Historical and contemporary applications of moxibustion at Gaohuang (BL 43). / 膏肓灸古今应用探析.

The relevant passages on moxibustion at Gaohuang (BL 43) in the Chinese Medical Code (fifth edition), and relevant literature on moxibustion at Gaohuang (BL 43) published up to January 17th, 2023 in the CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase and Scopus were searched. The localization and selection methods of Gaohuang (BL 43), types of moxibustion at Gaohuang (BL 43), moxibustion quantity, and the main clinical indications were analyzed. As a result, a total of 227 ancient passages were included, with 51 related to moxibustion quantity and 171 related to clinical indications, encompassing 33 different diseases. A total of 50 modern articles were reviewed, covering 26 different diseases. The key of selection methods of Gaohuang (BL 43) is exploring sensitivity around the scapula, with direct moxibustion as a preferred technique; the optimal moxibustion dose is detenuined by arrival and withdrawal of deqi, and primary indications were related to syndrome of heart and lung deficiencies.

Longitudinal dynamics of gut microbiota in the pathogenesis of acute graft-versus-host disease.

AIM: The gut microbiota has been reported to be associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota is required to understand the detailed pathogenesis involved in the process of aGvHD. METHODS: Fecal samples were collected prospectively at four timepoints, including pre-HSCT (T1), graft infusion (T2), neutrophil engraftment (T3), and 30 days after transplantation (T4). Fecal samples were profiled by 16S ribosomal RNA gene sequencing to assess the microbiota composition. RESULTS: From the T1 to T4 timepoint, the diversity of the gut microbiota decreased, and the dominant species also changed, with a decrease in the obligate anaerobic bacteria and a shift toward a "pathogenic community". Compared with non-aGvHD patients, aGvHD patients had a lower abundance of Roseburia at T1 and a higher abundance of Acinetobacter johnsonii at T2. Furthermore, Acinetobacter johnsonii was negatively correlated with the secretion of IL-4 and TNF-α. At T3, Rothia mucilaginos was demonstrated to be linked with a decreased risk of aGvHD, which was accompanied by decreased secretion of IL-8. At T4, higher abundances of Lactobacillus paracasei and Acinetobacter johnsonii were identified to be related with aGvHD. Lactobacillus paracasei was associated with the downregulation of IL-10, and Acinetobacter johnsonii was associated with the downregulation of IL-2 and TNF-α. CONCLUSIONS: Dynamic changes in gut microbiota composition and related cytokines were found to be related to aGvHD, including pathogenic or protective changes. These findings suggested that manipulation of gut microbiota at different timepoints might be a promising avenue for preventing or treating this common complication.

The novel HLA-DQB1*02:01:44 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DQB1*02:01:44 differs from HLA-DQB1*02:01:01:01 by one nucleotide in exon 2.

[Discussion of novel mode of acupuncture and moxibustion based on identifying the acupoint sensitization].

On the base of the paradigms of clinical studies on modern moxibustion by identifying the acupoint sensitization, the records of ancient literature in successive dynasties were collected on "identifying the sensitization" of acupoints in acupuncture. In association with acupoint detection of acupuncture recorded in current textbooks, a novel concept, "exerting acupuncture by identifying the acupoint sensitization" is proposed. Acupoint sensitization is the common initial link of effect achieved by both acupuncture and moxibustion. Hence, on the basis of the routine acupoint selection by differentiating syndrome, the state of acupoint must be considerably emphasized in either acupuncture or moxibustion. The clinical curative effect may be improved by selecting the sensitized points and identifying sensitization. This novel mode of diagnosis and treatment focuses on identifying acupoint sensitization by unifying acupuncture with moxibustion and in coincidence with the modern clinical characteristics of either acupuncture or moxibustion.

