Clinical and cytological characteristics of serous effusions in 69 cases of lymphoma patients.

BACKGROUND: To explore the value of cell morphology, immunophenotype, and gene alterations of serosal effusion in the diagnosis of lymphoma. METHODS: Serosal effusion of 69 cases of lymphoma patients were collected, including 36 cases with malignant effusion and 33 cases with nonmalignant effusion. Ordinary cytology, liquid-based cytology, cellblock, and immunocytochemical staining were performed in each case, some cases were detected by fluorescence in situ hybridization for C-MYC, BCL2, and BCL6 gene translocations. T/B cell ratio in malignant and nonmalignant serosal effusions was analyzed and compared by flow cytometry (FCM) and immunohistochemical (IHC), respectively. The prognostic value of serous effusion in diffuse large B-cell lymphoma (DLBCL) was investigated and another 20 DLBCL cases without effusion were successively selected as control. RESULTS: The number of naive lymphocytes, apoptotic bodies, and mitotic figures were more common in malignant effusions compared with nonmalignant effusions (p < .01). The top three lymphomas in malignant effusion were DLBCL (19/36, 52.8%), mantle cell lymphoma (MCL) (4/36, 11.1%, 3 blastoid variant) and high-grade B-cell lymphoma (HGBL) (4/36, 11.1%). T/B cell ratio by FCM analysis ranged from 0.00 to 0.55 (mean 0.084) in malignant effusion, and 2.58 to 984.00 (mean 249.9) in nonmalignant effusion. The difference was significant (p = .017). The T/B cell ratio by IHC analysis ranged from 0.02 to 3.00 (mean 0.200) in malignant effusion, and 2.00-100.00 (mean 34.10) in nonmalignant effusion. The difference was significant (p = .017). In the effusions involving DLBCL, most effusions were present at the time of diagnosis (57.9%); single pleural effusions were more common (36.8%). The median overall survival times of patients with malignant effusion, nonmalignant effusion and DLBCL without serous effusion were 11, 17, and 23 months respectively (p = .04). Three patients of HGBL died, and the overall survival times were 5, 8, and 9 months, respectively. CONCLUSIONS: The cytomorphological characteristics combined with immunophenotype, FCM, gene rearrangement, and other tests can diagnose and classify patients with effusion as the first symptom. The T/B cell ratio is less than 1 by FCM or IHC suggesting a malignant serosal effusion. The presence of malignant effusion in DLBCL patients is an important clue for poor prognosis.

[Effects of electroacupuncture on gait and proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle].

OBJECTIVE: To observe the effects of electroacupuncture on threshold of pain, gait, proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle, and to explore the possible mechanism of electroacupuncture in promoting the repair of acute injury of skeletal muscle. METHODS: A total of 48 SD rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an electroacupuncture group (18 rats). In the model group and the electroacupuncture group, the model of acute blunt trauma of gastrocnemius muscle was established by self-made impactor. In the electroacupuncture group, electroacupuncture was applied at "Chengshan" (BL 57) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once a day, 30 min each time. Electroacupuncture intervention was performed for 3, 7 and 14 days according to the sampling time. On the 1st, 3rd, 7th and 14th days after modeling, the mechanical withdrawal pain threshold of hindfoot was detected by Von Frey method; the standing time and the maximum contact area of the right hindfoot were recorded by Cat Walk XTTM animal gait analysis instrument; the morphology of the right gastrocnemius muscle and the number of inflammatory cells were observed by HE staining; the positive expression of paired box gene 7 (Pax7) and myogenic differentiation (MyoD) of the right gastrocnemius muscle was detected by immunofluorescence. RESULTS: After modeling, the muscle fiber rupture and massive infiltration of red blood cells and inflammatory cells were observed in the right gastrocnemius muscle; after electroacupuncture intervention, the morphology of muscle fiber was intact and the infiltration of inflammatory cells was improved. Compared with the blank group, in the model group, the differences of mechanical withdrawal pain threshold between the left and right foot were increased (P<0.05), the standing time was shortened and the maximum contact area of the right hindfoot was decreased (P<0.05), the number of inflammatory cells and the positive expression of Pax7 and MyoD of the right gastrocnemius muscle were increased (P<0.05) on the 1st, 3rd, 7th and 14th days after modeling. Compared with the model group, in the electroacupuncture group, the differences of mechanical withdrawal pain threshold were decreased (P<0.05), the standing time was prolonged (P<0.05), the number of inflammatory cells of right gastrocnemius muscle was decreased (P<0.05) on the 7th and 14th days after modeling; the maximum contact area of the right hindfoot was increased (P<0.05), the positive expression of MyoD of the right gastrocnemius muscle was increased (P<0.05) on the 3rd, 7th and 14th days after modeling; the positive expression of Pax7 of the right gastrocnemius muscle was increased (P<0.05) on the 3rd day after modeling. CONCLUSION: Electroacupuncture can effectively improve the pain threshold and gait in rats with acute blunt trauma of gastrocnemius muscle, and promote the repair of skeletal muscle injury, the mechanism may be related to the up-regulation of Pax7 and MyoD, so as to promoting the proliferation and differentiation of muscle satellite cell.

