Construction of a prognostic model for lung adenocarcinoma based on m6A/m5C/m1A genes.

BACKGROUND: Developing a prognostic model for lung adenocarcinoma (LUAD) that utilizes m6A/m5C/m1A genes holds immense importance in providing precise prognosis predictions for individuals. METHODS: This study mined m6A/m5C/m1A-related differential genes in LUAD based on public databases, identified LUAD tumor subtypes based on these genes, and further built a risk prognostic model grounded in differential genes between subtypes. The immune status between high- and low-risk groups was investigated, and the distribution of feature genes in tumor immune cells was analyzed using single-cell analysis. Based on the expression levels of feature genes, a projection of chemotherapeutic and targeted drugs was made for individuals identified as high-risk. Ultimately, cell experiments were further verified. RESULTS: The 6-gene risk prognosis model based on differential genes between tumor subtypes had good predictive performance. Individuals classified as low-risk exhibited a higher (P < 0.05) abundance of infiltrating immune cells. Feature genes were mainly distributed in tumor immune cells like CD4+T cells, CD8+T cells, and regulatory T cells. Four drugs with relatively low IC50 values were found in the high-risk group: Elesclomol, Pyrimethamine, Saracatinib, and Temsirolimus. In addition, four drugs with significant positive correlation (P < 0.001) between IC50 values and feature gene expression were found, including Alectinib, Estramustine, Brigatinib, and Elesclomol. The low expression of key gene NTSR1 reduced the IC50 value of irinotecan. CONCLUSION: Based on the m6A/m5C/m1A-related genes in LUAD, LUAD patients were divided into 2 subtypes, and a m6A/m5C/m1A-related LUAD prognostic model was constructed to provide a reference for the prognosis prediction of LUAD.

Novel risk prediction models, involving coagulation, thromboelastography, stress response, and immune function indicators, for deep vein thrombosis after radical resection of cervical cancer and ovarian cancer.

This study aimed to investigate the predictive value of coagulation, thromboelastography, stress response, and immune function indicators for the occurrence of deep venous thrombosis (DVT) following radical resection of cervical cancer and ovarian cancer. We conducted a prospective, single-centre, case-control study that included 230 cervical cancer patients and 230 ovarian cancer patients. In the testing cohort, the final predictive model for cervical cancer patients was: Logit(P)=9.365-0.063(R-value)-0.112(K value) +0.386(α angle)+0.415(MA)+0.276(FIB)+0.423(D-D)+0.195(IL-6)+0.092(SOD). For ovarian cancer patients, the final model was: Logit(P)= -2.846-0.036(R-value)-0.157(K value) +0.426(α angle) +0.172(MA) +0.221(FIB)+0.375(CRP) -0.126(CD4+/CD8+). In the validation cohort, these models exhibited good predictive efficiency, with a false-positive rate of 12.5% and a false-negative rate of 2.9% for cervical cancer patients, and a false-positive rate of 14.3% and a false-negative rate of 0% for ovarian cancer patients. In conclusion, the risk prediction models developed in this study effectively improve the predictive accuracy of DVT following radical resection of cervical and ovarian cancer.

Construction of a diagnostic classifier for cervical intraepithelial neoplasia and cervical cancer based on XGBoost feature selection and random forest model.

BACKGROUND: The pathological phenotype of early-stage cervical cancer (CC) is similar to that of cervical intraepithelial neoplasia (CIN), which provides a challenge for the diagnosis of cervical precancerous lesions. Meanwhile, the existing diagnostic methods have certain subjectivity and limitations, resulting in the possibility of misdiagnosis or missed diagnosis. Hence, some methods are needed to assist diagnosis of CC and CIN. METHODS: Based on the data of CIN and CC in gene expression omnibus (GEO) dataset, the eXtreme Gradient Boosting (XGBoost) algorithm was used to screen the feature genes between CIN and CC for constructing the classifier. Incremental feature selection (IFS) curve was also used for screening. The classifier was validated for reliability using principal component analysis (PCA) dimensionality reduction analysis and heat map analysis of gene expression. Then, differentially expressed genes of CIN and CC were intersected with the classifier genes. Genes in the intersection were used as seeds for protein-protein interaction network construction and restart random walk analysis. And the genes with the top 50 affinity coefficients were selected for gene ontology (GO) and kyoto encyclopedia of genes and genome (KEGG) enrichment analyses to observe the biological functions with differences between CIN and CC. RESULTS: The peripheral blood genes of CIN and CC were analyzed, and seven genes were screened. Using this gene for classifier construction, IFS curve screening revealed that the three-feature gene classifier constructed according to the random forest model had the best effect. The results of PCA dimensionality reduction analysis and gene expression heat map analysis showed that the three-gene classifier could effectively distinguish CIN from CC. CONCLUSION: A three-gene diagnostic classifier can effectively distinguish CIN patients from CC patients and provide a reference for the clinical diagnosis of early CC.

