[Effect of Recombinant Human Thrombopoietin on Platelet Reconstitution after Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma].

OBJECTIVE: To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM). METHODS: The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups. RESULTS: There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group. CONCLUSION: When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.

[Retracted] Tremella polysaccharides inhibit cellular apoptosis and autophagy induced by Pseudomonas aeruginosa lipopolysaccharide in A549 cells through sirtuin 1 activation.

[This retracts the article DOI: 10.3892/ol.2018.8554.].

Sijunzi decoction enhances sensitivity of colon cancer cells to NK cell destruction by modulating P53 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Sijunzi Decoction (SJZD), a traditional Chinese herbal remedy, is frequently employed in the treatment of various cancers, including colon cancer. Previous research suggests that SJZD plays a pivotal role in modulating the immune system and enhancing immunity against tumors. However, the precise role of SJZD in combating colon cancer and its potential molecular functions in regulating natural killer cells remain elusive. AIMS OF THE STUDY: To elucidate the potential mechanism underlying the anticolon cancer effects of SJZD in synergy with natural killer (NK) cells through both in vivo and in vitro experiments. MATERIALS AND METHODS: In vivo experiments: A subcutaneous tumor mouse model of colon cancer and in vivo NK cell depletion experiments were conducted to observe the anticolon cancer effects of SJZD. Flow cytometry assessed immune cell depletion in mouse spleens, while immunohistochemical (IHC) staining detected the expression of apoptotic genes in tumor tissues. In vitro experiments: The mechanism by which SJZD regulates the sensitization of colon cancer cells to NK cells was investigated using real-time polymerase chain reaction (RT-PCR), western blotting (WB), and co-culture experiments with NK cells. RESULTS: Sijunzi Decoction (SJZD) significantly impeded tumor growth in mice; however, NK cell depletion markedly attenuated the tumor-suppressive effect of SJZD. Immunohistochemical (IHC) results indicated that SJZD increased the expression of P53, death receptor 4 (DR4), and death receptor 5 (DR5) in tumor tissues. In vitro experiments, 24 h SJZD-pretreated colon cancer cells showed a substantial elevation in P53, DR4, and DR5 levels, and the activity of colon cancer cells significantly diminished after co-culture with NK cells. These effects of SJZD were reversed with the addition of the P53 inhibitor pifithrin-α (PFT-α), resulting in reduced inhibition of colon cancer cells by NK cells. CONCLUSION: SJZD enhances the levels of DR4 and DR5 through the modulation of P53 expression, consequently increasing the sensitivity of colon cancer cells to NK cell-mediated killing. These findings provide a theoretical foundation for the clinical application of SJZD in patients with colon cancer. In this study, we first investigated the effect of SJZD on subcutaneous tumor growth in mice with colon cancer using in vivo assays and assessed the impact of NK cells on the anticolon cancer effect of SJZD in vivo through NK cell depletion. In vitro experiments were conducted to explore the potential mechanism of action of SJZD in NK cell-mediated anticolon cancer effects.

Evaluation of next-generation sequencing versus next-generation flow cytometry for minimal-residual-disease detection in Chinese patients with multiple myeloma.

PURPOSE: To evaluate the efficacy of next-generation sequencing (NGS) in minimal-residual-disease (MRD) monitoring in Chinese patients with multiple myeloma (MM). METHODS: This study analyzed 60 Chinese MM patients. During MRD monitoring in these patients' post-therapy, clonal immunoglobulin heavy chain (IGH) rearrangements were detected via NGS using LymphoTrack assays. MRD monitoring was performed using NGS or next-generation flow cytometry (NGF), and the results were compared. Additionally, the sensitivity and reproducibility of the NGS method were assessed. RESULTS: The MRD detection range of the NGS method was 10-6-10-1, which suggested good linearity, with a Pearson correlation coefficient of 0.985 and a limit of detection of 10-6. Intra- and inter-assay reproducibility analyses showed that NGS exhibited 100% reproducibility with low variability in clonal cells. At diagnosis, unique clones were found in 42 patients (70.0%) with clonal IGH rearrangements, which were used as clonality markers for MRD monitoring post-therapy. Comparison of NGS and NGF for MRD monitoring showed 79.1% concordance. No samples that tested MRD-positive via NGF were found negative via NGS, indicating the higher sensitivity of NGS. MRD could be detected using NGS in 6 of 7 samples before autologous hematopoietic stem-cell transplantation, and 5 of them tested negative post-transplantation. In contrast, the NGF method could detect MRD in only 1 sample pre-transplantation. CONCLUSION: Compared with NGF, NGS exhibits higher sensitivity and reproducibility in MRD detection and can be an effective strategy for MRD monitoring in Chinese MM patients.

