Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

B lymphocytes (B cells) play a complex and paradoxical role in tumorigenesis. They can recognize tumor-associated antigens, present these antigens to T cells, and produce antibodies that directly target and eliminate tumor cells. This makes B cells a potentially powerful ally in combating cancer. However, B cells also exhibit immunosuppressive functions, secreting cytokines like IL-10 or generating tumor-promoting antibodies that dampen the anti-tumor immune response, and some tumor cells have even been shown to exploit B cells to promote their growth and metastasis. This dual nature of B cells presents both opportunities and challenges for tumor immunotherapy. In this review, we summarize the mechanisms underlying the multifaceted functions of B cells and their current applications in cancer immunotherapy. Furthermore, we also explore the key issues and future directions in this field, emphasizing the need for further research to fully harness the anti-tumor potential of B cells in the fight against cancer.
Humans ; B-Lymphocytes/immunology* ; Neoplasms/therapy* ; Carcinogenesis/immunology* ; Immunotherapy/methods* ; Animals

Thirteen novel diterpenoids, comprising seven tiglianes (walliglianes G-M, 1-7), four rhamnofolanes (wallinofolanes A-D, 8-11), and two daphnanes (wallaphnanes A and B, 12 and 13), together with two known rhamnofolane diterpenoids (euphorwallside H and euphorwallside I, 14 and 15), were isolated and characterized from Euphorbia wallichii(E. wallichii). The chemical structures of these compounds were elucidated through nuclear magnetic resonance (NMR), mass spectrometry (MS), and quantum chemical calculations. Compounds 9 and 11 demonstrated protective effects against H₂O₂-induced BV-2 microglial cell damage. Molecular docking analyses indicated that compound 9 exhibited binding affinity to the anti-oxidant-related targets HMGCR, GSTP1, and SHBG.
Euphorbia/chemistry* ; Antioxidants/isolation & purification* ; Diterpenes/isolation & purification* ; Molecular Structure ; Mice ; Molecular Docking Simulation ; Animals ; Hydrogen Peroxide/toxicity* ; Cell Line ; Microglia/drug effects*

ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg^-1） group， and low- and high-dose （8.4 and 33.6 g·kg^-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.

WANG Qishi put forward the theory of "yang deficiency with three lackings， controlled by the spleen" in Lixu Yuanjian （《理虚元鉴》）， which regarded that yang deficiency can lead to consumptive diseases with changes of lacking essence， lacking qi， and lacking fire， so the treatment should start from the spleen to restore the middle yang urgently. This article summarised the experience of treating type 4 cardiorenal syndrome based on the theory of "yang deficiency with three lackings， controlled by the spleen"， and proposed that lacking essence is the beginning of the onset of type 4 cardiorenal syndrome， lacking qi is the gradual development of the disease， and lacking fire is the changes of the disease， and ultimately resulted in the complex situation of kidney and qi deficiency， and edema due to yang deficiency， combined with syndromes variation. In the clinical evidence， in the stage of lacking fire， therapies should warm the middle and strengthen the spleen in order to rescue the middle yang， prescribed with modified Baoyuan Decoction （保元汤） plus Lizhong Decoction （理中汤）； in the stage of lacking qi， prescriptions can add Taoren （Juglans regia）， Tubiechong （Eupolyphaga sinensis）， Fuling （Smilax glabra）， Guizhi （Neolitsea cassia） to activate blood and drain water to transport and restore the center qi； in the stage of lacking essence， prescriptions can add Gouqizi （Lycium barbarum）， Tusizi （Cuscuta chinensis）， Duzhong （Eucommia ulmoides）， Bajitian （Gynochthodes officinalis） to supplement deficiency and resolve masses to consolidate the root and supplement essence.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis （HF）. METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the pathological changes in liver tissue， mRNA and protein expressions of HF indexes [α-smooth muscle actin （α-SMA）， collagen type Ⅰ] and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway-related factors were detected， and the improvement effects and possible mechanism of low-dose， medium-dose and high-dose （50， 100， 200 mg/kg） of alcoholic extract from S. comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic extract from S. comosa at a concentration of 1 800 mg/（kg·d） （calculated by the amount of raw material）. The effects of drug- containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of HSC-T6 cells with low， medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa （diluted to 10%， 15%， 20%）. miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells， and the mRNA and protein expressions of factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low， medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of HF rats， and the percentage of collagen was significantly reduced （P＜0.01）； mRNA and protein expressions of the indicators related to HF as well as PI3K and Akt were significantly reduced （P＜0.01）， and mRNA and protein expressions of phosphatase and tensin homolog deleted on chromosome ten （PTEN） were increased in liver tissue of rats （P＜0.01）. The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S. comosa significantly inhibited the expression of miRNA-21 at low， medium and high concentrations （P＜0.01）； whereas after transfection with miRNA-21 mimics， it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt （P＜0.01）， while significantly decreased mRNA and protein expressions of PTEN （P＜0.01）； after transfection with miRNA-21 inhibitor， the changes of above indexes were opposite to the above results （P＜0.01）. CONCLUSIONS Alcoholic extracts of S. comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21， so as to achieve the effect of anti-hepatic fibrosis.