Evaluating the use of fibrin glue for sealing low-output enterocutaneous fistulas: study protocol for a randomized controlled trial.

BACKGROUND: The management of an enterocutaneous fistula poses a significant challenge to surgeons and is often associated with a costly hospital stay and long-term discomfort. The use of fibrin glue in the fistula tract has been shown to promote closure of low output enterocutaneous fistulas. Our previous nonrandomized study demonstrated that autologous platelet-rich fibrin glue treatment significantly decreased time to fistula closure and promoted closure rates. However, there are several limitations in the study, which may lead to bias in our conclusion. Thus, a multicenter, randomized, controlled clinical trial is required. METHODS/DESIGN: The study is designed as a randomized, open-label, three-arm, multicenter study in nine Chinese academic hospitals for evaluating the efficacy and safety of fibrin glue for sealing low-output fistulas. An established number of 171 fistula patients will undergo prospective random assignment to autologous fibrin glue, commercial porcine fibrin sealants or drainage cessation (1:1:1). The primary endpoint is fistula closure time (defined as the interval between the day of enrollment and day of fistula closure) during the 14-day treatment period. DISCUSSION: To our knowledge, this is the first study to evaluate the safety and efficacy of both autologous and commercial fibrin glue sealing for patients with low-output volume fistulas. TRIAL REGISTRATION: NCT01828892 . Registration date: April 2013.

[Risk factors of surgical site infection in definitive surgery of intestinal fistulas].

OBJECTIVE: To investigate the risk factors of surgical site infection (SSI) in definitive surgery of intestinal fistulas. METHODS: Patients with gastrointestinal fistula undergoing definitive operation during November 2011 to November 2013 in Jinling Hospital were prospectively enrolled in the study. Risk factors of SSI were analyzed. Patients' characteristics, surgery-related data and fistula-related data were prospectively collected. Risk factors of SSI were analyzed. RESULTS: A total of 191 cases were enrolled and 51 cases developed SSI. Univariate analysis showed that patients with risk index category (RIC)≥2, length of abdominal incisions>15 cm, and duration of drainage tubes>10 days had significantly higher incidence of SSI (P<0.05). Multivariate Logistics analysis demonstrated that RIC and duration of drainage tube were independent risk factors for SSI (P=0.02, P=0.01, respectively). CONCLUSIONS: RIC≥2 and duration of drainage tubes>10 days are independent risk factors for development of SSI.

Fistula output microorganism-susceptible antimicrobial prophylaxis is associated with a lower risk of surgical site infection in gastrointestinal fistula patients undergoing one-stage definitive surgery.

BACKGROUND: Empiric broad-spectrum antimicrobial prophylaxis (AMP) may not be sufficient to minimize the risk of surgical site infections (SSIs) after definitive surgical treatment of gastrointestinal (GI) fistula. This study investigates whether AMP targeted toward fistula microbiology is associated with a lower risk of SSIs in GI fistula patients undergoing one-stage definitive surgery. METHODS: Fistula output was sampled from the abdominal fistula opening for microbial growth and drug sensitivity prior to surgery. The primary outcome measure was the overall incidence rate of SSIs. RESULTS: A total of 191 patients were examined. Pre-operative microbial culture identified microbial growth in 149 patients (76.0%). Post-operative SSIs occurred in 51 patients (26.7%). Risk index category, abdominal incision length, and time of peritoneal drain removal had significantly negative impacts on SSIs frequency. Sensitive AMP agents were associated with a significantly lower risk of SSIs, compared with insensitive AMP agents, but with a similar risk to indefinite AMP agents (23.2% vs. 45.2% vs. 23.1%; odds ratio [95% confidence interval]: 2.724 [1.063, 6.979], p=0.034; 1.008 [0.467-2.177], p=0.984). CONCLUSIONS: Antimicrobial prophylaxis targeted toward fistula output AMP may minimize the occurrence of SSIs after one-stage definitive surgical treatment of GI fistula.

[Protein loss in critically ill patients during continuous veno-venous hemofiltration].

