[Research progress of prognostic biomarkers in diffuse large B-cell lymphoma].

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy. A variety of indicators have been identified to predict the prognosis of DLBCL. However, with the emerging new drugs and new therapeutic options in recent years, the prognostic value of these risk prediction models becomes limited, failing to accurately guide treatment. The rapid development of high throughput technologies has led to dramatic improvement in understanding of the biology of DLBCL. The emergence of various new biomarkers contributes to further understanding the pathogenesis, treatment optimization and prognostic stratification of this disease. This review summarizes the prognostic biomarkers related to DLBCL, which mainly covers the hematological, genetic and tumor microenvironment factors, aiming to provide some theoretical basis for the precision treatment of DLBCL.

[Four-steps surgery for infected pancreatic necrosis based on "Step-up" strategy: a retrospective study].

Objective: To examine the effect of the "four-steps" treatment on infectious pancreatic necrosis(IPN). Methods: The data of 207 patients who were diagnosed with IPN from January 2013 to December 2017 at Department of Pancreaticobiliary Surgery, the First Affiliated Hospital of Harbin Medical University were analyzed retrospectively. Among 207 patients, 132(63.8%) were males and 75(36.2%) were females. The median age was 45 years old (range: 19 to 80 years old). One hundred and fifty-eight patients(76.3%) suffered severe acute pancreatitis and 49 patients(23.7%) suffered moderately severe acute pancreatitis. Percutaneous catheter drainage(PCD) was performed on all the patients(Step 1). Patients received "four-steps" minimally invasive treatment strategy in step-up group(173 patients). The following steps after PCD were mini-incision access pancreatic necrosectomy(MIAPN) (Step 2), sinus tract endoscopic debridement and(or) PCD for residual infections(Step 3) and finally conventional open pancreatic necrosectomy(OPN) (Step 4). Patients(34 cases) received conventional open pancreatic necrosectomy after invalided PCD in OPN group. The perioperative parameters and prognosis were compared between Step-up group and OPN group. Normally distributed quantitative variables were analyzed by t-test, non-normally distributed quantitative variables were analyzed by Wilcoxon chi-square test and categorical variables were analyzed by χ(2) test or Fisher exact test, respectively. Results: The basic characteristics of the two groups of patients were similar, but the referral rate of patients and the rate of preoperative 3 days organ failure in the OPN group were significantly higher than those of step-up group patients(47.1% vs. 28.9%, χ(2)=4.313, P=0.038; 26.5% vs. 9.2%, χ(2)=2.819, P=0.011). The frequency of PCD and the number of PCD tube (root) were less than those in the step-up group(1(1) vs. 2(1), Z=-3.373, P=0.018; 2(1) vs. 3(2), Z=-2.208, P=0.027). Compared with the OPN group, the interval time from onset to surgery and the MIAPN operation time were significantly shorter in the step-up group(29(15) days vs. 36(17)days, Z=-0.567, P=0.008; 58(27)minutes vs. 90(56)minutes, Z=-3.908, P<0.01); postoperative mortality was lower(5.8% vs.17.6%, χ(2)=4.070, P=0.044); the overall incidence of postoperative complications was reduced(23.1% vs. 55.9%, χ(2)=14.960, P<0.01) and the incidence of new-onset organ failure was decreased after operation in the step-up group(37.5% vs.47.4%, χ(2)=7.133, P=0.007). The incidence of local abdominal complications (pancreatic fistula, intra-abdominal hemorrhage, gastrointestinal fistula) showed no significant difference between the two groups (P>0.05). Fewer patients required ICU treatment after operation in the step-up group compared with OPN group(22.0% vs. 44.1%, χ(2)=6.204, P=0.013). Patients in the Step-up group has shorter hospital stay than patients in OPN group (46(13) days vs. 52(13)days, Z=-1.993, P=0.046). Conclusions: The clinical effects of "four-steps" exhibited the superiority of minimally invasive treatment of IPN.And MIAPN is a simple, safe and effective procedure to remove pancreatic necrotic tissue and decrease complications.

[Research advances on the therapy of pancreatic fistula after pancreatic surgery].

