Cytochrome P450 1A (CYP1A), one of the major CYP subfamily in humans, not only metabolizes xenobiotics including clinical drugs and pollutants in the environment, but also mediates the biotransformation of important endogenous substances. In particular, some single nucleotide polymorphisms (SNPs) for genes may affect the metabolic ability of endogenous substances, leading to some physiological or pathological changes in humans. This review first summarizes the metabolism of endogenous substances by CYP1A, and then introduces the research progress of SNPs, especially the research related to human diseases. Finally, the relationship between SNPs and diseases is discussed. In addition, potential animal models for gene editing are summarized. In conclusion, CYP1A plays an important role in maintaining the health in the body.

OBJECTIVE: To investigate the clinical effect of One-stage posterior debridement combined with lumbar-ilium fixation and bone graft fusion for the treatment of lumbosacral tuberculosis. METHODS: The clinical data of 31 patients with lumbosacral tuberculosis treated by one-stage posterior debridement combined with lumbar-ilium fixation and bone graft fusion from January 2013 to February 2018 were retrospectively analyzed. There were 18 males and 13 females, aged from 18 to 77 years old with an average of (45.9±9.1) years. The lesion segment was form L to S. The preoperative ASIA grading showed that 2 cases were grade B, 17 cases were grade C, 12 were grade D. Pre- and post-operative C reactive protein (CRP), visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), ASIA grade, lumbosacral angle and intervertebral space height were analyzed, the surgery complications, stability of internal fixation, bone fusion were observed. RESULTS: All the 31 patients were followed up for 10 to 24 months with an average of (16.0±3.1) months. One patient with local infection and subcutaneous hydrops was cured by dressing change. Other 30 cases got primary healing without sinus formation and no recurrence of spinal tuberculosis. All the patients were cured, no internal fixation loosening and breakage were found. All bone fusion was successful with an average fusion time of (4.7±1.1) months. At the final follow-up, ESR and CRP were normal, the VAS was decreased from (6.13±1.21) points preoperatively to (1.92±0.57) pioints, the ASIA grading showed that 2 cases were grade C, 6 cases were grade D, and 23 cases were grade E. The lumbosacral angle and intervertebral space height was increased from preoperative (21.42±3.75) °, (7.84±0.41) mm to (27.21±3.12) °, (9.80±0.38) mm at the final follow-up, respectively. CONCLUSION One-stage posterior debridement combined with lumbar-ilium fixation and bone graft fusion is a practicable, effective and safe method for the treatment of lumbosacral tuberculosis. It can be recommended in clinical application.

Objective: To recover broad-neutralizing monoclonal antibodies (BnAbs) from avian influenza A (H5N1) virus infection cases and investigate their genetic and functional features. Methods: We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients. The genetic basis, biological functions, and epitopes of the obtained BnAbs were assessed and modeled. Results: Two BnAbs, 2-12D5, and 3-37G7.1, were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset. Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity (ADCC) activity. Albeit derived from distinct Ab lineages, , V 1-69-D2-15-J 4 (2-12D5) and V 1-2-D3-9-J 5 (3-32G7.1), the BnAbs were directed toward CR6261-like epitopes in the HA stem, and HA I45 in the hydrophobic pocket was the critical residue for their binding. Signature motifs for binding with the HA stem, namely, IFY in V 1-69-encoded Abs and LXYFXW in D3-9-encoded Abs, were also observed in 2-12D5 and 3-32G7.1, respectively. Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus. The HA stem epitopes targeted by the BnAbs, and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.

