OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

Objective:To explore the predictive value of serum interleukin-6(IL-6)combined with Montreal Cognitive Assessment(MoCA)score and CHANGE risk score for post-stroke cognitive impairment(PSCI),and to provide a basis for early identification and intervention of high-risk patients.Methods:The general data of 200 patients with acute stroke who were admitted to our hospital from October 2022 to September 2024 were retrospectively analyzed,they were divided into PSCI group(49 cases)and non PSCI group(151 cases)based on whether PSCI occurred 3 months after acute stroke.The general data of two groups were compared,multiple logistic regression was used to analyze the influencing factors of PSCI,and receiver operating characteristic(ROC)curves were used to evaluate predictive efficiency of serum IL-6,MoCA score and CHANGE risk score for of PSCI.Results:There was a statistically significant difference in age and education level between the two groups(P＜0.05).The serum IL-6 level and CHANGE risk score in the PSCI group were higher than those in the non PSCI group,while the MoCA score was lower than that in the non PSCI group(P＜0.05).Multivariate logistic regression showed that elevated IL-6 levels(OR=1.851,P=0.001)and elevated CHANGE risk scores(OR=1.076,P=0.016)were independent risk factors of the occurrence of PSCI,while elevated in MoCA score(OR=0.806,P=0.001)was a protective factor(P＜0.05).IL-6 levels,MoCA scores and CHANGE risk scores have high predictive efficiency for the occurrence of PSCI,the area under the curve(AUC)for predicting occurrence of PSCI by the three alone were 0.783,0.825 and 0.857 respectively,the AUC for the combined detection of the three indicators was 0.912,significantly higher than that of each indicator detected separately.Conclusion:Elevated serum IL-6,decreased MoCA score and increased CHANGE risk score are risk factors for PSCI,the combined detection model of the three has the highest predictive efficiency for occurrence of PSCI and can provide scientific basis for early clinical intervention.

Objective:To explore the predictive value of serum interleukin-6(IL-6)combined with Montreal Cognitive Assessment(MoCA)score and CHANGE risk score for post-stroke cognitive impairment(PSCI),and to provide a basis for early identification and intervention of high-risk patients.Methods:The general data of 200 patients with acute stroke who were admitted to our hospital from October 2022 to September 2024 were retrospectively analyzed,they were divided into PSCI group(49 cases)and non PSCI group(151 cases)based on whether PSCI occurred 3 months after acute stroke.The general data of two groups were compared,multiple logistic regression was used to analyze the influencing factors of PSCI,and receiver operating characteristic(ROC)curves were used to evaluate predictive efficiency of serum IL-6,MoCA score and CHANGE risk score for of PSCI.Results:There was a statistically significant difference in age and education level between the two groups(P＜0.05).The serum IL-6 level and CHANGE risk score in the PSCI group were higher than those in the non PSCI group,while the MoCA score was lower than that in the non PSCI group(P＜0.05).Multivariate logistic regression showed that elevated IL-6 levels(OR=1.851,P=0.001)and elevated CHANGE risk scores(OR=1.076,P=0.016)were independent risk factors of the occurrence of PSCI,while elevated in MoCA score(OR=0.806,P=0.001)was a protective factor(P＜0.05).IL-6 levels,MoCA scores and CHANGE risk scores have high predictive efficiency for the occurrence of PSCI,the area under the curve(AUC)for predicting occurrence of PSCI by the three alone were 0.783,0.825 and 0.857 respectively,the AUC for the combined detection of the three indicators was 0.912,significantly higher than that of each indicator detected separately.Conclusion:Elevated serum IL-6,decreased MoCA score and increased CHANGE risk score are risk factors for PSCI,the combined detection model of the three has the highest predictive efficiency for occurrence of PSCI and can provide scientific basis for early clinical intervention.

The p53 protein is an essential tumor suppressor in the human body that plays a critical role in preventing tumor formation by controlling cell cycle arrest and promoting apoptosis. Mutations in the p53 gene are frequently observed in more than 50% of tumor tissues and lead to the generation of mutant p53 proteins, which not only have a dominant-negative effect (DN) that hinders the function of wild-type p53 protein but also have gain-of-function (GOF) effects that stimulate tumor development by regulating cell metabolism, invasion, migration, and other processes. Therefore, mutant p53 protein has become a specific drug target for cancer therapy. However, the lack of a drug-binding pocket and smooth surface of mutant p53 proteins have made them undruggable targets for a long time. In recent years, with the development of high-throughput screening technology and an enhanced understanding of the structure and conformational changes exhibited by mutant p53 proteins, a multitude of small molecule compounds directed against mutant p53 protein have been identified, exhibiting substantial in vitro anti-tumor efficacy. Moreover, some of these compounds have entered clinical trials. This review summarized the direct and indirect strategies for the treatment of cancers targeting mutant p53, with a primary focus on the mechanisms of action of small molecule compounds that reactivate mutant p53 protein or degrade mutant p53 protein. The aim is to provide assistance for the development of innovative drugs targeting mutant p53 protein in the future.

