[Analysis of pathogen monitoring results of infectious diarrhea in Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical University from 2016 to 2019].

Objective: to analyze the distribution characteristics of major enteropathogens in infectious diarrhea cases attending the intestinal outpatient clinic of Beijing Traditional Chinese medicine hospital, Capital Medical University. Methods: From 2016 to 2019, 588 fecal samples of patients with infectious diarrhea in Beijing Hospital of traditional Chinese Medicine Affiliated to Capital Medical University were collected for microbial isolation, culture, identification and pathogen gene detection. Using VITEK 2 compact full-automatic microbial identification/drug sensitivity analysis system to identify the bacteria isolated from the culture; using serum agglutination test to classify the pure colonies; using multiple fluorescence quantitative PCR amplification technology to detect the gene amplification of the samples. Results: In 2016-2019, the total physical examination rate of pathogen was 39.796%. The top three pathogen were diarrhea Escherichia coli (21.769%, n=128), Salmonella (5.782%, n=34), Vibrio (4.762%, n=28). The difference of positive rates of different pathogens in four years was statistically significant (P=0.021), and the peak of incidence was from July to September. The positive rate of norovirus was 5.612% (n=33), and the highest incidence occurred in May. Conclusion: The pathogen of infectious diarrhea patients in Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University from April to October 2016-2019 is mainly diarrhea Escherichia coli, and the pathogen type of norovirus is GⅡ genome.

[Quality assessment of global breast cancer screening guidelines].

Objective: To evaluate the quality of the published breast cancer screening guidelines to provide a reference for domestic studies in the future. Methods: PubMed, Embase, Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure, VIP, and Wanfang Data were searched to identify breast cancer screening guidelines on until August 2020. Two reviewers screened literature and extracted data independently. The Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREEⅡ) and Reporting Items for Practice Guidelines in Healthcare(RIGHT) tools were used to evaluate the quality of the included guidelines. Results: A total of 15 breast cancer screening guidelines were included, of which seven were published in the United States, with publication years focusing on 2015 to 2019, and 11 guidelines had updated versions. "Rigour of development" (47.0%±22.1%) and "Applicability" (44.0%±15.1%) of AGREEⅡ scored lower than other domains. "Review and quality assurance" (46.7%±39.9%) and "Funding, declaration, and management of interests" (41.7%±24.4%) of RIGHT were reported poorer than others. There were six guidelines recommended and another nine recommended with modifications based on the overall AGREEⅡ score. There were four guidelines with a good level, and another 11 were with a moderate level of RIGHT. The National Comprehensive Cancer Network published the best overall quality guidelines in 2018 (AGREEⅡ: 83.3%, RIGHT: 80.0%) and by the American Cancer Society in 2015 (AGREEⅡ: 83.3%, RIGHT: 85.7%). Conclusion: The quality of breast cancer screening guidelines was predominantly of moderate quality, and greater attention should be paid to the guideline development process and quality control of the guidelines.

[Effect of traditional Chinese medicine treatment as maintenance therapy on regulating the serum concentration of sCTLA-4 in patients with advanced non-small-cell lung cancer and its relationship with prognosis].

Objective: To evaluate the effect of traditional Chinese medicine (TCM) treatment as maintenance therapy on regulating the serum concentration of soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in patients with advanced non-small-cell lung cancer (NSCLC) and the relationship between sCTLA-4 and time to progression (TTP). Methods: This study was conducted as a prospective, randomized, controlled trial. 64 non-progressive patients who responded to initial therapy were randomized 1∶1 to the TCM arm (treated with cinobufacini injection, herbal decoction and Chinese acupoint application, n=32) or to the chemotherapy arm (n=32). Each cycle was 21 days. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient requested therapy discontinuation.The serum concentration of sCTLA-4 was detected by enzyme linked immunosorbent assay (ELISA) in the 64 patients with advanced NSCLC before and after two cycles of maintenance treatment. Cox regression was used to analyze the relative ratio for the risk of disease progression. Results: After 2 cycles of maintenance TCM treatment, the serum concentration of sCTLA-4 in patients with advanced NSCLC was (12.77±2.37 pg/ml), significantly lower than that before treatment (40.30±10.75)(P=0.013). After 2 cycles of maintenance chemotherapy, the serum concentration of sCTLA-4 was higher than that before treatment, but was not significantly different (44.48±10.12 vs. 46.64±11.21 pg/ml, P=0.612). After 2 cycles of maintenance treatment, TCM treatment can significantly bring down the serum concentration of sCTLA-4 compared to chemotherapy (12.77±2.37 vs. 46.64±11.21 pg/ml, P=0.004). The multivariate analysis indicated that sCTLA-4 levels and treatment regimen were independent prognostic factors for TTP (P<0.05 for both). Conclusions: Regulating the serum concentration of sCTLA-4 may be one of the mechanisms of TCM maintenance treatment of NSCLC. Trial registration Chinese Clinical Trial Register, ChiCTR-TRC-10001017.

