Objectives:This study aims to investigate the expression changes of transient receptor potential vanilloid type 1 (TRPV1) channel and inflammatory factors in the peripheral blood of patients with schizophrenia, and to evaluate their potential value for diagnostic prediction.Methods:This cross-sectional study was conducted at Renmin Hospital of Wuhan University from September 2023 to June 2024. A total of 35 patients with schizophrenia (patient group) from the outpatient/inpatient departments and 35 age-and sex-matched healthy individuals (control group) were recruited. Psychiatric symptoms and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The between-group comparisons of the total scores of these two instruments were calculated using independent samples t-tests. Fasting peripheral blood samples were collected from all participants. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated for subsequent analysis. TRPV1 protein expression was quantified by Western blotting, while inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10), were measured using enzyme-linked immunosorbent assay (ELISA). The between-group differences in TRPV1 and inflammatory cytokines were analyzed using the analysis of covariance (ANCOVA), controlling for age and sex. Pearson correlation analysis was employed to examine relationships between continuous variables, controlling for years of education, age, and sex. The diagnostic performance of TRPV1 and inflammatory cytokines for schizophrenia was assessed using receiver operating characteristic (ROC) curve analysis. Results:Significant between-group differences were observed in BACS total and subscale scores ( t=2.57-9.72, all P<0.01). Compared with the control group, the patient group exhibits significantly decreased expression of TRPV1, IL-4, and IL-10 ( t=6.78, 2.75, 2.53, all P<0.01), increased expression of TNF-α, IL-2, and IL-6 ( t=4.08, 2.64, 2.63, all P<0.01), and an increased IL-6/IL-10 ratio ( t=3.18, P<0.01). Correlation analyses revealed that in the patient group, the TRPV1 expression level was negatively correlated with levels of TNF-α and IL-6, and positively correlated with levels of IL-4 and IL-10 ( r=-0.589, -0.234, 0.341, 0.293, all P<0.05). In the patient group, the TRPV1 expression level was negatively correlated with the negative symptom score of PANSS ( r=-0.299, P<0.05), and the IL-6 level was positively correlated with the negative symptom score, the general pathology score, and the total score of PANSS ( r=0.387, 0.356, 0.321, all P<0.05). The TRPV1 level was positively correlated with the total score of BACS in both the control group and the patient group ( r=0.144, 0.828, all P<0.01). The IL-6/IL-10 ratio was positively correlated with the total score of PANSS and negatively correlated with the total score of BACS in the patient group ( r=0.623, -0.333, all P<0.05). The area under the ROC curve for the combination of TRPV1 level and IL-6/IL-10 ratio was 0.98 (95% confidence interval=0.96 to 1.00). Conclusions:Patients with schizophrenia exhibit reduced expression levels of TRPV1 along with an imbalanced inflammatory response. The combined assessment of TRPV1 level and IL-6/IL-10 ratio has demonstrated a high predictive and diagnostic value for schizophrenia.