Case report: Circulating tumor DNA technology displays temporal and spatial heterogeneity in Waldenström macroglobulinemia during treatment with BTK inhibitors.

Background: Waldenström macroglobulinemia (WM) is a rare subtype of B-cell lymphoma. Rituximab-based combination therapy and Bruton's tyrosine kinase (BTK) inhibitors have greatly improved the prognosis of WM. Despite the high response rate and good tolerance of BTK inhibitors in treatment of WM, a proportion of patients still experience disease progression. Case presentation: We report a 55-year-old man with relapsed WM. The patient achieved partial remission after six courses of CHOP chemotherapy and multiple plasma exchanges in initial treatment. He was admitted to the hospital with abdominal distension, and was diagnosed with relapsed WM and subsequently started on zanubrutinib. Disease progression and histological transformation occurred during treatment. We performed liquid biopsies on transformed plasma, tumor tissue and ascites at the same time and found high consistency between ascites and tissues. Moreover, we detected resistance mutations of BTK inhibitors (BTK, PLCG2) in ascites that were not detected in plasma or tissue. Eventually, the patient died during the 15-month follow-up after relapse. Conclusion: We describe a rare case of WM transformation to DLCBCL treated with chemoimmunotherapy and BTK inhibition. We analyzed tumor DNA obtained at different anatomic sites and circulating tumor DNA (ctDNA) derived from plasma and ascites specimens, with apparent significant temporal and spatial heterogeneity. The case specifically highlights the clinical value of ctDNA of ascites supernatant from WM patients, which is a more convenient and relatively noninvasive method compared with traditional invasive tissue biopsy.

Effect of arsenic trioxide plus etoposide, solumedrol, high­dose cytarabine and cisplatin chemotherapy on the treatment of relapsed or ref7ractory ALK+ anaplastic large cell lymphoma.

It has been reported that arsenic trioxide (ATO) regulates lymphoma cell cycle, apoptosis, autophagy and mitochondrial activity, while it synergizes with other cytotoxic agents. In addition, ATO targets anaplastic lymphoma kinase (ALK)-fusion oncoprotein to repress anaplastic large cell lymphoma (ALCL). The current study aimed to investigate the efficacy and safety of ATO plus etoposide, solumedrol, high-dose cytarabine and cisplatin (ESHAP) chemotherapy compared with ESHAP chemotherapy alone in patients with relapsed or refractory (R/R) ALK+ ALCL. A total of 24 patients with R/R ALK+ ALCL were enrolled in the present study. Among them, 11 patients were treated with ATO plus ESHAP, while the remaining 13 patients received ESHAP chemotherapy alone. Subsequently, treatment response, event-free survival (EFS), overall survival (OS) and adverse event (AEs) rates were recorded. Both complete response (72.7% vs. 53.8%; P=0.423) and objective response (81.8% vs. 69.2%; P=0.649) rates were higher in the ATO plus ESHAP group compared with the ESHAP group. However, statistical significance was not reached. In addition, EFS was significantly prolonged (P=0.047), while OS was not significantly increased (P=0.261) in the ATO plus ESHAP group compared with the ESHAP group. More specifically, the 3-year accumulating EFS and OS rates were 59.7 and 77.1% in the ATO plus ESHAP group, respectively, and 13.8 and 59.8% in the ESHAP group, respectively. The majority of AEs, such as thrombocytopenia (81.8% vs. 46.2%; P=0.105), fever (81.8% vs. 46.2%; P=0.105) and dyspnea (36.4% vs. 15.4%; P=0.182), were more prevalent in the ATO plus ESHAP group compared with the ESHAP group. However, no statistical significance was observed. In conclusion, the current study indicated that ATO plus ESHAP chemotherapy could exert a superior efficacy compared with ESHAP chemotherapy alone in patients with R/R ALK+ ALCL.

