Update and latest advances in mechanisms and management of colitis-associated colorectal cancer.

Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD). Patients with IBD, including ulcerative colitis and Crohn's disease, are known to have an increased risk of developing CAC. Although the incidence of CAC has significantly decreased over the past few decades, individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer, and the incidence of CAC increases with duration. Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC. CAC has been shown to progress from colitis to dysplasia and finally to carcinoma. Accumulating evidence suggests that multiple immune-mediated pathways, DNA damage pathways, and pathogens are involved in the pathogenesis of CAC. Over the past decade, there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients. Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers. It is generally recommended that CAC patients undergo endoscopic removal or colectomy. This review summarizes the current understanding of CAC, particularly its epidemiology, mechanisms, and management. It focuses on the mechanisms that contribute to the development of CAC, covering advances in genomics, immunology, and the microbiome; presents evidence for management strategies, including endoscopy and colectomy; and discusses new strategies to interfere with the process and development of CAC. These scientific findings will pave the way for the management of CAC in the near future.

Gastrointestinal microbiome and cholelithiasis: Current status and perspectives.

Cholelithiasis is a common digestive disease affecting 10% to 15% of adults. It imposes significant global health and financial burdens. However, the pathogenesis of cholelithiasis involves several factors and is incompletely elucidated. In addition to genetic predisposition and hepatic hypersecretion, the pathogenesis of cholelithiasis might involve the gastrointestinal (GI) microbiome, consisting of microorganisms and their metabolites. High-throughput sequencing studies have elucidated the role of bile, gallstones, and the fecal microbiome in cholelithiasis, associating microbiota dysbiosis with gallstone formation. The GI microbiome may drive cholelithogenesis by regulating bile acid metabolism and related signaling pathways. This review examines the literature implicating the GI microbiome in cholelithiasis, specifically gallbladder stones, choledocholithiasis, and asymptomatic gallstones. We also discuss alterations of the GI microbiome and its influence on cholelithogenesis.

Integrated Network Pharmacology and Metabolomics Analysis to Reveal the Potential Mechanism of Siwu Paste on Aplastic Anemia Induced by Chemotherapy Drugs.

Purpose: This study aimed to reveal the multicomponent synergy mechanisms of SWP based on network pharmacology and metabolomics for exploring the relationships of active ingredients, biological targets, and crucial metabolic pathways. Materials: Network pharmacology, including TRRUST, GO, and KEGG, enrichment was used to discover the active ingredients and potential regulation mechanisms of SWP. LC-MS and multivariate data analysis method were further applied to analyze serum metabolomics profiling for discovering the potential metabolic mechanisms of SWP on AA induced by Cyclophosphamide (CTX) and 1-Acetyl-2-phenylhydrazine (APH). Results: A total of 27 important bioactive ingredients meeting the ADME (absorption, distribution, metabolism, and excretion) screening criteria from SWP were selected. Interaction networks were constructed and validated based on the 10 associated ingredients with the relevant targets. A total of 125 biomarkers were found by Metabolomics approach, which associated with the development of AA, mainly involved in amino acid metabolism and lipid metabolism. While SWP can reverse the above 12 metabolites changed by AA. Network analysis revealed the synergistic effects of SWP through the 43 crucial pathways, including Sphingolipid signaling pathway, Sphingolipid metabolism, Arginine and proline metabolism, VEGF signaling pathway, Estrogen signaling pathway. Conclusion: The study suggested that SWP is a useful alternative for the treatment of AA induced by CTX + APH. Its potential mechanisms are to improve hematopoietic microenvironment and promote bone marrow hematopoiesis therapies.

Development of a Nomogram Model for Treatment of Elderly Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

(1) Purpose: This study aims to explore risk-adapted treatment for elderly patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) according to their pretreatment risk stratification and the degree of comorbidity. (2) Methods: A total of 583 elderly LA-NPC patients diagnosed from January 2011 to January 2018 are retrospectively studied. A nomogram for disease-free survival (DFS) is constructed based on multivariate Cox regression analysis. The performance of the model is evaluated by using the area under the curve (AUC) of the receiver operating characteristic curve and Harrell concordance index (C-index). Then, the entire cohort is divided into different risk groups according to the nomogram cutoff value determined by X-tile analysis. The degree of comorbidities is assessed by the Charlson Comorbidity Index (CCI). Finally, survival rates are estimated and compared by the Kaplan-Meier method and the log-rank test. (3) Results: A nomogram for DFS is constructed with T/N classification, Epstein-Barr virus DNA and albumin. The nomogram shows well prognostic performance and significantly outperformed the tumor-node-metastasis staging system for estimating DFS (AUC, 0.710 vs. 0.607; C-index, 0.668 vs. 0.585; both p < 0.001). The high-risk group generated by nomogram has significantly poorer survival compared with the low-risk group (3-year DFS, 76.7% vs. 44.6%, p < 0.001). For high-risk patients with fewer comorbidities (CCI = 2), chemotherapy combined with radiotherapy is associated with significantly better survival (p < 0.05) than radiotherapy alone. (4) Conclusion: A prognostic nomogram for DFS is constructed with generating two risk groups. Combining risk stratification and the degree of comorbidities can guide risk-adapted treatment for elderly LA-NPC patients.