Objective: To investigate the clinical value of lymph node dissection (LND) in the radical resection of intrahepatic cholangiocarcinoma (ICC). Methods: The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 448 patients with ICC who were admitted to 12 medical centers from December 2011 to December 2017 were collected, including 279 in the Eastern Hepatobiliary Surgery Hospital of Navy Medical University, 32 in the Mengchao Hepatobiliary Hospital of Fujian Medical University, 21 in the First Hospital Affiliated to Army Medical University, 20 in the Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College, 19 in the West China Hospital of Sichuan University, 18 in the Second Hospital Affiliated to Zhejiang University School of Medicine, 18 in the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 16 in the Beijing Friendship Hospital Affiliated to Capital Medical University, 10 in the Xuanwu Hospital Affiliated to Capital Medical University, 7 in the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, 5 in the Beijing Tiantan Hospital Affiliated to Capital Medical University, and 3 in the Affiliated Hospital of North Sichuan Medical College. There were 281 males and 167 females, aged from 22 to 80 years, with a median age of 57 years. Of the 448 patients, 143 with routinely intraoperative LND were divided into LND group and 305 without routinely intraoperative LND were divided into control group, respectively. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups after matching; (2) intraoperative and postoperative situations; (3) follow-up; (4) survival analysis. Patients were followed up by outpatient examination, telephone interview and email to detect survival of patients and tumor recurrence up to October 31, 2018 or death. Follow-up was conducted once every 3 months within postoperative 1-2 years, once every 6 months within postoperative 2-5 years, and once a year after 5 years. The propensity score matching was realized using the nearest neighbor method with 1∶1 ratio. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Kaplan-Meier method was used to calculate survival rates and draw survival curve, and Log-rank test was used to perform survival analysis. Univariate analysis and multivaraiate analysis were conducted using the Log-rank test and COX regression model, respectively. Results: (1) The propensity score matching conditions and comparison of general data between the two groups after matching: 286 of 448 patients had successful matching, including 143 in each group. The number of males and females, cases with hepatitis, cases with grade A and B of Child-Pugh classification, cases with distance from margin to tumor <1 cm and ≥1 cm, cases with highly, moderately, and poorly differentiated tumor, cases with anatomical hepatectomy and nonanatomical hepatectomy before propensity score matching were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 204, 101, 121, 165, 140, 207, 98, 251, 54, 124, 181 in the control group, respectively, showing significant differences in the above indices between the two groups (χ²=7.079, 11.885, 7.098, 14.763, 5.184, 8.362, P<0.05). After propensity score matching, the above indices were 77, 66, 33, 96, 47, 70, 73, 105, 38, 79, 64 in the LND group, and 79, 64, 29, 88, 55, 71, 72, 112, 31, 74, 69 in the control group, respectively, showing no significant difference in the above indices between the two groups (χ²=0.056, 0.329, 2.158, 0.014, 0.936, 1.400, P>0.05). (2) Intraoperative and postoperative situations: the operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, cases with postoperative complications, and duration of postoperative hospital stay were 265 minutes (range, 160-371 minutes), 300 mL (range, 200-500 mL), 37, 46, 12 days (range, 9-17 days) for the LND group, and 59 minutes (range, 46-250 minutes), 200 mL (range, 100-400 mL), 24, 25, 9 days (range, 7-11 days) for the control group, respectively. There was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups (Z=1.700, χ²=3.520, P>0.05). There were significant differences in the operation time, cases with postoperative complications, and duration of postoperative hospital stay (Z=6.520, χ²=8.260, Z=4.270, P<0.05). (3) Follow-up: 143 patients in the LND group was followed up for 18-26 months. The 1-, 3-, 5-year survival rates were 66.9%, 32.8%, 25.0%, and the median survival time was 22.0 months (range, 18.0-26.0 months). In the control group, 143 patients were followed up for 11-32 months. The 1-, 3-, 5-year survival rates were 71.7%, 38.0%, 31.0%, and the median survival time was 22.0 months (range, 11.0-32.0 months). There was no significant difference in the overall survival between the two groups (χ²=0.466, P>0.05). (4) Survival analysis: results of univariate analysis showed that distance from margin to tumor, tumor diameter, the number of tumors, microvascular tumor thrombus, and lymph node metastasis by pathological examination were related factors for prognosis of patients undergoing radical resection of ICC (χ²=10.662, 9.477, 16.944, 6.520, 11.633, P<0.05). Results of multivariate analysis showed that distance from margin to tumor<1 cm, tumor diameter>5 cm, multiple tumors, microvascular tumor thrombus, positive lymph node metastasis by pathological examination were independent risk factors for prognosis of patients undergoing radical resection of ICC (hazard ratio=0.600, 1.571, 1.601, 1.750, 1.723, 95% confidence interval: 0.430-0.837, 1.106-2.232, 1.115-2.299, 1.083-2.829, 1.207-2.460, P<0.05). Conclusion Lymph node metastasis is an independent risk factor affecting the prognosis of ICC patients, and it is necessary to perform LND in radical resection for patients with ICC and lymph node metastasis.

