Regulation of mRNA and miRNA in the response to Salmonella enterica serovar Enteritidis infection in chicken cecum.

BACKGROUND: Salmonella enterica, serovar Enteritidis (SE) is a food-borne pathogen, which can cause great threat to human health through consumption of the contaminated poultry products. Chicken is the main host of SE. The mRNA and microRNA (miRNA) expression profiles were analyzed on cecum of Shouguang chicken via next-generation sequencing and bioinformatics approaches. The treated group was inoculated SE, and the control group was inoculated with phosphate buffer saline (PBS). RESULTS: There were 1760 differentially expressed mRNAs in the SE-infected group, of which 1046 were up-regulated mRNA, and 714 were down-regulated mRNA. In addition, a total of 821 miRNAs were identified, and 174 miRNAs were differentially expressed, of which 100 were up-regulated and 74 were down-regulated. Functional enrichment of differentially expressed mRNAs was similar to miRNA target genes. The functional analysis results of differentially expressed mRNAs and miRNAs were performed. Immune-related processes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were enriched by up-regulated mRNA. The down-regulated mRNAs were enriched in tissue development and metabolic-related KEGG pathways. The functional analysis of up-regulated miRNA target genes was similar to the down-regulated mRNAs. The down-regulated miRNA target genes were enriched in metabolic-related GO (Gene Ontology) -BP (Biological process) terms and KEGG pathways. The overlap of the up-regulated mRNA and the up-regulated miRNA target genes (class I) was 325, and the overlap of the down-regulated miRNA target genes (class II) was 169. The class I enriched in the immune-related GO-BP terms and KEGG pathways. The class II mainly enriched in metabolic-related GO-BP terms and KEGG pathways. Then we detected the expression of mRNA and miRNA through qRT-PCR. The results shown that the expression of HHIP, PGM1, HTR2B, ITGB5, RELN, SFRP1, TCF7L2, SCNN1A, NEK7, miR-20b-5p, miR-1662, miR-15a, miR-16-1-3p was significantly different between two groups. Dual-luciferase reporter assay was used to detect the relationship between miR-20b-5p and SCNN1A. The result indicated that miR-20b-5p regulate immune or metabolic responses after SE infection in Shouguang chickens by directly targeting SCNN1A. CONCLUSIONS: The findings here contribute to the further analysis of the mechanism of mRNA and miRNA defense against SE infection, and provide a theoretical foundation for the molecular disease-resistant breeding of chickens.

Zfp521 SUMOylation facilities erythroid hematopoietic reconstitution under stress.

Zinc finger protein 521 (Zfp521) is a key transcriptional factor in regulation of hematopoiesis. SUMOylation, a protein post-translational modification process, plays important roles in various biological process including hematopoiesis. However, whether Zfp521 can be SUMOylated and how it affects hematopoiesis is unknown. In this study, we confirmed that Zfp521 can be modified by SUMO1 and lysine 1146 was the primary SUMOylation site. Under homeostatic condition, Zfp521 SUMOylation-deficient mice had normal mature blood cells and primitive cells. However, in bone marrow (BM) transplantation assay, recipient mice transplanted with BM cells from Zfp521 SUMOylation-deficient mice had a significantly decreased R2 population of erythroid lineage in BM and spleen compared with those transplanted with BM cells from wild-type mice. Our results found a novel function of Zfp521 SUMOylation in erythroid reconstitution under stress, which might be a new therapeutic target in future.

Cecal MicroRNAome response to Salmonella enterica serovar Enteritidis infection in White Leghorn Layer.

