Changes in Serum Interleukin-8 Levels Predict Response to Immune Checkpoint Inhibitors Immunotherapy in Unresectable Hepatocellular Carcinoma Patients.

Background: Effective biomarkers are needed to predict the efficacy of immune checkpoint inhibitors (ICIs) therapy in hepatocellular carcinoma (HCC). We evaluated the early changes in serum interleukin-8 (IL-8) levels as a biomarker of response to ICIs in patients with unresectable HCC. Methods: Eighty patients who received ICIs therapy alone or in combination with other treatments for unresectable HCC were included. Serum was collected at baseline and 2-4 weeks after the first dose. Serum IL-8 levels were measured using by ELISA. Results: In the progressive disease (PD) group, serum IL-8 levels increased significantly before the second dose of ICIs therapy compared with baseline levels (P < 0.001). Early changes in serum IL-8 levels were significantly associated with the response to ICIs therapy (P < 0.001). A cutoff value of 8.1% increase over the baseline most effectively predicted the response to ICIs. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy in patients with unresectable HCC. Patients with increases in serum IL-8 levels > 8.1% had significantly shorter overall survival (OS) and progression-free survival (PFS) than those with increases in serum IL-8 levels ≤ 8.1% (P < 0.001). Increases in serum IL-8 levels > 8.1% were independent prognosticators of worse OS (P = 0.003) and PFS (P < 0.001). Conclusion: Early changes in serum IL-8 levels, measured only 2-4 weeks after starting therapy, could predict the response to ICIs therapy, as well as OS and PFS of patients with unresectable HCC. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy and predicted worse OS and PFS.

Effects of moxibustion on intestinal barrier function and TLR4/NF-κB p65 signaling pathway in obese rats. / è‰¾ç¸å¯¹è‚¥èƒ–å¤§é¼ è‚ é“å±éšœåŠŸèƒ½åŠTLR4/NF-κB p65信号通路的影响.

OBJECTIVES: To observe the effects of moxibustion on intestinal barrier function and Toll-like receptor 4 (TLR4)/nuclear factor-κB p65 (NF-κB p65) signaling pathway in obese rats and explore the mechanism of moxibustion in the intervention of obesity. METHODS: Fifty-five Wistar rats of SPF grade were randomly divided into a normal group (10 rats) and a modeling group (45 rats). In the modeling group, the obesity model was established by feeding high-fat diet. Thirty successfully-modeled rats were randomized into a model group, a moxibustion group, and a placebo-control group, with 10 rats in each one. In the moxibustion group, moxibustion was applied at the site 3 cm to 5 cm far from the surface of "Zhongwan" (CV 12), with the temperature maintained at (46±1 ) ℃. In the placebo-control group, moxibustion was applied at the site 8 cm to 10 cm far from "Zhongwan" (CV 12), with the temperature maintained at (38±1) ℃. The intervention was delivered once daily for 8 weeks in the above two groups. The body mass and food intake of the rats were observed before and after intervention in each group. Using ELISA methool, the levels of serum triacylglycerol (TG), total cholesterol (TC) and lipopolysaccharide (LPS) were detected and the insulin resistance index (HOMA-IR) was calculated. HE staining was used to observe the morphology of colon tissue. The mRNA expression of zonula occludens-1 (ZO-1), Occludin, Claudin-1, TLR4 and NF-κB p65 in the colon tissue was detected by quantitative real-time PCR; and the protein expression of ZO-1, Occludin, Claudin-1, TLR4 and NF-κB p65 was detected by Western blot in the rats of each group. RESULTS: Compared with the normal group, the body mass, food intake, the level of HOMA-IR, and the serum levels of TC, TG and LPS were increased in the rats of the model group (P<0.01); those indexes in the moxibustion group were all reduced when compared with the model group and the placebo-control group respectively (P<0.01, P<0.05). Compared with the normal group, a large number of epithelial cells in the mucosa of colon tissue was damaged, shed, and the inflammatory cells were infiltrated obviously in the interstitium in the rats of the model group. When compared with the model group, in the moxibustion group, the damage of the colon tissue was recovered to various degrees and there were few infiltrated inflammatory cells in the interstitium, while, the epithelial injury of the colon tissue was slightly recovered and the infiltrated inflammatory cells in the interstitium were still seen in the placebo-control group. The mRNA and protein expressions of ZO-1, Occludin and Caudin-1 were decreased in the model group compared with those in the normal group (P<0.01). When compared with the model group and the placebo-control group, the mRNA and protein expressions of these indexes were increased in the moxibustion group (P<0.01, P<0.05). In the model group, the mRNA and protein expressions of TLR4 and NF-κB p65 were increased when compared with those in the normal group (P<0.01), and the mRNA and protein expressions of these indexes were reduced in the moxibustion group when compared with those in the model group and the placebo-control group (P<0.01). CONCLUSIONS: Moxibustion can reduce the body mass and food intake, regulate the blood lipid and improve insulin resistance in the rats of obesity. It may be related to alleviating inflammatory response through improving intestinal barrier function and modulating the intestinal TLR4/NF-κB p65 signaling pathway.

