Risk factors for positive resection margins after endoscopic resection for gastrointestinal neuroendocrine tumors.

BACKGROUND: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.

Self-Assembly Behavior, Aggregation Structure, and the Charge Carrier Transport Properties of S-Heterocyclic Annulated Perylene Diimide Derivatives.

The construction of high-performance n-type semiconductors is crucial for the advancement of organic electronics. As an attractive n-type semiconductor, molecular systems based on perylene diimide derivatives (PDIs) have been extensively investigated over recent years. Owing to the fascinating aggregated structure and high performance, S-heterocyclic annulated PDIs (SPDIs) are receiving increasing attention. However, the relationship between the structure and the electrical properties of SPDIs has not been deeply revealed, restricting the progress of PDI-based organic electronics. Here, we developed two novel SPDIs with linear and dendronized substituents in the imide position, named linear SPDI and dendronized SPDI, respectively. A series of structural and property characterizations indicated that linear SPDI formed a long-range-ordered crystalline structure based on helical supramolecular columns, while dendronized SPDI, with longer alkyl side chains, formed a 3D-ordered crystalline structure at a low temperature, which transformed into a hexagonal columnar liquid crystal structure at a high temperature. Moreover, no significant charge carrier transport signal was examined for linear SPDI, while dendronized SPDI had a charge carrier mobility of 3.5 × 10-3 cm2 V-1 s-1 and 2.1 × 10-3 cm2 V-1 s-1 in the crystalline and liquid crystalline state, respectively. These findings highlight the importance of the structure-function relationship in PDIs, and also offer useful roadmaps for the design of high-performance organic electronics for down-to-earth applications.

Complex duodenal fistula after cholecystectomy successfully treated with endoscopic suturing.

We reported a 47-year-old female with a history of laparoscopic cholecystectomy presented with a complex duodenal fistula. The bleeding artery embolization and endoscopic suture of the duodenal fistula were performed successfully. We highlight the endoscopic tissue clip suture as a safe and feasible option when surgery is too risky.

Safety and efficacy of ESD for laterally spreading tumors with hemorrhoids close to the dentate line.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a curative treatment for laterally spreading tumors (LSTs). However, the outcomes of ESD for LSTs with hemorrhoids remain largely unknown. Our study aimed to evaluate the usefulness of ESD in managing LSTs with hemorrhoids. MATERIAL AND METHODS: We retrospectively collected 418 consecutive LST patients treated with ESD between 2011 and 2023. A retrospective comparative analysis was conducted. RESULTS: There were 85 patients included in the hemorrhoids group and 333 patients included in the other group. The en-bloc resection rate, R0 resection rate, and curative resection rate were comparable in these two groups (p > 0.05). The LSTs with hemorrhoids have a significantly higher intraoperative bleeding rate during ESD when compared to the other group (12.9% vs. 5.4%, p = 0.028). Rates of intraoperative perforation and anal pain in the hemorrhoid group were significantly higher than those in the no-hemorrhoid group (2.4% vs. 0%, p = 0.041; 9.4% vs.0.6%, p < 0.001; respectively). Moreover, most of the related manifestations caused by hemorrhoids were relieved to various degrees after ESD. CONCLUSIONS: ESD is a safe and effective treatment strategy for LSTs with hemorrhoids. A multi-center and prospective study should be conducted in the future to validate our results.

Effects of chronotype on antidepressant treatment and symptoms in patients with depression: a multicenter, parallel, controlled study.

