OBJECTIVE To investigate the effects and mechanisms of Buyang huanwu decoction （BYHWD） and its active fractions in ameliorating non-alcoholic fatty liver disease. METHODS BYHWD and its effective fractions obtained through ethanol precipitation， as well as 30% ethanol， 50% ethanol， and 75% ethanol fractions （namely， the CC effective fraction， 30YC effective fraction， 50YC effective fraction， and 75YC effective fraction）， were prepared. These preparations were administered to rats via intragastric administration to prepare corresponding drug-containing serum （blank serum and simvastatin-containing serum were prepared using the same protocol）. Human L02 hepatocytes were divided into control group， model group， simvastatin-containing serum group， BYHWD-containing serum group， CC-containing serum group， 30YC-containing serum group， 50YC-containing serum group， and 75YC-containing serum group. Except for the control group， other groups were given 0.2 mol/L oleic acid for 24 h to induce a lipid accumulation model， and then intervened with 20% drug-containing serum/blank serum for 24 h. The lipid deposition in cells was observed， and the proportion of lipid droplet area was calculated； the levels of triglycerides （TG） and indicators of oxidative stress [malondialdehyde （MDA）， superoxide dismutase （SOD）] as well as liver function [alanine amino- transferase （ALT）， aspartate amino-transferase （AST）] in cells were detected； protein and mRNA expressions of AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1 （SREBP-1）/glycerol-3-phosphate acyltransferase （GPAT） signaling pathway were also measured. RESULTS Compared with the control group， cells in the model group exhibited severe cellular steatosis， with a significantly increased proportion of lipid droplet area， as well as the elevated levels of TG， ALT， AST， and MDA in cells， along with significantly up-regulated mRNA and protein expression levels of SREBP-1 and GPAT （P＜0.05）. The level of SOD， mRNA expression of AMPK， as well as the protein phosphorylation level of AMPK were decreased significantly （P＜0.05）. Compared with the model group， cellular steatosis was alleviated in all drug-containing serum groups， and the levels of most of the aforementioned quantitative indicators were significantly reversed （P＜0.05）. CONCLUSIONS BYHWD and its active fractions can exert a therapeutic effect on improving non-alcoholic fatty liver disease by regulating the AMPK/SREBP-1/GPAT signaling pathway， inhibiting oxidative stress responses， and reducing lipid deposition.

This paper explores the therapeutic approach for glaucoma based on the concept of "jueyin （厥阴） as the closing phase" from the perspectives of time and space. In traditional Chinese medicine， jueyin governs inward， converging aspect of qi， representing the crucial turning point between the end of yin and the emergence of yang， as well as the transformation between yin and yang. When the closing and descending function of jueyin operates smoothly， it promotes the inward convergence and smooth descent of qi， enabling the internal retention of blood， spirit， and emotions， which nourishes the internal organs and moistens the meridian-sinews. Conversely， dysfunction of this "closing" mechanism results in a disturbance of yin and yang， a mixture of cold and heat， and disharmony of qi and blood. It is proposed that "failure of jueyin to properly close and descend" is a core pathomechanism of glaucoma. From the perspective of spatiotemporal theory， clinical treatment should focus on "regulating the closing function of jueyin and harmonizing yin and yang". The modified Wumei Pill （乌梅丸） is recommended to adjust the ascending-descending and entering-exiting dynamics of jueyin qi transformation， thereby restoring its free flow， achieving yin and yang balance， and ensuring nourishment to the ocular system.