mRNA Expression of Aquaporins in Human Luteinized Granulosa Cells from Different Diameter Follicles / 中山大学学报(医学科学版)

ObjectiveTo investigate the mRNA expression levels of various aquaporins （AQPs） in luteinized granulosa cells from follicles of different diameters. MethodsFrom March 25， 2022 to September 23， 2022 in our reproductive medicine center， 48 women undergoing in-vitro fertilization （IVF） were enrolled and divided into the antagonist group and the agonist group according to the ovarian stimulation protocol. Follicular fluid samples were collected on the day of oocyte pick-up and granulosa cells were extracted from follicles of different diameters： small （<13 mm）， medium （13~18 mm） and large （≥18 mm）. After RNA quantification， 22 cases （66 samples） were included for analysis and mRNA expression levels of AQPs were compared among the three follicle groups. ResultsThe mRNA expression of aquaporin 2 （AQP2） in luteinized granulosa cells increased with the increase of follicle diameter （linear trend P = 0.004） and the difference was statistically significant between two groups of large and small follicles （P = 0.017）. Statistical difference was found in the antagonist group （P = 0.049 6）， but not in the agonist group （P = 0.108）. ConclusionThe mRNA level of AQP2 in luteinized granulosa cells increases with the increase of follicle diameter and its expression is related to the ovarian stimulation protocol， suggesting that AQP2 may play a role in follicle growth and follicular fluid formation， and its mRNA expression level may be regulated by follicle stimulating hormone （FSH） and luteinizing hormone （LH）.

Effects of electroacupuncture on gait and proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture on threshold of pain, gait, proliferation and differentiation of muscle satellite cell in rats with acute blunt trauma of gastrocnemius muscle, and to explore the possible mechanism of electroacupuncture in promoting the repair of acute injury of skeletal muscle.@*METHODS@#A total of 48 SD rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an electroacupuncture group (18 rats). In the model group and the electroacupuncture group, the model of acute blunt trauma of gastrocnemius muscle was established by self-made impactor. In the electroacupuncture group, electroacupuncture was applied at "Chengshan" (BL 57) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave, in frequency of 2 Hz/100 Hz, once a day, 30 min each time. Electroacupuncture intervention was performed for 3, 7 and 14 days according to the sampling time. On the 1st, 3rd, 7th and 14th days after modeling, the mechanical withdrawal pain threshold of hindfoot was detected by Von Frey method; the standing time and the maximum contact area of the right hindfoot were recorded by Cat Walk XTTM animal gait analysis instrument; the morphology of the right gastrocnemius muscle and the number of inflammatory cells were observed by HE staining; the positive expression of paired box gene 7 (Pax7) and myogenic differentiation (MyoD) of the right gastrocnemius muscle was detected by immunofluorescence.@*RESULTS@#After modeling, the muscle fiber rupture and massive infiltration of red blood cells and inflammatory cells were observed in the right gastrocnemius muscle; after electroacupuncture intervention, the morphology of muscle fiber was intact and the infiltration of inflammatory cells was improved. Compared with the blank group, in the model group, the differences of mechanical withdrawal pain threshold between the left and right foot were increased (P<0.05), the standing time was shortened and the maximum contact area of the right hindfoot was decreased (P<0.05), the number of inflammatory cells and the positive expression of Pax7 and MyoD of the right gastrocnemius muscle were increased (P<0.05) on the 1st, 3rd, 7th and 14th days after modeling. Compared with the model group, in the electroacupuncture group, the differences of mechanical withdrawal pain threshold were decreased (P<0.05), the standing time was prolonged (P<0.05), the number of inflammatory cells of right gastrocnemius muscle was decreased (P<0.05) on the 7th and 14th days after modeling; the maximum contact area of the right hindfoot was increased (P<0.05), the positive expression of MyoD of the right gastrocnemius muscle was increased (P<0.05) on the 3rd, 7th and 14th days after modeling; the positive expression of Pax7 of the right gastrocnemius muscle was increased (P<0.05) on the 3rd day after modeling.@*CONCLUSION@#Electroacupuncture can effectively improve the pain threshold and gait in rats with acute blunt trauma of gastrocnemius muscle, and promote the repair of skeletal muscle injury, the mechanism may be related to the up-regulation of Pax7 and MyoD, so as to promoting the proliferation and differentiation of muscle satellite cell.