BACKGROUND: Salmonella enterica serovar Enteritidis (SE) is a food-borne pathogen and of great threat to human health through consuming the contaminated poultry products. MicroRNAs (miRNAs) play an important role in different biological activities and have been shown to regulate the innate immunity in the bacterial infection. The objective of this study is to identify miRNAs associated with SE infection in laying chicken cecum. RESULTS: Average number of reads of three libraries constructed from infected and non-infected chickens was 12,476,156 and 10,866,976, respectively. There were 598 miRNAs including 194 potential novel miRNAs identified in which 37 miRNAs were significantly differentially expressed between infected and non-infected chickens. In total, 2897 unique target genes regulated by differentially expressed miRNAs were predicted, in which, 841 genes were uniquely regulated by up-regulated miRNAs (G1), 636 genes were uniquely regulated by down-regulated miRNAs (G2), and 1420 were co-regulated by both up and down- regulated miRNAs (G3). There were 118, 73 and 178 GO (Gene ontology) BP (Biological process) terms significantly enriched in G1, G2 and G3 groups, respectively. More immune-related GO BP terms than metabolism-related terms were found in G1. Expression of 12 immune-related genes of four differentially expressed miRNAs was detected through qRT-PCR. The regulatory direction of gga-miR-1416-5p, gga-miR-1662, and gga-miR-34a-5p were opposite with the target genes of TLR21, BCL10, TLR1LA, NOTCH2 and THBS1, respectively. CONCLUSION: The miRNAs contribute to the response to SE infection at the onset of egg laying through regulating the homeostasis between metabolism and immunity. The gga-miR-125b-5p, gga-miR-34a-5p, gga-miR-1416-5p and gga-miR-1662 could play an important role in SE infection through regulating their target genes. The finding herein will pave the foundation for the studies of microRNA regulation in SE infection in laying hens.

Splenic gene expression profiling in White Leghorn layer inoculated with the Salmonella enterica serovar Enteritidis.

Salmonella enterica serovar Enteritidis (SE) is a foodborne pathogen that can threaten human health through contaminated poultry products. Live poultry, chicken eggs and meat are primary sources of human salmonellosis. To understand the genetic resistance of egg-type chickens in response to SE inoculation, global gene expression in the spleen of 20-week-old White Leghorn was measured using the Agilent 4 × 44 K chicken microarray at 7 and 14 days following SE inoculation (dpi). Results showed that there were 1363 genes significantly differentially expressed between inoculated and non-inoculated groups at 7 dpi (I7/N7), of which 682 were up-regulated and 681 were down-regulated genes. By contrast, 688 differentially expressed genes were observed at 14 dpi (I14/N14), of which 371 were up-regulated genes and 317 were down-regulated genes. There were 33 and 28 immune-related genes significantly differentially expressed in the comparisons of I7/N7 and I14/N14 respectively. Functional annotation revealed that several Gene Ontology (GO) terms related to immunity were significantly enriched between the inoculated and non-inoculated groups at 14 dpi but not at 7 dpi, despite a similar number of immune-related genes identified between I7/N7 and I14/N14. The immune response to SE inoculation changes with different time points following SE inoculation. The complicated interaction between the immune system and metabolism contributes to the immune responses to SE inoculation of egg-type chickens at 14 dpi at the onset of lay. GC, TNFSF8, CD86, CD274, BLB1 and BLB2 play important roles in response to SE inoculation. The results from this study will deepen the current understanding of the genetic response of the egg-type chicken to SE inoculation at the onset of egg laying.

Design and Driving Performance Study of Soft Actuators for Hand Rehabilitation Training.

Purpose: To address the application requirements of soft actuators in rehabilitation training gloves, and in combination with ergonomic requirements, we designed a segmented soft actuator with bending and elongation modules. This actuator can achieve independent or coupled movements of the finger joints. Methods: A finite element model of the joint actuator was established to compare the driving performance of actuators with different structural forms. Numerical calculations were used to analyze the effects of structural size parameters on the bending characteristics and end output force of the actuator. The design was then refined based on these analyses. Results: The joint actuator designed in this study demonstrated a 71% increase in bending angle compared to the standard fast pneumatic network structure. Key factors affecting the driving performance include the thickness of the constraint layer, the inner wall thickness of the chamber, chamber height, chamber width, chamber spacing, chamber length, and the number of chambers. After improvements, the bending angle of the joint actuator increased by 60.6%, and the output force increased by 145.9%, indicating significant improvement. Conclusion: This study designed and improved a soft actuator for hand rehabilitation training, achieving independent and coupled joint movements. The bending angle, bending shape, and joint driving force of the soft actuator meet the requirements for finger rehabilitation training.

Pulmonary Adenocarcinoma Patient with Complex Mutations on EGFR Benefits from Furmonertinib after Acquiring Gefitinib Resistance: A Case Report.