ObjectiveTo investigate the effects of rhizosphere organic acids secreted by the roots of Salvia miltiorrhiza on continuous cropping obstacles. MethodsThe mixed solution of organic acids in the rhizosphere of S. miltiorrhiza in continuous cropping and rotation cropping was added to the hairy roots subcultured for 21 days， and samples were collected on days 0， 2， 4， 6， 8， and 10. The changes of biomass， effective components， primary metabolites， secondary metabolites， antioxidant enzymes， and hormones in hairy roots of S. miltiorrhiza were observed and determined. ResultsCompared with the rotation cropping group and the blank control group， the simulation of organic acid secretion from the roots of S. miltiorrhiza had a significant inhibitory effect on the growth of hairy roots and decreased the content of effective components as well as total sugar and total protein in primary metabolites. Compared with the blank control group， the rotation cropping group and the continuous cropping group showed total sugar and total protein content decreases of 33.9% and 5.1%， respectively. On the other hand， the secretion of organic acids from S. miltiorrhiza roots significantly promoted the accumulation of total phenolic acids and total tanshinone， which showed increases of 14.6% and 1.6%， respectively， in continuous cropping group and rotation cropping group compared with the blank control group. ConclusionThe organic acid environment under continuous cropping significantly inhibited the growth of hairy roots and the accumulation of primary metabolites， while promoting the synthesis and accumulation of secondary metabolites of S. miltiorrhiza.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:To investigate the changes of T lymphocyte subsets in patients with stage Ⅰ and Ⅱ cervical cancer after surgery and their relationship with postoperative lymph node metastasis according to the International Federation of Gynecology and Obstetrics (FIGO) stage (2014) .Methods:A total of 192 patients with FIGO stage ⅠA, ⅠB1, ⅠB2 and ⅡA1 who received radical cervical cancer resection and pelvic lymph node dissection in People's Hospital of Yuechi County of Sichuan Province and West China Guang'an Hospital of Sichuan University from November 2018 to November 2020 were selected for this study. According to FIGO stage, patients were divided into stage Ⅰ group ( n=85) and stage Ⅱ group ( n=107) . The dynamic changes of T lymphocytes subsets in patients with different FIGO stages were compared before and after surgery. Repeated measurement of variance was used to analyze the levels of T lymphocytes subsets in patients of different stages during treatment. Logistic regression was used to analyze the influencing factors of postoperative lymph node metastasis in patients with cervical cancer. Multivariate logistic regression was used to analyze the relationship between T lymphocytes subsets and postoperative lymph node metastasis. Receiver operator characteristic (ROC) curve was used to analyze the predictive efficacy of T lymphocytes level in postoperative lymph node metastasis. Results:The postoperative lymph node metastasis rate in stage Ⅱ patients [32.71% (35/107) ] was higher than that in stage Ⅰ patients [14.12% (12/85) ], with a statistically significant difference ( χ2=8.86, P=0.003) . Compared with the stage Ⅱ group, the levels of CD3 +, CD4 + T lymphocytes and CD4 +/CD8 + ratio were significantly higher in the stage Ⅰ group 1 day before surgery (all P<0.001) , and the level of CD8 + T lymphocytes was significantly lower ( P<0.001) . The levels of CD3 +, CD4 +, CD8 + T lymphocytes and the ratio of CD4 +/CD8 + showed dynamic changes at different stages after surgery. On 1, 7 and 30 days after surgery, the levels of CD3 +, CD4 + T lymphocytes and the ratio of CD4 +/CD8 + in stage Ⅰ group were higher than those in stage Ⅱ group (all P<0.001) , CD8 + T cell levels were lower than those in stage Ⅱ group (all P<0.001) . There were statistically significant differences in T lymphocytes subsets CD3 +, CD4 +, CD8 + and CD4 +/CD8 + time effect, intergroup effect and interaction effect between the two groups (all P<0.001) . Univariate analysis showed that the pathological type ( OR=1.85, 95% CI: 1.14-2.33, P=0.015) , differentiation degree ( OR=1.93, 95% CI: 1.18-2.67, P=0.024) , depth of myometrial invasion ( OR=2.08, 95% CI: 1.26-2.59, P=0.012) , tumor morphology ( OR=2.17, 95% CI: 1.57-2.63, P=0.009) , parametrial invasion ( OR=1.95, 95% CI: 1.43-2.76, P=0.036) and lymphovascular space invasion ( OR=2.03, 95% CI: 1.28-2.57, P=0.021) were the influencing factors for postoperative lymph node metastasis in patients with FIGO stage Ⅰ and Ⅱ cervical cancer. Multivariate analysis showed that the degree of differentiation ( OR=1.75, 95% CI: 1.08-2.03, P=0.015) , depth of myometrial invasion ( OR=2.30, 95% CI: 1.43-2.84, P=0.021) , parametrial invasion ( OR=2.50, 95% CI: 1.76-2.97, P=0.018) and lymphovascular space invasion ( OR=1.96, 95% CI: 1.03-2.51, P=0.033) were independent factors for postoperative lymph node metastasis in patients with FIGO stage Ⅰ and Ⅱ cervical cancer. Multivariate logistic regression analysis showed that the levels of CD3 +, CD4 +, CD8 + T cells and the ratio of CD4 +/CD8 + in patients with stage Ⅰ and stage Ⅱ cervical cancer 1 day before surgery were independent influencing factors for postoperative lymph node metastasis (all P<0.05) . ROC curve analysis showed that the areas under the curve of CD3 +, CD4 +, CD8 + T lymphocytes levels and the ratio of CD4 +/CD8 + in stage Ⅰ patients 1 day before surgery for predicting postoperative lymph node metastasis were 0.86, 0.82, 0.83, 0.89, respectively, and those in stage Ⅱ patients were 0.90, 0.93, 0.87, 0.95, respectively. CD4 +/CD8 + ratio was significantly more effective in predicting postoperative lymph node metastasis than other indexes (all P<0.001) . Conclusions:The levels of CD3 +, CD4 + T lymphocytes, and the CD4 +/CD8 + ratio in patients with FIGO stage Ⅰ and Ⅱ cervical cancer are significantly higher in 1-30 days after surgery than before, while the level of CD8 + T lymphocytes is significantly lower than before. There is a significant correlation between T lymphocytes subsets and lymph node metastasis after surgery. In addition, low differentiation, depth of myometrial invasion ≥1/2, parametrial invasion, and lymphovascular space invasion are independent risk factors for postoperative lymph node metastasis.