Steroid-resistant intestinal aGVHD and refractory CMV and EBV infections complicated by haplo-HSCT were successfully rescued by FMT and CTL infusion.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) produces similar survival outcomes as HLA-matched sibling donor allogeneic HCST in younger patients with acquired severe aplastic anemia (SAA). This study reported a 29-years-old man with SAA and intracranial hemorrhage who underwent haplo-HSCT with a modified BU/CY + ATG conditioning regimen. Neutrophil and platelet engraftment were both achieved on day 14 after HSCT. The patient developed grade IV acute graft-versus-host disease (aGVHD) on day 20 and acquired cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections on day 47. After the failure of methylprednisolone, basiliximab, ruxolitinib, and antiviral treatment, the patient was diagnosed with steroid-resistant grade IV aGVHD and refractory CMV and EBV infections. We performed fecal microbiota transplantation and infused CMV- and EBV-specific cytotoxic T lymphocytes. After that the stool volume and frequency gradually decreased, and viral DNA was undetectable on day 80. This report provides helpful clinical experience for treating steroid-resistant aGVHD and refractory viral infections.

MYCN contributes to the sensitization of acute myelogenous leukemia cells to cisplatin by targeting SRY-box transcription factor 4.

Little was known about the role of MYCN in drug resistance in acute myeloid leukemia (AML). We investigated impacts of MYCN on sensitization of AML cell to cisplatin, and its interaction with SRY-box transcription factor 4 (SOX4). In vitro, human AML cell lines HL60 and KG-1 were transfected with the overexpression plasmids and specific small interfering RNA of MYCN (siMYCN), or siSOX4, and then treated with 2 µg/mL cisplatin. MTT and flow cytometry assays were performed to estimate the viability and apoptosis of AML cell. The expressions of MYCN and SOX4 in AML patients and the associations between these two were analyzed by bioinformatics analysis, luciferase assay and quantitative reverse transcription polymerase chain reaction (qRT-PCR). In vivo, transfected HL60 cells were injected into BALB/c nude mice. The tumor size and weight were recorded, and the expressions of MYCN and SOX4 were determined with immunohistochemistry. MYCY and SOX4 were highly-expressed in AML, and their expressions were positively correlated. In AML cells, the treatment using cisplatin induced higher MYCN expression and augmented apoptosis, whereas decreasing the viability. Silencing of MYCN enhanced the tumor-suppressive effects of cisplatin on AML by decreasing cell viability and increasing apoptosis. The promoter of SOX4 was targeted by MYCN. Lower cell viability and higher apoptosis rate were seen in AML cells transfected with siSOX4, the effects of which were partially reversed by overexpressed MYCN. Silencing of MYCN retarded the tumor growth and SOX4 expression in tumor in vivo. Collectively, MYCN sensitized AML cells to cisplatin by targeting SOX4.

Bone marrow mesenchymal stem cell-derived exosomes induce the Th17/Treg imbalance in immune thrombocytopenia through miR-146a-5p/IRAK1 axis.

Bone marrow mesenchymal stem cells (BMSCs) are associated with immune thrombocytopenia (ITP), the underlying mechanism has not been fully elucidated. Here, we attempted to investigate whether BMSCs can regulate Th17/Treg imbalance in ITP through the exosome pathway. We first assessed the proportions of Th17 cells and Tregs in ITP patients, showing that ITP patients exhibited an evident imbalance of Th17/Treg. BMSCs-exosomes' treatment significantly reduced Th17/Treg ratio in the CD4+ T cells of ITP patients. Moreover, miR-146a-5p was highly expressed in BMSCs-exosomes. The expression of miR-146a-5p was obviously increased in CD4+ T cells following the treatment of BMSCs-exosomes. BMSCs-exosomal miR-146a-5p silencing promoted the proportions of Th17 cells and repressed the proportions of Tregs in CD4+ T cells. In addition, miR-146a-5p directly interacted with IL-1R-associated kinase-1 (IRAK), and repressed IRAK1 expression. IRAK1 overexpression promoted Th17/Treg ratio in CD4+ T cells, which was abolished by BMSCs-exosomal miR-146a-5p. In conclusion, these findings demonstrate that BMSC-derived exosomal miR-146a-5p regulates Th17/Treg imbalance in ITP by repressing IRAK1 expression. Thus, this work suggests that BMSCs-exosomal miR-146a-5p may be a potential therapeutic target for ITP.

