Platelet indices and inflammatory bowel disease: a Mendelian randomization study.

Background: Platelets play a significant role in the innate and adaptive processes of immunity and inflammation. Inflammatory bowel disease (IBD) is an autoimmune disease that is widely understood to be caused by a combination of genetic predisposition, aberrant immune responses, etc. Methods: To examine the relationships between genetically determined platelet indices and IBD, we conducted a Mendelian randomization (MR) study. Data associated with platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT) were used from the UK Biobank. The outcome data, including IBD, Crohn's disease (CD), ulcerative colitis (UC), were from the FinnGen database. The inverse variance-weighted (IVW), MR-Egger, weighted median methods were used for MR analyses. Results: The MR estimations from the IVW approach show a significant connection between PLT and IBD. Similarly, PCT and IBD have a relationship following the IVW and MR-Egger approaches. While PLT and PCT have strong relationships with CD, according to the findings of all three approaches respectively. Nevertheless, PDW was the only relevant indicator of UC. The only significant result was IVW's. Conclusion: Our findings suggest that the fluctuation of platelet indicators is of great significance in the development of IBD. PLT and PCT have a close association with IBD and CD, respectively; PDW only has a connection with UC. Platelets play an important role in the progression of IBD (UC, CD).

Advances in genomics and genome editing for improving strawberry (Fragaria ×ananassa).

The cultivated strawberry, Fragaria ×ananassa, is a recently domesticated fruit species of economic interest worldwide. As such, there is significant interest in continuous varietal improvement. Genomics-assisted improvement, including the use of DNA markers and genomic selection have facilitated significant improvements of numerous key traits during strawberry breeding. CRISPR/Cas-mediated genome editing allows targeted mutations and precision nucleotide substitutions in the target genome, revolutionizing functional genomics and crop improvement. Genome editing is beginning to gain traction in the more challenging polyploid crops, including allo-octoploid strawberry. The release of high-quality reference genomes and comprehensive subgenome-specific genotyping and gene expression profiling data in octoploid strawberry will lead to a surge in trait discovery and modification by using CRISPR/Cas. Genome editing has already been successfully applied for modification of several strawberry genes, including anthocyanin content, fruit firmness and tolerance to post-harvest disease. However, reports on many other important breeding characteristics associated with fruit quality and production are still lacking, indicating a need for streamlined genome editing approaches and tools in Fragaria ×ananassa. In this review, we present an overview of the latest advancements in knowledge and breeding efforts involving CRISPR/Cas genome editing for the enhancement of strawberry varieties. Furthermore, we explore potential applications of this technology for improving other Rosaceous plant species.

[The Role of NK Cells in Allogeneic Hematopoietic Stem Cell Micro-Transplantation for Acute Myeloid leukemia].

OBJECTIVE: To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST) in the treatment of patients with acute myeloid leukemia(AML). METHODS: Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed. The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor (GPBSC), followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission (CR). The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated. Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype, including KIR ligand mismatch, 2DS1, haplotype, and HLA-Cw ligands on survival prognosis of patients. RESULTS: Forty-two patients received MST induction therapy, and the CR rate was 57.1% after 1 course and 73.7% after 2 courses. Multivariate analysis showed that, medium and high doses of NK cells was significantly associated with improved disease-free survival (DFS) of patients (HR=0.27, P =0.005; HR=0.21, P =0.001), and high doses of NK cells was significantly associated with improved overall survival (OS) of patients (HR=0.15, P =0.000). Donor 2DS1 positive significantly increases OS of patients (HR=0.25, P =0.011). For high-risk patients under 60 years old, patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group (P =0.036); donor 2DS1 positive significantly prolonged OS of patients (P =0.009). CONCLUSION: NK cell dose, KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST, improve the survival of AML patients.

Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), characterized by low survival rates and a high recurrence rate, is a major cause of cancer-related mortality. Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common driver of NSCLC. Within this study, the inhibitory activity of (+)-anthrabenzoxocinone ((+)-ABX), an oxygenated anthrabenzoxocinone compound derived from Streptomyces, against NSCLC is demonstrated for the first time both in vitro and in vivo. Mechanistically, it is confirmed that the PI3K/AKT/mTOR signaling pathway is targeted and suppressed by (+)-ABX, resulting in the induction of S and G2/M phase arrest, apoptosis, and autophagy in NSCLC cells. Additionally, the augmentation of intracellular ROS levels by (+)-ABX is revealed, further contributing to the inhibition of the signaling pathway and exerting inhibitory effects on tumor growth. The findings presented in this study suggest that (+)-ABX possesses the potential to serve as a lead compound for the treatment of NSCLC.

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

[Efficacy and Prognostic Factors of Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia].

OBJECTIVE: To retrospectively analyze the efficacy and complications of our institution's modified nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) in treating intermediate-risk acute myeloid leukemia (AML) - first complete remission (CR1) and prognostic factors. METHODS: Clinical data of 50 intermediate-risk AML-CR1 patients who underwent matched related NST at the Fifth Medical Center of Chinese People's Liberation Army General Hospital from August 2004 to April 2021 were collected, the hematopoietic recovery, donor engraftment and complications were observed, and overall survival (OS) rate, leukemia-free survival (LFS) rate, treatment-related mortality (TRM), and cumulative relapse rate were calculated. Statistical analysis of factors affecting prognosis was also preformed. RESULTS: The median times for neutrophil and platelet recovery after transplantation were 10 (6-16) and 13 (6-33) days, respectively. One month after transplantation, 22 patients (44%) achieved full donor chimerism (FDC), and 22 patients (44%) achieved mixed chimerism (MC), among whom 18 cases gradually transited to FDC during 1-11 months, 4 cases maintained MC status. The overall incidence of acute graft-versus-host disease (aGVHD) was 36%, with a rate of 18% for grade II-IV aGVHD and a median onset time of 45 (20-70) days after transplantation. The overall incidence of chronic GVHD (cGVHD) was 34%, with 20% and 14% of patients having limited or extensive cGVHD, respectively. The incidence rates of infections, interstitial pneumonia, and hemorrhagic cystitis were 30%, 10%, and 16%, respectively. The 5-year OS rate, LFS rate, TRM, and cumulative relapse rate were 68%, 64%, 16%, and 20%, respectively. The increase of the number of CD34+ cells infused had shortened the recovery time for neutrophils and platelets (r =0.563, r =0.350). The number of CD34+ cells infused significantly influenced the occurrence of extensive cGVHD (OR =1.36, 95%CI : 1.06-1.84, P =0.024). CONCLUSION: Modified NST is effective in treating intermediate-risk AML-CR1 patients, however, further expansion of sample size is needed to study prognostic factors.

Postoperative complications following Schwab-grade-I versus Schwab-grade-II PCO in treating severe rigid kyphoscoliosis patients: comparative matched-group outcomes with minimum 2-year follow-up.

