ObjectiveTo investigate the key targets of Jianpi Yiqi prescription （JYP） in the treatment of hepatocellular carcinoma （HCC） based on network pharmacology and explore the effect of JYP on the invasion and proliferation of hepatocellular carcinoma cells via protein tyrosine phosphatase， non-receptor type 1 （PTPN1） by bioinformatics analysis and CRISPR/Cas9. MethodsThe potential targets of JYP in the treatment of HCC were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， SwissTargetPrediction， GeneCards， NCBI， and CTD. Additionally， the active components of JYP that could interact with PTPN1 were screened out， and then molecular docking between the targets and active components was performed in Autodock 4.0. UALCAN， HPA， and LinkedOmics were used to analyze the expression of PTPN1 in the HCC tissue， and the relationship of PTPN1 expression with the overall survival （OS） of HCC patients was discussed. CRISPR/Cas9 was used to knock down the expression of PTPN1 in HepG2 and SK-hep-1 cells， and the knockdown effect was examined by sequencing， Real-time PCR， and Western blot. HepG2 cells were classified into blank control， low-， medium-， and high-dose JYP （5.25， 10.5， 21 g·kg^-1）， and PTPN1 knockout groups. Real-time PCR and Western blot were employed to determine the mRNA and protein levels， respectively， of PTPN1 in HepG2 cells of each group. The effects of JYP and PTPN1 knockdown on the proliferation， invasion， and apoptosis of HepG2 cells were detected by Cell Counting Kit-8 （CCK-8）， Transwell， and Annexin V-FITC/PI methods， respectively. ResultsJYP had the most active components targeting PTPN1， and 31 of the active components had the binding energy less than -5.0 kcal·mol^-1 in molecular docking. The mRNA and protein levels of PTPN1 in the HCC tissue were higher than those in the normal tissue （P<0.01）. Compared with that in the normal tissue， the mRNA level of PTPN1 in the HCC tissue was up-regulated at the pathological stages Ⅰ-Ⅲ and grades G₁-G₃ （P<0.01）， and it was not significantly up-regulated at the stage Ⅳ or grade G₄. The mRNA level of PTPN1 in the TP53-mutated HCC tissue was higher than that in the TP53-unmutated HCC tissue （P<0.01）. The high mRNA level of PTPN1 was associated with the OS reduction （P<0.01）. After treatment with the JYP-containing serum or knockdown of PTPN1， HepG2 cells demonstrated decreased proliferation and invasion and increased apoptosis （P<0.01）. ConclusionPTPN1 may be one of the core targets of JYP in the treatment of HCC. It is highly expressed in the HCC tissue and cells， which is associated with the poor prognosis of patients. The expression level of PTPN1 is significantly up-regulated in the HCC tissue of the patients with TP53 mutation. However， TP53 mutation or deletion does not affect the expression of PTPN1 in HCC cells. JYP can significantly down-regulate the expression of PTPN1 to inhibit the proliferation and invasion and promote the apoptosis of HCC cells.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective To analyse the clinical efficiency of endolymphatic sac surgery (ESS) in the management of Meniere’s disease (MD). Methods A retrospective analysis was conducted on 274 patients with MD who were hospitalized for treatment in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University from January 2009 to August 2023. All patients received lifestyle management and drug treatment such as diuretics. For those whose conditions were not well controlled 3 to 6 months after the initial treatment, intratympanic glucocorticoid (ITG) or ESS treatment was carried out. Six months after the treatment, the classes of vertigo relief and hearing changes in the patients were evaluated. After adjusting the confounding factors through propensity score matching (PSM), the impact of ESS on the prognosis of MD patients was evaluated. Results Among 274 patients, 194 and 80 patients underwent ITG and ESS, respectively. Eighty patients were enrolled into each group after PSM. Before and after PSM, the rate of patients reaching vertigo relief class A in ESS group was higher than that in the ITG group (P＝0.004); there was no significant difference in hearing preservation between the two groups. Kaplan-Meier curve analysis showed that vertigo relief in the ESS group was better than that in the ITG group (P=0.029); there was no statistically significant difference in hearing preservation between the two groups. Conclusion When the initial treatment for patients with MD is ineffective, choosing ESS is more beneficial than ITG for controlling vertigo.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

OBJECTIVES: To explore the role of C1q, the promoter of the classical pathway of the complement system, in regulating postpartum depressive-like behaviors in mice and the therapeutic mechanism of C1q-neutralizing antibodies. METHODS: Female C57BL/6 mouse models of postpartum depression established by hormone-simulated pregnancy (HSP) were evaluated for depression-like behaviors, and peripheral blood levels and hippocampal expressions of C1q were detected using ELISA and Western blotting. Immunofluorescence staining was used for detecting co-labeling of C1q and microglia, and the differentially expressed mRNAs in the hippocampus of HSP mice were analyzed using RNA sequencing. The Edinburgh Postnatal Depression Scale was used to screen patients with postpartum depression, from whom peripheral blood mononuclear cells were extracted for detecting C1q expression levels with Western blotting. The HSP mice were subjected to stereotactic injection of C1q-neutralizing antibody or a control IgG in the hippocampus, and the changes in depressive-like behaviors and hippocampal expression of C3 were examined. RESULTS: The HSP mice exhibited obvious depressive behaviors, demonstrated by significantly decreased preference for sugar water and increased forced swimming and tail suspension time. The mouse models showed significantly increased peripheral blood C1q level and hippocampal expression level of C1q, accompanied by an increase in Iba1 and C1q co-labeling in the hippocampus. The expression level of C1q in peripheral monocytes was also significantly increased in patients with postpartum depression. In HSP mice, stereotactic injection of C1q-neutralizing antibody, but not the control IgG, obviously alleviated depressive-like behaviors, shown by significantly increased preference for sugar water and decreased forced swimming and tail suspension time, resulting also in decreased expression of C3 in the hippocampus and lowered serum levels of IL-6 and TNF-α. CONCLUSIONS C1q-neutralizing antibodies improve postpartum depressive-like behaviors in mice possibly by regulating the C1q/C3 signaling pathway.
Animals ; Female ; Depression, Postpartum ; Complement C1q/metabolism* ; Antibodies, Neutralizing/pharmacology* ; Mice, Inbred C57BL ; Mice ; Hippocampus/metabolism* ; Pregnancy ; Disease Models, Animal

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*