MicroRNA-181b-5p insufficiency predicts treatment response failure risk and unfavorable event-free survival as well as overall survival in acute myeloid leukemia patients.

The present study aimed to explore the correlation of microRNA (miR)-181b-5p expression with treatment response and long-term prognosis in acute myeloid leukemia (AML) patients. miR-181b-5p was detected in the bone marrow of 84 AML patients before therapy. After induction therapy, the patients exhibiting complete remission (CR) were recorded. Next, event-free survival (EFS) and overall survival (OS) were calculated. miR-181b-5p had excellent potential to discriminate AML patients from healthy donors [area under the curve (AUC): 0.922, 95% confidence interval (CI): 0.873-0.971)]. In addition, miR-181b-5p expression was decreased in AML patients with the FLT3-ITD mutation (P=0.032) or WT1 mutation (P=0.017) when compared to AML patients without these genetic mutations. Meanwhile, miR-181b-5p expression was negatively correlated with the National Comprehensive Cancer Network (NCCN) risk classification of AML (P=0.036). Furthermore, miR-181b-5p expression was elevated in CR AML patients compared to non-CR AML patients (P=0.030). Moreover, higher miR-181b-5p expression was associated with favorable accumulating EFS (P=0.001) and OS (P=0.024). In addition, higher miR-181b-5p expression was independently associated with better EFS (hazard ratio: 0.698, P=0.012). In conclusion, miR-181b-5p insufficiency is associated with induction therapy response failure, unfavorable accumulating EFS and OS in AML patients.

Efficacy and Prognosis of Hyperbaric Oxygen as Adjuvant Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Meta-Analysis Study.

Background: Preclinical and clinical evidence suggests that hyperbaric oxygen therapy (HBOT) may benefit newborns. The effectiveness of HBOT for neonatal hypoxic-ischemic encephalopathy (HIE) remains controversial. We conducted a meta-analysis to evaluate the efficacy and prognosis of HBOT in neonates with HIE. Methods: A systematic search of eight databases was performed for available articles published between January 1, 2015, and September 30, 2020, to identify randomized controlled clinical trials (RCTs) on HBOT for neonatal HIE. Methodological quality assessment was performed by applying the simple procedure detailed by the Cochrane collaboration. Afterward, quality assessment and data analysis were performed using Revman 5.3 software. STATA 15 software was used to detect publication bias as well as for sensitivity analysis. Results: A total of 46 clinical RCTs were selected for the study and included 4,199 patients with neonatal HIE. The results indicated that HBOT significantly improved the total efficiency (TEF) of treatment for neonatal HIE patients [odds ratio (OR) = 4.61, 95% confidence interval (CI) (3.70, 5.75), P < 0.00001] and reduced the risk of sequelae (OR = 0.23, 95% CI (0.16, 0.33), P < 0.00001) and the neonatal behavioral neurological assessment (NBNA) scores [mean difference (MD) = 4.51, 95%CI (3.83,5.19, P < 0.00001)]. Conclusion: In light of the effectiveness of HBOT neonatal HIE, this meta-analysis suggested that HBOT can be a potential therapy for the treatment of neonatal HIE. Due to the heterogeneity of studies protocol and patient selection being only from China, more research is needed before this therapy can be widely implemented in the clinic. Protocol Registration: PROSPERO (ID: CRD42020210639). Available online at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020210639.

JPHYD Inhibits miR-21-5p/Smad7-Mediated Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells.

Background: Studies have shown that Jianpi Huayu Decoction (JPHYD) can inhibit the growth of hepatocellular carcinoma cells, but the mechanism of its effect was not clear at present. Methods: We assessed the effect of JPHYD using liver cancer cells as in vitro cell model and xenograft tumor as in vivo model. CCK8, EdU, wound-healing, and transwell assays were performed to assess the cell growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines HepG2 and MHCC97H. Western blot assay was performed to observe the protein level of E-cadherin, Smad7, N-cadherin, Snail, Smad3, Vimentin, and Zeb1. qRT-PCR assay was used to observe the expression of miR-21-5p in clinical liver cancer tissue samples and in HepG2 and MHCC97H cells. Animal tumorigenesis experiments and in vivo imaging experiments were performed to assess the results of in vitro experiments. Results: We found that JPHYD could inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells and JPHYD decreased the level of N-cadherin, Snail, Vimentin, Smad3, and Zeb1 and increased E-cadherin and Smad7 proteins. The expression of miR-21-5p was increased while that protein of Smad7 was decreased in HCC tissues. The vivo experiments also showed that miR-21-5p could promote the migration of HCC cells. JPHYD decreased miR-21-5p expression. The same results have been found in animal studies. Conclusion: Our results indicated that JPHYD inhibited epithelial-mesenchymal transition by increasing Smad7 expression and inhibiting miR-21-5p. Therefore, blocking the occurrence and development of EMT may be a new mechanism of JPHYD's anti-liver cancer effect.