Efficacy and safety of moxibustion in the treatment of cancer-related fatigue: A protocol for systematic review and meta-analysis.

BACKGROUND: Cancer-related fatigue, a common symptom of cancer patients caused by the interaction of multiple factors, runs through the whole process of tumorigenesis, development, treatment, and prognosis. The main clinical manifestations are weakness, tiredness, exhaustion, fatigue, or slow movement, heavy limbs, low mood or irritability, sleep disturbance or lethargy, lack of attention, etc. CRF is different from the fatigue after daily body fatigue. It has no obvious relief or relief after rest or sleep, and exists for a long time in the relevant treatment and rehabilitation process. It seriously affects the physiological, psychological and social functions of patients, and reduces the quality of life of patients. Moxibustion therapy has shown strong advantages in the treatment of CRF, and the curative effect is accurate. Therefore, this paper will carry out a systematic evaluation and meta analysis of the efficacy and safety of moxibustion in the treatment of CRF. METHODS: we will searching 8 electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, Wanfang Database, and Chinese Biomedical Literature Database. We will search above electronic databases from the beginning to January 2021, without any language restriction. Clinical efficacy, including total effective rate or cure rate, clinical symptom integral, and recurrence rate will be accepted as the primary outcomes. The fatigue scale score, quality of life improvement rate will be used as secondary outcomes. RevMan 5.3 software will be used for statistical analysis. The result about the curative effect and safety of moxibustion for cancer-related fatigue will be presented as risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data. RESULTS: When this research program is completed, the relevant results can be obtained. CONCLUSIONS: The results of this study will provide reliable evidence for the efficacy and safety of moxibustion in the treatment of cancer-related fatigue. ETHICS AND DISSEMINATION: This article does not need to pass the ethics committee review, because this article does not involve the ethics question, only collates the related literature research. INPLASY REGISTRATION NUMBER: INPLASY202110072.

Small-sized extracellular vesicles (EVs) derived from acute myeloid leukemia bone marrow mesenchymal stem cells transfer miR-26a-5p to promote acute myeloid leukemia cell proliferation, migration, and invasion.

Bone marrow mesenchymal stem cells (BMSCs) in acute myeloid leukemia (AML) microenvironment undergo modification that includes expression of contents in the small-sized extracellular vesicles (EVs) they secrete. This study aims to investigate whether small-sized EVs from BMSCs of AML patients regulate AML progression by modifying the expression of miR-26a-5p. Small-sized EVs from BMSCs of AML patients (AML-BMSC-EVs) or healthy controls (HC-BMSC-EVs) were isolated by ultra-centrifugation and administered to AML cells (OCI/AML-2 and THP-1). Cell proliferation, migration, and invasion were evaluated by CCK-8 assay, Transwell migration and invasion assays, respectively. Compared with HC-BMSC-EVs, AML-BMSC-EVs contained higher expression of miR-26a-5p and promoted AML cell proliferation, migration, and invasion. Inhibition of miR-26a-5p expression in AML-BMSC-EVs could abrogate the promoting effects of AML-BMSC-EVs on AML cell proliferation, migration, and invasion. Furthermore, GSK3ß was a direct target of miR-26a-5p. Moreover, AML-BMSC-EVs inhibited GSK3ß expression and activated Wnt/ß-catenin signaling in AML cells. Additionally, GSK3ß overexpression in THP-1 cells counteracted the promoting effects of AML-BMSCs-EVs on THP-1 cell proliferation, migration, and invasion. AML-BMSC-EVs promoted AML progression by transferring miR-26a-5p to AML cells and subsequently activating the Wnt/ß-catenin pathway.

Moxibustion for the treatment of Alzheimer's disease: A protocol for a systematic reviews and meta-analysis.

