Objective:To investigate the effect of high-dose vitamin B6 on stress-induced liver cell death in rats with severe trauma and its possible mechanism.Methods:Thirty-two male SD rats were selected and divided into sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group by using a random number table, with 8 rats in each group. Rat models of severe trauma were established by inducing abdominal wall injury, bilateral femoral fractures, unilateral cranial injury, and withdrawal of 4 ml blood from the femoral artery. The sham surgery+B6 group and trauma+B6 group were treated with saline solution plus high-dose vitamin B6, while the sham surgery group and trauma group with infusion of saline solution only. At 36 hours after injury, rat liver tissues were collected for the following experiments: (1) the genes differentially expressed in the liver tissues of the rats of the trauma group and the trauma+B6 group were screened with next-generation sequencing, followed by an analysis of the possible involvement of cell death pathways; (2) validation was conducted to ascertain whether high-dose vitamin B6 could influence various cell death pathways in the liver cells in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group: apoptosis was confirmed through terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining; necroptosis was verified by mixed lineage kinase domain-like protein (MLKL) immunohistochemical staining; autophagy was examined via transmission electron microscopy; ferroptosis was confirmed by detecting oxidative malondialdehyde (MDA) levels, oxidized glutathione levels, Prussian blue staining with diaminobenzidine (DAB) enhancement, transmission electron microscopy, and immunohistochemical staining for acyl-CoA synthetase long-chain family member 4 (ACSL4); (3) Biological information analyses [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Enrichment analysis (GSEA)] were performed for biological processes and signaling pathways represented by liver tissue sequencing results of rats between the trauma group and the trauma+B6 group.Results:(1) In the liver tissues of rats, there were 344 significantly differentially expressed genes between the trauma group and trauma+B6 group, comprising 137 upregulated genes and 207 downregulated genes, of which 18 genes were associated with apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. (2) No significant differences were found in TUNEL staining among the sham surgery group, sham surgery+B6 group, trauma group or trauma+B6 group; MLKL protein expression levels in the liver tissues after trauma were improved, of which the trauma+B6 group was lower than that of the trauma group; Electron microscopy showed that autophagic activity in the liver cells were significantly increased after trauma, which was significantly lower of the trauma+B6 group than that of the trauma group; MDA levels in the rat liver tissues were (0.20±0.05)nmol/mg, (0.17±0.07)nmol/mg, (0.69±0.11)nmol/mg and (0.52±0.07)nmol/mg in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group respectively ( P<0.01), with the trauma group having the highest MDA levels and trauma+B6 group having lower MDA levels than the trauma group; Oxidized glutathione levels in the liver tissues of the four groups were (11.75±2.09)μmol/g, (11.69±1.66)μmol/g, (19.75±3.40)μmol/g, and (14.51±1.46)μmol/g respectively ( P<0.01), with the trauma group having the highest levels and trauma+B6 group having lower levels than the trauma group; Significantly increased iron deposition was observed in the liver tissues after trauma, with lower iron deposition in trauma+B6 group than the trauma group; Electron microscopy revealed significantly lower mitochondrial membrane density in the trauma+B6 group compared to the trauma group. ACSL4 protein expression level was lower in the trauma+B6 group compared to the trauma group; (3) GO, KEGG and GSEA enrichment analyses suggested that high-dose vitamin B6 may enhance cholesterol synthesis metabolism in the liver cells and alleviate oxidative stress to reduce liver cell damage and restore normal liver cell function after trauma. Conclusions:High-dose vitamin B6 attenuates stress-induced liver injury in rats with severe trauma by inhibiting the progression of necroptosis, autophagy and ferroptosis. Its molecular mechanism may be associated with enhanced hepatic cholesterol synthesis metabolism and alleviation of oxidative stress in the liver cells.

Familial hyperaldosteronism type Ⅲ(FH-Ⅲ) is extremely rare, and there are no reported cases in China. Herein, we reported two cases with FH Ⅲ, both of which presented with severe hypertension and hypokalemia in their early childhood. One patient had significantly enlarged adrenal glands and developed clinical manifestations of Cushing′s syndrome at the age of 20. Complete relief of symptoms was achieved after bilateral adrenalectomy. The other case had normal adrenal imaging, and with spironolactone treatment, blood pressure and potassium levels were well-controlled. Both cases had germline mutation of KCNJ5 gene which were c. 433G>C(p.Glu145Gln) and c. 452G>A(p.Gly151Glu), respectively.

