Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.
Female ; Humans ; Male ; Bilirubin ; Esophageal and Gastric Varices ; Gastrointestinal Hemorrhage/surgery* ; Portasystemic Shunt, Transjugular Intrahepatic ; Postoperative Period ; Retrospective Studies ; Treatment Outcome ; Adult ; Middle Aged ; Glucuronosyltransferase/genetics*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective To explore the clinicopathological features and prognosis of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification.Methods The pathological sections were reviewed.EGFR mutation was detected by amplification refractory mutation system-quantitative real-time polymerase chain reaction,and C-MET amplification by fluorescence in situ hybridization.The clinicopathological features and survival data of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification were analyzed retrospectively.Results In 11 cases of EGFR mutation combined with C-MET amplification,complex glands and solid high-grade components were observed under a microscope in 10 cases except for one case with a cell block,the tissue structure of which was difficult to be evaluated.The incidence of lung adenocarcinoma in the patients with EGFR mutation combined with C-MET amplification at clinical stage Ⅳ was higher than that in the EGFR mutation or C-MET amplification group (all P<0.001),whereas the difference was not statistically significant between the EGFR mutation group and C-MET amplification group at each clinical stage (all P>0.05).There was no significant difference in the trend of survival rate between EGFR gene group and C-MET amplification group (χ²=0.042,P=0.838),while the survival of the patients with EGFR mutation combined with C-MET amplification was worse than that of the patients with EGFR mutation (χ²=246.72,P<0.001) or C-MET amplification (χ²=236.41,P<0.001).Conclusions The patients newly diagnosed with lung adenocarcinoma with EGFR mutation plus C-MET amplification demonstrate poor histological differentiation,rapid progress,and poor prognosis.The patients are often in the advanced stage when being diagnosed with cancer.Attention should be paid to this concurrent adverse driving molecular event in clinical work.With increasing availability,the inhibitors targeting C-MET may serve as an option to benefit these patients in the near future.
Humans ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Mutation ; Lung Neoplasms/genetics* ; ErbB Receptors/genetics*

WRKY, a class of conserved transcription factors in plants, plays important roles in plant growth, development and secondary metabolism. In the present study, 65 WRKY members were identified from de novo transcriptome sequencing data of three different tissues (root, stems and leaves) of Baphicacanthus cusia. BcWRKY proteins contained from 221 to 706 amino acids and the isoelectric point is from 4.68 to 9.68. Molecular weights range from 25 711.8 to 75 475 Da. The main secondary structures of BcWRKYs protein are random coil. A subcellular localization prediction indicated that the putative BcWRKY proteins were enriched in the nuclear region. Phylogenetic analysis showed that BcWRKYs could be categorized into three groups and five subgroups (Group IIa, Group IIb, Group IIc, Group IId and Group IIe) in Group II. Structural analysis found that all BcWRKY proteins contained a highly conserved motif WRKYGQK. Finally, the transcriptional profiles of ten BcWRKY genes highly expressed in root, stem and leaf tissues under abscisic acid (ABA), methyl jasmonate (MeJA), or salicylic acid (SA) treatment were systematically investigated using qRT-PCR analysis. Results showed that a total of ten BcWRKY genes were differentially expressed in response to ABA, MeJA, and SA treatment. This work would be provided a basis for further elucidating the molecular mechanism of WRKY transcription factors in the biosynthesis of indole alkaloids in B. cusia.

Esophagus/surgery* ; Foreign Bodies/surgery* ; Gastroscopes ; Humans ; Ultrasonography

Synthetic biology and metabolic engineering have been widely used to construct microbial cell factories for efficient production of bio-based chemicals, which mainly focus on the modification and regulation of metabolic pathways. The characteristics of microorganisms themselves, e.g. morphology, have rarely been taken into consideration in the biotechnological production processes. Morphology engineering aims to control cell shapes and cell division patterns by manipulating the genes related to cell morphology, providing a new strategy for developing efficient microbial cell factories. This review summarized the proteins related to cell morphology, followed by illustrating a few examples of using morphology engineering strategies for improving production of bio-based chemicals. This includes increasing intracellular product accumulation by regulating cell size, enhancing extracellular secretion of target products by improving cell permeability, reducing production cost by achieving high cell density, and improving product performance by controlling the degree of product hydrolysis. Finally, challenges and perspectives for the development of morphology engineering were discussed.
Biotechnology ; Metabolic Engineering ; Metabolic Networks and Pathways ; Synthetic Biology