AIM: To analyze the changes of chronotypes in patients with depression before and after treatment, and explore the effects of different chronotypes on antidepressant treatment and the dimensions of common symptoms in patients with depression. METHODS: 180 patients with depression were selected from 10 tertiary psychiatric hospitals in Zhejiang province, according to the scores of morningness-eveningness questionnaire (MEQ), the patients were divided into three groups: early-type group, middle-type group and late-type group. The 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale anxiety Scale (HAMA), Snaith Hamilton Pleasure Scale (SHAPS), multidimensional fatigue inventory-20(MFI-20) and Pittsburgh sleep quality index (PSQI) were measured at baseline and at the end of the 2nd, 4th, 8th and 12th weeks, the variance analysis of repeated measures was used to analyze the change of each index in the study. The remission rate of depression at each time point was statistically analyzed. RESULTS: Of the 180 patients included in the study, 26 were lost to follow-up, and 154 were finally included in the analysis. At baseline, 14.93%, 56.5% and 28.57% of the subjects were diagnosed as middle-late type, middle-late type and early-late type respectively, the total scores of Shaps and MFI-20 in the early-type group were higher than those in the late-type group and the middle-type group (p < 0.05). During the 12-week antidepressant treatment period, the time effect of PSQI, Shaps, MFI-20 and MEQ had interaction with different time groups (p < 0.05). During the treatment, the multiple symptom dimensions of depression were improved to different degrees, but the changing trend was not the same, and the recovery of the anhedonia was obviously delayed, in early-type patients, there are many symptoms such as loss of pleasure and sleep disorders. There was no significant effect on the remission rate of depression in different time type (p > 0.05) . CONCLUSION: The disorder of chronotypes is common in patients with depression. The time effect of different time type on different symptom dimension of depression was affected, but the effect on remission rate of depression was not significant. To strengthen the management of biological chronotype rhythm in patients with depression may be of great significance in the treatment of depression.

Peroral Endoscopic Myotomy for Achalasia in Older Adults: A Retrospective Analysis of 39 Cases with a Minimum Follow-Up of 5 Years.

Peroral endoscopic myotomy (POEM) has demonstrated favorable short-term safety and efficacy in older adults, while a comprehensive understanding of the long-term outcomes were vague. We aimed to evaluate clinical outcomes in older adults' 5-year postop after undergoing POEM to treatment achalasia. Older adults from a single hospital who received POEM between January 2010 and January 2017 were analyzed. Older persons were reached to evaluate their symptoms at present and encouraged repeat examinations for objective follow-up. The clinical success, POEM-related indicators, POEM-related adverse events, and quality of life were assessed. Thirty-nine older adults with a mean age of 70.82 ± 4.72 who underwent POEM were studied at a mean 84.23 ± 25.06 month follow-up. The preoperative diagnosis was achalasia type I in 7 older adults, achalasia type II in 26 older adults, and achalasia type III in 2 older adults. Sixteen older adults had prior treatment and 21 older adults suffered from comorbidities. The median operative time was 50 (25-120) minutes, and perioperative adverse events were recorded in four older adults. The current Eckardt scores were significantly lower than that before POEM (2.08 ± 2.12 vs. 6.58 ± 1.78, P < 0.001). Besides, long-term clinical success was gained in 66.7% of older adults. Three older adults received postop treatment for symptom recurrence. Ultimately, 80.6% of old adults expressed satisfaction with POEM, while 27.8% of older adults suffered from symptomatic reflux. In conclusion, POEM can provide symptomatic improvement in a large proportion of older adults with achalasia at 5-year postop.

A multicenter, randomized controlled study on the efficacy of agomelatine in ameliorating anhedonia, reduced motivation, and circadian rhythm disruptions in patients with major depressive disorder (MDD).