OBJECTIVE: To evaluate protein loss in critically ill patients with acute renal failure during continuous veno-venous hemofiltration (CVVH) and analysis the major factor impacting protein clearance. METHODS: A analysis was carried out in eighteen (twelve male and six female) sepsis or severe acute pancreatitis patients with acute renal failure from September 2008 to September 2009. The average age was 45 years (39 - 62 years). CVVH was conducted for 24 h in all patients. Effluent volume, blood speed, ultrafiltration rate and transmembrane pressure (TMP) were 4000 ml/h, (277 ± 89) ml/h, (179 ± 4) ml/min and (173 ± 48) mm Hg (1 mm Hg = 0.133 kPa) respectively. Blood samples were collected before and after filtration in order to detect protein concentration. Ultrafiltrate was obtained hourly to measure protein concentration and calculate protein loss during session. RESULTS: Mean protein concentration was (231 ± 67) mg/L and protein loss was (22 ± 6) g/d in ultrafiltrate samples. The difference in serum protein level during hemofiltration was not significant [(56 ± 6) g/L vs. (55 ± 10) g/L, P > 0.05], while there was a weak, but statistically significant correlation between the ultrafiltrate protein concentration and the corresponding value for serum protein (r = 0.481, P < 0.05). However, there was a strong and statistically significant correlation between the ultrafiltrate protein concentration and the TMP (r = 0.564, P < 0.01). Stepwise multiple regression analysis showed that TMP and serum protein concentration played a pivotal role in ultrafiltrate protein loss. CONCLUSIONS: In addition to renal replacement therapy, serum protein would be cleared through hemofilter during CVVH. TMP and serum protein concentration are the main factors that affect protein loss in ultrafiltrate. As a result, it is necessary to take account of the protein loss in ultrafiltrate when setting nutritional schedule.

Effects of glutamine supplementation on patients undergoing abdominal surgery.

OBJECTIVE: To evaluate the effects of supplementation of glutamine (GLN) on maintaining glutathione (GSH) level, immune system function, liver function, and clinical outcome of patients receiving abdominal operation. METHODS: Forty patients undergoing elective abdominal surgical treatment were randomly divided into 2 groups: study group (n = 20) and control group (n = 20). All patients received total parenteral nutrition (TPN) for up to 7 days during perioperative period. The study group received TPN supplemented with GLN dipeptide while the control group received TPN without GLN dipeptide. Patients in both groups received equivalent nitrogen and caloric intake. Blood sample was taken on preoperative day, and the 1st, 3rd, 6th postoperative day to measure GSH level, immune indexes, and liver function indexes. RESULTS: The decrease of GSH level in plasma and red blood cell (RBC) in study group was less than that in control group during postoperative period. Ratio of GSH/glutathione disulfide (GSSG) in plasma in study group was higher than that in control group on the 3rd postoperative day (52.53 +/- 11.46 vs. 31.43 +/- 7.27, P = 0.001). Albumin level in study group was higher than that in control group on the 3rd postoperative day (37.7 +/- 3.8 g/L vs. 33.8 +/- 4.2 g/L, P = 0.02). There was no significant difference in the levels of immunoglobin (IgG, IgM, IgA) or T lymphocyte subgroup (CD4, CD8, CD4/CD8) in both groups during postoperative period. There was one case with infectious complication in control group, while none in study group. A trend of shortened hospital stay was observed in study group compared with control group (22.3 +/- 2.1 d vs. 24.9 +/- 1.7 d, P = 0.32). CONCLUSIONS: Supplementation of GLN-enriched TPN has beneficial effects on maintaining GSH levels in plasma and RBC, sustaining GSH/GSSG ratio and albumin level, and keeping antioxidant abilities during postoperative period in patients with abdominal operation, with the trends of decreasing incidence of infectious complication and shortening hospital stay.

[Noninvasive quantification of glutamine and glutamate in skeletal muscles of perioperative rabbits with proton magnetic resonance spectroscopy].

OBJECTIVE: To evaluate the feasibility of noninvasive quantification of the metabolic changes of glutamine (Gln) and glutamate (Glu) in the skeletal muscles caused by abdominal surgery with proton magnetic resonance spectroscopy (MRS). METHODS: Abdominal surgery were performed on 15 healthy Zelanian rabbits. MRS data, blood specimens, and muscular tissues were obtained on the day before surgery and the second day after surgery. MRS data included peak amplitude and peak area of Gln + Glu (Glx) and total creatine (TCr). The reproducibility of peak amplitude with peak area was compared and the better one was chosen to calculate the ratio of Glx to TCr. Free Gln and Glu concentrations in serum and muscles were analyzed by reversed phase high-performance liquid chromatography (RP-HPLC). The results of MRS were compared with those of RP-HPLC to evaluate the feasibility of MRS application in Gln and Glu metabolism. RESULTS: Peak amplitude had better reproducibility than peak area under our conditions. The coefficient of variation (CV) of the ratio of the amplitude of Glx to TCr was (15.62 +/- 9.87)%. The ratio of the amplitude of Glx to TCr significantly decreased on the second day after surgery (P <0.05, P <0.01). The mean free Glx concentrations in both the serum and the muscles different were not significant between on the second day after surgery and on the day before surgery. CONCLUSIONS: The results of MRS application in reflecting the effects of surgical trauma on muscular Glx metabolism are consistent with those of RP-HPLC. It is feasible to apply MRS in the study of muscular Gln and Glu metabolism.