BackgroundWomen may develop severe symptoms of stress disorder following childbirth， which may be exposed to a risk of developing mental health problems， and even lead to the recurrence of the illness in female patients with schizophrenia， while comparatively limited research has been undertaken concerning the clinical characteristics and treatment of puerperal schizophrenia in China. ObjectiveTo explore the clinical characteristics of puerperal schizophrenia， so as to provide references for the clinical treatment. MethodsA total of 24 patients with puerperal schizophrenia who were hospitalized in the female ward of adult psychiatry department of the Affiliated Brain Hospital of Guangzhou Medical University from 2012 to 2020 and met the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） diagnostic criteria for schizophrenia were included as puerperal group. Another 48 non-puerperal women with schizophrenia were concurrently enrolled as control group. Then the basic data， scores on Positive and Negative Symptom Scale （PANSS） and the discharge medication were recorded. ResultsThe percentages of newly onset and positive family history of psychosis in puerperal group were larger than those in control group， with statistical significance （χ²=9.321， 5.240， P<0.05 or 0.01）. Puerperal group scored higher on PANSS excitement factor （t=-2.220， P<0.05） and lower on negative factor （t=3.377， P<0.01） compared with control group. In terms of discharge medication， puerperal group reported a higher dosage of antipsychotic drugs （t=-2.095， P<0.05）， and a larger proportion of combined use of benzodiazepines or antidepressants （χ²=21.316， 5.114， P<0.05 or 0.01） compared with control group， with statistical significance. ConclusionPatients with puerperal schizophrenia display increased ratings of excitement symptoms and decreased ratings of negative symptoms， which necessitates the use of high doses of antipsychotic drugs， and combined use of benzodiazepines and antidepressants.

OBJECTIVE To investigate the effects of Buyang huanwu decoction on red blood cells in hyperlipidemia model mice. METHODS Male C57BL/6 mice were fed a high-fat diet to prepare a hyperlipidemia model. Successfully modeled mice were randomly assigned to the model group， atorvastatin calcium group （0.26 g/kg）， fenofibrate group （1.3 mg/kg）， and high-， medium-， and low- dose groups of Buyang huanwu decoction （18.6， 9.3， 4.6 g/kg）， with 10 mice in each group. Additionally， 10 mice fed with regular chow served as the normal group. Each group of mice received intragastric administration with the corresponding drug or normal saline once daily for 21 consecutive days. After the last administration， the body weight of the mice in each group was measured， and blood glucose， total cholesterol （TC）， triglyceride （TAG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels were measured. Red blood cell morphology changes were observed， and the expression levels of glucose transporter type 1 （GLUT1）， erythrocyte membrane protein band 4.2 （protein 4.2）， caveolin-1， and flotillin-1 in erythrocyte membrane were determined. RESULTS Compared with the model group， the body weight and levels of TC， TAG， HDL-C， LDL-C， and the expression levels of GLUT1， caveolin-1 and flotillin-1 in the Buyang huanwu decoction groups were significantly decreased， while blood glucose levels and the expression levels of protein 4.2 were significantly increased （P＜0.05）. The red blood cell morphology in the low- and medium-dose groups of Buyang huanwu decoction was significantly promoted. CONCLUSIONS Buyang huanwu decoction can reduce blood lipid levels in hyperlipidemia model mice and strengthen the morphology and function of red blood cells in a hyperlipidemic environment， which has the potential to be used for preventing hyperlipidemia complications such as atherosclerosis.

Alzheimer′s disease (AD) is a neurodegenerative disorder. In the past few decades, the exact mechanisms underlying the onset of the disease have remained unclear, and treatment options are still lacking. Due to the inability of two-dimensional cell and animal models to fully simulate the pathogenesis of AD, there have been shortcomings in clinical trials of new drugs. The development of organoids and organ-on-a-chip technologies has improved the dilemma of AD research, providing reliable in vitro research models for studying pathogenic mechanisms and drug screening. This article elaborates on the applications and progress of organoids and organ-on-a-chip in AD modeling, pathogenesis, and drug development, and discusses the current limitations of organoids and organ-on-a-chip and their future perspectives.

Microcephaly is a common pediatric neurodevelopmental disorder with complex etiology. In recent years, with the development of brain organoid technology, there has been rapid progress in understanding the pathogenesis and treatment strategies of microcephaly using this technology. This article elucidates the advantages of brain organoids over traditional experimental models, reviews the research progress of brain organoid technology in disease modeling and drug screening for various causes of microcephaly, and discusses the limitations and future prospects of brain organoids.

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.