BACKGROUND: Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been proven a long-lasting treatment effect in pulmonary adenocarcinoma, most patients still progressed within one year due to the acquired resistance. Complex mutations of rare rare sites after acquiring resistance are rarely reported in pulmonary adenocarcinoma. CASE PRESENTATION: A 62-year-old woman was diagnosed with pulmonary adenocarcinoma with stage IV. Genetic testing at the initial treatment showed EGFR L858R positive. After being treated with gefitinib, persistent 2 years disease progression occurred due to drug resistance. The genetic testing showed that EGFR L858R was eliminated, while a rare rare complex mutation of L861Q/G719X appeared. After 160 mg furmonertinib was treated for 1 month, the primary tumor regressed and the intracranial lesions disappeared. The patient has achieved progression-free survival (PFS) for more than 20 months. CONCLUSION: Pulmonary adenocarcinoma with rare rare complex mutations in EGFR induced by gefitinib resistance and disease progression might benefit from furmonertinib treatment.

Combination of anti-thymocyte globulin with post-transplant cyclophosphamide for GVHD prophylaxis in patients undergoing haploidentical hematopoietic stem cell transplantation: systematic review and meta-analysis.

A new strategy combining anti-thymocyte globulin with post-transplant cyclophosphamide (ATG/PTCy) for graft-versus-host disease (GVHD) prevention was developed. This study aims to perform a systematic review and meta-analysis of studies comparing ATG/PTCy with ATG or PTCy in patients with hematological malignancies undergoing haploidentical hematopoietic stem cell transplantation. Meta-analysis was conducted with Review Manager version 5.4, pooled risk ratios (RRs) and hazard ratios (HRs) were calculated for dichotomous data and time-to-event data respectively. Fixed-effects model was used if there is no significant heterogeneity. Literature search and study selection identified 14 eligible studies, including both randomized controlled trial and retrospective comparative studies. Different dosage adjustment strategies were applied, the total dose is 2.5-10 mg/kg for ATG and 29-100 mg/kg for PTCy. Meta-analysis results suggest that ATG/PTCy is associated with significantly lower risk of grade II-IV acute GVHD compared with ATG (RR 0.52; 95% CI: 0.41-0.65; P < 0.00001) and PTCy (RR 0.53; 95% CI: 0.34-0.83; P = 0.005) without increasing risk of disease relapse. In addition, ATG/PTCy is associated with significantly better overall survival and GVHD-free/relapse-free survival than ATG and PTCy. Future researches are required to further establish the benefits of ATG/PTCy and determine the optimal dosage adjustment strategies. BACKGROUND: Haploidentical stem cell transplantation (haplo-HSCT) is associated with higher incidences of graft-versus-host disease (GVHD). A new strategy combining anti-thymocyte globulin with post-transplant cyclophosphamide (ATG/PTCy) for GVHD prevention has been developed, but its benefits and risks remain unclear. OBJECTIVE: This study aims to performs a systematic review and meta-analysis of studies comparing ATG/PTCy with ATG or PTCy in patients with hematological malignancies undergoing haplo-HSCT. STUDY DESIGN: Literature search was performed in databases including Ovid Medline, Embase, Cochrane Library and China Biology Medicine (CBM). Two investigators independently screened eligible studies and extracted data. Meta-analysis was conducted with Review Manager version 5.4, pooled hazard ratios (HRs) for time-to-event outcomes were obtained using generic inverse-variance method, and pooled risk ratios (RRs) for dichotomous data were obtained using Mantel-Haenszel method. Fixed-effects model was adopted if there is no significant heterogeneity. The primary outcome is incidence of acute GVHD. RESULTS: Literature search and study selection identified 14 eligible studies, including both 1 randomized controlled trial and 13 retrospective comparative studies. Different dosage adjustment strategies were applied, the total dose is 2.5-10 mg/kg for ATG and 29-100 mg/kg for PTCy. Meta-analysis results suggest that ATG/PTCy is associated with significantly lower risk of grade II-IV acute GVHD compared with ATG (RR 0.52; 95% CI: 0.41-0.65; P < 0.00001) and PTCy (RR 0.53; 95% CI: 0.34-0.83; P = 0.005) without increasing risk of disease relapse. In addition, ATG/PTCy is associated with significantly lower risk of grade III-IV acute GVHD (RR 0.33; 95% CI: 0.23-0.49; P < 0.00001) and chronic GVHD (RR 0.65; 95% CI: 0.51-0.81; P = 0.0002) in comparison with ATG. Further analyses suggest that ATG/PTCy is associated with significantly better overall survival and GVHD-free/relapse-free survival than ATG and PTCy, but the risks of CMV (RR 1.42; 95% CI: 1.03-1.95; P = 0.03) and EBV (RR 3.17; 95% CI: 1.61-6.23; P = 0.0008) reactivation are higher when compared with PTCy. CONCLUSIONS: Our results suggest that combination of ATG with PTCy for GVHD prevention in haplo-HSCT is associated with improved efficacy but higher risk of infection. Future researches are required to further establish the benefits and risks of ATG/PTCy and determine the optimal dosage adjustment strategies.