Acupuncture for cancer pain: a scoping review of systematic reviews and meta-analyses.

Background: Due to the effectiveness and safety, acupuncture, one of the traditional therapies of Chinese medicine, has been widely used in clinical practice globally. A few systematic review or meta-analyses have proved its effectiveness and safety towards patients with cancer pain, while there are no syntheses among those evidence. The aim of this scoping review is to summarize the evidence from systematic reviews of acupuncture for the treatment of cancer pain and evaluate the breadth and methodological quality of these evidence as well. Methods: The scoping review process was guided by the methodology framework of Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA ScR) and "Arkseyand O'Malley six-stage framework". Electronic searches were carried out in several online databases from inception to Jan 2022. Systematic reviews and meta-analyses that involve any type of acupuncture for patients with cancer pain will be included. A pair of reviewers independently screened full texts. Moreover, review characteristics were extracted, and methodological quality was assessed using the AMSTAR 2 tool. Results: Twenty-five systematic reviews and meta-analyses were included. Manual acupuncture is the most frequently included types of test group intervention (48%), followed by acupuncture + medicine (28%), and auricular acupuncture (12%). All the reviews have declared that acupuncture is an effective method for cancer pain treatment. Eleven reviews (44%) aiming at evaluating the safety also have confirmed that acupuncture is safe for treating cancer pain. However, most included studies were conducted in China. With certain geographical limitations, the findings were not representative within the region. The results of our review may owe to the synthesis of all kinds of cancer pain, and only 2 reviews described the type of cancer pain in detail. Conclusions: This scoping review synthesizes and evaluates existing evidence of acupuncture for cancer pain. From this scoping review of systematic reviews and meta-analyses, there are clear recommendations for future studies: expanding the region of research in the world and trying to conduct the study of different types of cancer pain in details as much as possible. Evidences of acupuncture for cancer pain can inform clinical decision-making. Systematic review registration: https://inplasy.com/inplasy-2022-1-0073/, identifier INPLASY202210073.

Effect of extremely low frequency electromagnetic field on the pathogenicity of Magnaporthe oryzae.

Numerous works have reported that extremely low frequency electromagnetic fields (ELF-EMFs) were associated with human health; however, little is known about their effects on the occurrence of agricultural diseases. In this study, Magnaporthe oryzae was used as a model organism, and its pathogenicity under 50 Hz, 3 mT ELF-EMF was studied. Our results showed that the pathogenicity, growth rate, and conidia generation of M. oryzae were enhanced under ELF-EMF exposure. In addition, M. oryzae exposed to ELF-EMF showed enhanced tolerance to cell wall-perturbing agents sodium lauryl sulphate, and increased expression of cell wall integrity-related genes, including RAC1, CDC42, RHO2, and NOX2. In addition, the level of reactive oxygen species (ROS) and the expression level of ROS scavenger system-related gene MoAP1 increased in ELF-EMF-exposed samples, whereas the total antioxidant capacity and the activities of superoxide dismutase and catalase did not change. Results of our study demonstrated that exposure to 50 Hz, 3 mT ELF-EMF enhanced the infection ability of M. oryzae, which present new important challenges for understanding the effect of ELF-EMF exposure on farmland ecology, especially on agricultural diseases.