BACKGROUND: Alzheimer's disease (AD) occurs in the elderly and the early stage of aging, with early clinical manifestations of memory impairment, cognitive impairment, behavioral change and decline in language function, etc., and eventually loss of the ability to live independently, requiring 24-hour care, and a variety of complications. However, these complications are the direct cause of death in AD patients. With the acceleration of the aging process of society, the incidence of AD is increasing year by year, seriously threatening the physical health and quality of life of the elderly. There are many ways to treat AD, however, moxibustion is especially popular in China. Therefore, our systematic review aims to evaluate the efficacy and safety of moxibustion in the treatment of ADand to provide reliable evidence for clinical decision-makers. METHODS: We will search electronic databases including PubMed, Embase, Cochrane Library, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Database (WF), and China Scientific Journals Database (VIP) from inception to January 2021. Two authors will independently screen the studies, extract data information, and assess methodological quality through the Cochrane risk of bias (ROB) tool. The RevmanV.5.3 software will be used for statistical analysis. RESULTS: The results of this study will evaluate the current status of moxibustion therapy for AD, aiming to prove the effectiveness and safety of moxibustion therapy, and will be published in a peer-reviewed journal. CONCLUSION: This systematic review will provide a credible evidence-based for moxibustion in the treatment of AD. INPLASY REGISTRATION NUMBER: INPLASY202110021.

Roles, molecular mechanisms, and signaling pathways of TMEMs in neurological diseases.

Transmembrane protein family members (TMEMs) span the entire lipid bilayer and act as channels that allow the transport of specific substances through biofilms. The functions of most TMEMs are unexplored. Numerous studies have shown that TMEMs are involved in the pathophysiological processes of various nervous system diseases, but the specific mechanisms of TMEMs in the pathogenesis of diseases remain unclear. In this review, we discuss the expression, physiological functions, and molecular mechanisms of TMEMs in brain tumors, psychiatric disorders, abnormal motor activity, cobblestone lissencephaly, neuropathic pain, traumatic brain injury, and other disorders of the nervous system. Additionally, we propose that TMEMs may be used as prognostic markers and potential therapeutic targets in patients with various neurological diseases.

42 cases of coronavirus disease 2019 of the ordinary type with the adjuvant treatment of heat-sensitive moxibustion 42.

OBJECTIVE: To observe the clinical therapeutic effect of adjuvant treatment with heat-sensitive moxibustion for coronavirus disease 2019 (COVID-19) of the ordinary type. METHODS: A total of 42 patients with COVID-19 of the ordinary type were adopted. Shénquè ( CV8) and Tianshu ( ST25) were selected. Heat-sensitive moxibustion was operated according to the required standard, 40 min to 60 min each time, once daily. Before and after moxibustion, the improvements in clinical symptoms were evaluated, such as chest oppression, poor appetite, lassitude and negative emotions. RESULTS: (1) The number of cases and the incidence was 21 cases (50.0%), 24 cases (57.1%) and 26 cases (61.9%) for chest oppression, poor appetite and lassitude before heat-sensitive moxibustion. The number of cases was reduced to be 10 cases (23.8%), 7 cases (16.7%) and 4 cases (9.5%) after the 1st treatment of heat-sensitive moxibustion for chest oppression, poor appetite, and lassitude. It was reduced to be 11 cases (26.2%), 8 cases (19.0%) and 4 cases (9.5%) after the 2nd treatment of moxibustion and it was reduced to be 18 cases (42.9%), 10 cases (23.8%) and 6 cases (14.3%) after the 3rd treatment of moxibustion. The incidences of the symptoms were all reduced obviously as compared with those before treatment. (2) Before treatment with heat-sensitive moxibustion, there were 24 cases of negative emotions (57.1%). It was reduced to be 16 cases (38.1%), 11 cases (26.2%) and 3 cases (7.1%) after the 1st, 2nd and 3rd treatment of heat-sensitive moxibustion successively. The incidences were all reduced obviously as compared with those before treatment. (3) After the 1st treatment, the active acceptance rate of heat-sensitive moxibustion was 100% (42/42) in the patients, higher than 11.9% (5/42) before treatment. CONCLUSION: Adjuvant treatment with heat-sensitive moxibustion effectively relieves the symptoms of COVID-19 such as chest oppression, poor appetite and lassitude, and alleviates the negative emotions, such as tension and anxiety. This therapy improves the therapeutic effect of COVID-19 and deserves to be promoted in clinical practice.