OBJECTIVE: To study the clinical effect and complications of continuous blood purification (CBP) in the treatment of multiple organ dysfunction syndrome (MODS) in neonates. METHODS: A retrospective analysis was performed for the clinical data of 21 neonates with MODS who were admitted to the neonatal intensive care unit from November 2015 to April 2019 and were treated with CBP. Clinical indices were observed before treatment, at 6, 12, 24, and 36 hours of CBP treatment, and at the end of treatment to evaluate the clinical effect and safety of CBP treatment. RESULTS: Among the 21 neonates with MODS undergoing CBP, 17 (81%) had response to treatment. The neonates with response to CBP treatment had a significant improvement in oxygenation index at 6 hours of treatment, a significant increase in urine volume at 24 hours of treatment, a stable blood pressure within the normal range at 24 hours of treatment, and significant reductions in the doses of the vasoactive agents epinephrine and dopamine at 6 hours of treatment (P<0.05), as well as a significant reduction in serum K+ level at 6 hours of treatment, a significant improvement in blood pH at 12 hours of treatment, and significant reductions in blood lactic acid, blood creatinine, and blood urea nitrogen at 12 hours of treatment (P<0.05). Among the 21 neonates during CBP treatment, 6 experienced thrombocytopenia, 1 had membrane occlusion, and 1 experienced bleeding, and no hypothermia, hypotension, or infection was observed. CONCLUSIONS CBP is a safe, feasible, and effective method for the treatment of MODS in neonates, with few complications.
Blood Gas Analysis ; Blood Urea Nitrogen ; Hemofiltration ; Humans ; Infant, Newborn ; Multiple Organ Failure ; Retrospective Studies

Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Retrospective Studies ; Stomach Neoplasms/surgery*

OBJECTIVE: To investigate the value of optic disc retinal nerve fiber layer (RNFL) thickness in the diagnosis of diabetic peripheral neuropathy (DPN). METHODS: Ninety patients with type 2 diabetes, including 60 patients without DPN (NDPN group) and 30 patients with DPN (DPN group), and 30 healthy participants (normal group) were enrolled. Optical coherence tomography (OCT) was used to measure the four quadrants and the overall average RNFL thickness of the optic disc. The receiver operator characteristic curve was drawn and the area under the curve (AUC) was calculated to evaluate the diagnostic value of RNFL thickness in the optic disc area for DPN. RESULTS: The RNFL thickness of the DPN group was thinner than those of the normal and NDPN groups in the overall average ((101.07± 12.40) µm vs. (111.07±6.99) µm and (109.25±6.90) µm), superior quadrant ((123.00±19.04) µm vs. (138.93±14.16) µm and (134.47±14.34) µm), and inferior quadrant ((129.37±17.50) µm vs. (143.60±12.22) µm and (144.48±14.10) µm), and the differences were statistically significant. The diagnostic efficiencies of the overall average, superior quadrant, and inferior quadrant RNFL thicknesses, and a combined index of superior and inferior quadrant RNFL thicknesses were similar, and the AUCs were 0.739 (95% confidence interval (CI) 0.635-0.826), 0.683 (95% CI 0.576-0.778), 0.755 (95% CI 0.652-0.840), and 0.773 (95% CI 0.672-0.854), respectively. The diagnostic sensitivity of RNFL thickness in the superior quadrant reached 93.33%. CONCLUSIONS The thickness of the RNFL in the optic disc can be used as a diagnostic method for DPN.

Background: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a contributing factor for non-alcoholic fatty liver disease (NAFLD). Non-invasive algorithms including fatty liver index (FLI) and hepatic steatosis index (HSI) have been used as a screening test for NAFLD in epidemiologic studies. The aim of this study is to compare the diagnostic accuracy of FLI and HSI for NAFLD detection in adults with OSAHS. Methods: We enrolled consecutive adult subjects who were newly diagnosed with OSAHS from March 2016 to January 2018. NAFLD was diagnosed by ultrasonography. The accuracy and cut-off point of the FLI and HSI to detect NAFLD were assessed by analyzing the area under the receiver operating characteristic (AUROC) curve and the maximum Youden index analysis, respectively. Results: The 326 subjects were diagnosed as NAFLD according to ultrasound findings, while 105 subjects who had normal abdominal ultrasonography were grouped as controls. Both FLI and HSI values were significantly higher in patients with NAFLD compared with controls. The AUROC of FLI and HSI for predicting NAFLD was 0.802 (95% confidence interval [CI] 0.762-0.839) and 0.753 (95% CI 0.710-0.793), respectively. The AUROC of FLI was significantly higher than that of HSI (P = 0.0383). The optimal cut-off value of FLI and HSI was 60 (sensitivity 66% and specificity 80%) and 35 (sensitivity 81% and specificity 60%), respectively. Conclusions: Both FLI and HSI can serve as screening tools for NAFLD in OSAHS adults. The FLI shows better performance in diagnosing NAFLD than HSI. Trial registration Chinese Clinical Trial Registry (No. ChiCTR-OOB-15007253), http://www.chictr.org.cn/showproj.aspx?proj=11606.