Efficacy and Safety of Moxibustion for Menopausal Obesity: A Multicentre, Randomized, Controlled Trial Protocol.

Background. In the past, moxibustion has been widely used to treat endocrine system disorders, but evidence of its effectiveness is scarce at this point. The aim of this multicenter, randomized, controlled trial is to evaluate the efficacy and safety of treating menopausal obesity with moxibustion. Methods/Design. There are six centers taking part in this randomized, controlled, parallel trial. A total of 216 patients with menopausal obesity will be randomly divided into two equal groups: the "moxibustion for harmonization of Yin and Yang" group and the gentle moxibustion group. A 12-week study period with moxibustion will be preceded by a 1-week baseline, followed by a 12-week follow-up. We will conduct an interim analysis to determine whether or not the treatment is efficacious and safe after 216 participants have completed a 12-week treatment period. Evaluations will be conducted at weeks 0, 4, 8, 12, 18, and 24. The main outcome is waist circumference (WC), and the rate of WC reduction will be compared to the baseline. An intention-to-treat analysis will be performed with a two-sided P value of <0.05 considered significant. Participants who withdraw from the trial will be analyzed according to the intention-to-treat formula (ITT). Discussion. These results will be used to support selecting the right moxibustion prescription and guiding the improvement of clinical efficacy. This trial will provide convincing evidence of moxibustion's effectiveness and safety in the treatment of obesity by "moxibustion for harmonization of Yin and Yang," which will be conducive to the promotion and clinical application of the theory of "moxibustion for harmonization of Yin and Yang." Trial Registration. This trial is registered with Clinical Trials.gov: NCT04943705 (registered on June 27, 2021).

Acupoint catgut embedding for the treatment of sciatica: A protocol for a systematic review.

BACKGROUND: Sciatica is a common and frequent peripheral neuropathic pain disease, which causes a great burden on peoples life. Recently, acupoint catgut embedding (ACE) has been widely applied for treating sciatica in China, however, there is no enough evidence to prove the efficiency and safety of ACE for sciatica. Our study aims to evaluate the efficiency and safety of ACE for sciatica. METHODS AND ANALYSIS: Searches of the Cochrane Library, PubMed, Springer Medline, EMBASE, China National Knowledge Infrastructure (CNKI), Wan-Fang Data (WANFANG), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP databases) will be performed from inception to November 2020. The main outcomes are the pain intensity and the whole efficiency assessment. The secondary outcomes will include Oswestry Disability Index (ODI), life quality, physical examination, and adverse events. Two reviewers will separately conduct the study selection, data extraction and study quality assessments. RevMan 5.3 software will be used for meta-analysis. RESULTS: This study will provide an evidence-based review of acupoint catgut embedding therapy for sciatica according to the pain intensity, the whole efficiency assessment, life quality, DOI index and adverse events. CONCLUSIONS: This systematic review will present the current evidence for acupoint catgut embedding therapy for sciatica. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference. TRIAL REGISTRATION NUMBER: INPLASY2020110087.

Acupoint catgut embedding for obesity: A protocol of systematic review.

