Immediate Effect of Electro-acupuncture on Endometrial Blood Flow in Patients with Recurrent Implantation Failure: A Randomized Controlled Trial.

OBJECTIVE: To investigate the immediate effects of electro-acupuncture (EA) on endometrial blood flow among recurrent implantation failure (RIF) patients. METHODS: Eighty RIF patients, enrolled from March 2022 to December 2022, were randomly allocated into either the EA group (40 cases) or the waiting-list (WL) group (40 cases) by using a random number table. The EA group underwent acupuncture at points of Shenting (GV 24), Baihui (GV 4), Benshen (GB 13), bilateral Zigong (EX-CA 1), Huangshu (KI 16), Sanyinjiao (SP 6) and Xuehai (SP10), and electric acupuncture apparatus was connected to EX-CA 1, KI 16, SP 6, and SP 10 with disperse-dense waves at 4/20 Hz frequencies for 30 min after transvaginal ultrasound, while the WL group received no intervention. The primary outcome measured was the endometrial volume blood flow. The secondary outcomes included the bilateral uterine artery index, endometrial volume, endometrial blood flow type, vascular distribution index (VIMV) for endometrial and ovary, clinical pregnancy rate, and embryo implantation rate. RESULTS: In the EA group, there was a notable decrease in the bilateral pulsatility index and a significant improvement in the endometrial blood flow type post-EA (P<0.05). Both the endometrial blood flow type and VIMV for the endometrium and right ovary were markedly higher in the EA group compared to the WL group post-treatment (P<0.05). Conversely, no significant disparities were observed in vascular index, flow index, vascular blood flow index, uterine arterial blood flow indices, endometrial volume, clinical pregnancy rate and embryo implantation rate between the two groups after treatment (P>0.05). Besides, no adverse events related to EA were observed. CONCLUSIONS: EA can promptly ameliorate VIMV for the endometrial and right ovary, and endometrial blood flow type. Future randomized controlled trials are warranted to investigate the long-term effects of EA on blood flow of RIF patients and its implications for pregnancy outcomes. (Trial registration No. ChiCTR2200057377).

Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial.

BACKGROUND: Transvaginal oocyte retrieval is frequently followed by adverse events related to anesthesia and the procedure. Some research showed that transcutaneous electrical acupoint stimulation (TEAS) can relieve intraoperative pain and postoperative nausea. OBJECTIVE: This study examined whether TEAS can alleviate pain and relieve adverse symptoms after oocyte retrieval. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Altogether 128 patients were randomly divided into the TEAS group and the mock TEAS group. The two groups received a 30-minute-long TEAS or mock TEAS treatment that began 30 min after oocyte retrieval. MAIN OUTCOME MEASURES: The primary outcome was the visual analog scale (VAS) pain score. Secondary outcomes were pressure pain threshold, McGill score, pain rating index (PRI), present pain intensity (PPI), VAS stress score, VAS anxiety score, and postoperative adverse symptoms. RESULTS: The baseline characteristics of the two groups were comparable (P > 0.05). The VAS pain scores of the TEAS group were lower than those of the mock TEAS group at 60 and 90 min after oocyte retrieval (P < 0.05). The McGill score, PRI and PPI in the TEAS group were significantly lower than those in the control group at 60 min after oocyte retrieval (P < 0.05). However, the two groups had equivalent beneficial effects regarding the negative emotions, such as nervousness and anxiety (P > 0.05). The TEAS group was superior to the mock TEAS group for relieving postoperative adverse symptoms (P < 0.05). CONCLUSION: TEAS treatment can relieve postoperative pain and postoperative adverse symptoms for patients undergoing oocyte retrieval. Please cite this article as: Liu LY, Su Y, Wang RR, Lai YY, Huang L, Li YT, Tao XY, Su MH, Zheng XY, Huang SC, Wu YN, Yu SY, Liang FR, Yang J. Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial. J Integr Med. 2024; 22(1): 32-38.

Acupuncture benefits to women with recurrent implantation failure: A propensity score-matched cohort study.