Busulfan/Cyclophosphamide Compared with Melphalan as a Conditioning Regimen for Autologous Transplantation of Multiple Myeloma: A Long-Term Assessment.

BACKGROUND: Melphalan was poorly available in mainland China. The aim of this study is to explore the dose-adjusted busulfan/cyclophosphamide (BU/CY) as an alternative regimen in auto stem cell transplantation (ASCT) for multiple myeloma (MM). METHODS: A total of 105 newly diagnosed MM patients undergoing ASCT during May 2012 and August 2017 were retrospectively analyzed. The BU/CY regimen was applied to 64 patients. Busulfan (9.6 mg/kg or 8.0 mg/kg in total) and cyclophosphamide (3.6 g/m2 or 3.0 g/m2 in total) were administered according to the creatinine clearance rate (CCR). A high-dose melphalan (HDMEL) regimen (200 mg/m2) was given to the other 41 patients. RESULTS: At a median follow-up of 65 (1~119) months, estimated overall survival (OS) and progression-free survival (PFS) at 104 months in the BU/CY and HDMEL groups were 35.6% vs. 20.5% (p = 0.263) and 20.2% vs. 2.4% (p = 0.035), respectively. The median overall survival (OS) and PFS of the HDMEL and BU/CY groups were 55 vs. 70.5 months and 26 vs. 46.5 months, respectively. In multivariate analysis, the BU/CY regimen was found to be the only protective factor for PFS. No lethal toxicity was found in the BU/CY group, and treatment-related mortality (TRM) in 100 days was similar to the HDMEL group. CONCLUSIONS: MM patients may also benefit from the dose-adjusted BU/CY regimen.

The prognostic significance of circulating plasma cells in newly diagnosed multiple myeloma patients.

Objective: Multiple myeloma (MM) is a highly characteristic tumor that is influenced by numerous factors that determine its prognosis. Studies indicate that the presence of circulating plasma cells (cPCs) is a detrimental factor that significantly impacts the prognosis of patients with MM. Methods: This study retrospectively analyzed the prognostic value of cPCs quantified by 10-color flow cytometry in 145 newly diagnosed MM (NDMM) cases in the First Affiliated Hospital of Soochow University from November 2018 to February 2021. The study was approved by the Ethics Committee of the hospital (2021 No. 93). Results: Of the 145 patients, 99 (68.2%) were detected cPCs. Through receiver operating characteristics (ROC) analysis, an optimal threshold of 0.165% was identified as a predictor for overall survival (OS). The median progression-free survival (PFS) was 33 months in patients with cPCs ≥0.165%, whereas those with cPCs <0.165% had a PFS of <33 months (p=0.001). The median OS was not reached for two groups; the 3-year OS for patients with cPCs ≥0.165% was 71% compared with 87% for those with cPCs <0.165% (p=0.003). In transplant patients, cPCs ≥0.165% also predicted worse prognosis. Similarly, when considering cytogenetic risk factors in conjunction with cPC levels, comparable results were obtained. To evaluate whether the Revised International Staging System (R-ISS) groups could be further stratified based on different prognostic factors related to cPCs, our study revealed similar median PFS and OS rates in R-ISS II stage patients with cPCs ≥0.165% compared to those in the III stage (p=0.659 and 0.249, respectively). Conclusion: This study demonstrates that a high ratio of cPCs serves as a reliable indicator for predicting a poorer prognosis in MM cases. Furthermore, incorporating the R-ISS system and cytogenetic risk factors alongside the level of cPCs enhances the accuracy of prognostic predictions for patients with MM.

[Changes in Health Risks and Pollution Sources of Atmospheric PM2.5-bound Metals in a Background Site in North China].