BACKGROUND: Obesity is a chronic metabolic disease in which patients are overweight due to the excessive accumulation of fat in the body. As a subtype of acupuncture, catgut embedding at acupoints has increased in clinical application for obesity. The aim of this study is to evaluate the effectiveness and safety of acupoint catgut embedding therapy for simple obesity. METHODS AND ANALYSIS: Electronic searches of the Cochrane Library, PubMed, Springer Medline, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wan-Fang Data (WANFANG), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP databases) will be performed. The Chinese Clinical Trial Registry Center and the ClinicalTrials.gov registry will also be searched for ongoing trials. Databases will be searched from inception to August 2020.Randomized controlled clinical trials (RCTs) will be included if acupoint catgut embedding was evaluated as the sole treatment (diet or exercise therapy as the control group will be allowed) for simple obesity. The primary outcomes will consist of the improvement rate and reduction in body weight (BW). The secondary outcomes will include body mass index (BMI), waist circumference (WC), fat percentage (F %) and adverse effects. Two reviewers will undertake the study selection, data extraction and assessments of study quality. After screening the studies, the quality of the included studies will be assessed according to the quality criteria specified by the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). Meta-analysis will be performed by RevMan 5.3 software. RESULTS: According to the data of improvement rate and reduction in BW, BMI, WC, and F %, this study will provide an evidence-based review of acupoint catgut embedding therapy for simply. CONCLUSIONS: This systematic review will present the current evidence for acupoint catgut embedding therapy for obesity. ETHICS AND DISSEMINATION: Ethical approval is not necessary since this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference. TRIAL REGISTRATION NUMBER: INPLASY2020110045.

Clinical effect of catgut implantation at acupoints for the treatment of simple obesity: A multicentre randomized controlled trial.

BACKGROUND: Catgut implantation at acupoints (CIA) is a subtype of acupuncture that has been widely used to treat simple obesity, but evidence for its effectiveness remains scarce. The aim of this study is to evaluate the efficacy and safety of treating simple obesity with CIA. OBJECTIVE: This clinical trial aims to evaluate the effectiveness and safety of CIA used for treatment of simple obesity. METHODS: This is a multicentre, randomized, parallel, sham-controlled clinical trial. A total of 216 patients with simple obesity will be recruited. They will be randomly assigned in a 1:1 ratio to either the CIA group or the sham control group. All treatments will be given once every 2 weeks. The primary outcome measure is the rate of waistline reduction. Secondary outcome measures are the rates of reduction of body measurements, including weight, body mass index (BMI), hipline, waist-hip-ratio (WHR) and body fat percentage (BFP), the changes in scores on scales, including the Impact of Weight on Quality of Life Questionnaire (IWQOL-Lite), Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HAD) and the Self-Esteem Scale (SES), Outcomes will be evaluated at baseline and at weeks 4, 8, 12, 16, 28, and 40, respectively. All adverse events that occur during this study will be recorded. If any participant withdraws from the trial, an intention-to-treat analysis (ITT) will be performed. CONCLUSION: This is a randomized, sham-controlled trial of CIA treatment for simple obesity. The results of this trial will provide more evidence on whether CIA is efficacious and safe for treating obesity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02936973. Registered on October 18, 2016.

Genome-Wide Regulation of Electroacupuncture and Treadmill Exercise on Diet-Induced Obese Rats.

Acupuncture has been widely used for obesity treatment, but its mechanism is still unclear. To investigate the molecular mechanisms, we applied electroacupuncture (EA) at the Zusanli (ST36) acupoint and treadmill exercise (TE) in a diet-induced obese (DIO) rat model and used RNA sequencing (RNA-seq) to identify molecular consequences. Forty Sprague-Dawley male rats were selected and randomly divided into five groups: control (C), DIO model (M), EA, TE, and EA + TE groups. According to the results, acupuncture reduced body weight and the ratio of retroperitoneal white adipose tissue (retro-WAT) to body weight. Total RNA was extracted from the retro-WAT from five groups for RNA-seq. Differentially expressed genes (DEG) analysis showed that there were obvious differences among the four comparisons of C vs. M, M vs. EA, M vs. TE, and M vs. EA + TE, followed by 1383, 913, 3324, and 2794 DE genes. Gene ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to further classify the DEGs. Several GO terms were commonly significantly enriched in both M vs. TE and M vs. EA, such as myofibril and muscle contraction. In addition, some pathways were regulated by EA and TE, such as the peroxisome proliferator activated receptor signaling pathway and calcium signaling pathway. This study is the first to compare and analyze the differences in gene expression profiles in the retro-WAT of rats in different groups, which provide a clue for further investigation into the molecular mechanisms of obesity treatment by EA and TE.