Objectives:This study aims to investigate the expression changes of transient receptor potential vanilloid type 1 (TRPV1) channel and inflammatory factors in the peripheral blood of patients with schizophrenia, and to evaluate their potential value for diagnostic prediction.Methods:This cross-sectional study was conducted at Renmin Hospital of Wuhan University from September 2023 to June 2024. A total of 35 patients with schizophrenia (patient group) from the outpatient/inpatient departments and 35 age-and sex-matched healthy individuals (control group) were recruited. Psychiatric symptoms and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The between-group comparisons of the total scores of these two instruments were calculated using independent samples t-tests. Fasting peripheral blood samples were collected from all participants. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated for subsequent analysis. TRPV1 protein expression was quantified by Western blotting, while inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10), were measured using enzyme-linked immunosorbent assay (ELISA). The between-group differences in TRPV1 and inflammatory cytokines were analyzed using the analysis of covariance (ANCOVA), controlling for age and sex. Pearson correlation analysis was employed to examine relationships between continuous variables, controlling for years of education, age, and sex. The diagnostic performance of TRPV1 and inflammatory cytokines for schizophrenia was assessed using receiver operating characteristic (ROC) curve analysis. Results:Significant between-group differences were observed in BACS total and subscale scores ( t=2.57-9.72, all P<0.01). Compared with the control group, the patient group exhibits significantly decreased expression of TRPV1, IL-4, and IL-10 ( t=6.78, 2.75, 2.53, all P<0.01), increased expression of TNF-α, IL-2, and IL-6 ( t=4.08, 2.64, 2.63, all P<0.01), and an increased IL-6/IL-10 ratio ( t=3.18, P<0.01). Correlation analyses revealed that in the patient group, the TRPV1 expression level was negatively correlated with levels of TNF-α and IL-6, and positively correlated with levels of IL-4 and IL-10 ( r=-0.589, -0.234, 0.341, 0.293, all P<0.05). In the patient group, the TRPV1 expression level was negatively correlated with the negative symptom score of PANSS ( r=-0.299, P<0.05), and the IL-6 level was positively correlated with the negative symptom score, the general pathology score, and the total score of PANSS ( r=0.387, 0.356, 0.321, all P<0.05). The TRPV1 level was positively correlated with the total score of BACS in both the control group and the patient group ( r=0.144, 0.828, all P<0.01). The IL-6/IL-10 ratio was positively correlated with the total score of PANSS and negatively correlated with the total score of BACS in the patient group ( r=0.623, -0.333, all P<0.05). The area under the ROC curve for the combination of TRPV1 level and IL-6/IL-10 ratio was 0.98 (95% confidence interval=0.96 to 1.00). Conclusions:Patients with schizophrenia exhibit reduced expression levels of TRPV1 along with an imbalanced inflammatory response. The combined assessment of TRPV1 level and IL-6/IL-10 ratio has demonstrated a high predictive and diagnostic value for schizophrenia.

Glycyrrhizae Radix et Rhizoma is the most commonly used herb in ZHANG Zhongjing′s Treatise on Cold Pathogenic Diseases and Synopsis of Golden Chamber. It serves as a crucial entry point for understanding ZHANG Zhongjing′s prescription system. The role of Glycyrrhizae Radix et Rhizoma in ZHANG Zhongjing′s prescription system differs from its current recognized efficacy. By analyzing the typhoid prescriptions and referring to ancient materia medica texts from various dynasties, this study categorizes the formulas containing Glycyrrhizae Radix et Rhizoma and identifies four fundamental efficacies associated with it: fluid retention, preservation of gastric qi, support of yang qi, and protection of the triple energizer. These basic efficacy principles align with the core treatment principles implied in ZHANG Zhongjing′s prescription system, suggesting that Glycyrrhizae Radix et Rhizoma is one of the key herbs in constructing ZHANG Zhongjing′s prescription system. To elucidate the logical expansion of prescriptions, formulas containing Glycyrrhizae Radix et Rhizoma are deconstructed and classified into first-order, second-order, tertiary-order, quaternary-order, and other formulas based on the affinity of the paired herbs. Similarly, the corresponding herbs are classified accordingly. Using Cinnamomi Ramulus, Zingiberis Rhizoma, Paeonia lactiflora Pall., and Ephedrae Herba as examples, the study analyzes the principles behind formulas containing Glycyrrhizae Radix et Rhizoma. ZHANG Zhongjing′s prescription system strategically added or subtracted other herbs to fully utilize or extend the four fundamental effects of Glycyrrhizae Radix et Rhizoma, resulting in the majority of existing formulas through continuous expansion. This provides new insights and approaches for further in-depth study of ZHANG Zhongjing′s prescription system.