Liquid biopsy posttreatment surveillance in endemic nasopharyngeal carcinoma: a cost-effective strategy to integrate circulating cell-free Epstein-Barr virus DNA.

BACKGROUND: The optimal posttreatment surveillance strategy for nasopharyngeal carcinoma (NPC) remains unclear. Circulating cell-free Epstein-Barr virus (cfEBV) DNA has been recognized as a promising biomarker to facilitate early detection of NPC recurrence. Therefore, we aim to determine whether integrating circulating cfEBV DNA into NPC follow-up is cost-effective. METHODS: For each stage of asymptomatic nonmetastatic NPC patients after complete remission to primary NPC treatment, we developed a Markov model to compare the cost-effectiveness of the following surveillance strategies: routine follow-up strategy, i.e., (1) routine clinical physical examination; routine imaging strategies, including (2) routine magnetic resonance imaging plus computed tomography plus bone scintigraphy (MRI + CT + BS); and (3) routine 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT); cfEBV DNA-guided imaging strategies, including (4) cfEBV DNA-guided MRI + CT + BS and (5) cfEBV DNA-guided PET/CT. Clinical probabilities, utilities, and costs were derived from published studies or databases. Sensitivity analyses were performed. RESULTS: For all disease stages, cfEBV DNA-guided imaging strategies demonstrated similar survival benefits but were considerably more economical than routine imaging strategies. They only required approximately one quarter of the number of imaging studies compared with routine imaging strategies to detect one recurrence. Specifically, cfEBV DNA-guided MRI + CT + BS was most cost-effective for stage II (incremental cost-effectiveness ratio [ICER] $57,308/quality-adjusted life-year [QALY]) and stage III ($46,860/QALY) patients, while cfEBV DNA-guided PET/CT was most cost-effective for stage IV patients ($62,269/QALY). However, routine follow-up was adequate for stage I patients due to their low recurrence risk. CONCLUSIONS: The cfEBV DNA-guided imaging strategies are effective and cost-effective follow-up methods in NPC. These liquid biopsy-based strategies offer evidence-based, stage-specific surveillance modalities for clinicians and reduce disease burden for patients.

Assessment of Modifiable Factors for the Association of Marital Status With Cancer-Specific Survival.

Importance: Married patients with cancer have better cancer-specific survival than unmarried patients. Increasing the early diagnosis and definitive treatment of cancer among unmarried patients may reduce the survival gap. Objectives: To evaluate the extent to which marriage is associated with cancer-specific survival, stage at diagnosis, and treatment among patients with 9 common solid cancers and to recommend methods for reducing the survival gap. Design, Setting, and Participants: This retrospective, population-based cohort study included patients older than 18 years who were diagnosed with 1 of 9 common cancers between January 1, 2007, and December 31, 2016. Patient data were retrieved from the Surveillance, Epidemiology, and End Results Program. Statistical analyses were performed from August 1 to October 1, 2020. Exposures: Marital status, classified as married and unmarried (including single, separated, divorced, widowed, and unmarried patients or domestic partners). Main Outcomes and Measures: The primary outcome was the time ratio (TR) of cancer-specific survival (married vs unmarried). Mediation analyses were conducted to determine the extent to which the association of marriage with cancer-specific survival was mediated by stage at diagnosis and treatment. Results: This study included 1 733 906 patients (894 379 [51.6%] women; 1 067 726 [61.6%] married; mean [SD] age, 63.76 [12.60] years). Multivariate analyses found that those who were married were associated with better cancer-specific survival than unmarried patients (TR, 1.36; 95% CI, 1.35-1.37). Early diagnosis in breast cancer, colorectal cancer, endometrial cancer, and melanoma mediated the association between marital status and cancer-specific survival (breast cancer: proportion mediated [PM], 11.4%; 95% CI, 11.2%-11.6%; colorectal cancer: PM, 10.9%; 95% CI, 10.7%-11.2%; endometrial cancer: PM, 12.9%; 95% CI, 12.5%-13.3%; melanoma: PM, 12.0%; 95% CI, 11.7-12.4%). Surgery mediated the association between marital status and cancer-specific survival in lung (PM, 52.2%; 95% CI, 51.9%-52.4%), pancreatic (PM, 28.9%; 95% CI, 28.6%-29.3%), and prostate (PM, 39.3%; 95% CI, 39.0%-39.6%) cancers. Chemotherapy mediated the association of marital status with cancer-specific survival in lung (PM, 37.7%; 95% CI, 37.6%-37.9%) and pancreatic (PM, 28.6%; 95% CI, 28.4%-28.9%) cancers. Improved cancer-specific survival associated with marriage was greater among men than women (men: TR, 1.27; 95% CI, 1.25-1.28; women: TR, 1.20; 95% CI, 1.19-1.21). The contribution of receiving an early diagnosis and treatment with surgery or chemotherapy to the association between marital status and cancer-specific survival was greater among men than women (early diagnosis: PM, 21.7% [95% CI, 21.5%-21.9%] vs PM, 20.3% [95% CI, 20.2%-20.4%]; surgery: PM, 26.6% [95% CI, 26.4%-26.7%] vs PM, 11.1% [95% CI, 11.0%-11.2%]; chemotherapy: PM, 6.8% [95% CI, 6.7%-6.8%] vs PM, 5.1% [95% CI, 5.0%-5.2%]). Conclusions and Relevance: In this study, survival disparities associated with marital status were attributable to early diagnosis in breast, colorectal, and endometrial cancers as well as melanoma and to treatment-related variables in lung, pancreatic, and prostate cancers. The findings also suggest that marriage may play a greater protective role in the cancer-specific survival of men than of women.