(-)-Epigallocatechin gallate alleviates chronic unpredictable mild stress-induced depressive symptoms in mice by regulating the mTOR autophagy pathway and inhibiting NLRP3 inflammasome activation.

Depression is a global public health issue that is widely studied due to the large number of people it affects and its serious consequences. Clinical studies have shown that regular tea consumption may reduce depression risk. (-)-Epigallocatechin gallate (EGCG), the main tea polyphenol, was observed to alleviate depression, but the underlying mechanism has not been elucidated. In this study, chronic unpredictable mild stress (CUMS) was used to induce depression-like behavior in mice, and behavioral tests, such as sucrose preference test and forced swim test, were performed. Then, ELISA, western blot and QT-PCR tests were used to assess the expression of the key components of the NLRP3 inflammasome and its downstream inflammatory effectors (e.g., IL-1ß, IL-18), autophagy markers (Beclin-1, LC3, P62) and apoptosis markers (Bax, Bcl-2) in mouse brain tissues. Changes in serum lipid levels were also assessed. EGCG alleviated CUMS-induced depression-like behavioral changes in mice, reduced activation of the NLRP3 inflammasome, inhibited the mTOR signaling pathway, restored autophagy levels, reduced apoptosis marker expression and attenuated abnormal changes in blood lipid levels. Our study demonstrates that EGCG exerts antidepressive effects through multiple mechanisms, providing new insight into the pathological mechanism of depression and laying the foundation for the development of new therapeutic measures.

SENP3 Promotes Mantle Cell Lymphoma Development through Regulating Wnt10a Expression.

OBJECTIVE: SUMO-specific protease 3 (SENP3), a member of the SUMO-specific protease family, reverses the SUMOylation of SUMO-2/3 conjugates. Dysregulation of SENP3 has been proven to be involved in the development of various tumors. However, its role in mantle cell lymphoma (MCL), a highly aggressive lymphoma, remains unclear. This study was aimed to elucidate the effect of SENP3 in MCL. METHODS: The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR, Western blotting or immunohistochemistry. MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs. Cell proliferation was assessed by CCK-8 assay, and cell apoptosis was determined by flow cytometry. mRNA sequencing (mRNA-seq) was used to investigate the underlying mechanism of SENP3 knockdown on MCL development. A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo. RESULTS: SENP3 was upregulated in MCL patient samples and cells. Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis. Meanwhile, the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown. Furthermore, the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model. CONCLUSION: SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.

Myeloablative conditioning regimens in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission: a systematic review and network meta-analysis.

The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation (allo-HSCT) in complete remission (CR) remain unclear. We performed a systematic review and network meta-analysis to compare the effects of different MAC regimens. Bayesian network meta-analysis was performed using WinBUGS version 1.4.3. The commonly used MAC regimen Bu/Cy (4-day busulfan for toal 16 mg/kg orally or 12.8 mg/kg intravenously, plus 2-day cyclophosphamide for toal 120 mg/kg intravenously) is chosen as the common comparator. Pooled hazard ratios (HRs) with the associated 95% credibility interval (95% CrI) are obtained for all comparisons. We included 19 eligible studies, involving 8104 AML patients and 9 MAC regimens. Compared with Bu/Cy, 3-day busulfan plus fludarabine and thiotepa (Bu3/Flu/TT) is associated with significantly better overall survival (HR, 0.70; 95% CrI, 0.51 to 0.96) and lower risk of relapse (HR, 0.59; 95% CrI, 0.35 to 0.98). Bu3/Flu/TT is also associated with superior overall survival than Cy/TBI (cyclophosphamide plus total body irradiation), and lower risk of relapse than Bu4/Flu (4-day busulfan plus fludarabine). These results suggest that thiotepa-based new MAC regimen Bu3/Flu/TT is associated with improved outcomes in AML patients undergoing allo-HSCT in CR and worth further investigation.