To explore the change features of PM2.5-bound metals in a background site of North China in the past ten years, 71 and 160 samples were collected from December 2011 to January 2013 (period Ⅰ) and from September 2019 to November 2021 (period Ⅱ) in Tuoji Island National Atmospheric Monitoring Station, respectively.The concentration of metals sampled was determined using ICP-MS, and the concentrations, sources, and health risks of heavy metals were compared. The results revealed that the average concentration of PM2.5 was (54.06±39.71) µg·m-3during period Ⅱ, which was 3.53 ng·m-3 lower than that during period Ⅰ. The concentrations of Zn, Mn, As, Pb, and V in stage Ⅱ decreased by 54.53, 172.63, 0.8, 79.06, and 3.81 ng·m-3, respectively, whereas the concentrations of Cr, Cu, Cd, and Ni increased by 2.01, 5.42, 3.03, and 3.55 ng·m-3, respectively. The PMF model results indicated that the biggest contributor to PM2.5-bound metal was industrial emissions (32.32%), followed by coal combustion (27.47%), vehicle emissions (23.70%), ship emissions (9.69%), and dust sources (6.83%) during period Ⅱ. The contribution ratio of dust sources and ship emissions decreased by 20.73% and 8.83%, respectively, whereas for coal combustion and industrial emissions it increased by 2.50% and 13.52%, respectively, when compared with that during period Ⅰ. The total carcinogenic risk induced by PM2.5-bound heavy metals of period Ⅱ increased, with the highest contributions by Cr and Cd. The total non-carcinogenic risk decreased, with Mn contributing the most. Therefore, in the process of air pollution control, the control of pollution sources of heavy metals such as Cr and Mn should be reinforced.

MiR-506 targets polypyrimidine tract-binding protein 1 to inhibit airway inflammatory response and remodeling via mediating Wnt/ß-catenin signaling pathway.

BACKGROUND: Airway remodeling, which contributes to the clinical course of childhood asthma, occurs due to airway inflammation and is featured by anomalous biological behaviors of airway smooth muscle cells (ASMCs). microRNA (miRNA) plays an essential role in the etiopathogenesis of asthma. OBJECTIVE: This research was aimed to characterize miR-506 in asthma and uncover potential regulatory machinery. MATERIAL AND METHODS: The asthmatic cell model was established by treating ASMCs with transforming growth factor-beta1 (TGF-ß1) and assessed by the levels of interleukin (IL)-1ß and interferon gamma (IFN-γ). Using real-time quantitative polymerase chain reaction, mRNA expression of miR-506 and polypyrimidine tract-binding protein 1 (PTBP1) was measured. Cell counting kit-8 and Transwell migration tests were used for estimating the capacity of ASMCs to proliferate and migrate. Luciferase reporter assay was used to corroborate whether miR-506 was directly bound to PTBP1. Expression of PTBP1, collagen I and III, and essential proteins of the wingless-related integration (Wnt)/ß-catenin pathway (ß-catenin, c-MYC and cyclin D1) was accomplished by Western blot analysis. The involvement of Wnt/ß-catenin signaling in asthma was confirmed by Wnt signaling pathway inhibitor (IWR-1). RESULTS: miR-506 was poorly expressed in asthmatic tissues and cell model. Functionally, overexpression of miR-506 reduced aberrant proliferation, migration, inflammation and collagen deposition of ASMCs triggered by TGF-ß1. Mechanically, miR-506 directly targeted the 3' untranslated region (3-UTR) of PTBP1 and had a negative regulation on PTBP1 expression. Moreover, overexpression of miR-506 suppressed the induction of Wnt/ß-catenin pathway. The administration of IWR-1 further validated negative correlation between miR-506 and the Wnt/ß-catenin pathway in asthma. CONCLUSION: Our data indicated that targeting miR-506/PTBP1/Wnt/ß-catenin axis might point in a helpful direction for treating asthma in children.

Chang Wei Qing Decoction enhances the anti-tumor effect of PD-1 inhibitor therapy by regulating the immune microenvironment and gut microbiota in colorectal cancer.

