutase, glutathione peroxidase, and levels of malonic dialdehyde and reactive oxygen species were used to assess oxidative stress damage. Molecular mechanisms were evaluated by chromatin immunoprecipitation, dual luciferase assay, and co-immunoprecipitation. ATF4 was up-regulated in the DC and MI mice (P < 0.01). Down-regulation of ATF4 improved cardiac function as evidenced by changes in cardiac functional parameters (P < 0.01), inhibited myocardial collagen I (P < 0.001) and collagen III (P < 0.001) expression, apoptosis (P < 0.001), and oxidative stress (P < 0.001) in diabetic mice. Collagen I (P < 0.01) and collagen III (P < 0.01) expression was increased in MI mice, which was reversed by ATF4 silencing (P < 0.05). ATF4 depletion enhanced viability (P < 0.01), repressed apoptosis (P < 0.001), oxidative damage (P < 0.001), and collagen I (P < 0.001), and collagen III (P < 0.001) expression of HG-stimulated HL-1 cells. ATF4 transcriptionally activated Smad ubiquitin regulatory factor 2 (Smurf2, P < 0.001) to promote ubiquitination and degradation of homeodomain interacting protein kinase-2 (P < 0.001) and subsequently caused inactivation of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathway (P < 0.001). The inhibitory effects of ATF4 silencing on HG-induced apoptosis (P < 0.01), oxidative injury (P < 0.01), collagen I (P < 0.001), and collagen III (P < 0.001) expression were reversed by Smurf2 overexpression. CONCLUSIONS: ATF4 facilitates diabetic cardiac fibrosis and oxidative stress by promoting Smurf2-mediated ubiquitination and degradation of homeodomain interacting protein kinase-2 and then inactivation of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 pathway, suggesting ATF4 as a treatment target for DC.