Normal tissue complication probability (NTCP) models for predicting temporal lobe injury after intensity-modulated radiotherapy in nasopharyngeal carcinoma: A large registry-based retrospective study from China.

PURPOSE: To develop predictive models with dosimetric and clinical variables for temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Data of 8194 NPC patients who received IMRT-based treatment were retrospectively reviewed. TLI was diagnosed by magnetic resonance imaging. Dosimetric factors were selected by penalized regression and machine learning, with area under the receiver operating curve (AUC) calculated. Cox proportional hazards models containing the most predictive dosimetric factor with/without clinical variables were performed. A nomogram was generated as a visualization of Cox regression for predicting TLI-free survival. RESULTS: During median follow-up of 66.8 months (interquartile range [IQR] 54.2-82.2 months), 12.1% of patients (989/8194) developed TLI. Median latency from IMRT to TLI was 36 months (IQR 28-47 months). D0.5cc (dose delivered to 0.5-cm3 temporal-lobe volume) was the most predictive dosimetric factor (AUC: 0.799). Tolerance dose for 5% and 50% probabilities to develop TLI in 5 years were 65.06 Gy (95% confidence interval [CI]: 64.19-65.92) and 89.75 Gy (95% CI: 87.39-92.11), respectively. A nomogram comprising age, T stage, and D0.5cc significantly outperformed the model with only D0.5cc in predicting TLI (C-index: 0.78 vs. 0.737 in train set; 0.775 vs. 0.73 in test set; both P < 0.001). The nomogram-defined high-risk group had worse 5-year TLI-free survival. CONCLUSIONS: D0.5cc of 65.06 Gy was the tolerance dose of the temporal lobe. Reducing D0.5cc decreased risk of TLI, especially in older patients with advanced T stage. The nomogram could predict TLI precisely and allow individualized follow-up management.

Development and validation of a web-based calculator to predict individualized conditional risk of site-specific recurrence in nasopharyngeal carcinoma: Analysis of 10,058 endemic cases.

BACKGROUND: Conditional survival (CS) provides dynamic prognostic estimates by considering the patients existing survival time. Since CS for endemic nasopharyngeal carcinoma (NPC) is lacking, we aimed to assess the CS of endemic NPC and establish a web-based calculator to predict individualized, conditional site-specific recurrence risk. METHODS: Using an NPC-specific database with a big-data intelligence platform, 10,058 endemic patients with non-metastatic stage I-IVA NPC receiving intensity-modulated radiotherapy with or without chemotherapy between April 2009 and December 2015 were investigated. Crude CS estimates of conditional overall survival (COS), conditional disease-free survival (CDFS), conditional locoregional relapse-free survival (CLRRFS), conditional distant metastasis-free survival (CDMFS), and conditional NPC-specific survival (CNPC-SS) were calculated. Covariate-adjusted CS estimates were generated using inverse probability weighting. A prediction model was established using competing risk models and was externally validated with an independent, non-metastatic stage I-IVA NPC cohort undergoing intensity-modulated radiotherapy with or without chemotherapy (n = 601) at another institution. RESULTS: The median follow-up of the primary cohort was 67.2 months. The 5-year COS, CDFS, CLRRFS, CDMFS, and CNPC-SS increased from 86.2%, 78.1%, 89.8%, 87.3%, and 87.6% at diagnosis to 87.3%, 87.7%, 94.4%, 96.0%, and 90.1%, respectively, for an existing survival time of 3 years since diagnosis. Differences in CS estimates between prognostic factor subgroups of each endpoint were noticeable at diagnosis but diminished with time, whereas an ever-increasing disparity in CS between different age subgroups was observed over time. Notably, the prognoses of patients that were poor at diagnosis improved greatly as patients survived longer. For individualized CS predictions, we developed a web-based model to estimate the conditional risk of local (C-index, 0.656), regional (0.667), bone (0.742), lung (0.681), and liver (0.711) recurrence, which significantly outperformed the current staging system (P < 0.001). The performance of this web-based model was further validated using an external validation cohort (median follow-up, 61.3 months), with C-indices of 0.672, 0.736, 0.754, 0.663, and 0.721, respectively. CONCLUSIONS: We characterized the CS of endemic NPC in the largest cohort to date. Moreover, we established a web-based calculator to predict the CS of site-specific recurrence, which may help to tailor individualized, risk-based, time-adapted follow-up strategies.