Objectives: The current study aims to assess the effectiveness of acupuncture in improving the live birth rate (LBR), ongoing pregnancy rate (OPR), clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), and pregnancy loss (early abortion rate, late abortion rate, ectopic pregnancy rate) in patients with recurrent implantation failure (RIF). Design: This retrospective study compares the outcomes of patients with RIF who underwent frozen embryo transfer (FET) with or without acupuncture. Setting: The medical records of patients diagnosed with RIF and visiting Chengdu Xi'nan Gynecological Hospital between January 2018 and June 2021 were reviewed. The Chengdu Xi'nan Gynecological Hospital Ethics Committee approved this retrospective study (No. 2021-029). Participants: A total of 923 patients with RIF who underwent FET were included in this study. The patients were divided into two groups: the Acupuncture (n = 303) and the Non-acupuncture groups (n = 620). Exposure: The Acupuncture group consisted of 303 RIF patients who received acupuncture therapy in addition to standard hormone replacement therapy (HRT)/delayed hormone replacement therapy (d-HRT) for FET. The Non-acupuncture group consisted of 620 RIF patients who received only standard HRT/d-HRT for FET. Primary and secondary outcome measures: The primary outcome was the LBR. The secondary outcome referred to OPR, CPR, BPR, and pregnancy loss. Results: The Acupuncture group had significantly higher BPR (P = 0.08) and CPR (P = 0.049) than the Non-acupuncture group. A potentially higher LBR (P = 0.16) and OPR (P = 0.248) were observed in the Acupuncture group than in the Non-acupuncture group. However, the survival analysis did not show that acupuncture significantly promoted live birth. Conclusions: Acupuncture is an appropriate adjunctive technique in the in vitro fertilization process as it improves biochemical and clinical pregnancies. Therefore, it is necessary to be cautious about the role of acupuncture throughout the whole pregnancy cycle.

Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. The gut microbiota can help maintain healthy metabolism and immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical factor in promoting health and homeostasis; it promotes intestinal immunity, stimulates bone marrow precursors to generate macrophage colonies, and enhances the antibacterial and antitumor activity of circulating monocytes. As such, GM-CSF may protect against HCC development by regulating immunity as well as intestinal microecology. AIM: To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC. METHODS: Thirty-six male BALB/c nude mice were divided into three groups: Control (n = 10), HCC (n = 13), and HCC + GM-CSF (GM-CSF overexpression, n = 13). We utilized HCC cells to establish orthotopic transplantation tumor models of HCC with normal and over-expressing GM-CSF. Liver injury, immune inflammatory function and intestinal barrier function were evaluated. The fecal microbiome and metabolome were studied using 16S rRNA absolute quantification sequencing and gas chromatography-mass spectrometry. RESULTS: GM-CSF overexpression significantly affected the gut microbiome of mice with HCC and resulted in a high abundance of organisms of the genera Roseburia, Blautia and Butyricimonass, along with a significant reduction in Prevotella, Parabacteroides, Anaerotruncus, Streptococcus, Clostridium, and Mucispirillum. Likewise, GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid levels, along with a prominent decrease in the fecal succinic acid, adenosine, fumaric acid, lipoic acid, and maleic acid levels. Correlation analysis revealed that the intestinal microbiota and fecal metabolites induced by GM-CSF were primarily involved in pathways related to reducing the inflammatory response, biotin metabolism, and intestinal barrier dysfunction. CONCLUSION: GM-CSF can protect against HCC development by regulating immunity and modulating the abundance of specific intestinal microorganisms and their metabolites. This study provides new insights into the therapeutic approaches for HCC.

NRP1 is a Prognostic Factor and Promotes the Growth and Migration of Cells in Intrahepatic Cholangiocarcinoma.

BACKGROUND: Neuropilin-1 (NRP-1) participates in cancer cell proliferation and metastasis as a multifunctional co-receptor by interacting with multiple signaling pathways. However, few studies have addressed the precise function and prognosis analysis of NRP1 in intrahepatic cholangiocarcinoma (ICC). We aimed to study the correlations between NRP1 and clinicopathological characteristics and NRP1 effect on ICC cell line functions. METHODS: NRP1 mRNA and its protein levels in human ICC tissues and cell lines were detected by IHC, qRT-PCR, and WB method. Transwell, wound healing, and CCK-8 assays were performed to verify the effects of NRP1 knockdown and overexpression on cell migration and proliferation capability. RESULTS: NRP1 proteins and mRNA levels increased in ICC tissues compared to those in paired adjacent non-tumor tissues. High NRP1 expression of ICC tissues was related to poor prognosis. NRP1 expression level was expected to be an independent prognosticator for overall survival and cumulative tumor recurrence, and was closely related to tumor number (P=0.047). Knockdown of NRP1 inhibited cell proliferation and migration capability of RBE cells in vitro, and NRP1 overexpression in 9810 cells accelerated proliferation and migration. Additionally, NRP1 may promote cell proliferation and migration in ICC via the FAK/PI3-K/AKT pathway. CONCLUSION: As an oncogene, NRP1 may function as a candidate target and prognostic biomarker of value for ICC therapy.