In the differentiation and treatment of recurrent urinary tract infection （rUTI） from the perspective of the seminal orifice， it is proposed that the urinary tract belongs to the category of "seminal orifice"， and the physiological process of urination is closely related to the function of the seminal orifice. From the three dimensions of orifice body， orifice pivot and orifice spirit， the physiological relationship between seminal orifice and the function of five zang-organs （脏） is constructed， that is， lung heat， yin damage and pathogen counter-restriction lead to malnutrition of orifice body； burning heart fire and spirit disorder lead to unfavorable orifice spirit， and kidney deficiency， liver constraint and spleen stagnation lead to unfavorable orifice pivot. In the early stage of rUTI， there is usually unfavo-rable orifice pivot， for which the treatment principle should be treating the root and the branch simultaneously， consi-dering both deficiency and excess， and paying attention to the management of accompanied symptoms. Zishui Qinggan Beverage （滋水清肝饮） and Modified Shenzhuo Decoction （肾着汤加减） are often selected based on syndrome differentiation. In the middle stage， lack of nourishment of the orifice body and unfavorable orifice spirit and pivot coexist， and the treatment should be draining the orifice and unblocking strangury， commonly withmodified Qingxin Lianzi Beverage （清心莲子饮）. In the late stage， loss of nourishment of the orifice body is the main pathogenesis， and it is necessary to further nourish the orifice body to prevent recurrence， and modifed Wuzi Yanzong Pills and Erxian Decoction （五子衍宗丸合二仙汤） is often used. Furthermore， the specific medicinals should be selected targeting at the orifice body， orifice pivot， and orifice spirit， so as to nourish orifice body by dispelling external pathogens and rectify healthy qi， to drain orifice pivot by freeing emotions and minds and unblocking qi movement， and to calm orifice spirit by unblocking heart and kidney and nourishing heart spirit.

Currently,electroencephalogram(EEG),functional near-infrared spectroscopy(fNIRS),and functional magnetic resonance imaging have been widely studied and applied to neuropsychiatric disorders.In recent years,the devices which can realize the simultaneous acquisition of EEG and fNIRS has been developed and gradually applied in the studies on neuropsychiatric disorders.The review provides an introduction of the techniques of synchronized detection and data analysis for EEG-fNIRS,summarizes the analysis methods and new findings of the recent studies of stroke,epilepsy,and other neuropsychiatric disorders using EEG-fNIRS,and also discusses the future research directions.

AIM:To investigate the effect of Huangqi-Danggui decoction(HQDG)on the brain tissue of rats with cerebral ischemia/reperfusion(I/R)injury for 7 d by regulating macroautophagy and chaperone-mediated autophagy(CMA),and to explore its mechanism.METHODS:Male SD rats were randomly divided into sham group,model group,HQDG group and Xuesaitong(XST)group.Determination of main chemical components of HQDG by liquid chro-matography-mass spectrometry.The model of middle cerebral artery occlusion/reperfusion in rats was established by the left modified thread embolism method,and the changes of cerebral blood flow were observed by laser speckle blood flow imager.Zea Longa score was used to observe the neurological deficit.HE staining was used to observe the degree of nerve cell injury.The changes of neurovascular unit and autophagosomes in brain tissue were observed by transmission electron microscopy.Immunohistochemical method was used to detect the expression of LC3,P62,lysosome-associated membrane protein-2A(LAMP-2A),heat shock protein 70(HSP70)and myocyte enhancer factor 2D(MEF2D)proteins.Western blot was used to detect the expression of autophagy-related proteins P62 and LC3-Ⅱ/LC3-I.RESULTS:Compared with the sham group,the neurological deficit score in model group was significantly higher(P<0.01).A large number of nerve cells showed necrosis and nuclear dissolution,with the cell arrangement being disordered.The number of autophagosomes increased.The protein expression levels of LC3,LAMP-2A,HSP70 and MEF2D in brain tissue increased,while the ex-pression level of P62 protein decreased(P<0.05 or P<0.01).Compared with the model group,the scores of neurological deficit in brain tissue in HQDG and XST groups were significantly lower(P<0.01).Cell damage was significantly re-duced.The number of autophagosomes further increased.The expression levels of LAMP-2A,HSP70,MEF2D and P62 proteins in brain tissue decreased,while the expression levels of LC3-Ⅱ/LC3-I protein increased(P<0.05 or P<0.01).CONCLUSION:HQDG can alleviate cerebral ischemia/reperfusion injury in rats and exert neuroprotective effects by ac-tivating macroautophagy and reducing CMA.