Objective: To evaluate the accuracy of the new non-invasive liver disease model platelet-albumin-bilirubin index (PALBI) in the diagnosis of patients with acute upper gastrointestinal hemorrhage (AUGIB) due to cirrhosis. Methods: 277 patients with AUGIB due to cirrhosis were analyzed retrospectively. The data of platelet, total bilirubin, albumin, creatinine, international standardized ratio and etiology of cirrhosis were collected. Univariate and multivariate logistic regression analysis was used to identify independent risk factors for death in patients with cirrhosis complicated by AUGIB. Analysis of variance was used to compare the differences between the model for end-stage liver disease (MELD) and PALBI grades. Pearson correlation analysis was used to assess the association between MELD and PALBI. The operating characteristic curve (ROC) was used to compare the predictive power of both for short-term and long-term mortality in patients with cirrhosis complicated by AUGIB. Results: The short-term and long-term mortality rates of patients with cirrhosis complicated by AUGIB were 13.7% and 23.5%, respectively. The average hospital stay was (9.1±3.9)days. The high MELD score and high PALBI index were confirmed as independent risk factors of death by single factor and multiple factors [odds ratio (OR)=1.17, 4.43; P<0.05]; the Pearson correlation analysis showed there was a positive correlation between MELD score and PALBI index (r=0.735, P<0.05). The PALBI score was scored in MELD-a patients, further subdivided into PALBI-1a and PALBI-1b. There were statistical difference in the 1-year mortality rate between the two groups (7.0% vs 17.8%, χ²=4.033, P<0.05). The ROC curve was used to compare the predictive power of MELD and PALBI for short-term mortality. The area under curve (AUC) of PALBI was 0.767 (95% CI: 0.712-0.815), while the AUC of the MELD score was 0.651 (95% CI: 0.591-0.707), with statistically significant difference (Z=2.328, P<0.05). The predictive power of PALBI and MELD for long-term mortality were 0.731(95% CI: 0.674-0.782), 0.754 (95% CI: 0.699-0.804), but the difference was not statistically significant (Z=0.828, P>0.05). Conclusions PALBI has a better predictive effect on patients with cirrhosis complicated by AUGIB than MELD scores. PALBI can achieve a more precise prognosis classification for patients with MELD-a, and maintain a good prediction ability on the short-term (within 30 days of hospitalization and discharge) and long-term (within 1 year after discharge) mortality of patients. As a new liver disease model, PALBI can be used as an effective non-invasive means to judge the prognosis of patients with liver cirrhosis complicated by AUGIB .

Objective: To retrospectively analyze the characteristics of nasopharyngeal carcinoma, long-term efficacy, adverse reactions of intensity-modulated radiotherapy (IMRT) in non-endemic northwest China and summarize the experience of IMRT in the treatment of nasopharyngeal carcinoma in the past decade. Methods: Clinical data of 658 patients newly diagnosed with nasopharyngeal carcinoma without distant metastasis admitted to First affiliated hospital from January 2006 to December 2016 were retrospectively analyzed. All patients were treated with IMRT. The survival analysis was performed by Kaplan-Meier method. The multivariate analysis was conducted with Cox’s regression model. Results: In non-endemic northwest China, a large proportion of patients were newly diagnosed with locally advanced nasopharyngeal carcinoma, and a majority of them were pathologically characterized as differentiated subtypes. The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) rates were 75.7%, 70.1%, 91.2%, 97.0% and 81.0%, respectively. Multivariate analysis showed that age, pathological type, nasopharyngeal tumor volume>23 cm³ and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DFS (all P<0.05). Age, pathological type, neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of OS (all P<0.05). N stage and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DMFS (both P<0.05). Conclusions Similar clinical efficacy has been achieved in terms of IMRT for nasopharyngeal carcinoma in non-endemic northwest China compared with that in endemic area. Induction chemotherapy combined with concurrent radiochemotherapy can provide clinical benefits for patients with locally advanced nasopharyngeal carcinoma in non-endemic area.