Intestinal Flora as a Potential Strategy to Fight SARS-CoV-2 Infection.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide, seriously endangering human health. In addition to the typical symptoms of pulmonary infection, patients with COVID-19 have been reported to have gastrointestinal symptoms and/or intestinal flora dysbiosis. It is known that a healthy intestinal flora is closely related to the maintenance of pulmonary and systemic health by regulating the host immune homeostasis. Role of the "gut-lung axis" has also been well-articulated. This review provides a novel suggestion that intestinal flora may be one of the mediators of the gastrointestinal responses and abnormal immune responses in hosts caused by SARS-CoV-2; improving the composition of intestinal flora and the proportion of its metabolites through probiotics, and personalized diet could be a potential strategy to prevent and treat COVID-19. More clinical and evidence-based medical trials may be initiated to determine the strategy.

Relationship between intestinal microbial dysbiosis and primary liver cancer.

BACKGROUND: Intestinal microbial dysbiosis is involved in liver disease pathogenesis. However, its role in primary liver cancer (PLC), particularly in hepatocarcinogenesis remains unclear. The present study aimed to study the changes in intestinal flora at various stages of PLC and clarify the relationship between intestinal microbes and PLC. METHODS: Twenty-four patients with PLC (PLC group), 24 patients with liver cirrhosis (LC group), and 23 healthy control individuals (HC group) were enrolled from October 2016 to October 2017. Stool specimens of the participants were collected and the genomic DNA of fecal bacteria was isolated. High-throughput pyrosequencing of 16S rDNA was used to identify differences in gut bacterial diversity among HC, LC, and PLC groups. We also analyzed the relationship between clinical factors and intestinal microorganisms in LC and PLC groups. RESULTS: Diversity of Firmicutes tended to decrease from the HC to LC and PLC groups at the phylum level. Among species, Enterobacter ludwigii displayed an increasing trend in the PLC group, wherein the relative abundance of Enterobacter ludwigii in the PLC group was 100 times greater than that in the HC and LC groups. The ratio of Firmicutes/Bacteroidetes was significantly decreased with the disease progression. In addition, the linear discriminant analysis effect size method indicated that Clostridia were predominant in the gut microbiota of the HC group, whereas Enterococcaceae, Lactobacillales, Bacilli and Gammaproteobacteria may be used as diagnostic markers of PLC. Redundancy analysis showed a correlation between intestinal microbial diversity and clinical factors AST, ALT, and AFP. Veillonella showed a significant positive correlation with AFP in the PLC group, whereas Subdoligranulum showed a negative correlation with AFP. CONCLUSIONS: This study indicates that dysbiosis of the gut microbiota might be involved in PLC development and progression.

Nocardia mangyaensis sp. nov., a novel actinomycete isolated from crude-oil-contaminated soil.

A Gram-stain-positive, aerobic, non-motile and mycolic-acid-containing strain, designated Y48T, was isolated from soil contaminated by crude oil located in the northern margin of the Qaidam Basin. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Y48T belongs to the genus Nocardia and is closely related to N. cummidelens DSM 44490T (99.0 % similarity), N. soli DSM 44488T (99.0 %), N. lasii 3C-HV12T (98.9 %), N. salmonicida NBRC 13393T (98.6 %), N. ignorata NBRC 108230T (98.6 %) and N. coubleae NBRC 108252T (98.6 %). The average nucleotide identity and DNA-DNA hybridization values between strain Y48T and the reference strains were 75.9-84.5 and 27.5-29.0 %, respectively, values that were below the thresholds for species delineation. Chemotaxonomic analysis indicated that the major fatty acids of strain Y48T were C16 : 0, summed feature 3 (C16 : 1ω6c/C16 : 1ω7c), C18 : 1ω9c and C18 : 0 10-methyl (TBSA). The respiratory quinone was MK-8(H4, ω-cycl). The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, two glycolipids and three unidentified lipids. The cell-wall hydrolysates contained meso-diaminopimelic acid, with ribose, arabinose, glucose and galactose as whole-cell sugars. A combination of 16S rRNA gene sequence analysis, and phenotypic and chemotaxonomic characterizations demonstrated that strain Y48T represents a novel species of the genus Nocardia, for which the name Nocardia mangyaensis sp. nov. is proposed. The type strain is Y48T (=JCM 32795T=CGMCC 4.7494T).

