Serum-derived exosomes promote CD8+ T cells to overexpress PD-1, affecting the prognosis of hypopharyngeal carcinoma.

BACKGROUND: Hypopharyngeal cancer (HPC) is associated with a poor prognosis and a high recurrence rate. Immune escape is one of the reasons for the poor prognosis of malignant tumors. Programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) have been shown to play important roles in immune escape. However, the role of PD-1/PD-L1 in HPC remains unclear. In this experiment, we investigated the effect of exosomes from HPC patient serum on CD8+ T cell function and PD-1/PD-L1 expression and, thus, on prognosis. We hope to provide guidance for the identification of new targets for HPC immunotherapy. METHODS: PD-1 and CD8 expression in 71 HPC tissues and 16 paracarcinoma tissues was detected by immunohistochemistry. Concurrently, the clinicopathological data of the patients were obtained to conduct correlation analysis. Exosomes were isolated from serum and then identified by Western blotting (WB), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Flow cytometry was used to assess the activity of CD8+ T cells after exosome stimulation. The effects of exosomes on the ability of CD8+ T cells to kill FaDu cells were assessed by CCK-8 assay. The expression of IL-10 and TGF-ß1 was measured by enzyme-linked immunosorbent assay (ELISA). PD-L1 expression in HPC tissue samples was evaluated by immunohistochemistry, and the relationship between PD-1/PD-L1 expression and prognosis was investigated with patient specimens. RESULTS: PD-1 expression was significantly upregulated on CD8+ T cells in tumor tissues compared with those in normal tissues. The overall survival (OS) and disease-free survival (DFS) of PD-1-overexpressing patients were decreased. Serum exosomes from patients can elevate PD-1 expression on CD8+ T cells and suppress their killing capacity and secretory function. The rate of positive PD-L1 expression was increased in HPC tissues compared with paracancerous tissues. The DFS and OS of the PD-1(+)-PD-L1(+) group were significantly lower than those of the PD-1(-)-PD-L1(-) group. CONCLUSION: Our findings indicate that serum exosomes from HPC patients can inhibit CD8+ T cell function and that the PD-1-PD-L1 pathway plays an important role in the immune escape of HPC. Exosomes combined with immunotherapy may guide the treatment of patients with advanced disease in the future.

[Study on Alkaloids of Fruit from Macleaya cordata].

Objective: To study the alkaloids from the fruit of Macleaya cordata. Methods: The alkaloids were isolated and purified by silica gel column chromatography and preparative high performance liquid chromatography,and the structures were elucidated based on the spectral data. Results: Eight alkaloids were obtained from the fraction of ethanol extract and identified as 6-cyanodihydrosanguinarine( 1),6-acetonyldihydrosanguinarine( 2),6-acetonyldihydrochelerythrine( 3),chelerythrine( 4),dihydrochelerythrine( 5),13,14-dehydrogen-N-methyl-coptisine( 6),N-methyl-canadine( 7) and berberine( 8). Conclusion: Compounds 1 and 6 are new nature products,and compound 7 is isolated from this plant for the first time.

[Re-evaluation of systematic reviews of acupuncture and moxibustion for children with cerebral palsy].

OBJECTIVE: To assess the methodological quality, report quality and evidence quality of the Meta-analysis and systematic reviews of acupuncture and moxibustion for children with cerebral palsy, aiming to provide decision-making basis for clinical treatment. METHODS: The systematic reviews and Meta-analysis of acupuncture and moxibustion for children with cerebral palsy were searched in CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed and EMbase. The retrieval time was from the database establishment to June 30th, 2022. AMSTAR 2 (a measurement tool to assess systematic reviews) was used to evaluate the methodological quality， and PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and GRADE was used to evaluate the quality of evidence. RESULTS: A total of 14 systematic reviews were included, including 37 primary outcome indexes. According to AMSTAR 2 evaluation results, there were 4 low quality studies, 10 very low quality studies, and low scores on items 2, 4, 7, 10 and 16. PRISMA scores ranged from 15 to 25, and the main reporting problems reflected in structured abstracts, program and registration, retrieval, and funding sources, etc. According to the GRADE classification results, there were 3 high quality evidences, 7 medium quality evidences, 10 low quality evidences and 17 very low quality evidences. The main downgrading factors were limitations, imprecision and publication bias. CONCLUSION: Acupuncture and moxibustion has a certain effect for cerebral palsy in children, but the quality of methodology, reporting and evidence in the included literature is poor, and the comparison of curative effect between different acupuncture and moxibustion methods is unclear.