Effects of donor-specific antibodies on engraftment and long-term survival after allogeneic hematopoietic stem cell transplantation-A systematic review and meta-analysis.

The presence of donor-specific antibodies (DSAs) have been reported to be associated with an increased risk of primary graft failure following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its effects on the time to engraftment and long-term outcomes remain unclear. We performed a systematic review and meta-analysis of studies investigating the impact of DSAs on engraftment and long-term survival of patients undergoing allo-HSCT. We systematically searched PubMed, Embase, the Cochrane Library, and CBM. Data were analyzed using RevMan5.4. Pooled hazard ratio (HR), standard mean difference (SMD) or odds ratio (OR) and corresponding 95% confidence interval (CI) are calculated for time-to-event data, continuous data, discontinuous data respectively. 17 eligible studies were included, involving 2169 patients main receiving haploidentical SCT (haplo-SCT) or umbilical cord blood transplantation (UCBT). Meta-analysis showed that DSAs-positive patients are associated with significantly higher risk of GF(OR = 12.87, 95%CI, 6.45-25.70; P < 0.00001; OR = 4.76, 95%CI, 2.88-7.87), poorer neutrophil engraftment (HR = 2.20, 95%CI, 1.02-4.73; P = 0.04; HR = 1.83, 95%CI, 1.46-2.30; P < 0.00001), worse OS (HR = 3.19, 95%CI, 1.85-5.50; P < 0.0001; HR = 1.68, 95%CI, 1.04-2.71; P = 0.03), and inferior PFS (HR = 4.25, 95%CI, 1.59-11.40; P = 0.004; HR = 4.83, 95%CI, 1.65-14.12; P = 0.004) in haplo-SCT and UCBT, respectively.

Albumin-to-fibrinogen ratio is an independent prognostic parameter in de novo non-M3 acute myeloid leukemia.

Inflammation and nutrition related proteins participate in the development of acute myeloid leukemia (AML). It has been reported that the albumin-to-fibrinogen ratio (AFR) could serve as a prognostic indicator in patients with malignancy, but the precise relevance of AML is unclear. This study aimed to evaluate the effect of AFR on survival prognosis in patients with AML. We analyzed 227 patients newly diagnosed with non-M3 AML. AFR was calculated as albumin divided by fibrinogen. Based on the cutoff point from X-tile program, patients were divided into AFR-high (38.8%) and AFR-low (61.2%) groups. AFR-low group showed a poorer complete remission rate (P < 0.001) and median time to relapse (P = 0.026), while the mortality was higher (P = 0.009) than AFR-high ones. According to the log-rank test, AFR-low group had shorter OS (P < 0.001) and DFS (P = 0.034). Multivariate analysis identified AFR, ELN risk, bone marrow transplant, and hemoglobin as independent prognostic variables associated with OS. A visualized nomogram for predicting OS was performed. The C-index (0.75), calibration plots, and decision curve analyses of new model showed better discrimination, calibration, and net benefits than the ELN risk model. The time-dependent receiver operating characteristic (ROC) curve of 1-, 2-, and 3-year also functioned well (AUC, 0.81, 0.93 and 0.90, respectively). Our study provided a comprehensive view of AFR which could be an independent prognostic indicator in AML patients. The prognostic model utilized readily available information from ordinary clinical practice to improve predictive performance, identify risks, and assist in therapeutic decision-making.

Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials.

Objective: Steroids-refractory (SR) acute graft-versus-host disease (aGVHD) is a life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal second-line therapy still has not been established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of different second-line therapy regimens. Methods: Literature search in MEDLINE, Embase, Cochrane Library and China Biology Medicine databases were performed to retrieve RCTs comparing the efficacy and safety of different therapy regimens for patients with SR aGVHD. Meta-analysis was conducted with Review Manager version 5.3. The primary outcome is the overall response rate (ORR) at day 28. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated with the Mantel-Haenszel method. Results: Eight eligible RCTs were included, involving 1127 patients with SR aGVHD and a broad range of second-line therapy regimens. Meta-analysis of 3 trials investigating the effects of adding mesenchymal stroma cells (MSCs) to other second-line therapy regimens suggested that the addition of MSCs is associated with significantly improvement in ORR at day 28 (RR = 1.15, 95% CI = 1.01-1.32, P = 0.04), especially in patients with severe (grade III-IV or grade C-D) aGVHD (RR = 1.26, 95% CI = 1.04-1.52, P = 0.02) and patients with multiorgan involved (RR = 1.27, 95% CI = 1.05-1.55, P = 0.01). No significant difference was observed betwwen the MSCs group and control group in consideration of overall survival and serious adverse events. Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy. Conclusions: Adding MSCs to other second-line therapy regimens is associated with significantly improved ORR, ruxolitinib showed significantly better efficacy outcomes in comparison with other regimens in patients with SR aGVHD. Further well-designed RCTs and integrated studies are required to determine the optimal treatment. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487.