OBJECTIVE: To evaluate the clinical efficacy and safety of Agomelatine in improving symptoms in patients with major depressive disorder (MDD), providing more scientific evidence for the treatment of depression, and offering more effective therapeutic options for patients. METHODS: A total of 180 MDD patients in acute phase from 10 psychiatric hospitals of Grade three in Zhejiang Province were enrolled in this 12-week study with the competitive and consecutive pattern, and they were randomized into two different groups treated with flexible-dosage antidepressants of selective serotonin reuptake inhibitors (SSRI) or agomelatine, respectively. The subjects were evaluated with psychological scales of HAMD-17, HAMA, SHAPS for anhedonia, MFI-20 for fatigue, PQSI for sleep quality and MEQ for disturbances in chronobiologic rhythms at baseline, 2, 4, 8 and 12-weekend points, and TESS was used for side-effect. The results were analyzed with repeated measurement analysis of variance. RESULTS: The two groups each had 90 participants, and there were no significant differences at baseline. The scores of various assessment scales showed statistically significant time main effects during the visits (P < 0.01). The Agomelatine group demonstrated faster efficacy within 2 weeks, with better improvement in SHAPS, MEQ, and PSQI compared to the SSRIs group. However, the remission rate at 12 weeks was lower in the Agomelatine group than in the SSRIs group (63.3% and 72.2%), but the difference between the groups was not statistically significant. The Agomelatine group had fewer adverse reactions (14.4% and 16.7%), but there was a slightly higher incidence of liver function impairment (6.7% and 4.4%), with no statistically significant difference between the groups. CONCLUSION: Agomelatine, as a novel antidepressant, shows certain advantages in improving depression and anxiety symptoms and is comparable to SSRIs in terms of safety. However, its long-term efficacy and safety on MDD or other depressive subtypes still require further observation and research.

Associations between changes of smartphone pedometer-assessed step counts and levels of obesity-related breast cancer biomarkers in non-cancer women: A population-based observational study.

While a higher level of physical activity (PA) is inversely associated with a higher breast cancer (BC) risk, the health benefits of daily steps on obesity-related BC biomarkers remain unclear. We aimed to understand the associations of changes in step counts with levels of five obesity-related BC biomarkers during a two-year follow-up. In total, 144 non-cancer women (47.96 ± 5.72) were observed on both 2019 and 2021. A structured questionnaire, daily steps and fasting blood samples were collected before (t0, 2019) and after (t1, 2021). Levels of biomarkers (IGF-binding proteins 3, adiponectin, soluble leptin receptor, C-reactive protein, and resistin) were assayed by ELISA. Participants were divided into persistent low steps, decreasing steps, increasing steps, and persistent high steps. Associations of categories on proposed biomarkers were estimated using linear regression models, with persistent low steps as reference. Associations between time-varying step counts with biomarkers were quantified using mixed linear models. Compared with persistent low steps, increasing steps is associated with a reduction in C-reactive protein level (ß=-0.74, 95%CI=-1.23--0.26, P-value = 2.98 × 10-3). An inverse association between time-varying step counts with C-reactive protein level was identified, consistent across different obesity types and baseline step level categories. No association with daily step counts was observed for other proteins.

Effects and mechanisms of FBXO31 on Taxol chemoresistance in esophageal squamous cell carcinoma.

Taxol is commonly used chemotherapy regimen for esophageal squamous cell carcinoma (ESCC). Study of the underlying mechanisms of Taxol chemoresistance provides better understanding of esophageal cancer treatment and may provide a rational molecular target for diagnosis and intervention. Here we showed FBXO31, which was reported to be highly expressed in ESCC and significantly associated with poor prognosis, could regulate ESCC chemosensitivity to Taxol. Silencing of FBXO31 in ESCC cells sensitized cells to Taxol treatment, evidenced by FACS analysis and TUNEL assay, showing as an increased apoptotic population in FBXO31-knockdown cells compared to the control cells. The mass spectrometry data and coimmunoprecipitation results showed FBXO31 could bind with cofilin-1. Cofilin-1 knockdown in FBXO31-overexpression cells reversed FBXO31-induced suppression of cell apoptosis, suggesting FBXO31-mediated Taxol chemoresistance is associated with cofilin-1. Furthermore, in vivo experiments confirmed that knockdown of FBXO31 sensitized ESCC to Taxol treatment. This finding substantiated a pivotal role of FBOX31 in ESCC chemoresistance, indicating that FBXO31 may be a potential indicator or target for drug resistance in ESCC.

MiR-196a promotes the proliferation and migration of esophageal cancer via the UHRF2/TET2 axis.