[Clinical observation of heat-sensitive moxibustion treatment for coronavirus disease 2019].

OBJECTIVE: To observe clinical effect of heat-sensitive moxibustion on coronavirus disease 2019 (COVID-19) and to discusses the effective moxibustion treatment program. METHODS: A total of 42 patients with COVID-19 (general type) were treated with heat-sensitive moxibustion at the acupoint area of Shenque (CV 8) and Tianshu (ST 25). The treatment was conducted under the standards of heat-sensitive moxibustion manipulation, which were "locating acupoint by feeling, moxibustion by differentiate sensation, dosage varies individually, ending after sufficient dosage". The incidence of deqi after first heat-sensitive moxibustion, the reduction of negative emotions, the improvement of chest distress and impaired appetite, and the active acceptance rate of moxibustion before and after treatment were observed. RESULTS: ① The deqi rate of heat-sensitive moxibustion for 20 min、40 min、1 h were respectively 52.4% (22/42), 90.5% (38/42), 100.0% (42/42). ② The incidences of feeling relaxed and comfortable immediately after the first, second, and third heat-sensitive moxibustion were 61.9% (26/42), 73.8% (31/42), and 92.9% (39/42), which were higher than 42.9% (18/42) before heat-sensitive moxibustion treatment (P<0.05). ③ The incidences of chest distress after the first, second, and third heat-sensitive moxibustion were 23.8% (10/42), 16.7% (7/42), and 9.5% (4/42), which were lower than 50.0% (21/42) before heat-sensitive moxibustion treatment (P<0.05); the incidences of impaired appetite after the first, second, and third heat-sensitive moxibustion were 26.2% (11/42), 19.0% (8/42), 9.5% (4/42), which were lower than 57.1% (24/42) before heat-sensitive moxibustion treatment (P<0.05). ④ After the first treatment, the active acceptance rate of patients for heat-sensitive moxibustion was 100.0% (42/42), which was higher than 11.9% (5/42) before heat-sensitive moxibustion (P<0.05). CONCLUSION: The heat-sensitive moxibustion can effectively reduce the negative emotions and improve the symptoms of chest distress and impaired appetite with COVID-19. It is generally accepted by patients, and worthy of popularization and application in clinical treatment.

[Application of professor CHEN Ri-xin's academic thought "yang is often insufficient, but yin is often surplus" in heat-sensitive moxibustion for tumor rehabilitation].

Professor CHEN Ri-xin has explored the causes of the characteristics of TCM syndromes in modern disease spectrum and pointed out that the TCM syndromes are generally characterized by "yang is often insufficient, but yin is often surplus". Based on the clinical experience and the understanding of TCM classics and ancient literature on tumor, professor CHEN has proposed that TCM syndromes of patients with advanced tumor are also generally characterized by "yang is often insufficient, but yin is often surplus". The heat-sensitive moxibustion has the functions of warming and nourishing yang-qi, eliminating dampness, warming meridians and dispersing cold, activating blood circulation and clearing collaterals, therefore tumor patients with deficiency syndrome (yang-deficiency, qi-deficiency), cold syndrome, dampness syndrome, phlegm syndrome and blood-stasis syndrome belonging to the indications of heat-sensitive moxibustion. The heat-sensitive moxibustion has unique advantages in treating spleen-stomach dysfunction after chemotherapy and radiotherapy, bone marrow suppression after chemotherapy and radiotherapy, cancerous deficiency, cancerous pain, pleural effusion, ascites, constipation, which has important clinical value in improving the quality of life and prolonging the life time for patients with advanced tumors.

High concentration of miR-133 is a useful marker for the diagnosis of lymphoma- associated hemophagocytic syndrome.