The Chinese Spring Festival Impact on Air Quality in China: A Critical Review.

It is known that the sharp change of air pollutants affects air quality. Chinese Spring Festival is the most important holiday for Chinese people, and the celebration of the holiday with fireworks and the movement of people all around the country results in significant change in multiple air pollutant emissions of various sources. As many cities and rural areas suffer from the air pollution caused by firework displays and more residential fuel consumption, there is an urgency to examine the impact of the Chinese Spring Festival on air quality. Hence, this paper firstly gives an overall insight into the holiday's impact on ambient and household air quality in China, both in urban and rural areas. The main findings of this study are: (1) The firework displays affect the air quality of urban and rural atmosphere and household air; (2) the reduction in anthropogenic emissions improves the air quality during the Chinese Spring Festival; (3) the household air in urban areas was affected most by firework burning, while the household air in rural homes was affected most by fuel consumption; and (4) the short-term health impact of air pollution during the holidays also need more concern. Although there have been many publications focused on the holiday's impact on ambient and household air quality, most of them focused on the measurement of pollutant concentration, while studies on the formation mechanism of air pollution, the influence of meteorological conditions, and the health outcome under the effect of the Chinese Spring Festival are rare. In the future, studies focused on these processes are welcomed.

Treatment failure in a patient infected with Listeria sepsis combined with latent meningitis: A case report.

BACKGROUND: Listeria is a food-borne disease, which is rarely prevalent in the normal population; it mostly occurs in pregnant women, newborns, immunodeficiency patients, and the elderly. The main manifestations of this disease in patients include sepsis, meningitis, etc, and the mortality rate remains high, although the onset of meningitis is relatively insidious. CASE SUMMARY: A 75-year-old man presented with a fever for 1 wk and was admitted to the hospital for diagnosis and management of a lung infection. His condition improved after receiving anti-infective treatment for 2 wk. However, soon after he was discharged from the hospital, he developed fever again, and gradually developed various neurological symptoms, impaired consciousness, and stiff neck. Thereafter, through the cerebrospinal fluid metagenomic testing and blood culture, the patient was diagnosed with Listeria monocytogenes meningitis and sepsis. The patient died after being given active treatment, which included penicillin application and invasive respiratory support. CONCLUSION: This case highlights the ultimate importance of early identification and timely application of the various sensitive antibiotics, such as penicillin, vancomycin, meropenem, etc. Therefore, for high-risk populations with unknown causes of fever, multiple blood cultures, timely cerebrospinal fluid examination, and metagenomic detection technology can assist in confirming the diagnosis quickly, thereby guiding the proper application of antibiotics and improving the prognosis.

Toripalimab and anlotinib as a maintenance treatment for extensive-stage small-cell lung cancer: a case report.

Small-cell lung cancer (SCLC) is characterized by rapid proliferation, high growth fraction and early locoregional and distant metastases. SCLC has been found to be significantly sensitive to platinum-etoposide chemotherapy, but most patients relapse within 6 months of completing initial treatment and median overall survival is about 10 months. Despite the current immunotherapy-treatment approach, median survival time and progression-free survival remain short. This case shows the potential efficacy of maintenance therapy with toripalimab and anlotinib after first-line platinum-etoposide chemotherapy in a patient with extensive-stage SCLC. The combination treatment prolonged the progression-free survival to approximately 13 months and overall survival to 25 months; this is well above the existing standard, and this patient did not experience any major adverse effects during the course of therapy.