The aim of this study was to investigate the functions and molecular mechanism of miR-196a in esophageal cancer (EC). miR-196a as well as UHRF2 and TET2 mRNA and protein levels in EC tissues and cells were detected using quantitative real-time PCR or western blot, respectively. Cell proliferation was evaluated via MTT assay. Transwell assays were used to detect cell migration. In addition, the targeted relationship between miR-196a and UHRF2 was assessed through a dual luciferase reporter assay. Enzyme-linked immunosorbent assay was performed to detect the levels of the cytosine intermediates 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). We found increased miR-196a expression in EC tissues and cells but decreased UHRF2 and TET2 expression. Next, functional experiments showed that knockdown of miR-196a or UHRF2 overexpression suppress EC cell proliferation and migration. miR-196a negatively regulates TET2 expression by directly targeting UHRF2. UHRF2 overexpression decreased 5mC levels but increased 5hmC levels. Furthermore, TET2 downregulation reversed the functions of miR-196a inhibition on EC cell proliferation and migration. Collectively, our study suggested that miR-196a was closely related to the progression of EC possibly by regulating the UHRF2/TET2 axis. Thus, miR-196a represents a potential new EC therapeutic target.

Targeting CXCR4 to suppress glioma-initiating cells and chemoresistance in glioma.

Glioma initiating cells (GICs), also known as glioma stem cells, display the capacity to recapitulate the functional diversity within the tumor. Despite the great progress achieved over the last decades, defining the key molecular regulators of GICs has represented a major obstacle in this field. In our study, data from The Cancer Genome Atlas database illustrated a relationship between C-X-C motif chemokine receptor 4 (CXCR4) expression and the survival of glioma patients. Mechanistically, we further indicated that CXCR4 mediated the upregulation of Kruppel like factor 5 (KLF5), a zinc-finger-containing transcription factor, to facilitate the proliferation of GICs. What's more, CXCR4 also enhanced the chemoresistance through KLF5/Bcl2-like 12 (BCl2L12) in glioma. The elevated expression of KLF5 and BCL2L12 induced by CXCR4 was dependent on phosphoinositide 3-kinases (PI3K)/serine/threonine kinase (AKT) signaling. Importantly, combined application of temozolomide and a CXCR4 inhibitor efficiently reversed CXCR4 mediated drugs resistance and improved anticancer effects in vivo. Collectively, our findings confirmed that CXCR4 promoted GICs proliferation via the KLF5/BCL2L12 dependent pathway, which may enrich the understanding of GICs and help drive the design of efficacious therapeutic strategies.

Kynurenine produced by tryptophan 2,3-dioxygenase metabolism promotes glioma progression through an aryl hydrocarbon receptor-dependent signaling pathway.

The current studies associated with tumor biology continue to describe a high correlation between tryptophan (Trp) metabolism and tumor progression. These findings reflect the complex underlying mechanism of tumor development and highlight the need to explore additional drug targets for carcinoma-associated diseases. In our study, we reported that elevated Trp metabolism was observed in highly malignant glioma tumor tissues from patients. The elevated Trp metabolism in glioma cells were induced by the overexpression of Trp 2,3-dioxygenase 2 (TDO2), which further contributed to the production of the metabolite kynurenine (Kyn). Subsequently, the Kyn derived from Trp metabolism was able to mediate the activation of the aryl hydrocarbon receptor (AhR) and downstream PI3K/AKT signals, resulting in the strengthening of tumor stemness and growth. Meanwhile, the activation of the AhR could promote the process of epithelial-mesenchymal transition in gliomas through a TGF-ß-dependent mechanism, leading to enhanced tumor invasion in vitro and in vivo. Inhibition of the AhR using StemRegenin 1 was demonstrated to suppress glioma growth and improve the outcome of traditional chemotherapy in subcutaneous tumor-bearing mice, representing a promising therapeutic target for clinical glioma treatment.

The constricting effect of reduced coronary artery compliance on the left ventricle is an important cause of reduced diastolic function in patients with coronary heart disease.