BACKGROUND CONTEXT: Standard partial facetectomies, (Smith-Petersen Osteotomy, (SPO), (Schwab-grade-I) and complete facet resection also known as Ponte osteotomy, (PO), (Schwab-grade-II) are narrowly akin and collectively appreciated as posterior column shortening osteotomies (PCOs). The former is considered a gentler osteotomy grade than the latter. The spine literature provides very little information on their comparison regarding perioperative complications and major curve correction rate outcomes. PURPOSE: To determine whether Schwab-grade-I PCO (SPO) and Schwab-grade-II PCO (PO) are comparably safe in the surgical management of severe rigid scoliosis or kyphoscoliosis patients. STUDY DESIGN/SETTING: Retrospective single-center comparative clinical study. PATIENT SAMPLE: A total of 38 patients with severe rigid scoliosis or kyphoscoliosis were propensity score matched in this study, (SPO-treated); n=21 (55.30%) and (PO-treated); n=17 (44.70%), who underwent primary spinal deformity corrective surgery, respectively. OUTCOME MEASURES: Outcomes included demographics, baseline pulmonary functional outcomes, perioperative complications incidence, hospital costs, Oswestry disability index (ODI), and the Scoliosis Research Society-22 (SRS-22) questionnaire scores. METHODS: Following approval by the Institutional Review Board (IRB) of Beijing Chaoyang Hospital-Affiliated Capital Medical University in Beijing, out of a total of 82 consecutive surgical patients with complete data demonstrating severe and/or rigid spinal deformity, a pool of 38 of the 82 (46.3%) propensity-matched adult (≥18 years) patients with severe rigid scoliosis or kyphoscoliosis defined with a preoperative major curve magnitude of ≥80° on anteroposterior plain radiographs, and flexibility of <25% on bending plain radiographs who underwent primary spinal deformity corrective surgery were retrospectively evaluated. The patients were dichotomized into two osteotomy groups: standard (partial) facetectomy (SPO-treated), n=21 with an average age of 24.67 years, (Schwab-grade-I PCO) and complete facet excision, (PO-treated), (ie, Schwab-grade-II PCO), n=17 with an average age of 23.12 years. The minimum follow-up period was 2 years. Primary outcomes included baseline demographics and clinical features. Secondary outcomes included perioperative [intraoperative, immediate, and 2-year postoperative] complication rates. Tertiary outcomes included perioperative ODI and SRS-22 scores. Statistical analyses were carried out by Student t-test and Pearson's Chi-square test (Fisher's Exact Test), through Python statistical software package. Statistical significance was set at (p<.05). RESULTS: Of the 38 matched severe rigid scoliosis or kyphoscoliosis patients, 55.30% (n=21) were SPO-treated and 44.70% (n=17) were PO-treated patients, respectively. The overall average age of patients was 23.97 years, with a female incidence of 76.32%. Major curve correction rates were 49.19% and 57.40% in SPO-treated and PO-treated patients, respectively, (p>.05). Immediately following surgery, comparable overall complication rates of 28.57% (n=6/21) versus 29.41% (n=5/17) were observed in the SPO-treated and PO-treated patients, respectively, (p=.726). We observed incidences of 9.52%, (n=2/21) versus 5.88%, (n=1/17) for surgical intensive care unit (SICU) admission, and incidences of 4.76%, (n=1/21) versus 5.88%, (n=1/17) for cardiopulmonary events in SPO-treated versus PO-treated patients following corrective surgery, respectively, (p>.05). The incidences of neurological deficits in the SPO-treated and PO-treated patients were respectively, 14.29%, (n=3/21) versus 17.65%, (n=3/17) immediately following surgery, (p>.05), and 0.00%, (n=0/21) in SPO-treated versus 14.28%, (n=3/21) in PO-treated patients at ≥2 years postoperative, (p<.05). Among the three patients that reported neurological deficits in the PO-treated group at ≥2 years postoperative, two patients had pre-existing baseline neurological deficits. The ODI score in the PO-treated group was significantly inferior at a minimum 2-year follow-up, (p<.05). CONCLUSIONS: In the current study, both SPO-treated and PO-treated patients demonstrated statistically comparable surgical complications immediately following corrective surgery. Severe rigid kyphoscoliosis patients with preexisting baseline neurological deficits were more inclined to sustain neurological morbidity following corrective surgery. PCO corrective techniques are warranted as safe options for treating patients with severe rigid spine deformity phenotypes.

[Analysis on Cellular Immune Function Recovery after HLA Mismatched Allogeneic Hematopoietic Stem Cell Micro-Transp- lantation in Elderly AML Patients].