Prognostic value of radiation interruption in different periods for nasopharyngeal carcinoma patients in the intensity-modulated radiation therapy era.

We aimed to investigate the prognostic value of radiation interruptions at different times on the overall survival (OS) and disease-free survival (DFS) of patients with nasopharyngeal carcinoma receiving intensity-modulated radiation therapy. Totally, 4510 patients were identified from a well-established big-data intelligence platform. Optimal interruption thresholds were identified using Recursive partitioning analyses. Actuarial rates were plotted using the Kaplan-Meier method and were compared using the log-rank test. Patients with preceding interruptions ≥1 d (5-year OS, 89.6% vs. 85.7%, p < 0.001; 5-year DFS, 81.4% vs. 76.4%, p < 0.001), or latter interruptions ≥4 d (88.4% vs. 82.3%, p < 0.001; 79.2% vs. 75.1%, p = 0.006) showed significant detrimental effects on OS and DFS than patients without those interruptions. However, no significant lower survival was identified in latter interruptions ≥1 d (5-year OS: 89.0% vs. 86.7%, p = 0.053; 5-year DFS, 80.2% vs. 77.8%, p = 0.080). Latter interruptions ≥4 d was an independent unfavorable prognostic factor for OS (HR, 1.404; 95% CI, 1.143-1.723, p = 0.001) and DFS (HR, 1.351; 95% CI, 1.105-1.652, p = 0.003) in multivariate analysis. Radiation interruptions longer than 3 days that occurred in the latter period of treatment with IMRT were independent factors in poorer survival. Efforts are needed to minimize radiation interruptions and improve the timely provision of treatment.

The Value of Umbilical Cord Blood Erythrocyte Index in the Screening of Neonatal Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship between umbilical cord blood erythrocyte index and thalasse-mia, and reveal its clinical value in the screening of thalassemia in neonates.@*METHODS@#2 919 cases of umbilical cord blood from neonatal who were born in Boai Hospital of Zhongshan Affiliated with Southern Medical University from July 2017 to December 2018 were collected, the routine blood tests were preformed to detect the umbilical cord blood. Thalassemia gene in peripheral blood of neonates was collected. The cut-off values of cord blood indexes were determined, and the sensitivity, specificity and other evaluation indexs were calculated.@*RESULTS@#Among the cord blood in 2 919 neonates, 314 cases were detected out as thalassemia(positive rate: 10.76%). The average level of RBC and RDW in 2 605 children with non-thalassemia was lower than those with 314 children with thalassemia. The levels of Hb, MCV, MCH, MCHC, HCT, Hb/RBC and MCV/RBC in children with non-thalassemia were higher than those with thalassemia, and there were significant differences in the neonates between the two groups. The RBC and RDW levels of neonates in the α-thalassemia group were higher than those in the non-thalassemia group, while the levels of Hb, MCV, MCH, MCHC, HCT, Hb/RBC and MCV/RBC of neonates were lower than those in the non-thalassemia group. The levels of MCV, MCH and Hb/RBC of neonates in the β-thalassaemia group were lower than those in the non-thalassaemia group. The levels of MCV, MCH, Hb/RBC, and MCV/RBC of neonates in the complex thalassemia group were lower than those in the non-thalassemia group. When the cut-off value of MCV was set to 106.05 fl, the sensitivity was 0.548, and the specificity was 0.907, the specificity was the highest among all indexes. The area under the ROC curve of the combined diagnosis of MCH+MCV/RBC was the largest(0.807), the sensitivity was 0.710, the specificity was 0.841, the positive predictive value was 0.348, and the negative predictive value was 0.960.@*CONCLUSION@#The single indicator of umbilical cord blood red blood cells has advantages and disadvantages for the screening of thalassemia, but the combination of MCH+MCV/RBC can improve the accuracy of the screening or diagnosis of thalassemia, it also has a positive effect to the reduction of the birth rate of children with thalassemia major, which showed a high popularization value in primary hospitals.