BACKGROUND: Previous studies of left ventricular diastolic function (LVDF) have focused on the decrease in active and passive diastolic function due to ischemic factors but have not investigated if the decrease in compliance of the coronary arteries that bypass the surface of the heart and travel between the myocardium could cause a constricting effect on the ventricular wall like that caused by myocardial fibrosis. METHODS AND RESULTS: 581 patients diagnosed with coronary heart disease (CHD) were divided into A group (patients are the control group), B group (patients with less than 50% coronary artery stenosis), C group (patients with coronary artery stenosis between 50 and 75%), D group (patients with coronary artery stenosis greater than 75%) according to the degree of coronary stenosis. The diastolic function of the ventricle is reflected by applying the relaxation time constant T value, which refers to the time between peak dp/dt and end-diastolic pressure in the left ventricle. It was concluded that there was a statistical difference in Gensini scores between patients in groups B, C and D (P < 0.001). And multiple linear regression analysis showed that T was correlated with Gensini score and C-dp/dtmax (R = 0.711, P < 0.001). Grouping according to the site of stent implantation and the number of stents implanted, it was found out that the changes in T values before and after left anterior descending artery (LAD) stent implantation were greater than left circumflex artery (LCX) and right coronary artery (RCA) (P < 0.001). And multiple linear regression revealed a correlation between T values and stent length, ventricular stiffness, and C-dp/dtmax (P = 0.001). CONCLUSIONS: The decrease in compliance of the coronary arteries bypassing the surface of the heart and travelling between the myocardium would cause a constricting effect on the ventricular wall like that caused by myocardial fibrosis.

Short- and long-term comparison of robotic and laparoscopic gastrectomy for gastric cancer by the same surgical team: a propensity score matching analysis.

BACKGROUND: Research on short-term outcomes and oncology results after robotic gastrectomy (RG) is still limited, especially from a single surgical team. The purpose of this study was to compare the short-term and long-term outcomes of robotic and laparoscopic gastrectomy (LG). METHODS: Between October 2014 and September 2019, 1686 consecutive patients who underwent MIS gastrectomy were enrolled. The patients were divided into RG and LG groups according to surgical type. Groups were matched at a 1:1 ratio using propensity scores based on the following variables: age, sex, ASA score, primary tumor location, histologic type, pathological stage, and neoadjuvant chemotherapy. The primary outcomes were 3-year overall survival (OS) and relapse-free survival (RFS). The secondary outcomes were postoperative short-term outcomes. RESULTS: Demographic and baseline characteristics were similar between the two groups after matching. Compared to the LG group, the RG group had a significantly higher retrieved lymph node (LN) number (32.15 vs 30.82, P = 0.040), more retrieved supra-pancreatic LNs (12.45 vs 11.61, P = 0.028), lower estimated blood loss (73.67 vs 98.08 ml, P < 0.001), but longer operation time (205.18 vs 185.27 min, P < 0.001) and higher hospitalization costs ($13,607 vs $10,928, P < 0.001) in the matched cohort. In the subgroup analysis, we observed that compared with LG, patients with advanced gastric cancer benefitted more from RG surgery. The matched cohort analysis demonstrated no statistically significant differences for 3-year OS or RFS (log-rank, P = 0.648 and P = 0.951, respectively): 80.3% and 77.0% in LG vs. 81.2% and 76.6% in RG, respectively. CONCLUSION: RG has certain technical advantages over LG, especially in patients with advanced gastric cancer. However, RG does not improve long-term oncology outcomes.

Clinical outcomes in central nervous system solitary-fibrous tumor/hemangiopericytoma: a STROBE-compliant single-center analysis.