OBJECTIVE: To investigate the recovery of cellular immunity in elderly patients with acute myeloid leukemia (AML) after micro-transplantation (MST) and the changes of cellular immunity during relapse, as well as their clinical significance. METHODS: A total of 41 elderly AML patients who received MST treatment in a single center and 25 healthy elderly people were included. Immune function among different age groups in normal population was compared. Furthermore, immune fuction was compared between elderly AML patients of different age groups who achieved continuous complete remission (CR) after MST treatment and normal controls, between high risk group and medium-low risk group, as well as among before diagnosis, after CR, and relapse. Peripheral blood of patients and normal controls was collected, and the percentage of lymphocyte subsets was detected by multi-color flow cytometry. RESULTS: Thirty-five patients achieved CR after MST treatment while six patients did not. After MST treatment, CD3+ T cells, CD8+T cells and activated T cells in all age groups were higher than normal. Significant recovery of CD3+ and CD8+T cells was observed in both high risk and medium-low risk groups, and the overall recovery of immune cells in medium-low risk group was better. It was also observed that B lymphocytes and NK cells could not return to normal levels within 1 year after MST treatment. The proportion of CD3+ T cells, CD4+ T cells, and CD4/CD8 ratio were significantly decreased during relapse compared with continuous CR after MST (P<0.05). CONCLUSION: MST treatment can promote the recovery of CD3+T cells, CD8+T cells and other killer cells, so as to improve the cellular immune function of elderly patients, which provides a new immune cell therapy for elderly AML.

Prognostic factors and treatment outcomes of spinal osteosarcoma: Surveillance, epidemiology, and end results database analysis.

Objective: Spinal osteosarcoma is a rare osseous neoplasm. The aim of this study is to make a comprehensive analysis of the demographic features, clinicopathologic characteristics and factors affecting prognosis of spinal osteosarcoma using the Surveillance, Epidemiology and End Results (SEER) database. Methods: SEER data were reviewed to identify patients diagnosed with spinal osteosarcoma between 1975 and 2016 and determine their overall survival (OS) and disease-specifc survival (DSS). Univariate and multivariate analyses were performed using the Cox-regression proportional hazards model and Kaplan-Meier method. Results: A total of 668 patients (53.1% males) with spinal osteosarcoma were identified. The mean age at diagnosis was 45.2 years, including 67.5% patients younger than 60 years. The median OS of these patients was 15 months, and the 5-year OS was 16.8%. Multivariate analysis showed that age ≥60 year (HR=2.271, p = 0.008), high grade (HR=1.323, p = 0.008), regional stage (HR=1.658, p = 0.017), metastasis stage (HR=3.045, p < 0.001) and no-surgery treatment (HR=1.761, p < 0.001) were adversely associated with OS; gender (HR=0.657, p = 0.044), tumor grade (HR=1.616, p = 0.006), tumor stage (HR=3.329, p = 0.011; HR=7.983, p < 0.001) and radiotherapy (HR=0.606, p = 0.031) were independent prognostic factors affecting DSS. Conclusion: Based on SEER data analysis, male, high tumor grade, regional stage, metastasis stage and radiotherapy are independent predictors of poor survival of patients with spinal osteosarcoma. The clinical treatment of spinal osteosarcoma still faces serious challenges. Future research should focus on the clinical impact and survival outcomes of the emerging targeted and immune therapies for the sake of improving the survival stalemate of spinal osteosarcoma.

Expert Consensus on Clinical Application of Lateral Lumbar Interbody Fusion: Results From a Modified Delphi Study.