Practitioners' perspectives on acupuncture treatment for postpartum depression: A qualitative study.

BACKGROUND: Acupuncture may become a treatment for postpartum depression (PPD). Currently, little is known about the use of acupuncture in the treatment of PPD from the point of view of practitioners. The aim of this study was to explore practitioners' perspectives on the treatment of PPD with acupuncture and provide suggestions for future improvement. METHODS: This study employed a qualitative descriptive method. Semistructured, open-ended interviews were conducted with 14 acupuncture practitioners from 7 hospitals via face-to-face or telephone interviews. The data were collected using interview outline from March to May 2022 and analysed using qualitative content analysis. RESULTS: In general, the use of acupuncture for treating PPD was positively regarded by practitioners. They claimed that acupuncture is both safe and helpful for breastfeeding women who are experiencing emotional discomfort and that it can alleviate a variety of somatic symptoms. The following three themes were extracted: (a) patient acceptance and compliance; (b) acupuncture as a treatment for PPD; and (c) the advantages and drawbacks of acupuncture treatment. CONCLUSION: Practitioners' optimistic outlooks demonstrated that acupuncture is a promising treatment option for PPD. However, the time cost was the most significant barrier to compliance. Future development will focus mostly on improving acupuncture equipment and the style of service.

Peripheral Blood Inflammatory Cytokine Factors Expressions are Associated with Response to Acupuncture Therapy in Postpartum Depression Patients.

Background: Increasing evidences demonstrate that immune dysregulation can result in depression, and it is reported that persistent inflammatory response is related to the unresponsiveness of antidepressant treatment. Purpose: This study aimed to explore the reason why some responded but some not responded to acupuncture in treating postpartum depression (PPD), and whether it related to the levels of inflammatory cytokines. Patients and Methods: Women diagnosed with PPD were recruited in to accept 8-week acupuncture. All subjects were assessed the 17-item Hamilton Depression Rating Scale (HDRS17) at baseline, week 1, week 2, week 4 and week 8 during the treatment. A panel of 9 cytokines was measured at baseline and 8 weeks. Results: Of the 121 participants, 96 completed the 8-week assessment and 46 completed the blood sample collection. HDRS17 scores of 96 subjects showed significant statistical reduction since the first week (P = 0.002) and reached to 5.31 (P < 0.000) at the end of therapy. And we divided the 46 subjects into responders and non-responders according to the response rate of HDRS17 scores. Responders and non-responders did not differ significantly between-group in changes in the 9 cytokines. In responders, IL-6, IL-10 and IFN-γ levels were statistically lower (P = 0.006; P = 0.033; P = 0.024), while TGF-ß1 was statistically higher after 8 weeks treatment (P < 0.000). In non-responders, the levels of IL-5, TNF-α and TGF-ß1 were statistically higher (P = 0.018; P < 0.000; P < 0.000), while IFN-γ was statistically lower (P = 0.005). Conclusion: Acupuncture could alleviate depressive symptoms of patients with PPD and might through adjusting peripheral inflammatory response by up-regulating anti-inflammatory cytokines and down-regulating pro-inflammatory cytokines.

Fecal microbiota as a predictor of acupuncture responses in patients with postpartum depressive disorder.