BACKGROUND: Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are rare mesenchymal tumors in the central nervous system with a high tendency to relapse, having a significant impact on quality of life (QoL). Due to the rarity of intracranial SFT/HPC, the prognostic factors and optimal treatment remain to be elucidated. Meanwhile, quality of life in patients with intracranial SFT/HPC is seldomly concerned. Thus, we aim to survey about the quality of life and underline some aspects demanding concern in intracranial SFT/HPC treatment through summarizing our case series in recent ten years. METHODS: Patients with intracranial SFT/HPC who underwent surgical resection from January 2009 to June 2019 were included in the study. Clinical features, such as age, gender, and resection extent, were collected. The EuroQol Five Dimensions Questionnaire (EQ-5D) was used to assess the patients' quality of life (QoL). Prognosis factors related to progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS: Thirty-six patients with a mean follow-up period of 61.6 months (range 13-123 months) were included in this study. Sixteen (44.4%) patients achieved gross total resection (GTR). Fourteen patients (38.9%) with tumor progression experienced adjuvant radiotherapy (11.1%) or Gamma Knife surgery (GKS, 27.8%). According to the 2016 WHO classification, there were 6 (16.7%) grade I SFT/HPC, 11 (30.5%) grade II SFT/HPC, and 19 (52.8%) grade III SFT/HPC. The PFS and OS were 29 months (range 4-96 months) and 38 months (range 4-125 months). The median EQ5D-3 L tariff with or without progression was 0.617 (95% CI 0.470-0.756) and 0.939 (95% CI 0.772-0.977) respectively. Gross total resection (GTR, p = 0.024) and grade I SFT/HPC (p = 0.017) were significantly associated with longer PFS. In multivariate analysis, GTR (HR 0.378, 95% CI 0.154-0.927) and adjuvant therapy (HR 0.336, 95% CI 0.118-0.956) result in significantly longer PFS in patients with SFT/HPC. CONCLUSIONS: Patients underwent GTR and adjuvant therapy had longer PFS. Similarly, patients with lower WHO grade had relatively longer PFS. Therefore, GTR is advocated for the treatment of SFT/HPC. And adjuvant therapy such as GKS could be an alternative treatment for patients who underwent STR or with tumor progression. Further, the QoL decreased in patients with tumor progression and metastasis, and more attention is demanded to the QoL of intracranial SFT/HPC patients.

A simplified model for the gas-vapor bubble dynamics.

This paper presents a full numerical model accounting for the heat transfer and phase-change by combining the modified Keller-Miksis equation with the second order term of compressibility of liquid, partial differential equations (PDEs), and Hertz-Knudsen-Langmuir equation. Then, a simplified model for studying the dynamics of the cavitation bubble or bubble excited by the acoustic waves is proposed. The major contribution is to simplify the full model with PDEs to a set of coupled ordinary differential equations (ODEs). Specifically, two energy PDEs are converted to three ODEs by coupling the boundary conditions. The comparison among the full model and other simplified models is used to validate the accuracy and superiority of the simplified model, from which the application range of the proposed simplified model can be determined.

First Report of Anthracnose Caused by Colletotrichum jinshuiense on Goldthread in China.