Tumor-suppressive role of HACE1 in hepatocellular carcinoma and its clinical significance.

An increasing body of evidence suggests that downregulation or deletion of HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) gene plays an important role in the occurrence, invasion and metastasis process in many human malignancies and is closely related to prognosis. However, sparse evidence exists concerning the precise function and clinical significance of HACE1 in hepatocellular carcinoma (HCC). In the present study, we investigated the expression pattern of HACE1 in HCC tissues and cell lines, and determined the potential functions of HACE1 in HCC cell lines and evaluated the relationships between HACE1 expression and clinicopathological characteristics. Protein and mRNA expression levels of HACE1 in human HCC tissues and cell lines were examined by western blot analysis, quantitative real­time polymerase chain reaction and immunohistochemical (IHC) analyses. IHC was used to analyze the correlations between HACE1 expression and clinicopathological features. HACE1 was upregulated in SMCC7721 cells by transfection with pcDNA3.1-HACE1 and Huh7 cells were transfected with siRNA targeting HACE1 for downregulation. Cell Counting Κit-8, Transwell and wound healing assays were performed to investigate the effects of the overexpression and knockdown of HACE1 on cellular proliferation and migration. The results revealed that HACE1 expression was lower in the HCC tissues and cell lines at the mRNA and protein levels compared to levels noted in the matched non­tumor tissues and the normal liver cell line L02. Knockdown of HACE1 in Huh7 cells accelerated cell proliferation and migration (P<0.05), and overexpression of HACE1 in SMCC7721 cells was found to decrease the capacity for proliferation and migration (P<0.01). The results of IHC suggested that the HACE1 expression level was closely related to the serum AFP level, tumor differentiation and vascular invasion (P<0.05). Patients with low HACE1 expression levels exhibited poorer overall survival and HACE1 was found to be an independent prognostic factor for survival. In conclusion, as a tumor suppressor, HACE1 may be a valuable prognostic biomarker and potential therapeutic target for HCC treatment.

Improved Growth and Metabolite Accumulation in Codonopsis pilosula (Franch.) Nannf. by Inoculation of Bacillus amyloliquefaciens GB03.

Codonopsis pilosula (Franch.) Nannf. is a traditional Chinese herbal medicinal plant and a low-cost succedaneum for Panax ginseng and contains various bioactivity components. In this work, we first evaluated the effects of the inoculation of the plant growth-promoting rhizobacteria Bacillus amyloliquefaciens strain GB03 on growth and metabolite accumulation of C. pilosula. The results demonstrated that application of B. amyloliquefaciens GB03 significantly improved the growth of C. pilosula compared to DH5α, Luria broth medium, and water treatment, respectively. On the other hand, we observed that the content of lobetyolin, one of the most important secondary metabolites in C. pilosula, was obviously improved by inoculation of GB03 and almost reached twice that compared to the other three treatments. In addition, some amino acids of roots were elevated by GB03, although not significantly. In conclusion, B. amyloliquefaciens GB03 could induce positive effects on the growth and further stimulate accumulation of secondary metabolites in C. pilosula.

Protein tyrosine phosphatase receptor S acts as a metastatic suppressor in hepatocellular carcinoma by control of epithermal growth factor receptor-induced epithelial-mesenchymal transition.