[Comparison between bacteriophage-based assay and BACTEC-960 system in detection of ethambutol resistance in Mycobacterium tuberculosis].

OBJECTIVE: To set up phage amplified biologically assay (PhaB) for rapid detection ethambutol (EMB) resistance and to evaluate the use of PhaB in the detection of EMB resistance. METHODS: To detect the EMB resistance of 138 clinical isolates of Mycobacterium tuberculosis (MTB) by PhaB and compare it with the results of BACTEC-960 system. The minimal inhibitory concentration (MIC) was detected for all the discrepant isolates. RESULTS: Of all the 138 strains of MTB clinical isolates, 114 strains were EMB-susceptible and 24 strains were EMB-resistant with BACTEC-960 system while 118 strains were EMB-susceptible and 20 strains were EMB-resistant with PhaB. 112 of the 138 strains were EMB-susceptible and 18 strains were EMB-resistant with the two methods. The concordant isolates in determination of EMB resistance were 130 strains in the two methods and the concordance rate was 94.2%. The disconcordant isolates were 8 strains and the discrepancy rate was 5.8%. The sensitivity, specificity, positive and negative predictive value as well as overall accuracy for the PhaB assay was 75.0% (18/24), 98.2% (112/114), 90.0% (18/20), 94.9% (112/118) and 94.2% (130/138) respectively if the judgment standard was adopted by BACTEC-960 method. CONCLUSIONS: The PhaB assay can be used for detection of EMB resistance in isolates of MTB easily and quickly in three days. This method do not need special instrument and may be used in rapid screening method for EMB resistance of MTB.

[Comparison of four methods in the detection of isoniazid resistance in clinical isolates of Mycobacterium tuberculosis].

OBJECTIVE: To evaluate the use of phage amplified biologically (PhaB) assay, Bactec-960 system, minimum inhibitory concentration (MIC) method and gene chip in drug susceptibility testing of isoniazid (INH) in clinical isolates of Mycobacterium tuberculosis (MTB). METHODS: INH resistance of 167 clinical isolates of MTB was detected by PhaB assay, Bactec-960 system, MIC and gene-chip methods respectively, and the results of these four methods were compared. RESULTS: 111 INH resistant isolates and 56 INH sensitive isolates were detected by Bactec-960 system. If the result of Bactec-960 system was set as the golden standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PhaB assay were 96.4%, 96.4%, 93.1%, 98.2%, and 96.4% respectively; the sensitivity, specificity, PPV, NPV, and accuracy were 92.9%, 99.1%, 98.1%, 96.5%, and 97.0% for the MIC method, and they were 83.9%, 96.4%, 92.2%, 92.2%, and 92.2% respectively for the gene-chip method. If the result of the MIC method was set as the golden standard, the sensitivity, specificity, PPV, NPV, and accuracy of PhaB assay were 100%, 95.6%, 91.4%, 100%, and 97.0% respectively. The sensitivity, specificity, PPV, NPV, and accuracy were 98.1%, 96.5%, 92.9%, 99.1%, and 97.0% for the Bactec-960 system, and they were 88.7%, 96.5%, 92.2%, 94.8%, and 94.0% respectively for the gene-chip method. CONCLUSIONS: The PhaB assay is highly sensitive and specific, and its result is highly consistent with those of the Bactec-960 system and the MIC method. It is easy to use and took only three days in the detection of drug susceptibility of INH in clinical isolates of MTB. The results indicate that this low-cost assay can be used in rapid screening for INH resistance in MTB isolates. The MIC method proves to be as efficient as the Bactec-960 system, but whether it can be used as the standard method still needs further investigation. The sensitivity of the gene-chip method is lower as compared to the other methods, and therefore can only be used as an ancillary test.