Objective:To compare the differences in prefrontal activation patterns between major depressive disorder and schizophrenia during the eye basic emotion discrimination task (EBEDT).Methods:Using functional near infrared spectroscopy (fNIRS) technology and block design, the changes of prefrontal lobe oxyhemoglobin (Oxy-Hb) concentrations under EBEDT in 40 patients with major depressive disorder, 47 patients with schizophrenia and 55 normal controls were compared. Subsequently, employing years of education as a covariate, an analysis of covariance was performed on the EBEDT behavioral results and the changes in prefrontal Oxy-Hb concentrations in the three groups.The statistical software was SPSS 25.0.Results:(1)The correct number of EBEDT in schizophrenia group (13.93±7.67) was significantly lower than that in major depressive disorder group (19.26±8.07) and normal control group (21.79±6.36)(both P<0.05), and the EBEDT reaction time in schizophrenia group ((3.97±1.77) s) was significantly longer than those in major depressive disorder group ((3.21±1.27) s) and normal control group ((2.63±0.62) s)(both P<0.05).(2)During the EBEDT task block, the normal control group showed increased activation levels in the frontal polar region, Broca's area, anterior motor cortex and supplementary motor area (SMA) compared with the control block( t=2.02-3.18, all P<0.05); and the schizophrenia group showed increased activation levels in the frontal eye field compared with the control block( t=2.26, P=0.03); while the major depressive disorder group exhibited decreased activation levels in the entire prefrontal lobe compared with the control block( t=-3.47--2.34, all P<0.05). (3)During the emotion recognition task of EBEDT, the activation levels of the frontal polar area (ch37), dorsolateral prefrontal cortex (ch31), Broca's area (ch49, ch51, ch53), and SMA (ch1, ch47, ch52) were significantly different among the major depressive disorder, schizophrenia and normal controls( F=3.23-5.53, all P<0.05). Further pairwise comparisons showed that the activation levels in all the above pathways were lower in the major depressive disorder group than those in the normal control group, and the activation levels in Broca's area (ch53) and SMA area (ch52) were lower in the schizophrenia group than those in the normal control group, while the activation levels in the frontal polar area (ch37) and Broca's area (ch49) were lower in the major depressive disorder group than those in the schizophrenia group(all P<0.05). Conclusions:In EBEDT, the activation patterns of the prefrontal cortex are different between patients with major depressive disorder and patients with schizophrenia. Patients with major depressive disorder have a decrease in prefrontal cortex activation, while patients with schizophrenia have an increase in the frontal eye field activation.The activation levels in prefrontal cortex of both patients group are lower than that of normal controls. Meanwhile, the prefrontal cortex activation level of patients with major depressive disorder is lower than that of patients with schizophrenia.

ObjectiveTo study the effects of Huangjing Jiannao granules on learning and memory abilities and cerebral blood flow in the rat model of vascular cognitive impairment （VCI） and to explore the mechanism of Huangjing Jiannao granules in the treatment of VCI. MethodSeventy-two SPF-grade male SD rats were randomly selected， with 12 rats as the sham operation group. The remaining rats were subjected to bilateral carotid artery ligation （2-VO） for the modeling of VCI. According to the randomized block design， the successfully modeled rats were grouped as follows： model， donepezil hydrochloride （0.50 mg·kg^-1）， and low-， medium-， and high-dose （2.36， 4.72， 9.44 g·kg^-1， respectively） Huangjing Jiannao granules. After 6 weeks of treatment， Morris water maze test and new object recognition test were conducted to evaluate the learning and memory abilities of the rats. After continuous gavage for 8 weeks， the cerebral blood flow was recorded by a laser microcirculation blood flow imager， and the survival and injury of hippocampal neurons were observed by Nissl staining. The expression of neuronal nuclear antigen （NeuN） in the hippocampus was detected by immunohistochemistry （IHC）. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the serum were determined by enzyme-linked immunosorbent assay. The protein levels of phosphatidylinositol 3-kinase （PI3K）， phosphorylated protein kinase B （p-Akt）， nuclear factor-κB p65 （NF-κB p65）， and nuclear factor-κB inhibitor α （IκBα） in the hippocampus were determined by Western blot. ResultCompared with the sham operation group， the model group showed weakened learning and memory abilities （P<0.01）， reduced blood flow in the whole brain， forebrain， and hindbrain （P<0.01）， damaged neurons and reduced survived neurons in the hippocampal CA1 region （P<0.01）， down-regulated expression of NeuN （P<0.01）， elevated levels of IL-1β and TNF-α in the serum （P<0.01）， up-regulated protein levels of PI3K， p-Akt， and NF-κB p65 in the hippocampal tissue， and down-regulated protein level of IκBα （P<0.01）. Compared with the model group， medium- and high-dose Huangjing Jiannao granules improved the learning and memory abilities （P<0.05，P<0.01）. High-dose Huangjing Jiannao granules increased the blood flow in the whole brain， forebrain， and hindbrain （P<0.05，P<0.01）， and medium-dose Huangjing Jiannao granules increased the blood flow in the whole brain （P<0.05）. All the doses of Huangjing Jiannao granules increased the number of survived neurons （P<0.05，P<0.01） and up-regulated the protein level of NeuN （P<0.05，P<0.01）. Medium and high-dose Huangjing Jiannao granules lowered the level of TNF-α （P<0.05，P<0.01）， down-regulated the protein levels of PI3K， p-Akt， and NF-κB p65 （P<0.05，P<0.01）， and up-regulated the protein level of IκBα （P<0.01）. ConclusionHuangjing Jiannao granules can improve the learning and memory abilities and promote the recovery of cerebral blood flow in the rat model of VCI induced by 2-VO by regulating the expression of proteins involved in the PI3K/Akt signaling pathway， inhibiting inflammation， and reducing hippocampal neuron injury.