Objective:To explore the feasibility of staging Wilson's disease (WD) based on imaging indexes, and evaluate the clinical characteristic differences of WD patients at different stages.Methods:Sixty WD patients (40 with cerebral type and 20 with hepatic type) hospitalized in Department of Neurology, First Affiliated Hospital of Sun Yat-sen University from July 2015 to June 2022 and 20 age- and gender-matched normal controls were selected. All subjects accepted susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS); 7 regions of interest were selected: globus pallidus, caudate nucleus, putamen, thalamus, cerebellum, midbrain and pons; their fractional anisotropy (FA), corrected phase (CP), N-acetylaspartate/creatine (NAA/Cr) values were measured. According to DTI, SWI and MRS results, WD patients were divided into group of metal deposition stage (decreased CP, normal FA and NAA/Cr), group of fiber damage stage (abnormal FA, normal NAA/Cr), and group of neuron necrosis stage (decreased NAA/Cr); the clinical data (modified Young scale scores, Child-Pugh grading of liver function, serum copper content, and urinary copper content) and imaging indexes (FA, CP, and NAA/Cr) among the 3 groups and control group were compared. Results:Among the 60 patients, 19 patients were at metal deposition stage (including 18 with liver type and 1 with brain type), 28 patients at fiber injury stage (including 2 with liver type and 26 with brain type), and 13 patients at neuron necrosis stage (all brain type). (1) Compared with group of metal deposition stage and fiber damage stage, group of neuron necrosis stage had significantly decreased urinary copper content ( P<0.05). The modified Young scale scores in groups of metal deposition stage, fiber injury stage and neuronal necrosis stage increased successively; Child-Pugh grading in group of metal deposition stage was higher than that in groups of fiber injury stage and neuronal necrosis stage. (2) Compared with groups of metal deposition stage and neuron necrosis stage, CP values in the globus pallidus and substantia nigra in group of fiber injury stage group were significantly decreased ( P<0.05). Compared with groups of metal deposition stage and fiber injury stage, the FA value in the putamen and NAA/Cr value in the pallidum, thalamus and caudate nucleus in group of neuron necrosis stage were significantly decreased ( P<0.05). Conclusion:Disease stages of WD patients can be divided by imaging methods; neurological symptoms gradually worsen following progressed WD.

Objective:To assess the susceptibility of gonococcal clinical isolates to gentamicin in Guangxi region, China, and to analyze the correlation between the minimum inhibitory concentration (MIC) of gentamicin and MICs of 7 other antibiotics.Methods:From December 2020 to December 2021, 584 gonococcal clinical isolates were collected from 37 medical institutions in 14 prefecture-level cities in Guangxi region. The susceptibility of gonococcal clinical isolates to ceftriaxone, cefixime, azithromycin, spectinomycin, penicillin, tetracycline, ciprofloxacin and gentamicin was determined by using an agar dilution method. The MIC values of antibiotics were logarithmically transformed with base 2, and Spearman correlation analysis was carried out to evaluate the correlation between the MIC of gentamicin and MICs of the other 7 antibiotics.Results:The MIC of gentamicin ranged from 1 to 16 mg/L, and the MIC50 and MIC90 values were 4 and 8 mg/L, respectively; 361 strains (61.8%) were fully sensitive to gentamicin with the MIC ≤ 4 mg/L, 223 strains (38.2%) moderately sensitive with the MIC ranging from 8 to 16 mg/L, and no gentamicin-resistant strains were found. The number of strains resistant to azithromycin, penicillin, tetracycline and ciprofloxacin was 136 (23.3%), 415 (71.1%), 339 (58.0%) and 574 (98.3%) respectively, the number of lowly sensitive strains to ceftriaxone and cefixime was 17 (2.9%) and 6 (1.0%) respectively, and no spectinomycin-resistant strains were found. Spearman correlation analysis showed that the MIC of gentamicin was weakly correlated with the MICs of azithromycin, spectinomycin, penicillin, tetracycline, and ciprofloxacin (all P < 0.05), but was uncorrelated with the MICs of ceftriaxone and cefixime (both P > 0.05) . Conclusion:All gonococcal clinical isolates tested in this study showed a certain degree of susceptibility to gentamicin, and cross-resistance between gentamicin and other antibiotics was less likely to occur.