Cross-sectional study of traumatic stress disorder in frontline nurses 6 mo after the outbreak of the COVID-19 in Wuhan.

BACKGROUND: Frontline nurses in Wuhan directly fighting severe acute respiratory syndrome coronavirus-2 diseases are at a high risk of infection and are extremely susceptible to psychological stress, especially due to the global coronavirus disease 2019 (COVID-19) pandemic. The psychological after-effects of this public health emergency on frontline nurses will last for years. AIM: To assess factors influencing post-traumatic stress disorder (PTSD) among frontline nurses in Wuhan 6 mo after the COVID-19 pandemic began. METHODS: A total of 757 frontline nurses from five hospitals in Wuhan, China, participated in an online survey from July 27 to August 13, 2020. This cross-sectional online study used a demographic information questionnaire, the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders, the Connor-Davidson Resilience Scale, and the Patient Health Questionnaire-4. The chi-square test and logistic regression were used to analyze the association of demographics, COVID-19-related variables, and PTSD. Logistic regression was also conducted to investigate which variables were associated with PTSD outcomes. RESULTS: A total of 13.5%, 24.3%, and 21.4% of the frontline nurses showed symptoms of PTSD, depression, and anxiety, respectively. The multivariate logistic regression analysis showed that the following factors were strongly associated with PTSD: Having a relative, friend, or colleague who died of COVID-19; experiencing stigma; or having psychological assistance needs, depressive symptoms or anxiety. Showing resilience and receiving praise after the COVID-19 outbreak were protective factors. CONCLUSION: Frontline nurses still experienced PTSD (13.5%) six months after the COVID-19 outbreak began. Peer support, social support, official recognition, reward mechanisms, exercise, better sleep, and timely provision of information (such as vaccine research progress) by the government via social media, and adequate protective supplies could mitigate the level of PTSD among nurses responding to COVID-19. Stigmatization, depression, and anxiety might be associated with a greater risk of PTSD among nurses.

Formation and Properties of Superhydrophobic Al Coatings on Steel.

Thermal sprayed aluminum coatings are widely scalable to corrosion protection of the offshore steel structure. However, the corrosion rate of the Al coating increases considerably due to the severe marine environment. It has remained a challenge to improve the corrosion resistance and protective ability of Al coatings. The superhydrophobic surface provides a potential way to improve the corrosion resistance of metal materials. Hence, the development of superhydrophobic Al coatings with superior corrosion resistance is of great interest. In this work, the feasibility of the preparation of superhydrophobic Al coatings on a steel substrate was explored. First, Al coatings were prepared onto the steel substrate by the arc-spraying process, followed by ultrasonic etching with 0.1 M NaOH solution, and afterward passivated using 1% fluorosilanes. The effects of the etching time on morphology, contact angle, and corrosion resistance of the Al coatings were evaluated. The schematic model of the fluorosilane passivation process on the Al coating surface was provided. The micro/nanoscale surface structure of the low-surface-energy fluorosilanes promotes the wetting angle of 153.4° and a rolling angle to 6.6°, denoting the superhydrophobic properties. The superhydrophobic Al coating surface displays excellent self-cleaning performance due to its weak adhesion to water droplets. The corrosion current density of the superhydrophobic Al coating (1.36 × 10-8 A cm-2) is 2 orders of magnitude lower than that of the as-sprayed Al coating (1.18 × 10-6 A cm-2). Similarly, the charge-transfer resistance is found to be 12 times larger for the superhydrophobic Al coating and the corresponding corrosion inhibition efficiency reaches 98.9%. The superhydrophobic Al coating displays superior corrosion resistance and promising applications in a marine corrosion environment.

Whole Transcriptome Data Analysis Reveals Prognostic Signature Genes for Overall Survival Prediction in Diffuse Large B Cell Lymphoma.