Efficacy of hematopoietic stem cell mobilization regimens in patients with hematological malignancies: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Efficient mobilization of hematopoietic stem cells (HSCs) from bone marrow niche into circulation is the key to successful collection and transplantation in patients with hematological malignancies. The efficacy of various HSCs mobilization regimens has been widely investigated, but the results are inconsistent. METHODS: We performed comprehensive databases searching for eligible randomized controlled trials (RCTs) that comparing the efficacy of HSCs mobilization regimens in patients with hematological malignancies. Bayesian network meta-analyses were performed with WinBUGS. Standard dose of granulocyte colony-stimulating factor (G-CSF SD) was chosen as the common comparator. Estimates of relative treatment effects for other regimens were reported as mean differences (MD) or odds ratio (OR) with associated 95% credibility interval (95% CrI). The surface under the cumulative ranking curve (SUCRA) were obtained to present rank probabilities of all included regimens. RESULTS: Databases searching and study selection identified 44 eligible RCTs, of which the mobilization results are summarized. Then we compared the efficacy of mobilization regimens separately for patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) by including 13 eligible trials for network meta-analysis, involving 638 patients with MM and 592 patients with NHL. For patients with MM, data are pooled from 8 trials for 6 regimens, including G-CSF in standard dose (SD) or reduced dose (RD) combined with cyclophosphamide (CY), intermediate-dose cytarabine (ID-AraC) or plerixafor. The results show that compared with G-CSF SD alone, 3 regimens including ID-AraC + G-CSF SD (MD 14.29, 95% CrI 9.99-18.53; SUCRA 1.00), G-CSF SD + Plerixafor SD (MD 4.15, 95% CrI 2.92-5.39; SUCRA 0.80), and CY + G-CSF RD (MD 1.18, 95% CrI 0.29-2.07; SUCRA 0.60) are associated with significantly increased total number of collected CD34+ cells (× 106/kg), among which ID-AraC + G-CSF SD ranked first with a probability of being best regimen of 100%. Moreover, ID-AraC + G-CSF SD and G-CSF SD + Plerixafor SD are associated with significantly higher successful rate of achieving optimal target (collecting ≥ 4-6 × 106 CD34+ cells/kg). For patients with NHL, data are pooled from 5 trials for 4 regimens, the results show that compared with G-CSF SD alone, G-CSF SD + Plerixafor SD (MD 3.62, 95% CrI 2.86-4.38; SUCRA 0.81) and G-CSF SD plus the new CXC chemokine receptor-4 (CXCR-4) antagonist YF-H-2015005 (MD 3.43, 95% CrI 2.51-4.35; SUCRA 0.69) are associated with significantly higher number of total CD34+ cells collected. These 2 regimens are also associated with significantly higher successful rate of achieving optimal target. There are no significant differences in rate of achieving optimal target between G-CSF SD + Plerixafor SD and G-CSF + YF-H-2015005. CONCLUSIONS: In conclusion, ID-AraC plus G-CSF is associated with the highest probability of being best mobilization regimen in patients with MM. For patients with NHL, G-CSF in combination with plerixafor or YF-H-2015005 showed similar improvements in HSCs mobilization efficacy. The relative effects of other chemotherapy-based mobilization regimens still require to be determined with further investigations.

SENP1 promotes MCL pathogenesis through regulating JAK-STAT5 pathway and SOCS2 expression.

Mantle cell lymphoma (MCL) is highly aggressive and its treatment remains challenging, understanding its pathogenesis is critical for future targeted therapy. SUMO specific proteases 1 (SENP1) is an important protein that regulates the balance between SUMOylation and deSUMOylation. We found that SENP1 was upregulated in MCL patient samples and cell lines. Knockdown of SENP1 could inhibit the proliferation and promote the apoptosis of MCL cells. We also found that SENP1 knockdown caused inhibition of the JAK-STAT5 pathway and upregulation of tumor suppressor cytokine signaling 2 (SOCS2). Moreover, MCL tumor growth in vivo was significantly suppressed after SENP1 knockdown in a xenograft nude mouse model. In summary, our results showed that SENP1 is involved in the pathogenesis of MCL and may be a potential therapeutic target.

Comparison of the efficacy of hematopoietic stem cell mobilization regimens: a systematic review and network meta-analysis of preclinical studies.