STUDY DESIGN: Modified Delphi study. OBJECTIVE: The objective of this study was to establish expert consensus on the application of lateral lumbar interbody fusion (LLIF) by using the modified Delphi study. METHODS: From June 2019 to March 2020, Members of the Chinese Study Group for Lateral Lumbar Spine Surgery were selected to collect expert feedback using the modified Delphi method where 65 spine surgeons from all over China agreed to participate. Four rounds were performed: 1 face-to-face meeting and 3 subsequent survey rounds. The consensus was achieved with ≥a 70.0% agreement for each question. The recommendation of grade A was defined as ≥90.0% of the agreement for each question. The recommendation of grade B was defined as 80.0-89.9% of the agreement for each question. The recommendation of grade C was defined as 70.0-79.9% of the agreement for each question. RESULTS: A total of 65 experts formed a panelist group, and the number of questionnaires collected was 63, 59, and 62 in the 3 rounds. In total, 5 sections, 71 questions, and 382 items achieved consensus after the Delphi rounds including summary; preoperative evaluation; application at the lumbar spinal stenosis, lumbar disc herniation, lumbar spondylolisthesis, adult degenerative scoliosis, postoperative adjacent segmental degeneration, and revision surgery; complications; and postoperative follow-up evaluation of LLIF. CONCLUSION: The modified Delphi method was utilized to ascertain an expert consensus from the Chinese Study Group for Lateral Lumbar Spine Surgery to inform clinical decision-making in the application of LLIF. The salient grade A recommendations of the survey are enumerated.

A bioinformatics framework to identify the biomarkers and potential drugs for the treatment of colorectal cancer.

Colorectal cancer (CRC), a common malignant tumor, is one of the main causes of death in cancer patients in the world. Therefore, it is critical to understand the molecular mechanism of CRC and identify its diagnostic and prognostic biomarkers. The purpose of this study is to reveal the genes involved in the development of CRC and to predict drug candidates that may help treat CRC through bioinformatics analyses. Two independent CRC gene expression datasets including The Cancer Genome Atlas (TCGA) database and GSE104836 were used in this study. Differentially expressed genes (DEGs) were analyzed separately on the two datasets, and intersected for further analyses. 249 drug candidates for CRC were identified according to the intersected DEGs and the Crowd Extracted Expression of Differential Signatures (CREEDS) database. In addition, hub genes were analyzed using Cytoscape according to the DEGs, and survival analysis results showed that one of the hub genes, TIMP1 was related to the prognosis of CRC patients. Thus, we further focused on drugs that could reverse the expression level of TIMP1. Eight potential drugs with documentary evidence and two new drugs that could reverse the expression of TIMP1 were found among the 249 drugs. In conclusion, we successfully identified potential biomarkers for CRC and achieved drug repurposing using bioinformatics methods. Further exploration is needed to understand the molecular mechanisms of these identified genes and drugs/small molecules in the occurrence, development and treatment of CRC.

[Immunophenotypic Features and Clinical Prognosis of Patients with Mixed Phenotype Acute Leukemia].

OBJECTIVE: To retrospectively analyze the laborotary test results and clinical data of 31 patients with mixed phenotype acute leukemia (MPAL) in order to summarize and discuss the biological characteristics, curative effect, and prognosis of each subtype of MPAL based on immunophenotype results. METHODS: MPAL patients diagnosed and treated in our hospital from July 2013 to January 2019 were selected to analyze the data of cell morphology, immunophenotyping, cytogenetics, molecular biology (MICM), and routine blood at initial diagnosis. Follow-up was carried out until the last discharge time. RESULTS: Among 31 patients, there were 19 males and 12 females, with a median age of 41(12-76) years old. According to the results of immunophenotyping and EGIL score, there were 16 cases of myeloid-T lymphoid mixed phenotype (myeloid-T group), 9 cases of myeloid-B lymphoid mixed phenotype (myeloid-B group), 5 cases of T-B lymphoid mixed phenotype (T-B group), and 1 case of myeloid-T-B lymphoid mixed phenotype. Compared between different subtypes, the antigen expression characteristics were the highest positive rate and expression rate of HLA-DR in myeloid-B group, and the positive rate of CD2 in T-B group was significantly higher than that in the myeloid-T group. Meanwhile, the expression rates of CD7 and cCD3 (cytoplasmic CD3) in T-B group were higher than those in myeloid-T group, and cCD79a was positive in all cases of myeloid-B group and T-B group. The median WBC of T-B group was 81.92×109/L, which was significantly higher than that of the other two groups (P<0.05). The quantitative results of WT1 were higher than 10-4 in 92.6% of the patients, and the WT1 expression level in myeloid-B group was significantly lower than the other two groups (P<0.01). Among the 9 patients with myeloid-B mixed phenotype, 5 cases showed BCR-ABL positive. Among 28 patients followed up, 21 cases achieved complete remission (CR), the median time to first obtain CR was 32.5(9-75) days, and the median follow-up time was 16 months (range from 21 days to 6 years). The CR rate and median overall survival (OS) time in myeloid-B group were 88.9% and 40 months, which were higher than the other two groups. The CR rate and 3-year OS rate in T-B group were relatively lower (50.0%, 0). CONCLUSION: WT1 gene is highly expressed in patients with MPAL, and each subgroup of MPAL based on immuophenotype has its unique antigen expression characteristics. Compared with myeloid-T group and T-B group, myeloid-B group can acquire higher remission rate and have better prognosis.