ObjectiveTo investigate the risk factors for tumor recurrence and death after liver transplantation in patients with hepatocellular carcinoma (HCC) and their survival. MethodsThe patients with HCC who underwent liver transplantation in The Fifth Medical Center of Chinese PLA General Hospital from January 2005 to February 2019 were enrolled, and according to the presence or absence of HCC recurrence after liver transplantation, they were divided into recurrence group and non-recurrence group. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Cox proportional-hazards regression model analyses were used to determine the risk factors for HCC recurrence and death after liver transplantation. The Kaplan-Meier method was used for survival analysis, and the receiver operating characteristic (ROC) curve was used to investigate the predictive value of death-related risk factors after liver transplantation. ResultsA total of 391 HCC patients who underwent liver transplantation were enrolled, with a median follow-up time of 2 years, among whom 78(19.95%) experienced HCC recurrence. Preoperative alpha-fetoprotein (AFP) level＞200 ng/ml (recurrence: hazard ratio ［HR］=252, 95% confidence interval ［CI］: 1.58-4.03, P＜0.001; death: HR=2.99, 95%CI: 1.59-5.62, P＜0.001］, total tumor diameter (recurrence: HR=1.20, 95%CI: 1.12-1.28, P＜0.001; death: HR=1.10, 95%CI: 1.02-1.17, P=0.002), and vascular invasion (recurrence: HR=1.15, 95%CI: 1.04-1.26, P=0.016; death: HR=1.10, 95%CI: 1.03-1.18, P=0.004) were independent risk factors for tumor recurrence and death after liver transplantation. The 1-, 5-, and 10-year overall survival rates after liver transplantation were 94.8%, 84.2%, and 83.5%, respectively, and the 1-, 5-, and 10-year disease-free survival rates were 840%, 75.1%, and 75.1%, respectively. AFP, involvement of major blood vessels, body mass index, and total tumor diameter had a certain value in predicting the death of HCC patients with recurrence, with an area under the ROC curve of 0.789 (95% CI: 0.719-0858). ConclusionTumor biological features before transplantation are the key factors for tumor recurrence after transplantation.

Objective: To evaluate the preliminary efficacy and safety of the 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin (FOLF-OXIRI) and capecitabine, irinotecan, and oxaliplatin (CAPIRINOX) regimens as first-line therapy for unresectable advanced colorectal cancer. Methods: Between January 2013 and November 2018, 73 patients with metastatic colorectal cancer (mCRC) were analyzed. All patients received first-line chemotherapy. Of them, 45 patients were administered FOLFOXIRI, and the remaining 28 patients were ad-ministered CAPIRINOX. The clinical outcomes and safety profiles were evaluated according to the objective response rate (ORR), con-version resection rate, and adverse effects. Results: The ORR, median progression-free survival (mPFS), and R0 resection rate in the FOLFOXIRI group were not statistically different from those in the CAPIRINOX group (60% vs. 57.1%, 7.7 months vs. 9.6 months, 24.4% vs . 17.9% , respectively; P>0.05). No treatment-related deaths occurred. The major adverse events were leukopenia, neutropenia, fa-tigue, nausea, vomiting, diarrhea, alopecia, aspartate aminotransferase/alanine aminotransferase elevation, and neurotoxicity. The to-tal rate of grade 3/4 adverse events in the FOLFOXIRI group was 33.3% (15/45), while the total rate of grade 3/4 adverse events in the CAPIRINOX group was 46.4% (13/28). Toxicities between the two groups were not statistically significant (P=0.263). Conclusions: Both the FOLFOXIRI and CAPIRINOX regimens are effective as first-line treatment for metastatic colorectal cancer. The triple-agent chemo-therapy was associated with good efficacy and tolerable toxicity.