Goldthread (Coptis chinensis Franch) is one of the most widely used Chinese traditional medicine plants with remarkable medicinal properties (Mizrahi et al. 2014). In July 2019, a new anthracnose-like leaf spot disease was observed in Banqiao Town, Enshi, Hubei, China. The incidence rate ranged from 10% to 20%. Infected leaves firstly showed oil-like dots, further gradually expanded to irregular whorls with a pale center and dark-brown edge. Petiole infection led to leaves dropping when severe occurrence. Black acervuli were developed on the infected leaves with abundant setae, especially near veins. To identify the causal agent, 4-mm2 tissues were derived from the disease-health junction and surface-disinfected with 0.1% mercury dichloride for 1 min and 75% ethanol for 30 s respectively. They were placed on a PDA plate and incubated at 25°C after being rinsed with sterile water three times. Isolates were purified by single spore isolation. Colonies on PDA were white to pale-gray with dense aerial mycelia, and the underside was yellowish to olive. Colonies grow 77.5 to 81.5 mm in 1 week. No conidia were observed during vegetable growth, but conidiomatal acervuli were found on infected leaves. Setae were 1-3 septate, dark-brown, 78.0 to 134.5 µm (mean = 108 ± 23.4) long, 4.1 to 9.1 µm (mean = 6.1 ± 1.1) diameter, cylindrical to conical, apices acute. Conidiophores hyaline to pale brown, septate. Conidia were hyaline, unicellular, aseptate, curved, cylindrical, often guttulate, measuring 20.1 to 28.0 × 3.5 to 5.4 µm (mean = 25.4 ± 1.7 × 4.5 ± 0.5 µm), L/W ratio = 5.6. Hyphae septate branched, hyaline to pale brown, 1.6 to 4.5 in diameter. Hyphopodial appressoria pale to medium brown, smooth-walled, globose or obovoid, 6.3 to 9.9 × 4.1 to 7.6 µm (mean = 8.3 ± 0.9 × 7.6 ± 0.7 µm), L/W ratio = 1.1. Morphological features were similar to the description of C. jinshuiense (Fu et al. 2019). To identify its phylogenetic position, maximum-likelihood (ML) analyses of two isolates (Esh8 and Esh 11) were implemented with a concatenation of multiple sequences of the internal transcribed spacer region (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), beta-tubulin (TUB2), and chitin-synthase 1 (CHS-1) using MEGA 7. The sequences were amplified using primers ITS1/ITS4, GDF1/GDR1, ACT-512F/ACT-783R, T1/Bt2b, CHS-79F/CHS-354R (Weir et al. 2012) and deposited in GenBank with accession numbers MW440484 - MW440485 (ITS), MW676256 - MW676257 (GAPDH), MW676252 - MW676253 (ACT), MW676254 - MW676255 (TUB2) and MW676258 - MW676259 (CHS-1). Results indicated they were clustered with C. jinshuiense in the C. dematium species complex. Isolates were inoculated onto injured healthy leaves (20 leaves) with mycelial plugs, ten leaves being inoculated with blank plugs were used as control. Disease symptoms were consistent with those observed in the field after five days post-inoculation with a 100% incidence rate, while no symptom was observed on the control leaves. And same isolates were isolated from six inoculated leaves with 100% re-isolation frequency. These results fulfilled Koch's postulates. In a previous study, C. boninense was identified as the causal agent of goldthread anthracnose in Chongqing, China (Ding et al. 2020). To our knowledge, this study is the first report of anthracnose on goldthread caused by C. jinshuiense in China.

FBX4 mediates rapid cyclin D1 proteolysis upon DNA damage in immortalized esophageal epithelial cells.

It has been implied that deregulation of cyclin D1 turnover under stresses can facilitate genomic instability and trigger tumorigenesis. Much focus has been placed on identifying the E3 ligases responsible for mediating cyclin D1 degradation. However, the findings were quite controversial and cell type-dependent. Little is known about how cyclin D1 is regulated in precancerous cells upon DNA damage and which E3 ligases mediate the effects. Here we found cyclin D1 reduction is an early response to DNA damage in immortalized esophageal epithelial cells, with expression dropping to a low level within 1 h after γ-irradiation. Comparison of temporal expression of cyclin D1 upon DNA damage between immortalized NE083-hTERT and NE083-E6E7, the latter being p53/p21-defective, showed that DNA damage-induced rapid cyclin D1 reduction was p53-independent and occurred before p21 accumulation. Overexpression of cyclin D1 in NE083-E6E7 cells could attenuate G0/G1 cell cycle arrest at 1 h after irradiation. Furthermore, rapid reduction of cyclin D1 upon DNA damage was attributed to proteasomal degradation, as evidenced by data showing that proteasomal inhibition by MG132 blocked cyclin D1 reduction while cycloheximide facilitated it. Inhibition of ATM activation and knockdown of E3 ligase adaptor FBX4 reversed cyclin D1 turnover in immortalized NE083-hTERT cells. Further study showed that knockdown of FBX4 facilitated DNA breaks, as indicated by an increase in γ-H2AX foci in esophageal cancer cells. Taken together, the results substantiated a pivotal role of ATM and FBX4 in cyclin D1 proteolysis upon DNA damage in precancerous esophageal epithelial cells, implying that deregulation of the process may contribute to carcinogenesis of esophageal squamous cell carcinoma.

