Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.

Algae decomposition released dissolved organic matter subfractions on dark abiotic mercury methylation.

To understand the mechanism of dark abiotic mercury (Hg) methylation by algae-derived dissolved organic matter (DOM) and effectively manage the environmental risks of mercury methylation in aquaculture areas, we investigated the influence of subfractions of DOM released from algae (Ulothrix sp.) decomposition on mercury methylation. The results showed that the hydrophobic basic component (HOB) in DOM exhibited the most substantial promotion effect on Hg methylation. The methylmercury (MeHg) production in the HOB treatment increased significantly, while the production rate of MeHg (%MeHg represented the concentration ratio of MeHg to THg) in the six subfractions treated solutions decreased significantly with the increase of Hg concentration. The change of the %MeHg was more evident at low Hg concentration, indicating the limited number of binding sites and methyl donors on DOM. As a consequence, Hg(Ⅱ) in the solution could not be converted into MeHg in equal proportion. Furthermore, the production of MeHg in solution was significantly reduced by the decomposed algae DOM, and its concentration was in the range of 0.017-0.085 ng·L-1 (significantly lower than undecomposed algal). The difference between the decomposed and the non-decomposed algae DOM reached a significant level (P < 0.05). When the DOM decayed for 20 and 30 days, the Hg methylation ability of DOM was weakened most obviously. During the decomposition process, considerable variations were observed among the subfractions, with HOB consistently playing a dominant role in Hg methylation. At the same time, the hydrophilic acid component exhibited a significant inhibitory effect on Hg methylation. Generally, the main components (e.g. HOB and HIA (hydrophilic acid component)) of DOM affecting mercury methylation were found in our study, which provided a better understanding of algae-derived DOM subfractions on the Hg methylation, in an attempt to prevent and control water pollution in aquaculture areas.

The experience of diagnosis and treatment for TAFRO syndrome.

Early identification, diagnosis and treatment of TAFRO syndrome are very importants. We retrospectively analysed 6 patients with TAFRO syndrome. Their clinical manifestations, treatment methods, survival and other aspects were summarized. All patients were pathologically diagnosed with Castleman's disease, with fever, an inflammatory storm state and varying degrees of anasarca. All patients received steroid therapy; four of them also received chemotherapy, and 1 received rituximab. Of the 3 patients with severe disease, only 1 patient who received the recommended dose of glucocorticoids survived. Early administration of glucocorticoids can improve the prognosis, especially in patients with severe disease, and adequate glucocorticoids are important.

MicroRNA-126-3P targets PIK3R2 to ameliorate autophagy and apoptosis of cortex in hypoxia-reoxygenation treated neonatal rats.

Here, we explored a possible mechanism of microRNA-126-3p (miR-126-3p) on neonatal rats with hypoxia-reoxygenation injury (HI). After administering HI to newborn Sprague-Dawley rats, the expression of miR-126-3p in the brain injury was assessed by RT-PCR. A miR-126-3p mimic and inhibitor were treated in the HI neonatal rats. The water maze test, TTC, HE, Nissl and TUNEL staining were separately implemented to test the effects of miR-126-3p on the HI-treated neonatal rats. At the same time, the phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) expression in the damaged cortex region was analyzed. In vitro, cortical neurons were cultured and treated with oxygen and glucose deprivation (OGD), then transfected miR-126-3p mimic, PIK3R2 overexpression lentivirus vector or silence of PIK3R2. The cell viability was observed by CCK-8. The autophagy of neurons was detected by acridine orange staining. In contrast to the sham-operated rats, the miR-126-3p expression significantly decreased, but PIK3R2 expression markedly rose in the cortex of HI rats. Injection of miR-126-3p mimic raised the learning and memory abilities through down-regulating the cerebral ischemic area, improving pathological damage of the cortex, reducing the neurons apoptosis of the cortex and down-regulating the autophagy-related and apoptosis-related proteins. Overexpression of PIK3R2, a miR-126-3p target, may reduce cell viability and boost autophagy and apoptosis. Silence of PIK3R2 promoted cell viability and inhibited cell apoptosis and autophagy. The consequences of miR-126-3p were comparable to those of PIK3R2 silencing. A new therapeutic target for HI injury in newborn rats is provided by the overexpression of miR-126-3p, which inhibits autophagy and death of cortical neurons by targeting PIK3R2 in HI-treated neonatal rats.