BACKGROUND: Mobilization failure may occur when the conventional hematopoietic stem cells (HSCs) mobilization agent granulocyte colony-stimulating factor (G-CSF) is used alone, new regimens were developed to improve mobilization efficacy. Multiple studies have been performed to investigate the efficacy of these regimens via animal models, but the results are inconsistent. We aim to compare the efficacy of different HSC mobilization regimens and identify new promising regimens with a network meta-analysis of preclinical studies. METHODS: We searched Medline and Embase databases for the eligible animal studies that compared the efficacy of different HSC mobilization regimens. Primary outcome is the number of total colony-forming cells (CFCs) in per milliliter of peripheral blood (/ml PB), and the secondary outcome is the number of Lin- Sca1+ Kit+ (LSK) cells/ml PB. Bayesian network meta-analyses were performed following the guidelines of the National Institute for Health and Care Excellence Decision Support Unit (NICE DSU) with WinBUGS version 1.4.3. G-CSF-based regimens were classified into the SD (standard dose, 200-250 µg/kg/day) group and the LD (low dose, 100-150 µg/kg/day) group based on doses, and were classified into the short-term (2-3 days) group and the long-term (4-5 days) group based on administration duration. Long-term SD G-CSF was chosen as the reference treatment. Results are presented as the mean differences (MD) with the associated 95% credibility interval (95% CrI) for each regimen. RESULTS: We included 95 eligible studies and reviewed the efficacy of 94 mobilization agents. Then 21 studies using the poor mobilizer mice model (C57BL/6 mice) to investigate the efficacy of different mobilization regimens were included for network meta-analysis. Network meta-analyses indicated that compared with long-term SD G-CSF alone, 14 regimens including long-term SD G-CSF + Me6, long-term SD G-CSF + AMD3100 + EP80031, long-term SD G-CSF + AMD3100 + FG-4497, long-term SD G-CSF + ML141, long-term SD G-CSF + desipramine, AMD3100 + meloxicam, long-term SD G-CSF + reboxetine, AMD3100 + VPC01091, long-term SD G-CSF + FG-4497, Me6, long-term SD G-CSF + EP80031, POL5551, long-term SD G-CSF + AMD3100, AMD1300 + EP80031 and long-term LD G-CSF + meloxicam significantly increased the collections of total CFCs. G-CSF + Me6 ranked first among these regimens in consideration of the number of harvested CFCs/ml PB (MD 2168.0, 95% CrI 2062.0-2272.0). In addition, 7 regimens including long-term SD G-CSF + AMD3100, AMD3100 + EP80031, long-term SD G-CSF + EP80031, short-term SD G-CSF + AMD3100 + IL-33, long-term SD G-CSF + ML141, short-term LD G-CSF + ARL67156, and long-term LD G-CSF + meloxicam significantly increased the collections of LSK cells compared with G-CSF alone. Long-term SD G-CSF + AMD3100 ranked first among these regimens in consideration of the number of harvested LSK cells/ml PB (MD 2577.0, 95% CrI 2422.0-2733.0). CONCLUSIONS: Considering the number of CFC and LSK cells in PB as outcomes, G-CSF plus AMD3100, Me6, EP80031, ML141, FG-4497, IL-33, ARL67156, meloxicam, desipramine, and reboxetine are all promising mobilizing regimens for future investigation.

Prognostic Role of Serum Albumin Level in Patients with Lymphoma Undergoing Autologous Stem Cell Transplantation.

BACKGROUND High-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) plays a crucial role in the therapy of patients with lymphoma. This retrospective study aimed to analyze prognostic factors in patients undergoing HDT/ASCT for lymphoma. MATERIAL AND METHODS We included patients with lymphoma who underwent HDT/ASCT at our center. Time-to-event outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed with the Kaplan-Meier method and log-rank test. Receiver operating characteristic (ROC) curve analysis and Cox proportional hazard regression analysis were performed to explore the prognostic value of different factors. RESULTS A total of 113 patients with lymphoma were included. Patients with low serum albumin levels (<37 g/L) before transplantation had significantly lower PFS and OS (P<0.01). Albumin levels before transplantation significantly predicted early progression (progressed within 1 year) after transplantation (AUC=0.706, P=0.003). Multivariate Cox analysis indicated that low albumin level (hazard ratio [HR] 3.19, 95% confidence interval [CI] 1.54-6.63; P=0.002) and age >60 years (HR 2.92, 95% CI 1.27-6.71; P=0.012) were independent risk factors for PFS. Total protein <60 g/L was an independent risk factor for OS (HR 3.57, 95% CI 1.45-8.78; P=0.006). CONCLUSIONS Low albumin level before transplantation was an independent risk factor in patients with lymphoma undergoing HDT/ASCT. Intense care and effective maintenance therapy after transplantation are required for patients with low albumin levels.