Effect of Siwu Paste on Hematopoietic Function of Bone Marrow in Rats with Aplastic Anemia and Its Mechanism / 中国实验方剂学杂志

Objective:To explore the regulatory effect of Siwu paste on the bone marrow hematopoietic function of aplastic anemia （AA） model rats. Method:SD rats were randomly divided into normal control group， model group， positive drug （Fufang E'jiao Jiang 10.8 g·kg^-1） group， high-dose Siwu paste （22.68 g·kg^-1） group and low-dose Siwu paste （5.67 g·kg^-1） group. Acetophenazine （APH） combined with cyclophosphamide （CTX） injection was used to establish the aplastic anemia rat model. The administration groups were given the corresponding drugs （<italic>ig</italic>） for 15 consecutive days. The levels of white blood cells （WBC）， red blood cells （RBC）， hemoglobin （HGB）， hematocrit （HCT） and platelets （PLT） in peripheral blood cells of rats were detected， thymus and spleen indexes were calculated and compared. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-3 （IL-3） and interleukin-6 （IL-6） in rat serum. The pathological changes of bone marrow were observed by hematoxylin eosin （HE） staining. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） methods were used to detect Toll receptor 4 （TLR4） and nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） protein and gene expression in rat femoral bone marrow cells. Result:Compared with the normal control group， the WBC， RBC， HGB， HCT and PLT levels of the model group were significantly reduced， the thymus index was significantly decreased， the spleen index was significantly increased， the serum IL-3 level was significantly decreased， and the IL-6 level was significantly increased. The number of neutrophils and megakaryocytes in the femoral bone marrow was reduced， and the medullary cavity was filled with edema fibrofatty tissue. The expressions of TLR4 and NF-<italic>κ</italic>B protein and mRNA in bone marrow cells were significantly increased （<italic>P</italic><0.01）. Compared with the model group， the levels of WBC， RBC， HCT and PLT in peripheral blood cells of rats in the high-dose Siwu paste group increased， the thymus index increased， the spleen index decreased， the IL-3 level was significantly increased， the IL-6 level was significantly decreased， the pathological morphology of femoral bone marrow was slightly improved， and the expressions of TLR4 and NF-<italic>κ</italic>B protein and mRNA in bone marrow cells decreased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Siwu paste may improve the bone marrow hematopoietic function of rats with aplastic anemia by regulating the expression of the bone marrow inflammation signal pathway TLR4/NF-<italic>κ</italic>B.

Mechanism Analysis of Bianketong Tablet in Treatment of Constipation-predominant Irritable Bowel Syndrome Based on Network Pharmacology and Bioinformatics / 中国实验方剂学杂志

Objective:To explore the potential mechanism of Bianketong tablet （BKT） in the treatment of constipation-predominant irritable bowel syndrome （C-IBS） based on network pharmacology and bioinformatics. Method:The BKT-meridian network was constructed for analyzing the combined effect of the nine Chinese herbs in BKT. The active components and targets of BKT were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and then screened according to the oral bioavailability （OB） and drug likeness （DL） criteria. Following the acquisition of C-IBS target set from GeneCards， Online Mendelian Inheritance in Man （OMIM）， Drugbank and DisGeNet， the protein-protein interaction （PPI） network was constructed. Cytoscape 3.7.2 was utilized for network visualization. The screened key targets were subjected to gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using DAVID platform. The C-IBS mouse model was established via intragastric administration of ice water， and the key targets of BKT against C-IBS were verified by enzyme linked immunosorbent assay （ELISA） and immunohistochemistry. Result:The large intestinal meridian was the main site where BKT acted. There were 70 potential active components in BKT， which acted on 227 intersection targets. Through T helper cell 17（Th17） differentiation， Toll-like receptor （TLR）， tumor necrosis factor and other signaling pathways， BKT participated in inflammatory response， immune regulation， intestinal nerve regulation， hormonal regulation， and oxidative stress response， thus exerting the therapeutic effects against C-IBS. As reveled by <italic>in vivo</italic> experiments， BKT significantly improved the small intestinal propulsion rate， up-regulated the expression of vasoactive intestinal peptide （VIP） in serum and colon tissue of C-IBS mice， and down-regulated the expression of nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）， interleukin（IL）-6， and TLR2 in serum and colon tissue， which confirmed the reliability of integration analysis. Conclusion:BKT inhibits C-IBS via multiple components， multiple targets， and multiple pathways. This study has provided ideas for further clinical research and experimental verification of BKT in the treatment of C-IBS.

Fabrication and characterization of porous titanium-based PbO2 electrode through the pulse electrodeposition method: Deposition condition optimization by orthogonal experiment.