Factors associated with self-medication in children and the decomposition of rural-urban disparities in China.

BACKGROUND: Self-medication in children is one of the greatest threats to children health in China. OBJECTIVES: The purpose of this study was to examine the potential factors associated with self-medication in children and explore rural-urban disparities. METHODS: A total of 2798 children enrolled in the study. Informed consent was obtained from each primary caregiver following a detail explanation about the purpose of the study. Multivariable logistic regression analysis and Oaxaca-Blinder decomposition analysis were used. RESULTS: The results showed that 38.2% primary caregivers of rural areas self-medicated their children, compared to 18.7% of those in urban areas. The urban primary caregivers with college or above education were more likely to self-medicate their children, while rural primary caregivers with college or above education were less likely to self-medicate their children. Children having unhealthy eating habits were more likely to have been self-medicated by their primary caregivers in urban and rural areas. Urban primary caregivers who spend more than 10 min from home to the nearest medical institution were more likely to self-medicate their children. In rural areas, children aged 3-6 years old, primary caregivers with monthly household income per capita of 1001-3000 Yuan, and children with chronic diseases are another set of enabling factors which impacted on self-medication. Unhealthy eating habits of children were the largest contributor to the rural-urban self-medication gap. CONCLUSIONS: Children's factors explained the largest portion of the rural-urban difference in self-medication among children. The evidence presented in this study suggests that public health policies addressing rural-urban differences in children' s factors could serve as an effective method for reducing rural-urban disparities in self-medication among children.

Effects of effort-reward imbalance, job satisfaction, and work engagement on self-rated health among healthcare workers.

BACKGROUND: Healthcare workers, who protect and improve the health of individuals, are critical to the success of health systems and achieving national and global health goals. To respond effectively to the healthcare needs of populations, healthcare workers themselves must be in a good state of health. However, healthcare workers face various psychosocial pressures, including having to work night shifts, long working hours, demands of patient care, medical disputes, workplace violence, and emotional distress due to poor interactions with patients and colleagues, and poor promotion prospects. Constant exposure to these psychosocial hazards adversely impacts healthcare workers' health. Consequently, this study aimed to examine the influence of effort-reward imbalance, job satisfaction, and work engagement on self-rated health of healthcare workers. The results would be conducive to providing policy guidance to improve the health of healthcare workers. METHODS: We analysed the data of 1327 participants from The Chinese Sixth National Health and Services Survey in Sichuan Province that was conducted from August 2018 to October 2018. Structural equation modelling was used to test the hypothesized relationships among the variables. RESULTS: Only 40.1% of healthcare workers rated their health as 'relatively good' or 'good'. Effort-reward imbalance had a significant negative correlation with self-rated health (ß = - 0.053, 95% CI [- 0.163, - 0.001]). The associations of effort-reward imbalance and work engagement with self-rated health were both mediated by job satisfaction (95% CI [- 0.150, - 0.050] and [0.011, 0.022]), and work engagement mediated the relationship between effort-reward imbalance and self-rated health (95% CI [- 0.064, - 0.008]). CONCLUSION: In order to improve the health of healthcare workers, administrators should balance effort and reward and provide opportunities for career development and training. In addition, health managers should help healthcare workers realize the significance and value of their work and keep them actively devoted to their work through incentive mechanisms.

Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study.