Network meta-analysis of Chinese herb injections combined with FOLFOX chemotherapy in the treatment of advanced colorectal cancer.

WHAT IS KNOWN AND OBJECTIVE: Research has indicated that some Chinese herb injections (CHIs) might be beneficial in combination with chemotherapy, including remedies that might be used as effective chemosensitizers and radiosensitizers, or as palliative therapy. Here, we carried out a network meta-analysis to assess the clinical efficacy and safety of CHIs combined with oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX) for advanced colorectal cancer (CRC). METHODS: PubMed, EMBASE.com, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), Wanfang Database and Chinese Journal Full-text Database were searched from inception to 31 December 2014, to identify relevant randomized controlled trails (RCTs). The risk of bias in included RCTs was evaluated according to the Cochrane Handbook version 5.1.0. Standard pairwise meta-analysis and Bayesian network meta-analysis were performed to compare the efficacy and safety of different CHIs combined with FOLFOX. Data were analysed using STATA 12.0 and WinBUGS1.4 software. RESULTS AND DISCUSSION: We identified 63 eligible studies (with 4837 patients in total), involving 9 CHIs. Pairwise meta-analysis showed that compared with FOLFOX alone, combinations with Aidi injection and compound matrine injection could significantly improve the overall response rate and quality of life and reduce the incidence of nausea and vomiting (III-IV), diarrhoea (III-IV), thrombocytopenia (III-IV), leukopenia (III-IV) and peripheral neurotoxicity (III-IV). According to results of indirect comparison, there were no statistically significant differences for most of comparison groups. Aidi+FOLFOX, shenqifuzheng+FOLFOX and compound matrine+FOLFOX had the greatest probability of being the best treatment in clinical efficacy and safety, considering the small sample size. WHAT IS NEW AND CONCLUSIONS: Most of the included studies were of low quality, and there was a scarcity of eligible trials and numbers of participants. Based on currently limited evidence, aidi, shenqifuzheng and compound matrine were superior to other CHIs in patients receiving FOLFOX chemotherapy for advanced CRC. More studies are required to confirm the efficacy of CHIs in combination with FOLFOX for advanced CRC.

Functional studies using antibodies against orphanin FQ/nociceptin.

Orphanin FQ/nociceptin (OFQ) is a recently discovered endogenous ligand for the novel opioid receptor-like receptor (ORL-1). There are numerous reports in the literature demonstrating paradoxical effects of exogenous OFQ on pain modulation. For example, OFQ produces a pronociceptive effect in the brain and an analgesic effect in the spinal cord. In order to better understand the physiological actions of OFQ, the present study focused on the pain-modulatory effect of endogenously released OFQ measured using antibody microinjection techniques. We found that electroacupuncture analgesia (EA) was increased by intracerebroventricular (i.c.v.) injection of an OFQ-antibody and decreased following intrathecal injection. Furthermore, i.c.v. OFQ-antibody partially reversed tolerance to both chronic morphine and chronic EA. These data suggest that endogenously released OFQ plays an important role in pain modulation, where pain sensitivity in the brain and spinal cord is increased and decreased, respectively.

Endogenous orphanin FQ: evidence for a role in the modulation of electroacupuncture analgesia and the development of tolerance to analgesia produced by morphine and electroacupuncture.