Porous titanium-based PbO2 electrodes were successfully fabricated by pulse electrodeposition method. The primary pulse electrodeposition parameters, including pulse frequency (f), duty ratio (γ), average current density (Ja) and electrodeposition time (t) were considered in this study. An orthogonal experiment was designed based on those four factors and in three levels. SEM images and XRD results suggest that the surface morphology and structure of PbO2 electrodes could be easily changed by varying pulse electrodeposition parameters. Orthogonal analysis reveals that the increase of f and Ja could decrease the average grain size of PbO2 electrodes, which is conducive to create more active sites and promote the generation of hydroxide radicals. The electrochemical degradation of Azophloxine was carried out to evaluate the electrochemical oxidation performance of pulse electrodeposited electrodes. The results indicate that the influences of four factors can be ranked as follow: Ja >γ≈ t > f. The higher f, larger Ja and longer t could facilitate the optimization of the integrated electrochemical degradation performance of prepared PbO2 electrode. The accelerated life time is dominated by Ja and t, coincident with the average weight increase of ß-PbO2 layer. The optimal parameters of pulse electrodeposition turn out to be: f = 50 Hz, γ = 30%, Ja = 25 mA cm-2, t = 60 min. Together, the consequences of the experiments give assistance to uncover and roughly conclude the mechanism of pulse electrodeposition.

Individualized cumulative cisplatin dose for locoregionally-advanced nasopharyngeal carcinoma patients receiving induction chemotherapy and concurrent chemoradiotherapy.

OBJECTIVES: To screen subgroup potentially benefiting from cumulative cisplatin dose (CCD) ≥ 200 mg/m2 during concurrent chemoradiotherapy (CCRT) of patients with locoregionally-advanced nasopharyngeal carcinoma (LA-NPC) receiving induction chemotherapy (IC) and CCRT. MATERIALS AND METHODS: In total, 2 063 patients with non-disseminated LA-NPC diagnosed from 2009 to 2015 receiving IC plus CCRT were enrolled. Patients were restaged based on proposed stage groupings and risk groupings was established. After propensity score matching, survival outcomes were compared within different risk groupings with 200 mg/m2 CCD. Post-IC gross primary tumor (GTVp) and lymph node (GTVnd) volumes were calculated from planning computed tomography. The role of risk groupings and post-IC tumor volume to CCD was explored. RESULTS: Compared with the low-risk group, the high-risk group showed poor survival outcomes in terms of 5-year progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS). CCD ≥ 200 mg/m2 improved survival in terms of 5-year PFS, OS and DMFS in the high-risk group but not in the low-risk group. High-risk patients with unfavorable response to IC benefited from CCD ≥ 200 mg/m2 with respect to PFS and DMFS; while those in low-risk group or with favorable response to IC didn't. CONCLUSIONS: Risk groupings was effective for risk stratification. Combining risk groupings and post-IC tumor volume is a simple and useful method to guide individualized CCD treatment of CCRT for patients with LA-NPC receiving IC and CCRT. CCD ≥ 200 mg/m2 may be indicated for high-risk patients with unfavorable response to IC.

Prognostic potential of liquid biopsy tracking in the posttreatment surveillance of patients with nonmetastatic nasopharyngeal carcinoma.

BACKGROUND: The current study was performed to investigate whether circulating cell-free Epstein-Barr virus DNA (cfEBV DNA) would be useful for posttreatment surveillance in patients with nasopharyngeal carcinoma (NPC). METHODS: The authors identified a total of 1984 nondisseminated NPC patients from an institutional big-data research platform. Blood samples were collected within 3 months of the completion of radiotherapy and every 3 to 12 months thereafter for cfEBV DNA analysis. Patients were followed until disease recurrence was detected or for a median of 60 months. Diagnostic performance was assessed by calculating the sensitivity, specificity, and accuracy based on the clinical detection of disease recurrence by conventional surveillance modalities (imaging scans and pathological examination). RESULTS: During follow-up, a total of 767 patients (38.7%) had detectable cfEBV DNA. The recurrence rate among these patients was 63.8% (489 of 767 patients), which was significantly higher than that in patients with undetectable cfEBV DNA (8.6%; 105 of 1217 patients). cfEBV DNA sensitivity, specificity, and accuracy were 68.8%, 80.0%, and 78.2%, respectively, for local recurrence; 80.2%, 80.0%, and 85.9%, respectively, for regional recurrence; and 91.1%, 80.0%, and 92.8%, respectively, for distant metastasis. cfEBV DNA was found to have higher sensitivity for the detection of extrapulmonary metastases (94.9%-96.5%) compared with pulmonary metastases (78.4%). It is interesting to note that among the patients with disease recurrence with detectable cfEBV DNA, positive cfEBV DNA results preceded radiological and/or clinical evidence of disease recurrence by a median of 2.3 months (interquartile range, 0.1-9.5 months). In addition, of the 278 cfEBV DNA-positive patients who did not develop disease recurrence, 227 (81.7%) had transiently positive cfEBV DNA that fell to undetectable levels during long-term monitoring. CONCLUSIONS: Plasma cfEBV DNA in patients with NPC appears to be an early sign of tumor recurrence, especially extrapulmonary metastases.