Background: There are several clinical and molecular predictors of responses to antidepressant therapy. However, these markers are either too subjective or complex for clinical use. The gut microbiota could provide an easily accessible set of biomarkers to predict therapeutic efficacy, but its value in predicting therapy responses to acupuncture in patients with depression is unknown. Here we analyzed the predictive value of the gut microbiota in patients with postpartum depressive disorder (PPD) treated with acupuncture. Methods: Seventy-nine PPD patients were enrolled: 55 were treated with acupuncture and 24 did not received any treatment. The 17-item Hamilton depression rating scale (HAMD-17) was used to assess patients at baseline and after eight weeks. Patients receiving acupuncture treatment were divided into an acupuncture-responsive group or non-responsive group according to HAMD-17 scores changes. Baseline fecal samples were obtained from the patients receiving acupuncture and were analyzed by high-throughput 16S ribosomal RNA sequencing to characterize the gut microbiome. Results: 47.27% patients responded to acupuncture treatment and 12.5% patients with no treatment recovered after 8-week follow-up. There was no significant difference in α-diversity between responders and non-responders. The ß-diversity of non-responders was significantly higher than responders. Paraprevotella and Desulfovibrio spp. were significantly enriched in acupuncture responders, and these organisms had an area under the curve of 0.76 and 0.66 for predicting responder patients, respectively. Conclusions: Paraprevotella and Desulfovibrioare may be useful predictive biomarkers to predict PPD patients likely to respond to acupuncture. Larger studies and validation in independent cohorts are now needed to validate our findings.

Regulation of miR-30b in cancer development, apoptosis, and drug resistance.

miR-30b, which is encoded by the gene located on chromosome 8q24.22, plays an important role in a variety of diseases. In most types of tumors, miR-30b significantly inhibits the proliferation, migration, and invasion of cancer cells through the regulation of target genes. Moreover, miR-30b can inhibit the PI3K/AKT signaling pathway through the regulation of EGFR, AKT, Derlin-1, GNA13, SIX1, and other target genes, thus inhibiting the EMT process of tumor cells and promoting apoptosis. In addition, miR-30 plays a significant role in alleviating drug resistance in tumor cells. Although the use of miR-30b as a clinical diagnostic indicator or anticancer drug is still facing great difficulties in the short term, with the deepening of research, the potential application of miR-30b is emerging.

Acupoint Massage Therapy Alters the Composition of Gut Microbiome in Functional Constipation Patients.

RESULTS: Results showed the overall structure of gut microbiome has no significant difference between experimental and control groups. In the genus level, the abundance of Pseudobutyrivibrio and Ruminiclostridium is higher in the experiment group than in the control, whereas that of Fusicatenibacter is less. The 16S KEGG function prediction suggested that Parkinson disease, retinol metabolism, and arachidonic acid metabolism could explain the biological function of different gut microbiome. Furthermore, cytokines in the serum showed a correlation with the abundance of Pseudobutyrivibrio in CFC. CONCLUSION: AMT could change the composition of gut microbiome which is associated with cytokines in CFC patients.

[Status of acupuncture service quality control].

In order to guarantee and improve the quality of acupuncture service, the developments of the control of acupuncture service quality in the World Health Organization (WHO) and various countries were summarized. A number of normative documents that could improve acupuncture service security and effectiveness have been developed in WHO and many countries, in which, acupuncture training, safety manipulation and the guidelines for clinical practice of disease have been included. There are great differences in the qualification authentication and management of acupuncture practitioners among different countries. In China and South Korea, the official government departments are in charge of the management, but, in most of the countries, the qualification attestation examination of acupuncture is conduced mainly by the national/local industry organizations authorized by the state and operated by the commissioned experts. The medical service quality evaluation system is complicated. Because of the specific characteristics of acupuncture discipline itself, it is necessary to develop the service quality assessment system and the standard which is especially adaptable in acupuncture discipline.

Mass spectrometry-guided isolation of two new benzoquinoline alkaloids from Macleaya cordata.

Two new alkaloids, named 2,3-methylenedioxy-7,10-dimethyl-7,8,9,10-tetrahydro-benzoquinoline (1) and 2,3-methylenedioxy-7,10-dimethyl-8-carboxyl-benzoquinoline (2), were detected primarily from the fruits of Macleaya cordata by their different fragmentation pathways. And then isolation of the two compounds was performed by column chromatography and preparative HPLC under the guiding of mass spectrometry. Finally, their structures were determined by spectroscopic analysis.