BACKGROUND: The optimal chemotherapeutics of recurrent disseminated glioblastoma has yet to be determined. We analyzed the efficacy and safety of recombinant human endostatin (rh-ES) combined with temozolomide and irinotecan in patients with recurrent disseminated glioblastoma. METHODS: We retrospectively reviewed 30 adult patients with recurrent disseminated glioblastoma treated with this combination chemotherapy at Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University of China from November 2009 to August 2018. Temozolomide was given orally at 200 mg/m2 daily for 5 days and rh-ES was administrated 15 mg/d daily for 14 days of each 28-day treatment cycle. Irinotecan was given intravenously every 2 weeks on a 28-day cycle at 340 mg/m2 or 125 mg/m2 depending on antiepileptic drugs. Primary endpoint was progression-free survival (PFS) at 6 months (6 m-PFS). RESULTS: The 6 m-PFS was 23.3%. The median PFS was 3.2 months. The overall survival rate (OS) at 12 months was 28.6%. The median OS was 6.9 months. Six out of 30 (20%) patients demonstrated partial radiographic response and 11 (36.7%) remained stable. The PFS of the 6 patients who got partial response was 5.8, 6.3, 6.9, 13.6, 15.8 and 16.6 months, respectively, and the median time interval of first response was 4 (range, 2.0-6.6) months. The most common adverse events were hematologic toxicities and gastrointestinal effects. The Grade ≥ 3 adverse event was hematologic toxicities. The adverse events were manageable. CONCLUSIONS: Rh-ES, in combination with cytotoxic drugs, was an alternative effective regimen with manageable toxicities in treatment of recurrent disseminated glioblastoma.

[The Effects of Social Support and Health Literacy on Depression among Rural Patients with Hypertension].

OBJECTIVE: To explore the effects of social support and health literacy on depression among hypertensive patients in rural areas and to provide reference for improving depression in hypertensive patients. METHODS: A multi-stage stratified sampling method was used to select 549 hypertensive patients in a rural area of Chengdu city for a questionnaire survey. Structural equation model was used to analyze the effects of social support and health literacy on depression in hypertensive patients. RESULTS: Social support ( ß=-0.116, 95% CI: (-0.198)-(-0.132)) and health literacy ( ß=-0.209, 95% CI: (-0.289)-(-0.132)) had a direct negative effect on depression, and social support had a direct positive effect on health literacy ( ß=0.146, 95% CI: 0.064-0.229). Health literacy was a mediator between social support and depression ( ß=-0.030, 95% CI: (-0.054)-(-0.013)). The gender, employment status and per capita annual income of the patients affected the incidence of depression ( P<0.05). CONCLUSIONS: Social support and health literacy are important predictors of depression among hypertensive patients. We should construct a good social support network, strengthen the publicity of health knowledge, and improve social support and health literacy to alleviate the depression in hypertensive patients. At the same time, more attention should be paid to women, people with low per capita annual income and working hypertensive patients.

Increased fes1a thermotolerance is induced by BAG6 knockout.

KEY MESSAGE: (1) The fes1a bag6 double mutant shows an increased short term thermotolerance compared to fes1a. BAG6 is a suppressor of Fes1A; (2) IQ motif is essential to effective performance of BAG6. (3) Calmodulin was involved in signal transduction. (4) BAG6 is localized in the nucleus. HSP70s play an important role in the heat-induced stress tolerance of plants. However, effective HSP70 function requires the assistance of many co-chaperones. BAG6 and Fes1A are HSP70-binding proteins that are critical for Arabidopsis thaliana thermotolerance. Despite this importance, little is known about how these co-chaperones interact. In this study, we assessed the thermotolerance of a fes1a bag6 double mutant. We found that the fes1a bag6 double mutant shows an increased short-term thermotolerance compared to fes1a. However, calmodulin inhibitors diminished this enhanced thermotolerance in the fes1a bag6 double mutant. In addition, we found the IQ motif to be essential for effective BAG6 performance. Since BAG6 is localized in the nucleus, the signal transduction is likely to involve nuclear calcium signaling.

Intracellular sphingosine 1-phosphate contributes to collagen expression of hepatic myofibroblasts in human liver fibrosis independent of its receptors.