Study on Addition and Subtraction Syndrome Differentiation Method of Huanglian Ejiaotang and Baihe Dihuangtang in Regulation of Neuroendocrine Network for Menopausal Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of addition and subtraction syndrome differentiation method of Huanglian Ejiaotang and Baihe Dihuangtang in the treatment of menopausal syndrome （MPS） and symptoms of deficiency of yin and hyperactivity of fire， and investigate its regulation effects on neuroendocrine network. Method:One hundred and forty-eight patients were divided into control group （74 cases） and observation group （74 cases） according to the random number table method. The patients in control group received estradiol/norethisterone acetate tablets， 3 mg/time， 1 time/day， while the patients in observation group received addition and subtraction of Huanglian Ejiaotang and Baihe Dihuangtang based on the same western medicine treatment as control group， orally 1 dose/day， with a treatment course of 3 months in both groups. Kupperman index （KI） score was evaluated before treatment and at 1 month， 2 months and 3 months after treatment. The Menopausal Quality of Life （MENQOL）， self-rating depression scale （SDS）， Self-rating Anxiety Scale （SAS）， Pittsburgh Sleep Quality Index （PSQI） and score of deficiency of yin and hyperactivity of fire were evaluated before and after treatment. The levels of serum estradiol （E2）， follicle stimulating hormone （FSH）， luteinizing hormone （LH）， norepinephrine （NE）， 5-hydroxytryptamine （5-HT）， nitric oxide （NO）， endothelin-1 （ET-1） and calcitonin gene-related peptide （CGRP） were detected before and after treatment. Result:The clinical efficacy in observation group was better than that in control group （Z=2.115， P<0.05）， and the KI scores in observation group at 1 month， 2 months and 3 months after treatment were lower than those in control group （P<0.01）， and the decrease of KI score in observation group after treatment was larger than that in control group （P<0.01）. The scores of various dimensions of MENQOL scale in observation group were lower than those in control group （P<0.01）. The scores of deficiency of yin and hyperactivity of fire， SAS， SDS and PSQI in observation group were all lower than those in control group （P<0.01）， and the level of E2 in observation group after treatment was higher than that in control group （P<0.01） ，while the levels of FSH and LH were lower than those in control group （P<0.01）.The levels of 5-HT and NE in observation group were higher than those in control group （P<0.01）.The NO level in observation group was higher than that in control group （P<0.01）， while the levels of CGRP and ET-1 were lower than those in control group （P<0.01）. During the study period， there were 5 drop-out cases， 2 excluded cases， and 67 completed cases in the control group. There were 7 drop-out cases， 1 excluded case， 66 completed cases in the observation group. Conclusion:On the basis of hormone replacement therapy， addition and subtraction of Huanglian Ejiaotang and Baihe Dihuangtang for patients with MPS （with symptom of deficiency of yin and hyperactivity of fire） can improve clinical symptoms， relieve depression and anxiety， improve sleep quality and enhance quality of life， and its clinical efficacy is superior to hormone replacement therapy alone. It can also regulate endocrine hormones， vasomotor factors and monoamine neurotransmitters， thereby improving clinical symptoms.

Clinical observation on herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of herb-partitioned spreading moxibustion at Baliao points plus climen for diminished ovarian reserve (DOR). Methods: A total of 60 patients with DOR were randomized into a spreading moxibustion group and a Western medicine group by the random number table method, with 30 cases in each group. The Western medicine group was treated with climen, starting from the 5th day of the menstrual cycle for 21 d. The spreading moxibustion group was treated with herb-partitioned spreading moxibustion at Baliao points on the basis of the medication in the Western medicine group, 1 h per time, once a week. The treatment was performed for 1 month as one treatment course in both groups, for 3 courses in total. The serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) in the patients were measured before and after treatment. The peak systolic velocity (PSV) and resistance index (RI) were also detected. The traditional Chinese medicine (TCM) symptom score was evaluated. The clinical efficacy was evaluated after treatment. Results: The total effective rate in the spreading moxibustion group was 93.3％, which was significantly higher than 80.0％ in the Western medicine group, and the difference between the groups was statistically significant (P<0.05). After treatment, the TCM symptom scores, the serum FSH levels, FSH/LH ratios and RI in both groups decreased, and the intra-group differences were all statistically significant (all P<0.05). The serum E2 level and PSV increased compared with those in the same group before treatment, and the intra-group differences were statistically significant (all P<0.05). After treatment, the TCM symptom score, the serum FSH level, FSH/LH ratio and RI in the spreading moxibustion group were lower than those in the Western medicine group, while the serum E2 level and PSV were higher than those in the Western medicine group, and the differences between the groups were statistically significant (all P<0.05). Conclusion: Herb-partitioned spreading moxibustion at Baliao points plus climen can produce valid therapeutic efficacy for DOR. It can improve the clinical symptoms, regulate serum hormone levels and increase ovarian blood perfusion, thus improving ovarian reserve function, producing more significant efficacy than climen alone.