The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment (TIME). This study aimed to mechanistically assess whether Chang Wei Qing (CWQ) Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy. PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), rather than those with mismatch repair-proficient/microsatellite stable (pMMR/MSS) CRC. Hence, immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients. Flow cytometry was used to analyze T-lymphocytes in tumors from mice. Western blot was used to measure the expression of PD-L1 protein in mouse tumors. The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry. 16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice. Subsequently, Spearmanapos;s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes. The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins. In vivo, CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+ and PD-1+CD8+ T cells in tumors. Additionally, the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone. CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes, andActinobacteria. Additionally, the proportion of infiltrated CD8+PD-1+, CD8+, and CD3+ T cells were found to be positively correlated with the abundance of Akkermansia. Accordingly, CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-1 inhibitor therapy.

Autologous stem cell transplantation in multiple myeloma patients with renal impairment.

Renal impairment (RI) used to exclude multiple myeloma (MM) patients from autologous stem cell transplantation (ASCT) for safety concerns. Here, we retrospectively reviewed 34 consecutively transplanted patients with creatinine clearance < 60 ml/min at ASCT in recent 5 years at our institution. Busulfan/cyclophosphamide and high-dose melphalan were both employed as conditioning regimens. We found 62% grade 1-2 oral mucositis, 12% grade 3 oral mucositis, 48% grade 3 infection, 8% grade ≥ 4 infection, 50% grade 1 transient creatinine increase, 15% cardiac adverse events, and 12% engraftment syndrome. One case of secondary platelet graft failure and 1 case of transplantation-related mortality were observed. Interleukin-6 concentration was elevated among patients with increased body temperature and/or N-terminal pro-brain natriuretic peptide during engraftment, and close monitoring of these markers may help to predict susceptibility to cardiac events and engraftment syndrome. Adverse events occurred frequently, but the majority were manageable in this cohort. ASCT would further deepen the anti-myeloma efficacy and slightly ameliorated renal function. With a median follow-up of 26.2 months post transplantation (range: 1.6-74.8 months), the median progression-free survival (PFS) and overall survival (OS) post-transplantation of patients undergoing first-line transplantation were not reached; the median PFS post-transplantation of patients undergoing rescue transplantation was 19.2 months and the median OS was not reached.

Functional exercise on patients' rehabilitation with psoas muscle sports injuries / Exercício funcional na reabilitação de pacientes com lesão esportiva do músculo psoas / Ejercicio funcional en la rehabilitación de pacientes con lesión deportiva del músculo psoas