Sphingosine 1-phosphate (S1P) is involved in multiple pathological processes, including fibrogenesis. S1P participates in mouse liver fibrogenesis via a paracrine manner. Herein, we investigated the involvement of S1P in human liver fibrosis. Human fibrotic samples were obtained from livers of patients undergoing liver transplantation. Expression of sphingosine kinase (SphK1), collagen (Col) α1(I), Col α1(III), α-smooth muscle actin, and p-Smad2/3 was characterized by immunofluorescence, real-time RT-PCR, high-content analysis, or Western blot analysis in the fibrotic liver, human bone marrow-derived mesenchymal stem cells, and human hepatogenic profibrotic cells. The effect of SphK1 was assessed using siSphK1 or SphK-specific inhibitor. SphK1, which was expressed in human fibrotic liver myofibroblasts, could be detected in human bone marrow-derived mesenchymal stem cells or human hepatogenic profibrotic cells activated by transforming growth factor ß1 (TGF-ß1). TGF-ß1 evoked the activation of SphK1, increased intracellular S1P, and up-regulated expression of SphK1, Col α1(I), and Col α1(III) in a TGF-ß receptor-dependent manner. TGF-ß1 induced expression of Col α1(I) and Col α1(III) via SphK1, which was mediated by intracellular S1P, independent of S1P receptors. TGF-ß1 evoked nuclear translocation of p-Smad2 and p-Smad3 in TGF-ß receptor-dependent, but SphK1-independent, manner. In conclusion, intracellular S1P plays a crucial role in the TGF-ß1-induced expression of Col α1(I) and Col α1(III), which is required for human fibrosis development. S1P exerts its effects in S1P receptor-independent manner.

Crosstalk between the nervous system and tumor microenvironment: Functional aspects and potential therapeutic strategies.

Recent advancements in understanding the tumor microenvironment (TME) have highlighted the critical role of the nervous system in cancer progression. This review comprehensively examines how the nervous system influences various aspects of tumorigenesis, including growth, motility, immune response, angiogenesis, and the behavior of cancer-associated fibroblasts (CAFs). We delineate the neurodevelopmental mechanisms associated with cancer, such as the secretion of neurotrophins and exosomes by cancer cells. Furthermore, we explore the emerging therapeutic strategy of targeting nerves associated with tumors. Evidence supporting this approach includes studies demonstrating direct tumor growth inhibition, enhanced efficacy of immunotherapy when combined with nervous system-modulating drugs, and the suppression of tumor blood vessel formation through nerve targeting. Finally, we discuss the current challenges in this field and emphasize the need for further exploration within cancer neuroscience.

Bifurcations in a low-order nonlinear model of tropical Pacific sea surface temperatures derived from observational data.

Aiming at tackling the difficulty in exactly constituting the sea surface temperature (SST) dynamical model, the paper introduces the dynamical system reconstruction idea and establishes the nonlinear dynamical model of SST field based on 1963-2010 monthly average Hadley SST data. Time coefficients series after empirical orthogonal functions decomposition are taken as the dynamical model variables and Genetic Algorithms is used to optimize and retrieve the model parameters. The stability of the equilibrium in the reconstructed model is analyzed and dynamical actions such as bifurcation and mutation are discussed. Also the activity configuration and aberrance mechanism of the SST field are developed upon the actual activity characteristics of the SST field in the Tropical Pacific Ocean in that year. Results reveal that the bifurcation action of the SST field system from one stable high-value equilibrium to another stable low-value equilibrium accords with the La Niña process while the mutation action of the SST field system from two stable equilibriums to another stable equilibrium accords with the El Niño process.

Development and validation of a prognostic model for esophageal cancer patients with liver metastasis: a cohort study based on surveillance, epidemiology, and end results database.

PURPOSE: Our objective is to examine the independent prognostic risk factors for patients with Esophageal Cancer with Liver Metastasis (ECLM) and to develop a predictive model. METHODS: In this study, clinical data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression analysis was employed to identify independent prognostic factors and construct nomograms based on the results of multivariate regression. The predictive performance of the nomograms was assessed using several methods, including the consistency index (C-index), calibration curve, time-dependent receiver-operating characteristic curve (ROC), and decision curve analysis (DCA). Additionally, Kaplan-Meier survival curves were generated to demonstrate the variation in overall survival between groups. RESULTS: A total of 1163 ECLM patients were included in the study. Multivariate Cox analysis revealed that age, tumor differentiation grade, bone metastasis, therapy, and income were independently associated with overall survival (OS) in the training set. Subsequently, a prognostic nomogram was constructed based on these independent predictors. The C-index values were 0.739 and 0.715 in the training and validation sets, respectively. The area under the curve (AUC) values at 0.5, 1, and 2 years were all higher than 0.700. Calibration curves indicated that the nomogram accurately predicted OS. Decision curve analysis (DCA) showed moderately positive net benefits. Kaplan-Meier survival curves demonstrated significant differences in survival between high- and low-risk groups, which were divided based on the nomogram risk score. CONCLUSIONS: The nomogram we developed for ECLM patients has demonstrated good predictive capability, allowing clinicians to accurately evaluate patient prognosis and identify those at high risk, thereby facilitating the development of personalized treatment plans.