BACKGROUND: Lymphoma associated hemophagocytic syndrome (LAHS) is one of the major adult secondary hemophagocytic lymphohistiocytosis (HLH). Early diagnosis and treatment contribute to improved outcome. No enlarge lymph nodes can often delay the diagnosis of underlying lymphoma. OBJECTIVE: To find out criteria distinguishing LAHS from HLH induced by benign diseases. METHODS: clinical characteristic and laboratory feature of 31 patients with HLH (10 benign disease-associated HLH and 21 LAHS) were analyzed retrospectively. RESULTS: No significantly differences were observed in the levels of LDH, IL-6, IL-10, TNF-α; however, the level of CRP (C reactive protein) and the mean level of sIL-R (soluble interleukin-2 receptor) were higher in patients with LAHS than those with benign disease associated disease associated HLH while ferritin levels were higher in benign disease associated HLH than in LAHS. Consequently, the serum sIL-2R/ferritin ratio of patients with LAHS was markedly higher than that of patients with benign disease associated HLH (0.33 ± 0.23 vs 5.82 ± 3.26, P= 0.0001). In addition, we found out that the mean level of miR-133 (microRNA-133) was significant higher in LAHS than in benign disease associated HLH (18.83 ± 10.44 vs 5.82 ± 3.26, P⩽ 0.0001). CONCLUSION: Serum miR-133 is a new very useful marker for diagnosing of LAHS, but it need further confirmation by further clinical studies.

miRNA-301a induces apoptosis of chronic myelogenous leukemia cells by directly targeting TIMP2/ERK1/2 and AKT pathways.

We investigated the biological functions and mechanism of miRNA­301a on apoptosis in chronic myelogenous leukemia (CML). The expression of miRNA­301a in patient with CML cells was higher than the expression of normal patients. Overall survival (OS) of chronic granulocytic leukemia cell patient with low miRNA­301 expression was superior to that of CML patient with high miRNA­301 expression. Moreover, the upregulation of miRNA­301a increased cell proliferation, inhibited apoptosis and caspase-3 and -9 activity of K562 cells. Next, the upregulation of miRNA­301a suppressed Bax/Bcl-2 rate and TIMP2 protein expression, increased phosphorylation-ERK1/2 and decreased phosphorylation-AKT protein expression of K562 cells. Furthermore, si­TIMP2 expression enhanced the upregulation of miRNA­301a on the promotion of cell proliferation, inhibition of apoptosis and caspase-3 and -9 activity, suppression of Bax/Bcl-2 rate, increasing phosphorylation-ERK1/2 and decreasing phosphorylation-AKT protein expression of K562 cells. Taken together, our results clearly suggested that miRNA­301a induces apoptosis of CML cells by directly targeting the TIMP2/ERK1/2 and AKT pathways.

Identification of clinical features of lymphoma-associated hemophagocytic syndrome (LAHS): an analysis of 69 patients with hemophagocytic syndrome from a single-center in central region of China.

To identify the clinical features of lymphoma-associated hemophagocytic syndrome (LAHS), we retrospectively analyzed the clinical characteristics, laboratory findings and survival data of 16 LAHS patients from 69 adult hemophagocytic syndrome (HPS) patients. The results showed that the most common clinical manifestations and laboratory parameters were fever (100%), ferritin ≥ 500 g/L (100%), peripheral cytopenia in two or more lineages (100%), fibrinogen (Fbg) < 1.5 g/L (93.8%) and splenomegaly (81.3%) in LAHS patients. The percentages of patients with Fbg < 1.5 g/L, PLT < 40 × 10(9)/L and LDH ≥ 1,000 U/L in the LAHS group were significantly higher than those in non-LAHS patients (P = 0.010, 0.000, and 0.001, respectively). Survival analysis showed that HLH patients with rheumatological reasons had better prognosis (OS; median not reached), followed by patients in the infection group (350 days) and those with unexplained causes (140 days). LAHS had the worst prognosis (only 37 days). The symptoms of LAHS patients are usually confused with other HPS. Patients with LAHS had higher probabilities to have Fbg < 1.5 g/L, PLT < 40 × 10(9)/L, LDH ≥ 1,000 U/L and poor prognosis, so early diagnosis and systemic treatments are required.