BACKGROUND: With the improvement of clinical treatment outcomes in diffuse large B cell lymphoma (DLBCL), the high rate of relapse in DLBCL patients is still an established barrier, as the therapeutic strategy selection based on potential targets remains unsatisfactory. Therefore, there is an urgent need in further exploration of prognostic biomarkers so as to improve the prognosis of DLBCL. METHODS: The univariable and multivariable Cox regression models were employed to screen out gene signatures for DLBCL overall survival (OS) prediction. The differential expression analysis was used to identify representative genes in high-risk and low-risk groups, respectively, where student t test and fold change were implemented. The functional difference between the high-risk and low-risk groups was identified by the gene set enrichment analysis. RESULTS: We conducted a systematic data analysis to screen the candidate genes significantly associated with OS of DLBCL in three NCBI Gene Expression Omnibus (GEO) datasets. To construct a prognostic model, five genes (CEBPA, CYP27A1, LST1, MREG, and TARP) were then screened and tested using the multivariable Cox model and the stepwise regression method. Kaplan-Meier curve confirmed the good predictive performance of this five-gene Cox model. Thereafter, the prognostic model and the expression levels of the five genes were validated by means of an independent dataset. High expression levels of these five genes were significantly associated with favorable prognosis in DLBCL, both in training and validation datasets. Additionally, further analysis revealed the independent value and superiority of this prognostic model in risk prediction. Functional enrichment analysis revealed some vital pathways responsible for unfavorable outcome and potential therapeutic targets in DLBCL. CONCLUSION: We developed a five-gene Cox model for the clinical outcome prediction of DLBCL patients. Meanwhile, potential drug selection using this model can help clinicians to improve the clinical practice for the benefit of patients.

5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients.

BACKGROUND: Although R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard chemotherapy regimen for diffuse large B cell lymphoma (DLBCL) patients, not all patients are responsive to the scheme, and there is no effective method to predict treatment response. METHODS: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 86 DLBCL patients before they received R-CHOP chemotherapy. To investigate the correlation between 5hmC modifications and curative effectiveness, we separated patients into training (n = 56) and validation (n = 30) cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the treatment response in the validation cohort. RESULTS: In this study, we identified thirteen 5hmC markers associated with treatment response. The prediction performance of the logistic regression model, achieving 0.82 sensitivity and 0.75 specificity (AUC = 0.78), was superior to existing clinical indicators, such as LDH and stage. CONCLUSIONS: Our findings suggest that the 5hmC modifications in cfDNA at the time before R-CHOP treatment are associated with treatment response and that 5hmC-Seal may potentially serve as a clinical-applicable, minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.

The relationship between cardiac muscularis propria and clinical outcomes of peroral endoscopic myotomy in achalasia.

BACKGROUND AND AIM: Achalasia patients usually present lower esophageal sphincter thickening, which can impact the expansibility of cardia. We aimed to investigate the effect of cardiac muscularis propria (MP) on perioperative adverse events (AEs) and treatment outcomes of patients treated with peroral endoscopic myotomy (POEM). METHODS: We retrospectively reviewed 114 patients with achalasia undergoing pre-POEM endoscopic ultrasonography (EUS) between May 2013 and November 2019. Cardiac MP thickness was measured using EUS. POEM failure was defined as Eckardt score >3. Risk factors for perioperative AEs and POEM failure were identified. RESULTS: Patients were divided into the thin (n = 52) and the thick group (n = 62) based on the median of cardiac MP thickness (3.0 mm). Perioperative AEs rate of the thin group seemed to be slightly higher than that of the thick group (11.5% vs. 4.8%, P = 0.30). During a median follow-up of 30 months (range 1-77), 100 patients completed follow-up, 16 (16%) of which occurred clinical failure. The clinical outcomes of patients in the thin group were significantly poorer than those patients in the thick group (P = 0.006). Cardiac MP thickness was an independent risk factor for POEM failure (hazard ratio 3.9, P = 0.02; Cox regression), but not the risk factor for perioperative AEs (odds ratio 2.6, P = 0.2; logistic regression). CONCLUSION: Cardiac MP thickness could be a novel predictive factor for POEM failure in patients with achalasia.

MiRNA-340-5p mediates the functional and infiltrative promotion of tumor-infiltrating CD8+ T lymphocytes in human diffuse large B cell lymphoma.