Aim To explore the effect of serum contai-ning Duhuo Jisheng Decoction on the proliferation,ap-optosis and inflammation of fibroblast-like synoviocytes(FLS)induced by tumor necrosis factor-α(TNF-α)in rheumatoid arthritis(RA)and to reveal the under-lying mechanism.Methods The MH7A cells were divided into five groups:normal group(10％blank se-rum),model group(10 μg·L-1 TNF-α+10％blank serum),Duhuo Jisheng Decoction low(10 μg·L-1 TNF-α+2.5％drug-containing serum+7.5％blank serum),medium(10 pg·L-1 TNF-α+5％drug-con-taining serum+5％blank serum),high(10 μg·L-1 TNF-α+10％drug-containing serum)dose group.The concentration of serum containing Duhuo Jisheng Decoction was screened by MTT method.Cell prolifer-ation was detected using EdU staining.The expression of proliferation marker Ki67 was detected using immu-nofluorescence staining.The apoptosis rate was meas-ured by flow cytometry.The contents of IFN-γ,IL-4,IL-6 and IL-10 in each group were detected by ELISA.The mRNA and protein expression of Bax,Bcl-2,caspase-3 and TLR4/MyD88/NF-κB signaling pathway were detected by RT-qPCR and Western blot.Results Compared with the normal group,the cell prolifera-tion activity of the model group significantly increased,and the level of apoptosis decreased.The content of IFN-γ and IL-6 increased,and the content of IL-4 and IL-10 decreased.The TLR4/MyD88/NF-κB signaling pathway was activated.After the intervention of low,medium and high dose groups of serum containing Du-huo Jisheng Decoction,it could effectively improve the abnormal proliferation of cells and enhance apoptosis.At the same time,it inhibited the inflammatory re-sponse and the activation of TLR4/MyD88/NF-κB sig-naling pathway.Conclusions The serum containing Duhuo Jisheng Decoction can inhibit the abnormal pro-liferation of RA-FLS induced by TNF-α and the secre-tion of pro-inflammatory factors,and enhance apoptosis and anti-inflammatory levels.The mechanism may be related to the regulation of TLR4/MyD88/NF-κB sig-naling pathway.

Objective To analyze the changes of B lymphocyte(B cells)subsets in peripheral blood of patients with chronic hepatitis B(CHB)and to explore its clinical significance.Methods Peripheral blood samples were collected from 37 treatment-na?ve CHB patients who were admitted to the Fifth Medical Center of PLA General Hospital from July 2022 to October 2022,and peripheral blood samples collected from 18 healthy individuals who have received the hepatitis B vaccine as healthy controls(HC).The study subjects'clinical indexes such as age,HBV DNA viral load,HBsAg quantification,HBeAg semi quantification,ALT,AST,and AST/ALT ratio were collected.The change characteristics of the frequency,phenotypic and functional markers of peripheral blood B lymphocytes and their subsets were compared between CHB and HC.Using multi-color flow cytometry,and the correlation between them and clinical indexes was analyzed.Results Frequency analysis of each subset of B cells showed that compared with HC,the frequency of total B cells,transitional B cells and naive B cells was decreased(P<0.05),while the frequency of mature B cells,memory B cells,atypical memory B cells and activated memory B cells was increased in CHB patients(P<0.01).And there was no significant difference in the frequency of resting memory B cells between the two groups(P>0.05).The results of functional analysis showed that compared with HC,the expression levels of CD79b on total B cells,mature B cells,memory B cells,naive B cells,activated memory B cells,atypical memory B cells and resting memory B cells in CHB patients were increased(P<0.05).The expression level of programmed cell death protein-1(PD-1)on atypical memory B cells in CHB patients was also higher than that in HC group(P<0.05).The results of correlation analysis showed that the frequency of total B cells in CHB patients was slightly negatively correlated with age(r=-0.39,P<0.05),while the expression of programmed death-1(PD-1)on total B cells,mature B cells,transitional B cells,memory B cells and naive B cells were slightly positively correlated with age(r>0.36,P<0.05).Conclusions Chronic HBV infection leads to depletion of the frequency and function of a portion of B cells in the peripheral blood of CHB patients,and age is a potential risk factor for the decline in humoral immune function in CHB patients.

The quality markers(Q-markers) of Shujin Huoxue Capsules were comprehensively discriminated based on the five principles of transfer and traceability, specificity, compatibility, effectiveness and measurability. The compounds that could be transferred from the original medicinal materials to the preparation were selected with the principle of transfer and traceability. The specific components in the prescription were screened by reviewing literature with the principle of specificity. According to the principle of compatibility, the attributes of compounds were evaluated by the sovereign, minister, assistant and guide combination rules of the original medicinal materials in the prescription. According to the principle of measurability, the measurable components were summarized by reference to the pharmacopoeia and literature combined with the content. The mechanism of Shujin Huoxue Capsules in the treatment of osteoporosis was studied through network pharmacology based on the principle of effectiveness, which was the evaluation index of effectiveness. The chemical components screened out above were regarded as candidate Q-markers, and the cobweb model was plotted to obtain the comprehensive score of Q-markers. Hydroxysafflor yellow A, trachelosid, eleutheroside B, α-cyperone, protocatechuic acid, protocatechualdehyde and 4-methoxy salicylaldehyde were discriminated as the Q-markers of Shujin Huoxue Capsules based on the five principles combined with cobweb model.
Biomarkers ; Capsules ; Drugs, Chinese Herbal/pharmacology*

Asians ; China ; Humans ; Hypertension/drug therapy* ; Practice Guidelines as Topic ; Writing

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca²⁺ current. Using noise analysis of Ca²⁺ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca²⁺ channels along with Ca_V1.3 expression. All these changes could act synergistically to enhance the Ca²⁺ influx into IHCs. Inhibition of intracellular Ca²⁺ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.
Animals ; Calcium ; Exocytosis ; Hair Cells, Auditory, Inner ; Mice ; Sodium Salicylate/pharmacology* ; Tinnitus/chemically induced*