Pancreatic fistula is a common and serious complication after pancreatic surgery. Pancreatic fistula, intra-abdominal infection and hemorrhage are known as the " lethal triad" after pancreatic surgery, which seriously affect the curative efficacy of operation. Although the incidence of pancreatic fistula has not been significantly reduced, there have been a large number of studies on the risk factors of pancreatic fistula and the means of prevention and therapy, which try to minimize the harm of pancreatic fistula. In this article we review the recent development of the latest definition, high risk factors and treatment of postoperative pancreatic fistula according to relevant literatures at home and abroad, aiming at summarizing the research advances on the therapy of pancreatic fistula after pancreatic surgery.

[Clinicopathological features of thyroid papillary microcarcinoma of which the maximum diameter is less than 5 mm: a series of 487 cases].

Objective: To analyze the clinical and pathological features of papillary thyroid microcarcinoma(PTMC) of which the maximum diameter is less than 5 mm. Methods: Clinical data of 487 PTMC (≤5 mm) patients who underwent primary surgery by the same team of doctors between March 2013 to March 2016 at Department of Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University were analyzed retrospectively. Female patients accounted for 77.4%(377/487). The age ranged from 22 to 80 years, with an average of (46±11) years.χ2 test and multivariate Logistic regression analysis were used to analyze risk factors. Results: There were 93.6% (456/487) of the patients with preoperative definite diagnosis. There were 92.6% (452/487) of the patients underwent unilateral thyroid lobectomy with isthmectomy and ipsilateral central lymph node dissection. Multifocal carcinoma accounted for 20.3% (99/487), Ⅲ to Ⅳ phase cases accounted for 12.3% (60/487), patients with low risk of recurrence accounted for 67.6% (329/487). The central lymph node metastasis rate was 34.9% (170/487). Male (OR=2.149, 95%CI: 1.367 to 3.381), age<45 years (OR=0.451, 95%CI: 0.303 to 0.672), multifocal carcinoma (OR=1.798, 95%CI: 1.116 to 2.898), and capsular invasion (OR=3.678, 95%CI: 1.406 to 9.622) were the independent risk factors for lymph node metastasis (P<0.05). Conclusion: Regardless of tumor size, PTMC still needs to be taken seriously, especially male, age < 45 years, capsular invasion, or multifocal carcinoma patients.

Up-regulation of KCa3.1 promotes human airway smooth muscle cell phenotypic modulation.

Airway smooth muscle (ASM) cell phenotype modulation, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to proliferative diseases such as allergic asthma and chronic obstructive pulmonary disease (COPD). KCa3.1 has been suggested to be involved in regulating ASM cell activation, proliferation, and migration. However, little is known regarding the exact role of KCa3.1 in ASM cell phenotypic modulation. To elucidate the role of KCa3.1 in regulating ASM cell phenotypic modulation, we investigated the effects of KCa3.1 channels on ASM contractile marker protein expression, proliferation and migration of primary human bronchial smooth muscle (BSM) cells. We found that PDGF increased KCa3.1 channel expression in BSM cells with a concomitant marked decrease in the expression of contractile phenotypic marker proteins including smooth muscle myosin heavy chain (SMMHC), smooth muscle α-actin (α-SMA), myocardin and KCa1.1. These changes were significantly attenuated by the KCa3.1 blocker, TRAM-34, or gene silencing of KCa3.1. Pharmacological blockade or gene silencing of KCa3.1 also suppressed PDGF-induced human BSM cell migration and proliferation accompanied by a decrease in intracellular free Ca(2+) levels as a consequence of membrane depolarization, resulting in a reduction in cyclin D1 level and cell cycle arrest at G0-G1 phase. Additionally, PDGF-induced up-regulation of KCa3.1 and down-regulation of BSM contractile marker proteins were regulated by the ERK inhibitor U0126 and the AKT inhibitor LY294002. These findings highlight a novel role for the KCa3.1 channel in human BSM cell phenotypic modulation and provide a potential target for therapeutic intervention for proliferative airway diseases.

TNF-α-induced CXCL8 production by A549 cells: involvement of the non-neuronal cholinergic system.