Safety and efficacy of peroral endoscopic myotomy with standard myotomy versus short myotomy for treatment-naïve patients with type II achalasia: a prospective randomized trial.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) has emerged as an effective endoscopic treatment modality for achalasia. However, there is no consensus regarding the length of muscle bundle dissection during POEM. The most commonly used approach is standard myotomy (about 10 cm). We herein compared the outcomes between standard myotomy versus short myotomy for the management of treatment-naïve patients with type II achalasia. METHODS: This was a prospective, single-center, randomized trial in China. Previously untreated adults with a clinical diagnosis of type II achalasia, confirmed by manometric testing, were enrolled between February 2018 and February 2019. Patients were randomly assigned to POEM with standard myotomy or short myotomy. Clinical data on demographic characteristics, operative parameters, pre- and postoperative Eckardt scores, esophageal manometry results, 24-hour pH test, and adverse events were recorded and compared between the 2 groups. RESULTS: Of 100 randomized patients, 94 underwent treatment (48 in the standard myotomy group and 46 in the short myotomy group), and 91 (97%) completed the study. POEM was successfully accomplished in most patients (97.8%). The primary outcome of treatment success occurred in 45 of 48 patients (93.8%) in the standard myotomy group versus 44 of 46 (95.7%) in the short myotomy group, with no statistically significant difference between the 2 groups (P = .520). There were no significant between-group differences in postoperative esophageal manometry, Eckardt score, diameter of the esophageal lumen, quality of life, procedure-related adverse events, or reflux esophagitis (P > .05). Postoperative abnormal esophageal acid exposure occurred more often in the standard myotomy group than in the short myotomy group (21/48 patients [43.8%] vs 11/46 patients [23.9%], P = .042). Meanwhile, the short myotomy group showed a significant reduction in total procedure time compared with the standard myotomy group (31.2 ± 15.3 minutes vs 45.6 ± 16.2 minutes, respectively, P < .05). CONCLUSIONS: Among treatment-naïve patients with type II achalasia, standard and short POEM were comparable in terms of providing treatment efficacy and improving quality of life at 1 year, whereas short POEM is technically simpler to perform and requires less procedure time. Moreover, the short POEM approach resulted in fewer cases of postoperative abnormal esophageal acid exposure. (Clinical trial registration number: ChiCTR1800014989.).

Enhanced Recovery after Surgery in Elderly Gastric Cancer Patients Undergoing Laparoscopic Total Gastrectomy.

BACKGROUND: The aim of this study was to evaluate the effects of the enhanced recovery after surgery (ERAS) program versus conventional perioperative care on the short-term postoperative outcomes among elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. METHODS: Elderly patients with gastric cancer (age ≥ 65 y) who are undergoing laparoscopic total gastrectomy were randomized to ERAS or conventional perioperative care groups. Short-term postoperative outcomes, including postoperative hospital stay, mortality, complications, readmission rate, and reoperation rate were compared between the two groups. In addition, blood samples were taken preoperatively (baseline) and on postoperative days 1, 3, and 5. Systemic human leukocyte antigen (HLA)-DR expression on monocytes and C-reactive protein (CRP) were analyzed. RESULTS: Of the 171 eligible patients, 85 patients were assigned to receive ERAS program treatment (ERAS group) and 86 patients to receive conventional care (conventional group). The patients' characteristics were comparable. Postoperative hospital stay was shorter in the ERAS group than in the conventional group (11 [7-11] versus 13 [8-20] d, P < 0.001). Hospital mortality, overall morbidity, morbidity ≥ Clavien-Dindo (C-D) grade II, readmission rate, and reoperation rate did not show significant differences between the two groups. However, morbidity ≥ C-D grade IIIa was lower in the ERAS group than that in the conventional group (8.2% versus 18.6%, P = 0.047). The ERAS program shortened the number of days to postoperative first flatus, first defecation, semifluid diet, and soft bland diet. Moreover, the ERAS program increased the HLA-DR expression on monocytes and decreased the CRP levels on postoperative days 1, 3, and 5. CONCLUSIONS: The ERAS program was feasible and effective for elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. The benefits of ERAS were associated with improvement of impaired immune function and suppression of inflammatory reaction.