ABSTRACT Introduction Lumbar muscle strain is a chronic injury to soft tissues such as the lumbar muscles, ligaments, and fascia. Functional exercise has specific applications in treating lumbar muscle injuries caused by sports. However, analyses on the treatment results in the psoas muscle are inconclusive. Objective Analyze the clinical efficacy of functional exercise in treating psoas muscle dysfunction. Methods 10 athletes diagnosed with lumbar muscle strain received continuous training with a functional exercise protocol for two weeks, five times a week. Clinical efficacy was assessed by visual analog scale for pain score and Prokin254 for proprioception ability indices before and after treatment. The article adopts a mathematical statistics analysis method to analyze the therapeutic effect of motor function exercise with SPSS 13.0. Results Patients reported a reduction of pain in the muscles under exertion after functional exercise. The results were significantly different (P<0.05). Patients' lumbar strength was significantly improved. This index has a considerable statistical difference (P<0.05). Conclusion Functional exercise showed a positive effect on the treatment of psoas muscle injury. The research results of this article can provide an effective training protocol for the rehabilitation of people with a psoas muscle strain. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução A tensão muscular lombar é uma lesão crônica dos tecidos moles, tais como músculos lombares, ligamentos e fáscia. O exercício funcional tem certas aplicações no tratamento de lesões musculares lombares ocasionadas pelo esporte. Porém, as análises na intensidade dos resultados do tratamento no músculo psoas são inconclusivas. Objetivo Analisar a eficácia clínica do exercício funcional no tratamento da disfunção no músculo psoas. Métodos 10 atletas com diagnóstico de estiramento muscular lombar receberam treinamento contínuo com protocolo de exercícios funcionais por 2 semanas, 5 vezes por semana. A eficácia clínica foi avaliada pela escala analógica visual de score de dor e Prokin254 para índices de capacidade de propriocepção antes e depois do tratamento. O artigo adota um método de estatística matemática para analisar o efeito terapêutico do exercício da função motora com SPSS 13.0. Resultados Pacientes relataram uma redução da dor na musculatura sob esforço após o exercício funcional. Os resultados foram significativamente diferentes (P<0,05). A força lombar dos pacientes foi significativamente aprimorada. Esse índice tem diferença estatística considerável (P<0,05). Conclusão O exercício funcional revelou um efeito positivo sobre o tratamento da lesão muscular do psoas. Os resultados da pesquisa deste artigo podem fornecer um protocolo eficaz de treinamento para a reabilitação de pessoas com tensão do músculo psoas. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción La distensión muscular lumbar es una lesión crónica de los tejidos blandos como los músculos lumbares, los ligamentos y la fascia. El ejercicio funcional tiene ciertas aplicaciones en el tratamiento de las lesiones musculares lumbares causadas por el deporte. Sin embargo, los análisis sobre la intensidad de los resultados del tratamiento en el músculo psoas no son concluyentes. Objetivo Analizar la eficacia clínica del ejercicio funcional en el tratamiento de la disfunción del músculo psoas. Métodos 10 atletas con diagnóstico de distensión muscular lumbar recibieron un entrenamiento continuo con un protocolo de ejercicios funcionales durante 2 semanas, 5 veces por semana. La eficacia clínica se evaluó mediante la escala analógica visual para la puntuación del dolor y el Prokin254 para los índices de capacidad de propiocepción antes y después del tratamiento. El artículo adopta un método estadístico matemático para analizar el efecto terapéutico del ejercicio de la función motora con SPSS 13.0. Resultados Los pacientes informaron una reducción del dolor en los músculos bajo esfuerzo después del ejercicio funcional. Los resultados fueron significativamente diferentes (P<0,05). La fuerza lumbar de los pacientes mejoró significativamente. Este índice tiene una diferencia estadística considerable (P<0,05). Conclusión El ejercicio funcional reveló un efecto positivo en el tratamiento de la lesión del músculo psoas. Los resultados de la investigación de este artículo pueden proporcionar un protocolo de entrenamiento eficaz para la rehabilitación de personas con distensión del músculo psoas. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

The independent adverse prognostic significance of 1q21 gain/amplification in newly diagnosed multiple myeloma patients.

Objective: 1q21 gain/amplification (1q21+) is a common abnormal karyotype in multiple myeloma, and its proportion in Chinese patients is much higher. If 1q21+ is included as one of the poor prognostic factors, it will greatly increase the proportion of high-risk patients in newly diagnosed multiple myelome (NDMM) patients. Therefore, the poor prognostic significance of 1q21+ is still controversial. This study mainly analyzed the clinical characteristics, treatment response and prognostic significance of 1q21+ in NDMM patients. Methods: 248 NDMM patients admitted in The First Affiliated Hospital of Soochow University from September 01, 2018 to August 31, 2021 of a VRD registration study, were retrospectively analyzed. 135 cases (54.4%) had 1q21+ by CD38-sorted fluorescence in situ hybridization (FISH). The clinical characteristics, treatment response and prognosis of the general population and subgroups were analyzed, among which 153 patients were compared for the involved genes by CytoScan. Results: Compared with negative patients, 1q21+ patients were more likely to have anemia, hypoalbuminemia, renal insufficiency, high lactate dehydrogenase and high proportion of R-ISS-III stage. The patients with 1q21+ involving CKS1B detected by Cytoscan had a higher proportion of complex karyotypes and abnormal CNVs, and all at middle-risk or high-risk groups defined by Prognostic Index. Multivariate analysis showed that 1q21+ was an independent adverse prognostic factor (PFS HR=2.358, 95%CI 1.286-4.324, P=0.006; OS HR=2.598, 95%CI 1.050-6.425, P=0.039). 1q21+ subgroup had an inferior outcome (PFS P=0.0133, OS P=0.0293). Furthermore 1q21 amplification had a shorter PFS than 1q21 gain (24 months vs not reached, P=0.0403), but the OS difference was not clinically significant. The proportion of 1q had no effects on prognosis. In addition, 1q21+ in main clone rather than subclone was an adverse factor affecting the prognosis (PFS P=0.0172, OS P=0.1260). Autologous stem cell transplantation can effectively improve the survival of 1q21+ patients (P<0.05). Conclusion: Patients with 1q21+ have clinically significant end-stage organ damage and higher tumor burden, more likely to combine 13q14-, t(4;14), 1p32- and other cytogenetic abnormalities. 1q21+ is an independent high-risk cytogenetic factor for poor prognosis in NDMM patients, of which 4 or more copy numbers and main clone position significantly associated with prognosis results.

Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management.

Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. However, lack of guidelines leads to simple cognition and even ignorance of this disease for clinicians. Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. Next, although recently there has been an increasing awareness among researchers in terms of the relevant factors for BRG, further studies involving large samples are still required to certify the relationship between them explicitly. Besides, researches have established that BRG is closely associated with the development of precancerous lesions and gastric cancer. Till now, there is still no golden standard for diagnosis of BRG. Nevertheless, advances in techniques, especially extensive applications of endoscopy and chemical analysis of reflux contents, have improved our ability to identify the occurrence of this disease as well as distinguishing physiological reflux from pathological reflux. Finally, it is fortunate for patients that more and more importance has been attached to the treatment of BRG. From lifestyle modification to drug therapy to surgery, all of them with the view of realizing symptomatic relief are employed for patients with BRG. In this review, we briefly evaluate this disorder based on the best available evidence, offering an overview of its complicated pathogenesis, diverse relevant factors, potential carcinomatous risk, modern diagnostic investigations, and effective therapeutic plans.

Anti-CD19 and anti-BCMA CAR T cell therapy followed by lenalidomide maintenance after autologous stem-cell transplantation for high-risk newly diagnosed multiple myeloma.

Few prospective studies have examined posttransplant chimeric antigen receptor (CAR) T cell infusion as candidates for front-line consolidation therapy for high-risk multiple myeloma (MM) patients. This single-arm exploratory clinical trial is the first to evaluate the safety and efficacy of sequential anti-CD19 and anti-BCMA CAR-T cell infusion, followed by lenalidomide maintenance after autologous stem cell transplantation (ASCT), in 10 high-risk newly diagnosed multiple myeloma (NDMM) patients. The treatment was generally well tolerated, with hematologic toxicities being the most common grade 3 or higher adverse events. All patients had cytokine release syndrome (CRS), which was grade 1 in 5 patients (50%) and grade 2 in 5 patients (50%). No neurotoxicity was observed after CAR-T cell infusion. The overall response rate was 100%, with the best response being 90% for a stringent complete response (sCR), and 10% for a complete response (CR). At a median follow-up of 42 (36-49) months, seven (70%) of 10 patients showed sustained minimal residual disease (MRD) negativity for more than 2 years. The median progression-free survival (PFS) and overall survival (OS) were not reached. Although the sample size was small and there was a lack of control in this single-arm study, the clinical benefits observed warrant ongoing randomized controlled trials.

[Myxoid liposarcoma of the testis: A case report and review of the literature].

OBJECTIVE: To investigate the clinicopathological features, diagnosis, differential diagnosis, treatment and prognosis of myxoid liposarcoma (MLPS)of the testis. METHODS: We observed the clinicopathological and immunophenotypic characteristics of primary MLPS of the testis in a male patient and reviewed the relevant literature. RESULTS: The tumor was located in the right testicular parenchyma, of multi-nodular growth microscopically. The tumor cells were stellate, fusiform, foamy and signet ring-like, with abundant mucus and a network of fine branched or plexiform capillaries in the stroma. Immune phenotype-related findings included positive p16 and H3K27ME3 tumor cells and CD34 vascular network, negative CD99, CK, Desmin, FLI agreed-1, S-100, SMA, STAT6, TFE3, α-inhibin and SOX1, and a Ki-67 proliferation index of about 15%. CONCLUSION: Primary MLPS of the testis is rare, which needs to be differentiated from myxosarcoma, rhabdomyosarcoma, myxoma, spindle cell or pleomorphic liposarcoma, and lipophiloma. Immunohistochemical markers Vimentin, s-100 and CD34 can assist in the diagnosis of the tumor.

