Background: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

Tick-borne encephalitis is a central nervous system disease caused by infections with tick-borne pathogens, which is characterized by severe clinical symptoms, multiple sequelae, and a high fatality rate. Currently, there is no cure for tick-borne encephalitis. Tick-borne encephalitis virus (TBEV) is the most common pathogen of tick-borne encephalitis. Therefore, rapid and accurate detection of TBEV contributes to reducing the mortality of tick-borne encephalitis, improving patients' prognosis, and reducing the risk of TBEV transmission. The currently available serological tests for detection of TBEV infections mainly include neutralization test, enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay, and nucleic acid tests mainly include polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), reverse transcription polymerase spiral reaction, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas)-based assays. This review summarizes the progress of researches on serological and nucleic acid tests for detection of TBEV infections, so as to provide insights into prevention and control of tick-borne encephalitis.

Background: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

Background: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

Background: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

ObjectiveTo study the tumor inhibition and T helper cell （Th）1/Th2 balance regulation effect of modified Wenyang Sanjie prescription on lung cancer tumor-bearing mice and to elaborate its mechanism. MethodsA mouse model bearing a lung cancer tumor was established by subcutaneous injection of Lewis lung cancer cells into the armpit and was randomly divided into lung cancer model group， low-dose， medium-dose， and high-dose groups of modified Wenyang Sanjie prescription， and positive control group， with 12 mice per group. The low-dose， medium-dose， and high-dose groups of modified Wenyang Sanjie prescription were given modified Wenyang Sanjie prescription by dosing at 2.5， 5， 10 g·kg^-1， once a day， respectively. The positive control group was intraperitoneally injected with cisplatin （2 mg·kg^-1）， once every other day， for a total of 30 days. Serum interferon （IFN）-γ， interleukin （IL）-2， IL-4， IL-6， and IL-10 were determined by enzyme-linked immunosorbent assay （ELISA）， and spleen index， thymus index， and tumor growth inhibition rate were calculated. Tumor microvascular density was determined by immunohistochemistry， and tumor hypoxia inducible-factor （HIF）-1α， epidermal growth factor receptor （EGFR）， and vascular endothelial growth factor （VEGF） mRNA were determined by Real-time quantitative polymerase chain reaction （PCR）. The protein levels of HIF-1α， EGFR， and VEGF were determined by Western blot. ResultsCompared with lung cancer model group， IFN-γ and IL-2 were increased in the modified Wenyang Sanjie prescription groups and positive control group， while IL-4， IL-6， IL-10， spleen index， thymus index， tumor weight， and tumor microvascular density were decreased， as well as HIF-1α， EGFR， and VEGF mRNA and protein levels （P<0.05）. Compared to the low-dose group of modified Wenyang Sanjie prescription， IFN-γ and IL-2 were increased in the medium-dose and high-dose groups of modified Wenyang Sanjie prescription， while IL-4， IL-6， IL-10， spleen index， thymus index， tumor weight， and tumor microvascular density were decreased， as well as HIF-1α， EGFR， and VEGF mRNA and protein levels （P<0.05）. IFN-γ and IL-2 were increased in the high-dose group of modified Wenyang Sanjie prescription compared to the medium-dose group of modified Wenyang Sanjie prescription， and IL-4， IL-6， IL-10， spleen index， thymus index， tumor weight， and tumor microvascular density were decreased， as well as HIF-1α， EGFR， and VEGF mRNA and protein levels （P<0.05）. ConclusionModified Wenyang Sanjie prescription can significantly inhibit microangiogenesis， regulate Th1/Th2 balance， inhibit tumor growth， and significantly inhibit the progression of lung cancer in mice.