It was recently suggested that the non-neuronal cholinergic system has a regulatory role in pulmonary inflammation. We investigated this system's involvement in the control of cytokine production by the A549 human alveolar epithelial cell line. CXCL8 and acetylcholine (ACh) concentrations were measured using ELISA and LC-MS/MS, respectively. The mRNA expression of muscarinic receptor (MR) subtypes was determined using RT-PCR. In A549 cells, TNF-α increased the release of CXCL8 and ACh and the expression of the subtype 3 MR (M3R). Furthermore, TNF-α-induced CXCL8 secretion was (i) inhibited by the MR antagonist tiotropium and the M3R antagonist 4-DAMP and (ii) enhanced by the M1/M3R agonist pilocarpine and the cholinesterase inhibitor physostigmine. Taken as a whole, these results suggest that ACh release by A549 cells enhances TNF-α-induced CXCL8 secretion through activation of the M3R. Western blot analysis revealed that pilocarpine and physostigmine enhanced the TNF-α-induced phosphorylation of ERK1/2 and p38 MAPK and the degradation of IκBα. Inhibition of these pathways with specific inhibitors abrogated the pilocarpine-induced CXCL8 release. Our results suggest that the TNF-α-induced secretion of CXCL8 in A549 cells is regulated by the release of ACh, the latter's binding to the M3R and the downstream activation of NF-κB and the ERK1/2 and p38 MAPK signaling pathways. Our findings suggest that MR antagonists may have anti-inflammatory effects by preventing pro-inflammatory events driven by endogenous, non-neuronal ACh.

Functional analysis of DNA methylation in lung cancer.

OBJECTIVES: We aimed to explore the DNA methylation difference between lung cancer samples and non-cancer lung samples, and to investigate the role of DNA methylation in the mechanism of lung cancer development. Besides, we analyzed the transcriptional regulation network of DNA methylation and the miRNAs regulated by DNA methylation. This study provides a framework for DNA methylation in other tumors or diseases. MATERIALS AND METHODS: DNA methylation and gene expression profiles used were obtained from Gene Expression Omnibus. Firstly, we identified differentially methylated genes (DMGs) by Student's t-test. Then we detected the biological processes and pathways changed in lung cancer by Gene Ontology (GO) and KEGG pathway enrichment analysis. The transcriptional factors in differential genes were identified and the microRNAs regulated by them were also obtained in TransmiR. RESULTS: We obtained 108 DMGs between lung cancer samples and non-cancer samples. Besides development related biological processes and pathways were dramatically disordered. For the DMGs, we identified 11 transcriptional factors regulating them. Moreover, we screened out 21 relationships between DMGs and their transcriptional targets. Five microRNAs are reported to be regulated by DNA methylation genes. Finally a regulation network of DNA methylation was constructed. CONCLUSIONS: DNA methylation participates in carcinogenesis at the transcriptional and post-transcriptional level. Aberrant DNA methylation will prevent its binding with the upstream regulatory proteins, inhibit the function of downstream target genes and regulate the expression of downstream miRNA, and consequently affect cell development, immunoresponse and apoptosis.

Practising case-based learning in oral medicine for dental students in China.

INTRODUCTION: Teacher-centred education dominates dental education in China. Student-centred education has recently been introduced in the School of Stomatology, Wuhan University, and the effectiveness of such methods needs to be tested. The purpose of this study is to compare the learning outcomes of case-based learning (CBL) and lecture-based education (LBE) in an oral medicine curriculum. MATERIALS AND METHODS: We chose oral leukoplakia as the learning subject for dental students. Forty fourth-year dental students participated in the study. First, they were presented to basic knowledge of oral leukoplakia and related oral mucosal diseases. Then, they were divided into a CBL group (n=20) and an LBE group (n=20) by random numbers. The groups experienced the remaining course in separate groups. All students answered a questionnaire on their satisfaction with the education and the same standardised written test to analyse their learning outcomes. RESULTS: Both CBL and LBE courses were well accepted by students according to the satisfactory scores of the questionnaire. The test scores of the CBL group (90.00±6.69) were significantly higher (P<0.01) than those of the LBE group (83.00±6.77). The percentage of high test score (test score≥85) of the CBL group (85%) was also significantly higher (P<0.01) than that of the LBE group (45%). CONCLUSIONS: In this example, CBL was found to be more effective than LBE to teach dental students. These findings suggest that CBL should be added in our future oral medicine curriculum for dental students.