1. Our previous work has demonstrated that exogenously administered orphanin FQ (OFQ) antagonizes morphine analgesia and electroacupuncture analgesia (EAA) in the brain and potentiates morphine analgesia and EAA in the spinal cord of the rat. In the present study we evaluated the role of endogenously released OFQ in the development of tolerance to morphine and electroacupuncture (EA) and the analgesia produced by electroacupuncture, by use of the IgG fraction of an anti-OFQ antibody (OFQ-Ab) microinjected into the rat central nervous system (CNS). 2. EAA was produced by stimulating rats at a frequency of 100 Hz. Rats were classified as either high responders (HR) or low responders (LR) based on the analgesic effects of EA. LRs could be converted into HRs by the intracerebroventricular (i.c.v.) microinjection of OFQ-Ab at both 1:1 and 1:10 dilutions but not 1:100. HRs could be changed into LRs by the intrathecal (i.t.) injection of OFQ-Ab at both 1:1 and 1:10 dilutions, but not 1:100. 3. Acute morphine tolerance was induced in rats by repeated subcutaneous (s.c.) injections of morphine (5 mg kg, every 2 h) for 16 h. When injected i.c.v. the OFQ-Ab (1:1 dilution) had no effect on the development of acute morphine tolerance. 4. Chronic morphine tolerance was produced in rats by repeated injection of morphine (5-60 mg kg, s.c., 3 x a day) for 6 days. I.c.v. injection of OFQ-Ab (1:1 dilution) reversed this type of morphine tolerance in rats by 50% (P < 0.01). 5. Acute tolerance to the analgesia produced by EA developed after 6 h of continuous (100 Hz, 3 mA) stimulation. This tolerance was almost completely reversed by the i.c.v. injection of OFQ-Ab (1:1 dilution) (P < 0.05). 6. Chronic tolerance to the analgesic effect of EA was produced by repeatedly administering increasing current (1, 2 and 3 mA, each lasting for 10 min, for a total of 30 min) at a frequency of 100 Hz once a day for 6 days. I.c.v. injection of OFQ-Ab (1:1 dilution) reversed this kind of tolerance by 50% (P < 0.01). 7. Together these results suggest that 100 Hz EA may enhance the release of endogenous OFQ in the CNS of the rat, which in turn may act to antagonize EA-produced analgesia in the brain but potentiate EA produced analgesia in the spinal cord. Therefore, OFQ appears to play an important role in the development of tolerance to the analgesic effects produced by EA. 8. The mechanisms underlying the development of acute morphine tolerance and chronic morphine tolerance appear to be different. Central OFQ may play an important role in the development of tolerance after chronic morphine administration.

[2 Hz and 100 Hz electroacupuncture accelerate the expression of genes encoding three opioid peptides in the rat brain].

Previous findings from this laboratory have shown that low (2 Hz) and high (100 Hz)-frequency electroacupuncture (EA) accelerated the release of different kinds of opioid peptides in the CNS. In the present study, we tried to elucidate whether EA of different frequencies would affect the transcription of genes encoding different opioid peptides. Digoxin-labeled antisense cRNA probes were used for in situ hybridization to detect the mRNA encoding preproenkephalin (PPE), preprodynorphin (PPD) and proopiomelanocortin (POMC) in the rat brain. The results showed that: (1) Neither 2 Hz nor 100 Hz EA altered the POMC mRNA level in the rat brain. (2) EA of the two frequencies induced a similar degree of increase of PPE mRNA in rostromedial reticular formation (gigantocellular, paragigantocellular and lateral reticular nucleus); whereas in supraoptic nucleus, suprachiasmatic nucleus, arcuate nucleus, paraventricular hypothalamic nucleus, ventromedial nucleus and the nucleus of lateral lemniscus, 2 Hz EA induced a higher PPE mRNA expression than 100 Hz EA. (3) 100 Hz EA markedly increased the PPD mRNA levels in supraoptic nucleus, paraventricular hypothalamic nucleus, ventromedial nucleus and parabrachial nucleus, while 2 Hz was without effect. Since de novo peptide synthesis is regarded as a natural outcome following accelerated peptide release, the present results substantiate our previous observation that EA of different frequencies exert different acceleratory effects on the release and synthesis of different opioid peptides in the central nervous system.

Involvement of endogenous orphanin FQ in electroacupuncture-induced analgesia.

Recent studies suggest that the novel opioid peptide orphanin FQ (OFQ) is involved in pain modulation. We found that intracerebroventricular (i.c.v.) administration of OFQ in the rat produced a dose-dependent antagonism of the analgesia induced by 100 Hz electroacupuncture (EA) stimulation as measured in the radiant heat tail-flick assay. Antisense oligonucleotides injected i.c.v. potentiated EA analgesia, presumably by interfering with the expression of the OFQ receptor in brain. These results suggest that endogenous OFQ exerts a tonic antagonistic effect on EA-induced analgesia. No such antagonism was observed when OFQ was injected intrathecally (i.t.). Rather, it appears that spinal OFQ produced a marked analgesic effect and enhanced EA-induced analgesia. These findings are consistent with the experimental results obtained in rats where morphine-induced analgesia is antagonized by i.c.v. OFQ and potentiated by i.t. OFQ.