Knockdown of NOVA1 inhibits inflammation and migration of asthmatic airway smooth muscle cells to regulate PTEN/Akt pathway by targeting PTBP1.

NOVA1 (neuro-oncological ventral antigen 1) is a neuron specific RNA binding protein, belonging to the Nova family, which plays an important role in various diseases. However, the role of NOVA1 in childhood asthma remains unclear. This study was aimed to investigate the role of NOVA1 in TGF-ß1-induced ASMCs proliferation and migration as well as the potential mechanisms. In our study, the NOVA1 expression was significantly increased in asthmatic tissues and TGF-ß1-induced ASMCs. Inhibition of NOVA1 significantly inhibited TGF-ß1-induced ASMCs cell proliferation and migration, and alleviates TGF-ß1-induced inflammation. NOVA1 positively regulated the PTBP1 expression and si-NOVA1 inhibited the activation of PTEN/AKT signal pathway. Importantly, the overexpression of PTBP1 partially reversed the effect of NOVA1 on cell viability, migration, inflammation and the activation of PTEN/AKT signal pathway. Generally, our study demonstrated that si-NOVA1 inhibited TGF-ß1-induced inflammation and migration in ASMCs through PTBP1/PTEN/AKT pathway. Therefore, inhibition of NOVA1 may be useful for the prevention or treatment of asthma airway remodeling.

Atezolizumab-induced anaphylactic shock in a patient with hepatocellular carcinoma undergoing immunotherapy: A case report.

BACKGROUND: Atezolizumab is a programmed death ligand 1 (PD-L1) inhibitor, and its combination with bevacizumab has been proven an effective immunotherapy for unresectable hepatocellular carcinoma (HCC). Treatment with immune checkpoint inhibitors (ICIs) can lead to hypersensitivity reactions; however, anaphylactic shock is rare. We present a case of life-threatening anaphylactic shock during atezolizumab infusion and performed a relevant literature review. CASE SUMMARY: A 75-year-old man was diagnosed with HCC recurrence after hepatectomy. He was administered immunotherapy with atezolizumab plus bevacizumab after an allergy to a programmed death-1 (PD-1) inhibitor. The patient showed a sudden onset of dizziness, numbness, and lack of consciousness with severe hypotension during atezolizumab infusion. The treatment was stopped immediately. The patient's symptoms resolved after 5 mg dexamethasone was administered. Because of repeated hypersensitivity reactions to ICIs, treatment was changed to oral targeted regorafenib therapy. CONCLUSION: Further research is necessary for elucidating the hypersensitivity mechanisms and establishing standardized skin test and desensitization protocols associated with PD-1 and PD-L1 to ensure effective treatment with ICIs.

Sequential CD19 and BCMA-specific CAR T-cell treatment elicits sustained remission of relapsed and/or refractory myeloma.

The low rate of durable response against relapsed and/or refractory multiple myeloma (RRMM) in recent studies indicates that chimeric antigen receptor T-cell (CART) treatment is yet to be optimized. This study aims to investigate the safety and efficacy of sequential infusion of CD19-CART and B-cell maturation antigen (BCMA)-CARTs for RRMM with a similar 3 + 3 dose escalation combined with a toxicity sentinel design. We enrolled 10 patients, among whom 7 received autologous infusion and 3 received allogeneic infusion. The median follow-up time was 20 months. The most common grade 3/4 treatment-emergent toxicities were hematological toxicities. Cytokine-release syndrome (CRS) adverse reactions were grade 1/2 in 9 out of 10 subjects. No dose-limited toxicity (DLT) was observed for BCMA-CAR-positive T cells ≤5 × 107 /kg), while two patients with dose-levels of 5-6.5 × 107 /kg experienced DLTs. The overall response rate was 90% (five partial responses and four stringent complete responses). Three out of four patients with stringent complete responses to autologous CART had progression-free survival for over 2 years. The three patients with allogeneic CART experienced disease progression within 2 months. These results evidence the sequential infusion's preliminarily tolerability and efficacy in RRMM, and present a simple and safe design applicable for the establishment of multiple CART therapy.