Establishment and validation of a prognostic nomogram for postoperative patients with gastric cardia adenocarcinoma: A study based on the Surveillance, Epidemiology, and End Results database and a Chinese cohort.

BACKGROUND: Gastric cardia adenocarcinoma (GCA) is a highly fatal form of cancer in humans. The aim of this study was to extract clinicopathological data of postoperative patients with GCA from the Surveillance, Epidemiology, and End Results database, analyze prognostic risk factors, and build a nomogram. METHODS: In this study, the clinical information of 1448 patients with GCA who underwent radical surgery and were diagnosed between 2010 and 2015 was extracted from the SEER database. The patients were then randomly divided into training (n = 1013) and internal validation (n = 435) cohorts at a 7:3 ratio. The study also included an external validation cohort (n = 218) from a Chinese hospital. The study used the Cox and LASSO models to pinpoint the independent risk factors linked to GCA. The prognostic model was constructed according to the results of the multivariate regression analysis. To assess the predictive accuracy of the nomogram, four methods were used: C-index, calibration curve, time-dependent ROC curve, and DCA curve. Kaplan-Meier survival curves were also generated to illustrate the differences in cancer-specific survival (CSS) between the groups. RESULTS: The results of the multivariate Cox regression analysis showed that age, grade, race, marital status, T stage, and log odds of positive lymph nodes (LODDS) were independently associated with cancer-specific survival in the training cohort. Both the C-index and AUC values depicted in the nomogram were greater than 0.71. The calibration curve revealed that the nomogram's CSS prediction was consistent with the actual outcomes. The decision curve analysis suggested moderately positive net benefits. Based on the nomogram risk score, significant differences in survival between the high- and low-risk groups were observed. CONCLUSIONS: Race, age, marital status, differentiation grade, T stage, and LODDS are independent predictors of CSS in patients with GCA after radical surgery. Our predictive nomogram constructed based on these variables demonstrated good predictive ability.

Real-world evidence of ABVD-like regimens compared with ABVD in classical Hodgkin lymphoma: a 10-year study from China.

BACKGROUND: Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has been regarded as the standard treatment regimen for classical Hodgkin lymphoma. In recent years, ABVD-like regimens, which emerged due to shortages and the lung toxicity of bleomycin or the emergence of immune checkpoint inhibitors and antibody-drug conjugates, may be favorable, but have not yet been tested. METHODS: We compared the outcomes of ABVD with ABVD-like regimens, which include bleomycin was completely or partially omitted; meanwhile, etoposide or PD-1 inhibitors were added. RESULTS: 5-Year progression-free survival (PFS) was higher for ABVD than ABVD-like regimens in young patients (82.1% vs. 67.0%, p = 0.029), patients with serum beta-2 microglobulin (ß2-MG) ≥ 1.85 mg/L (75.8% vs. 57.6%, p = 0.046), and advanced-stage patients with IPS score 4-7(63.1%, 18.3%, p = 0.038). For elderly (60.5% vs.76.1%, p = 0.089), patients with ß2-MG < 1.85 mg/L (83.1% vs 76.1%, p = 0.282), and advanced-stage patients with IPS score 0-3(84.6% vs. 81.3%, p = 0.476), 5-year PFS for ABVD did not differ from ABVD-like regimens. Elderly patients treated with bleomycin-free regimens showed a better survival trend compared with ABVD (99.3% vs. 61.3%, p = 0.270). CONCLUSION: ABVD is superior to ABVD-like regimens in achieving PFS in young patients or patients with poor prognosis including high IPS score and ß2-MG level. ABVD-like regimens are as effective as ABVD in elderly or low-risk patients including low IPS score and ß2-MG level; elderly patients treated with bleomycin-free regimens exhibit a better survival trend compared with ABVD.

SUV39H1 is a prognosis and immune microenvironment-related biomarker in diffuse large B-cell lymphoma.