Objective To explore the effects of Kaixin Jieyu Pill(KJP)on peroxisome proliferator-activated receptor alpha(PPARα),serum and hippocampal tissue fibroblast growth factor 21(FGF21)and hippocampal tissue fibroblast growth factor receptor 1(FGFR1)in rats with depression model.Methods A rat chronic stress model was prepared using the chronic unpredictable mild stimulus method(CUMS)to observe behavioral changes in depression.Hippocampal FGF21,FGFR1 and liver PPARα protein and mRNA expression levels were measured in hippocampal tissues by western blot and real-time fluorescence quantification(RT-qPCT).Results The expression levels of PPARα,FGF21 and FGFR1's protein and their mRNA were dramatically decreased in the CUMS model rats compared with the normal group(P<0.001).KJP could modify the depressive-like behaviors of rats(P<0.001),upregulate the protein expression level of PPARα,FGF21,and FGFR1(P<0.05,P<0.01,P<0.01);markedly modify the mRNA expression levels of PPARα,FGF21,and FGFR1(P<0.001,P<0.01,P<0.01).Conclusion PPARα/FGF21/FGFR1 pathway may participate in the pathogenesis of depression;upregulation of PPARα/FGF21/FGFR1 pathway may be related to the antidepressant mechanism of KJP.

The purpose of this paper is to analyze the pathogenesis of depression from the correlation between Nao Xuanfu and neurovascular unit(NVU).Previous studies have shown that NVU instability is a common pathophysiological link in the pathophysiological mechanism of depression,which involves neurotransmitters,immunity,inflammation,oxidation,heredity and their interaction,multi-targets,multi-pathways,and more complex.Under the principles of TCM holistic view and syndrome differentiation and treatment,it is considered that there is a great similarity between NVU and Naozhixuanfu.Therefore,this paper verifies the correlation between Nao Xuanfu and NVU from four aspects:morphological structure,energy supply,waste excretion and information exchange,and holds that there is a common connotation between NVU instability and Xuanfu depression,and then discusses the etiology and pathogenesis of depression from the perspective of Nao Xuanfu theory.It is considered that depression is located in the brain,the lesion is in Xuanfu,and the blockage of brain Xuanfu is the core pathogenesis,"communication"should be the most important in the treatment.Through the analogy between Nao Xuanfu and NVU,we look for the same pathogenic link in the seemingly independent pathogenesis,so as to provide new ideas for the clinical research of integrated traditional Chinese and western medicine.On the other hand,applying the pathogenesis of Xuanfu depression to clinical diagnosis and treatment will also provide new ideas for the clinical treatment of depression.

