Multi-omics Analyses Reveal Function of Apolipoprotein E in Alternative Splicing and Tumor Immune Microenvironment in Kidney Renal Clear Cell Carcinoma via Pan-cancer Analysis.

Apolipoprotein E (APOE) regulates lipid metabolism, associated with the development of various cancers. However, its precise prognostic significance and functions in alternative splicing and the tumor immune microenvironment remain unclear. In this study, we extracted APOE expression in pan-cancer from TCGA and analyzed mRNA transcriptome, cell lines, and protein levels. Furthermore, we analyzed the alternative splicing expression of the APOE gene transcript with prognostic profiles using the OncoSplicing database. We obtained 73 common APOE genes to perform functional enrichment analysis, assess the correlation between genes and immune cells using TIMER, EPIC, and ssGSEA methods, and examine the prognostic significance using the UALCAN database. Finally, single-cell data was employed to assess the correlation between APOE genes and cell functions. Our findings revealed that APOE expression varies across different tumor types and cancer cell lines. The alternative splicing analysis demonstrated that APOE transcript expression levels have prognostic value in cancers such as LGG, KIRC, and KIRP. Functional enrichment analysis indicated significant associations between APOE and various immune cells, such as macrophages, CD8 T cells, and NK cells, with significant implications for prognosis. Moreover, single-cell data indicated that APOE was primarily expressed in renal epithelial cells among stromal cells and in macrophages among immune cells, significantly negatively correlated with five functional states. Our study represents the first comprehensive exploration of APOE's function in pan-cancers and identifies APOE as a potential biomarker in cancer pathogenesis, prognosis, and immune therapeutic target.

Comparison of therapeutic effects of different acupuncture and moxibustion therapies in the treatment of peripheral facial nerve paralysis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Previous evidences show that acupuncture and moxibustion therapy has positive effects on peripheral facial nerve paralysis (PFP), but there are many acupuncture treatments based on meridian theory, and there are differences in the efficacy of each program. This study will compare the clinical efficacy of different acupuncture treatments for PFP through mesh meta-analysis. METHODS: Randomized controlled trials of acupuncture therapy in the treatment of PFP are going to be retrieved from 8 Science databases including CNKI, Wanfang, VIP and Chinese Biomedical Science, PubMed, Embase, Web of Science and the Cochrane Library from establishment to January 2022. We will use the Cochrane Risk Bias Assessment Tool to assess the quality of the studies and the grading of recommendation assessment, development and evaluation method to assess the strength of the evidence. All data analyses will be performed by Revman5.3, Gemtc 0.14.3, and Stata 14.0. RESULTS: This study will evaluate the efficacy of different acupuncture treatments for PFP by evaluating clinical efficacy rate, facial nerve function score, facial disability score scale, facial electromyography, adverse reactions, etc, and further explore the mechanism of action of each therapy. CONCLUSION: This study will provide a reliable evidence-based basis for selecting the best acupuncture treatment for PFP. TRIAL REGISTRATION: Open science framework registration number: DOI 10.17605/OSF.IO/XQRK9.

Sequential treatment combining cladribine-based re-induction, myeloablative allogeneic HSCT, and prophylactic donor lymphocyte infusion: a promising treatment for refractory acute myeloid leukemia.

We describe the first multicenter prospective study to assess the efficacy, safety, and immune reconstitution of a novel sequential transplant approach in 24 patients with primary induction failure/relapsed acute myeloid leukemia (AML). The sequential regimen consisted of cladribine 5 mg/m2/day and cytarabine 2 g/m2/day for 5 days and mitoxantrone 7 mg/m2/day for 3 days, followed by myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) using intravenous busulfan (3.2 mg/kg/day) for 4 days and cyclophosphamide (60 mg/kg/day) for 2 days. Patients in CR without acute graft-versus-host disease at day + 90 received prophylactic donor lymphocyte infusion (pDLI). At the time of transplantation, a marrow blast infiltration > 20% or any level of circulating blasts was found in 62.5% of patients. The cumulative incidence of relapse at 2 years was 29.8%. Overall survival (OS) was 74.5% at 1 year and 56.5% at 2 years. Leukemia-free survival (LFS) at 1 and 2 years was 62.5 and 50.5%, respectively. Multivariate analysis demonstrated that haploidentical related donor, pDLI, and experiencing chronic graft-versus-host disease (cGVHD) were protective from relapse. Total T cells and T cell subsets in peripheral blood recovered at 3 months post-HSCT. The expressions of immune checkpoints (cytotoxic T lymphocyte antigen 4 and programmed death 1) were extremely low in T cells over the first 1 year post-transplantation.

[Discussion on Classical Morphological View of Acupoints: Taking Book A-B Classic of Acupuncture and Moxibustion as An Example].

After analyzing the contents of Volume Ⅲ of A-B Classic of Acupuncture and Moxibustion, we propose a concept of classical morphological view about acupoints in terms of their superficial signs and structure in Chinese ancient times. That is to say that the ancient medical experts' understanding about acupoints contain locality, layers and variability. These 3 aspects were applied to the classification and location of acupoints, as well as to the clinical treatment in the ancient times. Furthermore, the classical view about acupoints also contains the ideas of Shou-Xing (, keeping paying attention to needling the local acupoints only in the light of the focus) and Shou-Shen (, keeping paying attention to both the related acupoints and appropriate manipulations in the light of pattern identification of symptoms and signs as well as the patients' physical constitutions) in performing acupuncture treatment. Owing to the influence of the idea of Shou-Shen, the classical view about the signs and structure of acupoints presented a weakening trend gradually in ancient Chinese medical circle.