UNLABELLED: Hepatocellular carcinoma (HCC) is the third-most lethal cancer worldwide. Understanding the molecular pathogenesis of HCC recurrence and metastasis is the key to improve patients' prognosis. In this study, we report that protein tyrosine phosphatase receptor S (PTPRS) is significantly down-regulated in nearly 80% of HCCs, and its expression negatively correlates with aggressive pathological features, such as larger tumor size and advanced stage. In addition, PTPRS deficiency is independently associated with shorter survival and increased recurrence in patients, although 16.7% of HCCs show intratumor heterogeneous expression of PTPRS. Restoration of wild-type, but not mutant, PTPRS expression significantly inhibits HCC cell migration and invasion in vitro as well as lung metastasis in vivo, whereas knockdown of its expression significantly promotes invasion and metastasis. Notably, PTPRS-regulated HCC invasiveness is accompanied by typical changes of epithelial-mesenchymal transition (EMT). Moreover, PTPRS forms a complex with epithermal growth factor receptor (EGFR) and regulates its tyrosine residues' phosphorylation. Ectopic expression of EGFR reverses the metastasis-inhibiting effects of PTPRS, whereas silencing of EGFR or inhibiting phosphorylation of key molecules in EGFR downstream pathways reinhibits EMT and metastasis caused by PTPRS down-regulation. Meanwhile, promoter hypermethylation of PTPRS is frequently detected in HCC samples and cell lines. Treatment with a demethylation agent, 5-aza-2'-deoxycytidine, recovers PTPRS expression in a dose-dependent manner. CONCLUSIONS: Epigenetic inactivation of PTPRS may increase phosphorylation and activity of EGFR signaling to promote EMT and metastasis in HCC.

Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma.

A possible association between multiple drug resistance 1 gene (MDR1) polymorphisms and the risk of developing hepatocellular carcinoma (HCC) is currently under debate, and evidence from various epidemiological studies has yielded controversial results. To derive a more precise estimation of the association between MDR1 polymorphisms and HCC risk, the present meta-analysis was performed. A total of 8 studies containing 11 cohorts with 4407 cases and 4436 controls were included by systematic literature search of EMBASE, PubMed, Web of Science, and CNKI. All polymorphisms were classified as mutant/wild-type alleles. In particular, the variation type, functional impact, and protein domain location of the polymorphisms were assessed and used as stratified indicators. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the association. Overall, our results suggested that the mutant alleles of the MDR1 gene were associated with a significantly increased risk for HCC under all genetic models (allelic model: OR = 1.28, 95 % CI = 1.20-1.36, P < 0.001; dominant model: OR = 1.27, 95 % CI = 1.16-1.38, P < 0.001; recessive model: OR = 1.59, 95 % CI = 1.36-1.85, P < 0.001). Furthermore, increased risks for HCC were also revealed in stratified analyses by ethnicity, sample size, and quality scores of cohorts as well as variation type, functional impact, and protein domain location of polymorphisms. In conclusion, the present meta-analysis suggested that the presence of MDR1 mutant alleles might be a risk factor for HCC.

Beneficial soil bacterium Bacillus subtilis (GB03) augments salt tolerance of white clover.

Soil salinity is an increasingly serious problem worldwide that reduces agricultural output potential. Selected beneficial soil bacteria can promote plant growth and augment tolerance to biotic and abiotic stresses. Bacillus subtilis strain GB03 has been shown to confer growth promotion and abiotic stress tolerance in the model plant Arabidopsis thaliana. Here we examined the effect of this beneficial soil bacterium on salt tolerance in the legume forage crop, white clover. Plants of white clover (Trifolium repens L. cultivar Huia) were grown from seeds with or without soil inoculation of the beneficial soil bacterium Bacillus subtilis GB03 supplemented with 0, 50, 100, or 150 mM NaCl water into soil. Growth parameters, chlorophyll content, malondialdehyde (MDA) content and osmotic potential were monitored during the growth cycle. Endogenous Na(+) and K(+) contents were determined at the time of harvest. White clover plants grown in GB03-inoculated soil were significantly larger than non-inoculated controls with respect to shoot height, root length, plant biomass, leaf area and chlorophyll content; leaf MDA content under saline condition and leaf osmotic potential under severe salinity condition (150 mM NaCl) were significantly decreased. Furthermore, GB03 significantly decreased shoot and root Na(+) accumulation and thereby improved K(+)/Na(+) ratio when GB03-inoculated plants were grown under elevated salt conditions. The results indicate that soil inoculation with GB03 promotes white clover growth under both non-saline and saline conditions by directly or indirectly regulating plant chlorophyll content, leaf osmotic potential, cell membrane integrity and ion accumulation.