PURPOSE: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare subtype of non-Hodgkin lymphoma, and asparaginase-based regimens are the best first-line treatments. Data on the role of specific circulating lymphocyte subsets in the progression of ENKTL are limited. The aim of this study was to investigate the clinical correlation and distribution of circulating absolute CD4+ T-cell counts (ACD4Cs) in ENKTL. MATERIALS AND METHODS: We retrospectively searched medical records for 70 newly diagnosed ENKTL patients treated with pegaspargase-based regimens. Comparison of ACD4Cs as a continuous parameter in different groups was calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: Stage III/IV, B symptoms, elevated lactate dehydrogenase, monocytopenia, high-intermediate and high risk International Prognostic Index (IPI) and Korean Prognostic Index (KPI), high risk Prognostic Index of Natural Killer Lymphoma (PINK), and lower lymphocytes were significantly associated with low ACD4C at diagnosis. With a median follow-up time of 32 months, patients who had an ACD4C < 0.30×109/L had a worse OS. Median OS was 11 months and median PFS was 5 months in the low ACD4C cohort. There were significant differences in both OS and PFS between the two cohorts. Moreover, multivariate Cox analysis identified ACD4Cs as an independent predictor for OS and PFS. CONCLUSION: Low ACD4Cs were associated with poorer survival and could act as a negative predictor for ENKTL patients treated with asparaginase-based regimens.
Cell Count* ; Cohort Studies ; Diagnosis ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; L-Lactate Dehydrogenase ; Lymphocyte Subsets ; Lymphocytes ; Lymphoma* ; Lymphoma, Extranodal NK-T-Cell ; Lymphoma, Non-Hodgkin ; Medical Records ; Multivariate Analysis ; Prognosis* ; Retrospective Studies ; T-Lymphocytes

PURPOSE: The purpose of this study was to identify novel plasma biomarkers for distinguishing nasopharyngeal carcinoma (NPC) patients from healthy individuals who have positive Epstein-Barr virus (EBV) viral capsid antigen (VCA-IgA). MATERIALS AND METHODS: One hundred seventy-four plasma cytokines were analyzed by a Cytokine Array in eight healthy individuals with positive EBV VCA-IgA and eight patients with NPC. Real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry were employed to detect the expression levels of macrophage migration inhibitory factor (MIF) and CC chemokine ligand 3 (CCL3) in NPC cell lines and tumor tissues. Plasma MIF and CCL3 were measured by ELISA in 138 NPC patients, 127 EBV VCA-IgA negative (VN) and 100 EBV VCA-IgA positive healthy donors (VP). Plasma EBV VCA-IgA was determined by immunoenzymatic techniques. RESULTS: Thirty-four of the 174 cytokines varied significantly between the VP and NPC group. Plasma MIF and CCL3 were significantly elevated in NPC patients compared with VN and VP. Combination of MIF and CCL3 could be used for the differential diagnosis of NPC from VN cohort (area under the curve [AUC], 0.913; sensitivity, 90.00%; specificity, 80.30%), and combination of MIF, CCL3, and VCA-IgA could be used for the differential diagnosis of NPC from VP cohort (AUC, 0.920; sensitivity, 90.00%; specificity, 84.00%), from (VN+VP) cohort (AUC, 0.961; sensitivity, 90.00%; specificity, 92.00%). Overexpressions of MIF and CCL3 were observed in NPC plasma, NPC cell lines and NPC tissues. CONCLUSION: Plasma MIF, CCL3, and VCA-IgA combination significantly improves the diagnostic specificity of NPC in high-risk individuals.
Biomarkers* ; Blotting, Western ; Capsid* ; Cell Line ; Chemokine CCL3 ; Cohort Studies ; Cytokines ; Diagnosis ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Herpesvirus 4, Human* ; Humans ; Immunoglobulin A* ; Immunohistochemistry ; Macrophages* ; Plasma* ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Tissue Donors

PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.
Adenocarcinoma ; Chromogranin A ; Classification ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Neural Cell Adhesion Molecules ; Prognosis ; Stomach ; Stomach Neoplasms ; Synaptophysin