Objective Based on data mining technology, we discussed the correlation of different gene mutation, fusion or amplification in advanced lung cancer patients. Methods 630 cases in our hospital were collected and the drug database was established by Excel 2016. Frequency analysis and association rules were used for statistical analysis, and statistical analysis was performed on SPSS22.0 and SPSSModerler statistical software.Results There were 26 high frequency genes, such as EGFR-19 mutation, ALK fusion, RET mutation, EGFRL858 R-21 mutation, ALK mutation, and the first 6 cases of T790M mutation. The first 26 were NRAS-G12 D mutation and BRAF-G466 V mutation, MYC-R450 W mutation and CYP2D6 mutation, GATA3 M423 fs mutation and ESR1 mutation, abrupt mutation, mutation and sudden process. The variable classification values are associated with each other. The minimum value of gene association analysis was 50％ and support was 10％. After Apriori module analysis, EGFR-19 mutation and 14 genes were not found (confidence degree 46.667％) , EGFR-19 mutation and T790 M mutation (confidence degree 40％) , EGFR-19 mutation and TP53 mutation (confidence degree 13.333％) , ROS1 fusion and MET amplification (confidence 47.619％) , MET amplification and ROS1 melting (confidence level 50％) , T790 M mutation and EGFR amplification (confidence level 57.895％) , EGFR-19 mutation and EGFR amplification (confidence 42.105％). Cluster analysis BRAF-G466 V and NRAS-G12D, MYC-R450 W and CYP2 D6, GATA3 M423 fs and SRC, PIK3 CA amplification and PIK3CA, Pten and EGFEL861 Q-21, KRAS G12A and blending. Conclusion There are correlations between different genes and mutation, fusion, lack and amplification of lung cancer.

BACKGROUND: More and more patients with small pulmonary nodules (SPN) can be found along with the developing of chest low-dose computed tomography (LDCT). With current examinations not all the SPN can be diagnosed to be benign or malignant and not all the malignant nodules can be diagnosed to be lymphatic metastasis. We need to study the correlation between plasma D-dimer count of patients before surgery with pathology features of non-small cell lung cancer (NSCLC). METHODS: The study comprised 567 highly suspected lung cancer patients. Preoperative plasma D-dimer were qualified, and the relationship between plasma D-dimer with pathology features including benign or malignant nodules, tumor size and involvement of lymph nodes was examined using Kruskal-Wallis test and Spearman correlation coefficients. RESULTS: The median plasma D-dimer values were statistically higher in NSCLC patients than in those who suffered from benign lung nodules (P<0.001). The median plasma D-dimer values in NSCLC patients with malignant lymph nodes were statistically higher than in those without malignant lymph nodes (P<0.001). An obvious relationship was observed between elevated D-dimer with number of malignant lymph nodes involvement and tumer size. An obvious relationship was observed between elevated D-dimer (>112.5 ng/mL) and malignant lymph node involvement in stage T1 lung cancer. CONCLUSIONS The plasma D-dimer maybe useful for early diagnosis, staging and prognosis of the patients with NSCLC. The plasma D-dimer can be one of the indicator to identify what kind of patients need mediastinal lymph node cleaning.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; pathology ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Humans ; Lung Neoplasms ; blood ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Retrospective Studies

Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, patients with non-small cell lung cancer (NSCLC) usually have distant metastases, such as bone metastasis, brain metastasis, and lung metastasis. The purpose of this study was to explore the risk factors for bone metastasis in NSCLC patients. METHODS: A total of 176 cases of NSCLC were selected from May 2009 to May 2011, and patients were divided into two groups, namely the bone metastasis group and non-bone metastasis group. The general clinicopathological data of the two groups and analyzing the independent risk factors of bone metastasis were compared. RESULTS: In the general clinicopathological data of NSCLC patients. The thrombus or not and tumor-node-metastasis (TNM) stage were closely related to the occurrence of bone metastasis, and were statistically significant (all P<0.01). Prothrombin time, activated partial thromboplastin time, Fibrinogen, thrombin time, blood platelet, D-Dimer and alkaline phosphatase have significantly difference between the two groups (all P<0.05). Logistic regression analysis showed that fibrinogen, activated partial thromboplast in time, alkaline phosphatase, T4 phase, N3 phase and d-dimer were independent risk factors for bone metastasis in NSCLC patients. CONCLUSIONS Fibrinogen, alkaline phosphatase, T3, N2 stage and D-Dimer is the independent risk factors of bone metastases in patients with NSCLC.
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Aged ; Bone Neoplasms ; diagnosis ; secondary ; Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; pathology ; therapy ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Risk Factors