BACKGROUND: The tumor microenvironment plays a crucial role in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase Suppressor of variegation 3-9 homolog 1 (SUV39H1) is a significant gene that promotes the progression of various malignancies. However, the specific expression of SUV39H1 in DLBCL remains unclear. METHODS: By retrieving data from GEPIA, UCSC XENA and TCGA public databases, we observed the high expression of SUV39H1 in DLBCL. Combined with an immunohistochemical validation assay, we analyzed our hospital's clinical characteristics and prognosis of 67 DLBCL patients. The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. Furthermore, the experiments in vitro were deployed to evaluate the regulation of SUV39H1 on the DLBCL immune microenvironment. RESULTS: The results showed that high SUV39H1 expression was closely associated with age over 50 years (P = 0.014) and low albumin levels (P = 0.023) of patients. The prognostic analysis showed that the high SUV39H1 expression group had a lower disease-free survival (DFS) rate than the low SUV39H1 expression group (P < 0.05). We further discovered that SUV39H1 upregulated the expression of CD86+ and CD163+ tumor-associated macrophages by DLBCL patients' tissues and cell experiments in vitro (P < 0.05). And SUV39H1-associated T lymphocyte subsets and cytokines IL-6/CCL-2 were downregulated in DLBCL (P < 0.05). CONCLUSIONS: In summary, SUV39H1 might be not only a potential target for treating DLBCL but also a clinical indicator for doctors to evaluate the trend of disease development.

Inhibition of lncRNA NEAT1 sensitizes medulloblastoma cells to cisplatin through modulating the miR-23a-3p-glutaminase (GLS) axis.

Medulloblastoma (MB) is a commonly occurring brain malignancy in adolescence. Currently, the combination of chemotherapy with subsequent irradiation is a regular therapeutic strategy. However, high dosage of chemotherapy is associated with drug resistance and side effects. The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), which is frequently overexpressed in diverse human tumors, is correlated with worse survival rate in cancer patients. Currently, the precise roles of NEAT1 in MB and chemoresistance remain unclear. Our study aimed to investigate the biological functions of NEAT1 in cisplatin-resistant medulloblastoma. We report that NEAT1 was significantly upregulated in medulloblastoma patient specimens. Silencing NEAT1 significantly suppressed MB cell proliferation and sensitized MB cells to cisplatin. In cisplatin-resistant MB cell line, DAOY Cis R, NEAT1 expression, and glutamine metabolism were remarkably upregulated in cisplatin-resistant cells. Under low glutamine supply, cisplatin-resistant cells displayed increased cisplatin sensitivity. Bioinformatical analysis and luciferase assay uncovered that NEAT1 functions as a ceRNA of miR-23a-3p to downregulate its expressions in MB cells. Moreover, miR-23a-3p was apparently downregulated in MB patient tissues and cisplatin resistant MB cells. We identified GLS (glutaminase), a glutamine metabolism enzyme, was directly targeted by miR-23a-3p in MB cells. Rescue experiments demonstrated restoration of miR-23a-3p in NEAT1-overexpressing DAOY cisplatin resistant cells successfully overcame the NEAT1-promoted cisplatin resistance by targeting GLS. In general, our results revealed new molecular mechanisms for the lncRNA-NEAT1-mediated cisplatin sensitivity of MB.

The prognostic nutritional index, an independent predictor of overall survival for newly diagnosed follicular lymphoma in China.

Objective: The prognostic nutritional index (PNI) is an important prognostic factor for survival outcomes in various hematological malignancies. The current study focused on exploring the predictive value of the PNI in newly diagnosed follicular lymphoma (FL) in China. Materials and methods: The clinical indicators and follow-up data of 176 patients who received chemotherapy or immunotherapy combined with chemotherapy with FL in our hospital from January 2016 to March 2022 were retrospectively analyzed. Cox proportional hazard model was used for univariate and multivariate analyses. Kaplan-Meier curves were used to calculate survival rates and draw survival curves. The log-rank test was applied to compare differences between groups. Results: The optimal cut-off value of PNI was 44.3. All patients were divided into a high PNI group (>44.3) and a low PNI group (≤44.3). The low PNI group had a low CR rate and a high risk of death, with a tendency toward POD24, and Both OS and PFS were worse than those in the high PNI group. PNI was able to predict OS and PFS in FL patients and was the only independent predictor of OS (P = 0.014 HR 5.024; 95%CI 1.388∼18.178) in multivariate analysis. PNI could re-stratify patients into groups of high FLIPI score, high FLIPI2 score, no POD24, and rituximab combined with chemotherapy. Moreover, integrating PNI into the FLIPI and FLIPI2 models improved the area under the curve (AUC) for more accurate survival prediction and prognosis. Conclusion: PNI is a significant prognostic indicator for newly diagnosed FL in China that can early identify patients with poor prognosis and guide clinical treatment decisions.