Application of optimized LSTM in prediction of the cumulative confirmed cases of COVID-19.

This paper proposes an optimized Long Short-Term Memory (LSTM+) model for predicting cumulative confirmed cases of COVID-19 in Germany, the UK, Italy, and Japan. The LSTM+ model incorporates two key optimizations: (1) fine-adjustment of parameters and (2) a 're-prediction' process that utilizes the latest prediction results from the previous iteration. The performance of the LSTM+ model is evaluated and compared with that of Backpropagation (BP) and traditional LSTM models. The results demonstrate that the LSTM+ model significantly outperforms both BP and LSTM models, achieving a Mean Absolute Percentage Error (MAPE) of less than 0.6%. Additionally, two illustrative examples employing the LSTM+ model further validate its general applicability and practical performance for predicting cumulative confirmed COVID-19 cases.

Gate dependent photo-responses of carbon nanotube field effect phototransistors.

Gate dependent photoconductivity of carbon nanotube (CNT) field effect phototransistors (FEPs) was systematically investigated in this study. The photo-response comparisons of CNT FEPs with symmetric and asymmetric metal structures connecting to the same CNT revealed that the gate effect contributed to a sensitivity improvement with a lower dark current, a higher photocurrent, and an enhanced photovoltage. A functionalized asymmetric FEP, fabricated by partially doping the CNT utilizing a polyethylene imine (PEI) polymer, verified that FEPs delivered a better performance by using asymmetric structures. A multi-gate FEP, with three pairs of side-gates that can electrostatically dope different sections of a CNT independently, was fabricated to examine the gate structure dependent photo-responses. Experimental measurements showed an unconventional photocurrent improvement that was weakly dependent on the gate location, which was attributed to the unique charge distribution of one-dimensional semiconductors.

Successful organ donation from brain dead donors in a Chinese organ transplantation center.

Solid organ transplantation is an effective treatment for patients with end-stage organ failure. Donation after brain death (DBD) is a means of addressing the inadequate supply of acceptable donor organs but has only gradually begun to be accepted in mainland China. A major barrier has been the absence of brain death and organ transplant legislation. This paper describes our initial experience with organ transplantation using organs from brain dead donors and discusses strategies for encouraging organ transplantation and brain death legislation in China. Six patients underwent renal transplantation and two patients underwent liver transplantation with organs procured from three brain dead donors at the Organ Transplantation Center, the 181st Hospital. All patients are alive with excellent graft function. DBD is an important means of increasing the number of organs available for transplantation and its widespread implementation in China should be encouraged. Brain death and organ transplantation legislation is necessary to ensure the rights and obligations of donors, recipients and medical institutions.

Actin filaments altered distribution in wheat (Triticum aestivum) "Bending Root" to respond to enhanced Ultraviolet-B radiation.

Plants adjust their shoot growth to acclimate to changing environmental factors, such as to enhanced Ultraviolet-B (UV-B) radiation. However, people have ignored that plant roots can also respond to UV-B light. Here, we find the morphology curled wheat roots under UV-B radiation, that we call, "bending roots." The curly region is the transition zone of the root after observed at the cellular level. After exposed to enhanced UV-B radiation for 2 d (10.08 KJ/m2/d), cell size decreased and actin filaments gathered in wheat roots. We also find that H2O2 production increased and that content of the indole-3-acetic acid (IAA) increased remarkably. The pharmacological experiment revealed that actin filaments gathered and polymerized into bundles in the wheat root cells after irrigated H2O2 and IAA. These results indicated that actin filaments changed their distribution and formed the "bending root," which was related to H2O2 production and increase in IAA. Overall, actin filaments in wheat root cells could be a subcellular target of UV-B radiation, and its disruption determines root morphology.