Objective To evaluate the dynamic efficacy of Invigorating Qi and Dissipating Depression Herbs in the treatment of depressive disorders and its effect on recurrence rate and suicidal thoughts.Methods The prospective cohort study was used to divide the patients into three cohorts according to the different exposure factors(treatment regimens):Western medicine group,integrated traditional Chinese and Western medicine group,and Invigorating Qi and Dissipating Depression Herbs group,and followed up for 2 years,and the treatment effects of each cohort at half a year,one year,one and a half years,and two years were observed respectively,and the evaluation indicators were Montgomery Depression Scale(MADRS),Hamilton Anxiety Scale(HAMA)and Social Deficit Screening Scale(SDSS)reduction rates,and endpoint events(relapse,suicidal ideation)incidence;By comparing the efficacy and endpoint event rate of the three cohorts,the effect of Invigorating Qi and Dissipating Depression Herbs on improving depressive disorders was evaluated.Results A total of 409 patients(67 in the Western medicine group,131 in the integrated traditional Chinese and Western medicine group,and 211 cases in the Invigorating Qi and Dissipating Depression Herbs group)were enrolled,and the rate of score reduction after treatment with MADRS,HAMA and SDSS increased compared with the pre-treatment treatment with the extension of the drug taking time.The difference between the MADRS and SDSS reduction rates in the Invigorating Qi and Dissipating Depression Herbs group on taking the drug for half a year and the SDSS reduction rate on one year of taking the drug were statistically significant compared with the Western medicine group,and there was no significant difference compared with the integrated Chinese and Western medicine group.On one and a half years and two years of medication,the integrated Chinese and Western medicine group had more advantages in MADRS reduction rate than the Invigorating Qi and Dissipating Depression Herbs group.The recurrence rates of depression in the three groups within 2 years were 20.9％,30.5％and 36.0％,and the difference was not statistically significant,and the length of taking medication was used as a protective factor by logistic regression analysis.The incidence rates of suicidal thoughts were 44.8％,19.1％and 17.5％,and the differences were statistically significant,and the exposure factors and income level were the protective factors by logistic regression analysis.Conclusion Invigorating Qi and Dissipating Depression Herbs can significantly improve the depressive state of patients,promote the recovery of social function,reduce the occurrence of long-term suicidal ideation,and appropriately extend the time of taking medicine can increase the long-term efficacy and reduce recurrence.

Through the exploration of the Xuanfu theory,this article analyzes and summarizes the pathogenesis and treatment of depression,and explores the application of wind medicine in the treatment of depression in traditional Chinese medicine.On the basis of sorting out the connotation of Xuanfu theory and the historical changes of the wind medicine,it is concluded that the main pathogenesis of depression is Xuanfu opening and closing block,obstruction of qi,blood and body fluid,and dysfunction of mental machinery.The basic therapeutic method is to open the Xuanfu to treat depression,and the syndrome differentiation is assisted by regulating qi,resolving turbidity,promoting blood circulation and tonifying deficiency.The efficacy of the wind medicine and the effect of drug components were summarized,and the application of the wind medicine in the treatment of depression was discussed.The efficacy of the wind medicine and the effect of drug components were summarized,and the medication regularity of the wind medicine in the treatment of depression was discussed.Through the Xuanfu theory to understand depression again,and to recognize the wind medicine in the treatment of depression has a unique role,but also can help other drugs,significantly enhance its effect in the treatment of depression.

The research on the essence of triple energizer has not reached a consensus. The correspondence between the existing understanding and the classical theory of triple energizer is still limited in terms of structure and function. According to the traditional theory， nutrient-defense takes channels as the main circulatory system， while the operation of nutrient-defense in the triple energizer remains unclear. Since little is known about the physical structure of the triple energizer， the role of triple energizer as a collection of other Zang-fu organs has been ignored in most cases. The new progress in anatomy paves the way for the research on the essence of triple energizer. The function and structure of triple energizer are similar to those of interstitium and interfacial fluid flow， which enriches our understanding of the macro and micro structures of triple energizer. The triple energizer is distributed throughout the body and composed of membrane and interstitial space. The material structure of triple energizer includes fiber scaffold， collagen fiber， mesenchymal stem cells， histiocytes， pericytes， and interstitial fluid. The functions of triple energizer include passing body fluids， operating nutrient-defense， distributing original Qi， and transmitting and changing pathogenic Qi. According to the available theories and research achievements， we put forward the concept of vertical and horizontal triple energizer， pointed out that triple energizer had independent structure and the features of Zang-fu organs， and preliminarily defined the spatial distribution of triple energizer. The relationship between channels and triple energizer is essential for discussing the operation of nutrient-defense. Telocyte （Tc） and telopod （Tp） has the characteristics of channels in function and structure. The connective tissue with the distribution of Tc and Tp belongs to the same material as the basic structure of interstitial/interfacial fluid flow system and the fibrous skeleton of interstitium. It is clear that channels and triple energizer have material commonality. From the operation paths of nutrient-defense， we proposed that channels may be soaked and attached in triple energizer and put forward the model of channels soaked and attached in triple energizer. By combining the circulation of nutrient-defense with the vertical and horizontal triple energize， we developed the theory of triple energizer-nutrient-defense loop to comprehensively describe the generation， transport， and metabolism of nutrient-defense in channels and triple energizer， aiming to provide a theoretical model for future studies of disease transmission and change from exterior to interior.