ObjectiveTo study the tumor inhibition and T helper cell （Th）1/Th2 balance regulation effect of modified Wenyang Sanjie prescription on lung cancer tumor-bearing mice and to elaborate its mechanism. MethodsA mouse model bearing a lung cancer tumor was established by subcutaneous injection of Lewis lung cancer cells into the armpit and was randomly divided into lung cancer model group， low-dose， medium-dose， and high-dose groups of modified Wenyang Sanjie prescription， and positive control group， with 12 mice per group. The low-dose， medium-dose， and high-dose groups of modified Wenyang Sanjie prescription were given modified Wenyang Sanjie prescription by dosing at 2.5， 5， 10 g·kg^-1， once a day， respectively. The positive control group was intraperitoneally injected with cisplatin （2 mg·kg^-1）， once every other day， for a total of 30 days. Serum interferon （IFN）-γ， interleukin （IL）-2， IL-4， IL-6， and IL-10 were determined by enzyme-linked immunosorbent assay （ELISA）， and spleen index， thymus index， and tumor growth inhibition rate were calculated. Tumor microvascular density was determined by immunohistochemistry， and tumor hypoxia inducible-factor （HIF）-1α， epidermal growth factor receptor （EGFR）， and vascular endothelial growth factor （VEGF） mRNA were determined by Real-time quantitative polymerase chain reaction （PCR）. The protein levels of HIF-1α， EGFR， and VEGF were determined by Western blot. ResultsCompared with lung cancer model group， IFN-γ and IL-2 were increased in the modified Wenyang Sanjie prescription groups and positive control group， while IL-4， IL-6， IL-10， spleen index， thymus index， tumor weight， and tumor microvascular density were decreased， as well as HIF-1α， EGFR， and VEGF mRNA and protein levels （P<0.05）. Compared to the low-dose group of modified Wenyang Sanjie prescription， IFN-γ and IL-2 were increased in the medium-dose and high-dose groups of modified Wenyang Sanjie prescription， while IL-4， IL-6， IL-10， spleen index， thymus index， tumor weight， and tumor microvascular density were decreased， as well as HIF-1α， EGFR， and VEGF mRNA and protein levels （P<0.05）. IFN-γ and IL-2 were increased in the high-dose group of modified Wenyang Sanjie prescription compared to the medium-dose group of modified Wenyang Sanjie prescription， and IL-4， IL-6， IL-10， spleen index， thymus index， tumor weight， and tumor microvascular density were decreased， as well as HIF-1α， EGFR， and VEGF mRNA and protein levels （P<0.05）. ConclusionModified Wenyang Sanjie prescription can significantly inhibit microangiogenesis， regulate Th1/Th2 balance， inhibit tumor growth， and significantly inhibit the progression of lung cancer in mice.

OBJECTIVE: To explore the peripheral neural mechanism underlying representation along the distribution of stomach meridian induced by intestinal inflammatory reaction using diarrhea predominant-irritable bowel syndrome (IBS-D) mice. METHODS: Among 62 healthy male C57BL/6 mice of clean grade, 12 mice were randomly selected and divided into a control group and a model group, 6 mice in each group, additionally, 12 mice were randomly selected and divided into a Tianshu group, a Liangqiu group and a Zusanli group, 4 mice in each group. In the model group, citrobacter was administered orally to establish IBS-D model. In the control group and the model group, the visceral pain threshold was observed using fecal colorectal distension (fCRD) induced electromyography of external oblique muscle, the positive cell number of neutrophil in the colonic muscularis was detected by myeloperoxidase (MPO) staining, the number, location and distribution rule of Evans blue (EB) extravasation points were observed by injection of EB staining solution into the tail vein. In the Tianshu group, the Liangqiu group and the Zusanli group, fluorescent dye Dil was injected at bilateral "Tianshu" (ST25), "Liangqiu" (ST34) and "Zusanli" (ST36) respectively, to observe the dye-positive cell number in different dorsal root ganglion (DRG) segments. In the control group and the model group, the activation of satellite glial cells (SGCs) in different DRG segments was observed by immunofluorescence. RESULTS: Compared with the control group, in the model group, the area under curve of electromyography of external oblique muscle was increased at fCRD of 25, 50 and 75 μL distilled water (P<0.001, P<0.01); the MPO-positive cell number of neutrophil in the colonic muscularis was increased (P<0.01). Few EB extravasation points could be found in the control group, while there were much more EB extravasation points observed in the model group, which was specially distribution in the area of stomach meridian, from "Huaroumen" (ST24) to "Zusanli" (ST36), as well as the surface area dominated by L₂-L₅ segment of the spinal cord. The Dil-positive cells were mainly exhibited in the DRG of T₁₁, L₅ and L₄ segments in the Tianshu group, the Liangqiu group and the Zusanli group, respectively. Compared with the control group, the ratio of glial fibrillary acidic protein (GFAP)/glutamine synthetase (GS) co-expression was increased in the DRG of T₁₁, L₄ and L₅ segments in the model group (P<0.05, P<0.01). CONCLUSION The activation of SGCs within DRG of T₁₁, L₄ and L₅ segments may relate closely to the occurrence of the representation along the stomach meridian distribution in IBS-D mice.
Animals ; Male ; Mice ; Irritable Bowel Syndrome/therapy* ; Mice, Inbred C57BL ; Meridians ; Stomach/physiopathology* ; Humans ; Acupuncture Points ; Disease Models, Animal