Effectiveness of standardized ginkgo biloba extract on cognitive symptoms of dementia with a six-month treatment: a bivariate random effect meta-analysis.

INTRODUCTION: The objective of this study is to take into consideration the influence of baseline risk on the treatment effect and evaluate the effectiveness of standardized GINKGO BILOBA extract (GbE) on cognitive symptoms of dementia with the treatment period of approximately 6 months. METHODS: We systematically searched the literature to identify all randomized placebo-controlled clinical trials (English language) of GbE in the treatment of dementia. Data were extracted from selected trials and combined with standard meta-analysis methods. A bivariate meta-analysis was carried out to further estimate the effect size of GbE. RESULTS: The random effect estimate of standard mean difference (SMD) between GbE and placebo groups of 6 selected trials was -0.89 (95% CI -1.82 to 0.04) in the assessment of cognitive function. Bivariate random effect estimate of difference of change in ADAS-cog scores was -2.65 (95% CI --4.53 to -0.76), which showed a significant difference in favor of GbE. CONCLUSION: Considering baseline risk in the assessment of treatment effect, GbE was found to be effective for cognitive functions in dementia with the treatment of 6 months.

Surgical treatment of esophageal leiomyoma located near or at the esophagogastric junction via a thoracoscopic approach.

Esophageal leiomyoma can be enucleated safely and effectively by minimally invasive surgery. The laparoscopic approach has been a conventional option for this kind of tumor located near or at the esophagogastric (EG) junction. The aims of this study were to evaluate the surgical outcome of thoracoscopic resection of leiomyoma at the EG junction, and discuss factors affecting the incidence of postoperative gastroesophageal reflux. Fourteen patients who underwent thoracoscopic resection of esophageal leiomyoma located near or at the EG junction (<4 cm above the esophageal hiatus) from January 2002 to August 2007 were reviewed retrospectively. Tumor characteristics, surgical methods, and postoperative outcomes were evaluated. A left approach of video-assisted thoracoscopy was used in 13 patients; a right approach was used for the other patient, whose multiple tumors were located in the EG junction and mid-esophagus. Postoperative recovery was uneventful in all patients, with no mucosa leakage or other significant complications. Mean tumor size was 3.2 cm (1.2-6.0 cm). Of the 14 patients, two had serpiginous leiomyoma, two had multiple tumors, and the others had solitary tumors. Mean postoperative stay in hospital was 7 days (4-11 days). Postoperative dysphagia was not reported, although gastroesophageal reflux was noted in one patient. Thoracoscopic resection of esophageal leiomyomas near or at the EG junction is feasible, with a low prevalence of postoperative gastroesophageal reflux.

Unique histological features of the left atrial posterior wall.

The left atrial posterior wall (LAPW) plays a critical role in atrial fibrillation, but the underlying mechanism remains unclear. In the present study, we sought to characterize the histological features of the LAPW. Different atrial regions were dissected from hearts of normal Sprague-Dawley rats and humans. Haematoxylin/eosin and van Gieson staining were used to analyse atrial cardiomyocyte arrangement and collagen distribution, respectively. Intercellular junctions were evaluated by transmission electron microscopy. In contrast with other atrial regions, the LAPW exhibited more disorganized cardiomyocytes, larger intercellular spaces and variable myocardial fibre arrangement. The proportion of collagen was significantly higher in the LAPW than in other atrial regions. Interestingly, desmosomes were sparse along with intercellular gaps in the LAPW. In summary, distinct disarrangement of cardiomyocytes and an abundance of collagen exist in the LAPW. The sparsity of desmosomes in the LAPW may be related to the heterogeneous distribution and separation of atrial myocytes.

Discovery of talatisamine as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons.