Long Noncoding RNA SNHG7 Is a Diagnostic and Prognostic Marker for Colon Adenocarcinoma.

Numerous studies have shown that long noncoding RNAs (lncRNAs) play a critical role in the malignant progression of cancer. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) remains unexplored. In this study, the expression of lncRNA SNHG7 in colon cancer tissues and its correlation with clinical characteristics were analyzed based on data from The Cancer Genome Atlas (TCGA) database. SNHG7 was found to be highly expressed in 17 types of cancer, including COAD. Next, TCGA data were further investigated to identify differentially expressed genes, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. In addition, the relationship between SNHG7 expression and clinical features were analyzed. SNHG7 expression was found to be a potentially valuable indicator for COAD diagnosis and prognosis. Finally, gene set enrichment analysis showed that SNHG7 may affect lupus erythematosus and reactome cellular senescence, possibly influencing the prognosis of patients with COAD. Altogether, these results suggest that SNHG7 may be associated with the occurrence and development of COAD, having potential diagnostic and prognostic value.

Cryptococcus neoformans Infection Induces IL-17 Production by Promoting STAT3 Phosphorylation in CD4+ T Cells.

Cryptococcus neoformans infection in the central nervous system is a severe infectious disease with poor outcomes and high mortality. It has been estimated that there are 220,000 new cases each year. Over 90% of C. neoformans meningitis cases were diagnosed in AIDS patients with CD4+ T cell count <100 cells/µl; however, the mechanism of cryptococcal meningitis in patients with normal immune functions remains unclear. IL-17 is a pro-inflammatory cytokine and plays an important role in anti-fungal immunity. Here we report that significantly high levels of IL-17 were predominantly detected in the cerebrospinal fluid of patients with either AIDS- or non-AIDS-associated C. neoformans meningitis but not in patients with tuberculous meningitis or non-neurosyphilis. Antifungal therapy minimized the IL-17 level in the cerebrospinal fluid. An in vitro mechanistic study showed that C. neoformans stimulation of healthy peripheral blood mononuclear cells prompted IL-17 production, and CD4+ T cells were the predominant IL-17-producing cells. IL-17 production by C. neoformans stimulation was STAT3 signaling dependent. Inhibition of STAT3 phosphorylation attenuated the C. neoformans-mediated IL-17 expression. Our data highlighted the significance of CD4+ T cells in antifungal immunity and suggested IL-17 as a diagnostic biomarker of C. neoformans infection and STAT3 as a checkpoint for antifungal targeted therapies.

Bioassay-guided isolation of anti-tumor polyprenylphloroglucinols from Calophyllum polyanthum and primary mechanism.