[Research and thinking on needling sensation of acupoint Huantiao (GB 30)].

Taken Huantiao (GB 30) as breakthrough point, acupuncture manipulations of generating various needling sensations by different physicians are sorted. Types of acupoint needling sensations and conducting directions after acupuncture and all kinds of factors that affect needling sensations are analyzed from new perspectives. It is considered that attention should be paid to acupoint location, postures of patients, manipulation methods, types of needling sensations, transmission lines and duration time of needling sensations, etc.

Berberine targets epidermal growth factor receptor signaling to suppress prostate cancer proliferation in vitro.

Berberine is a well­known component of the Chinese herbal medicine Huanglian (Coptis chinensis), and is capable of inhibiting the proliferation of multiple cancer cell lines. However, information available regarding the effect of berberine on prostate cancer cell growth is limited. In the present study, LnCaP and PC­3 human prostate cancer cell lines were selected as in vitro models in order to assess the efficacy of berberine as an anticancer agent. A cell proliferation assay demonstrated that berberine inhibited cell growth in a dose­and time­dependent manner. Further investigation revealed berberine significantly accumulated inside cells that were in the G1 phase of the cell cycle and enhanced apoptosis. Western blot analysis demonstrated that berberine inhibited the expression of prostate­specific antigen and the activation of epidermal growth factor receptor (EGFR), and it attenuated EGFR activation following EGF treatment in vitro. In conclusion, the results indicate that berberine inhibits the proliferation of prostate cancer cells through apoptosis and/or cell cycle arrest by inactivation of the EGFR signaling pathway.

[Location of disease: acupoint view from the angle of clinic].

Doctor WANG Zhi-zhong in the Southern Song Dynasty proposed the acupoint view of "location of disease", which explained the connotation of acupoints from the angle of clinic. Its meaning included two levels, one level meant pathological change on the body surface, that was the location of acupuncture diagnosis-treatment, and the other one indicated that the body surface which was the reflecting point of pathological change on the distal area or inside the body was the location of acupuncture diagnosis-treatment. The specific connotations of clinical acupoints were: location of pathogenic factors or reflection of pathogenic factors, regularity between acupoints un- der disease and specific organ, morphological differences and positioning variability after acupoints under disease, and acupoints examination, diagnosis and treatment.

[The relationship of telomere and telomerase activity with outcome of aplastic anemia after immunosuppressive therapy].

OBJECTIVE: To observe the changes of telomere length and telomerase activity in patients with aplastic anemia (AA), and relationship with immunosuppressive therapy (IST) efficacy, to explore the pathogenesis of AA and the role of telomere length in evaluating immunosuppressive therapy efficacy. METHODS: 71 cases of AA patients between September 2010 and March 2013 were enrolled into this study. 3 ml peripheral blood specimens from this cohort of patients were collected to test the telomere length in peripheral blood mononuclear cell (PBMNC) with flow-FISH and detect telomerase activity with TRAP-PCR-ELISA method. RESULTS: Telomere length and age showed negative correlation (b=-0.387, P=0.001) in normal control, NSAA and SAA + VSAA groups, telomere length became shorter with the growth of age, and normal control group telomere length decreased along with the age growth slightly greater than the other two groups (NSAA, SAA+VSAA). Besides the effect of age on telomere length, no significant difference was observed between NSAA and SAA+VSAA groups (P=0.573), and NSAA, SAA+VSAA (30.957 ± 4.502,29.510 ± 5.911)groups were significantly shorter than normal control group (51.086±10.844) (P<0.01). Telomere length in NR group (25.357±4.848)was significantly lower than normal control group (51.086 ± 10.844) (P=0.005), telomere length in CR(32.808 ± 4.685)/PR groups (30.334±4.464) compared with normal control group had no significant difference (P=0.517, P=0.254). Telomere length below 29.21% obviously decreased outcomes of IST. Telomerase activity had significant difference (χ²=20.385, P<0.01). The telomerase activity had no significant difference in terms of age and gender in three groups, multiple comparison found that telomerase activities in SAA + VSAA (0.324±0.178) (P<0.01), and NSAA (0.234±0.175) groups (P=0.002) were significantly higher than normal control group (0.107±0.083). CONCLUSION: Telomere length of PBMNC in AA patients was significantly shortened than normal control group with telomerase activity increased, and telomere shorted more apparently in NR group, these patients should adjust the treatment as early as possible. Telomeres could predict the curative effect of IST.

[Magnetic-activated cell sorting combined with multiplex ligation-dependent probe amplification for detecting molecular cytogenetic abnormalities in multiple myeloma].

OBJECTIVE: To investigate the reliability of magnetic-activated cell sorting (MACS) combined with multiplex ligation-dependent probe amplification (MLPA) in the detection of the molecular cytogenetic abnormalities in multiple myeloma. METHODS: The bone marrow cells were collected from 29 patients with multiple myeloma. The immuno magnetically sorted and unsorted cells were detected for TP53 and RB1 expressions using MLPA probes and the results were compared with fluorescent in situ hybridization (FISH). RESULTS: The detection success rate was 100% for MLPA, which yielded results with an concordance rate of 99.1% with the FISH results. The positivity rates of MLPA and FISH were both increased after immunomagnetic sorting of the bone marrow cells. CONCLUSION: MLPA can well suit the clinical needs for detecting molecular cytogenetic abnormalities in multiple myeloma, and the samples should be immuno magnetically sorted before the assay.