[Measurement of glutamine concentration in Zelanian rabbits' skeletal muscle by non-invasive magnetic resonance spectroscopy].

OBJECTIVE: To study the feasibility of non-invasive magnetic resonance spectroscopy (MRS) in measuring glutamine (GLN) level in Zelanian rabbits' skeletal muscle. METHODS: Non-invasive MRS was used to get the data of peak height ratio of GLN + glutamic acid (GLx) at 3.8 ppm and creatine (Cr) at 3.0 ppm, peak area ratio of GLx at 3.8 ppm and Cr at 3.0 ppm. High performance liquid chromatography (HPLC) was used to examine the actual GLx levels of muscle from 22 Zelanian rabbits. The feasibility of MRS was then evaluated by HPLC method. RESULTS: The ratio of peak height and peak area of GLx and Cr by means of MRS were 0.162 +/- 0.045 and 0.092 +/- 0.065, respectively. The average concentration of GLx in skeletal muscle by means of HPLC was (4.19 +/- 2.50) micromol/g. The ratio of GLx and plasma Cr level by means of HPLC was 4.576 -/+ 0.599. The ratio of peak height and peak area of GLx and Cr by means of MRS were correlated significantly with the ratio of concentration of GLx in skeletal muscle and plasma Cr by means of HPLC (r = 0.7, P = 0.001; r = 0.6, P = 0.001). CONCLUSION: Non-invasive MRS is feasible to measure GLN level in skeletal muscle of rabbit.

[Effect of combination of glutamine and mitomycin C on human gastric carcinoma cell strain MGC-803].

OBJECTIVE: To evaluate the effect of combination of glutamine (GLN) and mitomycin C (MMC) on the human gastric carcinoma cell line MGC-803 in vitro. METHODS: The effects of GLN and MMC were measured by MTT assay, and the interaction between the two agents was evaluated by the median-effect principle. Flow cytometry was used for cell cycle analysis. RESULTS: GLN did not significantly stimulate the cell growth in vitro. High-concentration of GLN could inhibit the cell growth. MMC could effectively inhibit the cell growth in a time-dependent manner. The interaction of these two agents showed a weak antagonistic activity (1 < CI < 1.2703). MMC induced remarkable S-phase arrest. Low-dose GLN has limited effect on the S-phase arrest of MMC, while high-dose GLN significantly attenuated the S-phase arrest and lowered the proliferation index of MGC-803 cell. CONCLUSIONS: Combination of GLN and MMC has a a weak and dose-dependent antagonistic activity in the treatment of gastric carcinoma cell line MGC-803. The combination of high-dose MMC and low-dose GLN may achieve better efficacy.

[Effects on glutathione of patients received glutamine dipeptide enriched parenteral nutrition post abdominal surgery].

OBJECTIVE: To observe the effects of glutamine (GLN) enriched parenteral nutrition (PN) on glutathione level, immune function, liver function, infectious complication and hospital stay of patients undergone abdominal operation. METHODS: Forty patients with abdominal surgical disease undergoing elective surgical treatment were randomly divided into two groups (study and control group). All patients received total parenteral nutrition (TPN) for up to 7 days perioperatively. The control group received TPN while the study group received TPN including GLN dipeptide. Both groups received isonitrogen and isocaloric nutrition. Nonprotein caloric intake is 83.6 kJ.kg(-1).day(-1), glycogen: lipid ratio is 7:5, nitrogen intake is 0.16 g.kg(-1).d(-1), calories:nitrogen ratio is 489 kJ:1 g. RESULTS: The decreasing degree of glutathione levels of plasma and red blood cell in study group is lower than that in control group postoperatively. GSH/GSSG ratio of plasma in study group is higher than that in control group on 3rd day postoperatively (53 +/- 11 vs 31 +/- 7, F = 4.725, P = 0.001). Albumin (ALB) of both groups decreased slightly postoperatively. ALB level of study group was higher than that of control group on 3rd day postoperatively [(3.8 +/- 0.4) g.dl(-1) vs (3.4 +/- 0.4) g.dl(-1), F = 2.128, P = 0.02]. No significant differences were noted between immunoglobin (IgG, IgM and IgA) and T lymphocyte subgroup (CD4, CD8, CD4/CD8) levels of both groups postoperatively. There was no infectious complication in study group, while one in control group. There was shorten trend of hospital stay in study group compared with control group [(22.3 +/- 2.1) d vs (24.9 +/- 1.7) d, t = -0.935, P = 0.32]. CONCLUSIONS: Glutamine enriched PN has the trend of maintaining glutathione level of plasma and red blood cell in patients having undergone abdominal operation, and can sustain GSH/GSSG ratio and ALB level, protect antioxidant ability, promote liver function postoperatively. Glutamine enriched PN has the trend of shortening hospital stay, decreasing incidence of infectious complication.