The Role of Post-Neoadjuvant Chemotherapy Tumor Volume for Prognostication and Treatment Guidance in Loco-Regionally Advanced Nasopharyngeal Carcinoma.

The value of post-neoadjuvant chemotherapy (NACT) tumor volume for prognostication in loco-regionally advanced nasopharyngeal carcinoma (LA-NPC) is unascertained. Here, we recruited 4109 histologically proven LA-NPC (stage III-IVA) that were treated with radical chemo-intensive-modulated radiotherapy (IMRT). Post-NACT gross primary tumor (GTVp) and lymph node (GTVnd) volumes of each patient were calculated from planning computed tomography (CT). We observed similar linear association between GTVp/GTVnd and overall survival (OS); thresholds of 52 cm3 for GTVp and 12 cm3 for GTVnd were consistent for risk discretization for OS, disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). Recursive partitioning analysis (RPA) modelling incorporating T-/N-categories and GTVp/GTVnd yielded four T-N-volume (TNV) risk groupings with disparate OS (p < 0.001). TNV risk stratification outperformed GTVp/GTVnd and eighth edition TNM for predicting OS (AUC 0.643 vs. 0.541-0.591; p < 0.001), DFS (0.629 vs. 0.545-0.580; p < 0.001), and DMFS (0.652 vs. 0.522-0.621; p < 0.001). NACT + concurrent chemoradiotherapy (CCRT) over NACT + IMRT was not superior for low- and low-intermediate-risk groupings (p > 0.05 for both), but superior for intermediate- and high-risk groupings in terms of OS (HR 0.68 (95% CI 0.47-0.99) for intermediate risk, 0.73 (0.55-0.97) for high risk; both p < 0.05). Overall, GTVp/GTVnd represent effective indicators for prognostication and decision-making in LA-NPC after NACT.

Design and organization of neuroscience oriented training mode for medical postgraduates / 医学研究生学报

In order to promote the development of medical and biological fields and help the students trained under the existing system to form a clear overall view on neuroscience research, the author summarizes a systematic chart teaching method in the teaching process of neuroscience which helps the students understand easily. On the basis of theory studying, the article induces and interprets the priorities and hotspots in domestic neuroscience research, which not only cultivates students' interest and enthusiasm in scientific research but also facilitates the training process. It tries to seek the improvement of the education quality from the teachers' perspective and contribution and effectively inspire students' spontaneous excavation in research direction which combines mentor's research field and their own interest, leading students to innovate good learning habits constantly.

Correlation between the genotypes and clinical symptoms of human papilloma virus in male outpatients at STD clinics / 中华男科学杂志

<p><b>Objective</b>To investigate the distribution of the human papilloma virus (HPV) and its genotypes in the male outpatients at the clinics of sexually transmitted diseases (STD) in Changshu and analyze its association with the primary clinical symptoms so as to provide some evidence for the prevention and treatment of HPV infection in men.</p><p><b>METHODS</b>We collected exfoliated cell samples from the external genitals of 602 male outpatients at the STD clinics in Changshu from February 2016 to February 2018, extracted and amplified nucleic acids from the samples, and detected the HPV genotypes using the gene chip technique. We performed statistical analyses on the types of symptoms in clinical diagnosis and their correlation with the genotypes of HPV using the chi-square test.</p><p><b>RESULTS</b>The HPV positive rate in the male STD clinics was 48.2%, of which 47.2 % fell into the low-risk type, 30.0% with multiple infections. The main genotypes included HPV types 6, 11, 39, and 52, and the main HPV-related clinical symptoms were verruca (43.1%) and erythra (41.0%). Low-risk types 6 and 11 accounted for a significantly higher percentage than the high-risk types in the verruca patients (60.0% vs 15.0%, , P < 0.05), but showed no statistically significant difference from the latter in the erythra patients (38.7% vs 38.7%, P > 0.05). The incidence of low-risk infection was remarkably higher than that of high-risk infection in the acrobystitis and balanitis patients (P < 0.05), while the high-risk types constituted a markedly higher percentage than the low-risk and high- and low-risk mixed types in the asymptomatic men at physical examination (84.6% vs 0.0% and 15.4%, P < 0.05).</p><p><b>CONCLUSIONS</b>The HPV positive rate was as high as 48.2% in the males at the STD clinics in Changshu, and the main infection type was low-risk genotype single infection. The clinical symptoms of low-risk infection were mainly verruca and prepuce balanitis, and the high-risk type was mostly asymptomatic at physical examination.</p>