BACKGROUND: CD8+ tumor-infiltrating T lymphocytes (T-TILs) in the tumor microenvironment (TME) play an important role in tumor development, and miRNAs regulate tumor cell interactions with the microenvironment. T-TIL-based tumor immunotherapy provides a promising treatment strategy in diffuse large B-cell lymphoma (DLBCL). MiRNAs tend to be attractive targets for novel antitumor interventions. METHODS: Weighted gene coexpression network analysis (WGCNA), CIBERSORT analysis and Cox regression analysis were used to identify CD8+ T-TIL-related miRNAs. RT-PCR, western blotting, immunohistochemistry (IHC), in situ hybridization (ISH), luciferase reporter assay, coimmunoprecipitation and ubiquitination analyses were used to detect miRNA, mRNA and protein expression and their combination. The viability and function of CD8+ T cells after stimulation were evaluated by enzyme-linked immunosorbent assay (ELISA), cytotoxicity assay, functional avidity assessment, flow cytometry and Cell Counting Kit-8 (CCK-8) assay. DLBCL cell lines, primary cells and a murine xenograft model established with A20 cell injection were used as in vitro and in vivo experimental models. RESULTS: MiR-340-5p was positively correlated with CD8+ T-TILs in DLBCL patients, and KMT5A was a direct target gene of miR-340-5p. CD8+ T-cell function was significantly enhanced by miR-340-5p mimics both in vitro and in vivo, which was reversed by KMT5A overexpression. We demonstrated that COP1/CD73 was involved in the downstream mechanism of the miR-340-5p/KMT5A axis involving ubiquitination. In vivo, we validated an improved CD8+ T-TIL infiltration rate and tumor suppression with miR-340-5p treatment. Furthermore, miR-340-5p directly regulated the biological activity of DLBCL cells without CD8+ T-cell participation. CONCLUSIONS: MiR-340-5p promoted CD8+ T-TIL infiltration and antitumor function by regulating KMT5A and COP1 and further activating CD73 ubiquitination. MiR-340-5p is potentially a novel target for DLBCL immunotherapy.

Predictive value of serological factors, maximal standardized uptake value and ratio of Ki67 in patients diagnosed with non-Hodgkin's lymphoma.

The present study aimed to determine the prognostic value of serological factors, positron emission tomography/computed tomography maximal standardized uptake value (SUVmax) and the immunohistochemical index ratio of Ki67 (Ki67%) for patients diagnosed with non-Hodgkin's lymphoma (NHL). A total of 120 patients with NHL who received regular chemotherapy and underwent serological, radiological and pathological examinations at Shanghai Tongji Hospital between July 2015 and March 2019 were retrospectively analyzed. Spearman's correlation analysis was preformed to describe the associations between different categories of indicators. Kaplan-Meier analysis and log-rank test were used to compare the survival of different subgroups. Receiver operating characteristic curves were generated to assess the predictive value of prominent indicators derived from Cox regression analysis. The results indicated that inflammatory cytokines were strongly associated with tumor burden indicators. The correlation between SUVmax and Ki67% was significant, and SUVmax of the biopsy site exhibited a stronger association with Ki67% (Ρ=0.529, P<0.001) compared with SUVmax of the whole body (Ρ=0.395, P=0.017). C-reactive protein (CRP), lactate dehydrogenase (LDH) and interleukin-6 could differentiate the survival status of patients with NHL, whereas no statistical significance in the estimation of overall survival (OS) was obtained for SUVmax and Ki67%. SUVmax of the biopsy site had only a limited value in the estimation of progression-free survival (PFS), whereas LDH, ß2-microglobulin (ß2-mg) and CRP were independent predictors of both OS and PFS with high sensitivity and specificity. Among all indicators, CRP and ß2-mg could predict both survival status and complete remission of patients with NHL, whereas the prognostic value of SUVmax and Ki67% requires further study and discussion.

Circular RNA profile of acute myeloid leukaemia indicates circular RNA annexin A2 as a potential biomarker and therapeutic target for acute myeloid leukaemia.