Neural Function Recovery and Safety of Mild Hypothermia Therapy Combined with Monosialotetrahexosylganglioside on Neonatal Asphyxia Complicated by Hypoxic Ischemic Encephalopathy.

OBJECTIVE: To explore the effect and safety of mild hypothermia therapy combined with monosialotetrahexosylganglioside (GM1) on neural function recovery of neonatal asphyxia complicated by hypoxic ischemic encephalopathy (HIE). METHODS: The clinical data of 90 neonates with HIE were retrospectively analyzed. According to the treatment methods, the neonates were divided into a routine group, a mild hypothermia group, and a combination group, with 30 cases in each group. The differences in neural function recovery, biochemical indexes, clinical signs recovery, efficacy, and complications were observed in the three groups after treatment. RESULTS: After treatment, the score of neonatal behavioral neurological assessment (NBNA) and level of superoxide dismutase (SOD) in the combination group were higher than those of the other two groups (P < 0.05). The levels of neuron-specific enolase (NSE), S-100ß protein, and plasma neuropeptide Y (NPY) in the combination group were lower than those in the other two groups, and the recovery time of consciousness, muscle tension, and reflex was shorter (P < 0.05). The combination group showed higher total effective rate and lower incidence of complications as compared with the other two groups (P < 0.05). CONCLUSION: Mild hypothermia therapy combined with GM1 for the treatment of neonatal asphyxia complicated by HIE can promote the recovery of neural function and reduce the incidence of complications in neonates.

Analysis of Carbapenemase-Resistant Genotypes of Highly Virulent Klebsiella pneumoniae and Clinical Infection Characteristics of Different MLST Types.

Carbapenemase-resistant Klebsiella pneumoniae (CR-KP) has become one of the nosocomial infections that seriously threaten the lives of patients, greatly increasing the burden on patients. In order to explore the resistance mechanism of clinically isolated CR-KP to carbapenems and perform multilocus sequence typing (MLST), to study the clinical characteristics of patients with different ST types of infection, we collected 74 CR-KP strains clinically isolated from the main 6 hospitals in Zhejiang province from January 2018 to July 2020. The sensitivity of the tested strains to 23 antibacterial drugs was determined by the microbroth dilution method, and PCR was applied. Gene amplification technology and DNA sequencing methods were used to detect the carbapenemase gene of the tested strains. Through the MLST of the tested strains, the clonal correlation and molecular epidemiological characteristics of the tested strains were explored, and the characteristics of CR-KP resistance, resistance mechanisms, and clinical characteristics of bacterial infections under different MLST types were analyzed at the same time. The results showed that 74 carbapenem-resistant Klebsiella pneumoniae strains showed high resistance to 21 commonly used antibacterial drugs, and all carbapenemase phenotypic screening tests were positive. MLST typing showed that 74 CR-KP strains had 17 ST typings, and ST11 was the dominant type (54.05%). The study also found that these ST11 strains are more likely to be resistant to carbapenem antibiotics. Most of them produce KPC carbapenemase, and a few are IMP, VIM, and NDM. Univariate analysis suggested that the proportion of patients in the ST11 group receiving treatment in ICU, the use rate of mechanical ventilation, and the proportion of drainage tube indwelling were higher than those in the non-ST11 group, and the survival rate of the ST11 group was lower than that of the non-ST11 group. Clinical data suggested that the same hospital was dominated by the same clonal epidemic in the same period. In view of the analysis of clinical data suggesting that patients who have received ICU treatment, mechanical ventilation, and drainage tube indwelling are prone to the risk of CR-KP strain (especially ST11) infection and low survival rate, such patients should arouse extensive clinical attention.