Blocking specific K+ channels has been proposed as a promising strategy for the treatment of neurodegenerative diseases. Using a computational virtual screening approach and electrophysiological testing, we found four Aconitum alkaloids are potent blockers of the delayed rectifier K+ channel in rat hippocampal neurons. In the present study, we first tested the action of the four alkaloids on the voltage-gated K+, Na+ and Ca2+ currents in rat hippocampal neurons, and then identified that talatisamine is a specific blocker for the delayed rectifier K+ channel. External application of talatisamine reversibly inhibited the delayed rectifier K+ current (IK) with an IC50 value of 146.0+/-5.8 microM in a voltage-dependent manner, but exhibited very slight blocking effect on the voltage-gated Na+ and Ca2+ currents even at the high concentration of 1-3 mM. Moreover, talatisamine exerted a significant hyperpolarizing shift of the steady-state activation, but did not influence the steady state inactivation of IK and its recovery from inactivation, suggesting that talatisamine had no allosteric action on IK channel and was a pure blocker binding to the external pore entry of the channel. Our present study made the first discovery of potent and specific IK channel blocker from Aconitum alkaloids. It has been argued that suppressing K+ efflux by blocking IK channel may be favorable for Alzheimer's disease therapy. Talatisamine can therefore be considered as a leading compound worthy of further investigations.

EMA-CO chemotherapy for high-risk gestational trophoblastic neoplasia: a clinical analysis of 54 patients.

This study was designed to analyze the outcomes of chemotherapy for high-risk gestational trophoblastic neoplasia (GTN) with EMA-CO regimen as primary and secondary protocol in China. Fifty-four patients with high-risk GTN received 292 EMA/CO treatment cycles between 1996 and 2005. Forty-five patients were primarily treated with EMA-CO, and nine were secondarily treated after failure to other combination chemotherapy. Adjuvant surgery and radiotherapy were used in the selected patients. Response, survival and related risk factors, as well as chemotherapy complications, were retrospectively analyzed. Thirty-five of forty-five patients (77.8%) receiving EMA-CO as first-line treatment achieved complete remission, and 77.8% (7/9) as secondary treatment. The overall survival rate was 87.0% in all high-risk GTN patients, with 93.3% (42/45) as primary therapy and 55.6% (5/9) as secondary therapy. The survival rates were significantly different between two groups (chi(2)= 6.434, P =0.011). Univariate analysis showed that the metastatic site and the number of metastatic organs were significant risk factors, but binomial distribution logistic regression analysis revealed that only the number of metastatic organs was an independent risk factor for the survival rate. No life-threatening toxicity and secondary malignancy were found. EMA-EP regimen was used for ten patients who were resistant to EMA-CO and three who relapsed after EMA-CO. Of those, 11 patients (84.6%) achieved complete remission. We conclude that EMA-CO regimen is an effective and safe primary therapy for high-risk GTN, but not an appropriate second-line protocol. The number of metastatic organs is an independent prognostic factor for the patient with high-risk GTN. EMA-EP regimen is a highly effective salvage therapy for those failing to EMA-CO.

The role of bowel surgery with cytoreduction for epithelial ovarian cancer.

AIMS: To assess the efficiency and morbidity associated with bowel resection with the initial cytoreduction procedure for advanced ovarian cancer. MATERIALS AND METHODS: A review was carried of 95 patients with ovarian cancer who underwent cytoreductive surgery between 2000 and 2003. The relationship between dichotomised preoperative, intra-operative and postoperative outcome variables were tested using SPSS software. Kaplan-Meier curves were generated to compare survival. Cox proportional hazards regression was used to determine the independent significance of factors after cytoreductive surgery. RESULTS: In patients in whom bowel resection was carried out, the largest residual tumour mass was <1cm in 66.67% of patients, compared with 45.28% of patients undergoing surgery without bowel resection (P=0.038). The median survival in the optimally debulked patients was 50.38 months compared with 37.15 months in the patients who had suboptimal cytoreduction (P=0.0021). The median survival in patients undergoing bowel resection was 50.70 months compared with 44.62 months in the patients who had cytoreduction without bowel resection (P=0.2176). Multivariate analysis showed that optimal cytoreduction (P=0.005) was found to be independently prognostic for overall survival. Major adverse events, such as ileus, intestinal fistulae, urinary tract fistulae, were not significantly different between groups. CONCLUSION: Bowel resection is a worthwhile endeavour in selected patients with advanced ovarian cancer to increase therapeutic efficiency. The surgical morbidity rate from these procedures is not serious and seems acceptable.