This study was to investigate the circular RNA (circRNA) expression profile and the potential circRNAs as biomarkers and therapeutic targets for acute myeloid leukaemia (AML). CircRNA expression profile in bone marrow mononuclear cells from 5 AML patients and 5 healthy donor controls (HCs) was evaluated by microarray. Then, 10 candidate circRNAs (top 5 upregulated and top 5 downregulated) from microarray were validated by RT-qPCR in 130 AML patients and 50 HCs. Finally, the effects of circRNA annexin A2 (circ-ANXA2) knockdown on cell proliferation, apoptosis, chemosensitivity to cytarabine, daunorbicin and potential target microRNAs were assessed in THP-1 and KG-1 cells. By microarray, 173 upregulated and 181 downregulated circRNAs were found in AML patients than HCs, and these circRNAs were found in AML patients compared with HCs, and these circRNAs were implicated in AML-related pathways such as ErbB and EGFR pathways. By RT-qPCR, 9 of 10 candidate circRNAs (including circ-RPS6KB1, circ-CSMD2, circ-PTK2, circ-ANXA2, circ-PWP2, circ-RBM5, circ-ZZEF1, circ-GSK3B and circ-FOXP1) were dysregulated in AML patients compared with HCs. Circ-ANXA2 correlated with higher disease risk, poor risk stratification, lower complete remission level, shorter event-free survival and overall survival in AML. In cellular experiments, circ-ANXA2 was upregulated in AML cell lines, and its knockdown suppressed proliferation, enhanced apoptosis of THP-1 and KG-1 cells and increased their chemosensitivity to cytarabine and daunorbicin. Additionally, circ-ANXA2 knockdown promoted microRNA (miR)-23a-5p and miR-503-3p expression in THP-1 and KG-1 cells. In conclusion, our findings provide a macroscopic view of the circRNA expression profile in AML, and demonstrate that circ-ANXA2 may be a potential biomarker and therapeutic target for AML.

Manganese levels and hepatocellular carcinoma: A systematic review and meta-analysis based on Asian cohort.

Several studies have investigated the relationship between Manganese (Mn) levels and hepatocellular carcinoma (HCC), but the results were inconsistent. Thus, we conducted a systematic review and meta-analysis to evaluate the association between Mn levels and HCC. Nine studies focusing on hair Mn levels, 6 studies on serum Mn levels and 6 studies on tissue Mn levels were identified in a systematic search of PubMed, CNKI, Wanfang and SinoMed databases. Standard mean differences (SMD) with the corresponding 95% confidence intervals (CI) were pooled to compare the Mn levels between HCC and controls. In serum, the Mn levels in HCC were significantly lower than in healthy controls (SMD (95% CI): -0.941 (-1.559, -0.323)). In hair, the Mn levels in HCC were slightly lower than in healthy controls, but not significant (SMD (95% CI): -0.168 (-0.766, 0.430)). In tissue, the Mn levels in tumors were significantly lower than in adjacent normal tissues (SMD (95% CI): -4.867 (-7.143, -2.592)). Subgroup analysis showed consistent results. In conclusion, this meta-analysis suggested an inverse association between Mn levels and HCC.

Random mixed-metal Co1-xNix single-chain magnets with simultaneous azide, carboxylate and tetrazolate bridges.

This paper reports the magnetic properties of a series of isomorphous metal-organic frameworks based on random heterometallic Co1-xNix chains with simultaneous azide, carboxylate and tetrazolate bridges. All the mixed-metal compounds show intrachain FM interactions, field-induced metamagnetism, and SCM-like slow magnetic relaxation. These behaviors are quite different from the parent Co(ii) and Ni(ii) materials, and even a small amount of metal replacement can cause significant magnetic changes. The static properties such as AF ordering, metamagnetic critical field and the hysteresis parameters show complicated composition dependence. Most interestingly, the mixed-metal systems can show a higher blocking temperature than the Co(ii) compound, suggesting that the randomly distributed metal ions have synergistic effects on slow relaxation of magnetization. This is phenomenologically associated with the competitive effects of Δτ and τo.

Random Co(II)-Ni(II) Ferromagnetic Chains Showing Coexistent Antiferromagnetism, Metamagnetism, and Single-Chain Magnetism.

A series of isomorphous compounds of general formula [Co1- xNi x(tzpo)(N3)(H2O)2] n· nH2O ( x = 0, 0.19, 0.38, 0.53, 0.68, 0.84, and 1; tzpo = 4-(5-tetrazolate)pyridine- N-oxide) was prepared. The compounds consist of homometallic or heterometallic chains with simultaneous azide-tetrazolate bridges. The heterometallic systems feature random distribution of metal ions. All compounds across the series exhibit intrachain ferromagnetic coupling, interchain antiferromagnetic (AF) ordering, field-induced metamagnetic transition, and, except the Ni-only compound, single-chain magnetic dynamics. The AF ordering temperature, the metamagnetic critical field, and the relaxation parameters show different composition dependence. Notably, the blocking temperature for the Co-rich materials is higher than the Co-only compound, suggesting synergy between the randomly distributed Co(II) and Ni(II) ions in promoting slow relaxation. The results imply rich physics in the random mixed-metal systems and demonstrate the possibility of improving single-chain relaxation properties by blending metal ions.