Five compounds were isolated from Calophyllum polyanthum leaves (10.09 g) by bioassay-guided fractionation to evaluate their anti-tumor activity. Among these compounds, apetalic acid (1) demonstrated significant inhibitory activity against 8 types of tumor cells (MHCC97H, CNE1, CNE2, B16, LOVO, SW480, A549, 1299), especially against two colon cancer cells (LOVO, SW480). Apetalic acid could inhibit cell proliferation, migration, invasion and induce apoptosis. It could significantly up-regulate the expression levels of apoptosis-related genes (BAX, Caspase-9,) and proteins (BAX, Cleaved-caspase-9, Cleaved-caspase-3) and down-regulated the expression of inhibitor of apoptosis gene (Bcl-2) and proteins (Bcl-2, phosphorylated AKT). Possible mechanism of the antitumor activity of apetalic acid derived from Calophyllum polyanthum supports its use in the prevention and treatment of colorectal cancer.

Spinal cysticercosis: a rare cause of myelopathy.

BACKGROUND: Neurocysticercosis is a neuroinfectious disease caused by the larval stage of the tapeworm Taenia solium. Isolated spinal cysticercosis is rare, with limited cases having been reported in the literature. This entity poses great diagnostic and therapeutic challenges. METHODS: This retrospective study included seven patients pathologically diagnosed with spinal cysticercosis. The clinical manifestations, radiological features on magnetic resonance imaging (MRI), treatment, and outcomes were analyzed. RESULTS: This case series consisted of four male and three female patients, with an average age of 34.9 ± 10.9 years. Clinically, six patients manifested with localization-related myelopathy. There were four solid lesions, one cystic-solid lesion, and three cystic lesions. The solid and cystic-solid lesions showed characteristic MRI features: 1) within the lesion, there was a mural nodule with isointensity on T1WI and iso- to hyperintensity on T2WI; 2) the signals at the periphery of the mural nodule were variable, ranging from hypointense to hyperintense on T2WI; and 3) ring-like or cyst wall enhancement could be present, and dot-like enhancement could be noted in the mural nodule. Complete resection of the responsible lesion was achieved in all patients, and oral albendazole was administered in a patient with one more suspected homologous lesion. After a mean follow-up period of 56.7 ± 35.1 months, the patient's symptoms mostly regressed. CONCLUSION: Spinal cysticercosis is an extremely rare cause of myelopathy. Characteristic MRI features can facilitate preoperative diagnosis. Clinicians should be aware of this entity, and it should be included in the differential diagnosis of myelopathy.

A positive feedback loop of lncRNA-RMRP/ZNRF3 axis and Wnt/ß-catenin signaling regulates the progression and temozolomide resistance in glioma.

Drug resistance strikingly limits the therapeutic effect of temozolomide (TMZ) (a common drug for glioma). Long non-coding RNA (lncRNA) RMRP has been found to be implicated in glioma progression. However, the effect of RMRP on TMZ resistance along with related molecular mechanisms is poorly defined in glioma. In the present study, RMRP, ZNRF3, and IGF2BP3 were screened out by bioinformatics analysis. The expression levels of lncRNAs and mRNAs were measured by RT-qPCR assay. Protein levels of genes were detected by western blot and immunofluorescence assays. ZNRF3 mRNA stability was analyzed using Actinomycin D assay. Cell proliferative ability and survival rate were determined by CCK-8 assay. Cell apoptotic pattern was estimated by flow cytometry. The effect of RMRP knockdown on the growth of TMZ-treated glioma xenograft tumors was explored in vivo. The relationships of IGF2BP3, RMRP, and ZNRF3 were explored by bioinformatics prediction analysis, RNA immunoprecipitation, luciferase, and RNA pull-down, and chromatin immunoprecipitation assays. The results showed that RMRP was highly expressed in glioma. RMRP knockdown curbed cell proliferation, facilitated cell apoptosis and reduced TMZ resistance in glioma cells, and hindered the growth of TMZ-treated glioma xenograft tumors. RMRP exerted its functions by down-regulating ZNRF3 in glioma cells. IGF2BP3 interacted with RMRP and ZNRF3 mRNA. IGF2BP3 knockdown weakened the interaction of Argonaute 2 (Ago2) and ZNRF3. RMRP reduced ZNRF3 expression and mRNA stability by IGF2BP3. RMRP knockdown inhibited ß-catenin expression by up-regulating ZNRF3. The inhibition of Wnt/ß-catenin signaling pathway by XAV-939 weakened RMRP-mediated TMZ resistance in glioma cells. ß-catenin promoted RMRP expression by TCF4 in glioma cells. In conclusion, RMRP/ZNRF3 axis and Wnt/ß-catenin signaling formed a positive feedback loop to regulate TMZ resistance in glioma. The sustained activation of Wnt/ß-catenin signaling by RMRP might contribute to the better management of cancers.

RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating Runx2 mRNA and inhibiting osteogenic differentiation.

As a systemic disease, osteoporosis (OP) results in bone density loss and fracture risk, particularly in the hip and vertebrae. However, the underlying molecular mechanisms of OP development have not been fully illustrated. N6-Methyladenosine (m6A) is the most abundant modification of mRNAs, which is involved in many of pathological processes in aging disease. However, its role and regulatory mechanism in OP remains unknown. Here, we aimed to investigate the roles of m6A and its demethylase FTO in OP development. The results showed that m6A methylated RNA level was up-regulated in the bone marrow mesenchymal stem cells (BMSCs) from patients with OP. The level of N6-methyladenosine demethylase FTO was consistently decreased in the BMSCs from patients with OP. Functionally, lentivirus-mediated FTO overexpression in normal BMSCs to compromised osteogenic potential. Mechanism analysis further suggested that FTO overexpression decreased the m6A methylated and total level of runt related transcription factor 2 (Runx2) mRNA, subsequently inhibited osteogenic differentiation. We found that FTO inhibition could effectively improve the bone formation in ovariectomized osteoporotic mice in vivo. Together, these results reveal that RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating runx2 mRNA and inhibiting osteogenic differentiation.

Application of controlled low central venous pressure during hepatectomy: A systematic review and meta-analysis.

STUDY OBJECTIVE: Previous studies reported that controlled low central venous pressure (CVP) can reduce blood loss during liver resection. This systematic review and meta-analysis sought to explore the efficacy and safety of low CVP in patients undergoing hepatectomy. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). REVIEW METHODS: RCTs were searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical database, Chinese Scientific Journals Database, and Wanfang database from inception to April 30, 2021. Subgroup analyses were performed based on different surgical methods (open hepatectomy vs laparoscopic hepatectomy) and published countries (China vs other countries). The quality of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluation. MAIN RESULTS: Eighteen RCTs containing 1285 participants (626 patients in the low CVP group and 659 patients in the control group) were included in this study. The forest plot showed that low CVP effectively reduced blood loss during liver resection compared with the control group (MD = -311.92 mL, 95% CI [-429.03, -194.81]; P < 0.001, I2 = 96%). Furthermore, blood transfusion volume (MD = -158.85 mL, 95% CI [-218.30, -99.40]; P < 0.001, I2 = 55%) and the number of patients requiring transfusion (RR 0.41, 95% CI 0.27-0.65, P < 0.001, I2 = 0%) were decreased in the low CVP group. Subgroup analyses showed similar results. Notably, the alanine transaminase level was significantly lower in the low CVP group during the first five postoperative days. However, no significant differences were observed for other postoperative liver function indicators (aspartate aminotransferase, total bilirubin, serum albumin, and prothrombin time), renal function indicators (blood urea nitrogen and serum creatinine) and perfusion parameters (heart rate, mean arterial pressure, and urine volume). The incidence of complications was similar between the two groups. CONCLUSION: The findings of this study showed that low CVP is effective and safe during hepatectomy. Therefore, this technique is recommended to reduce blood loss during hepatectomy. PROSPERO registration number: CRD42021232829.