ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， the combination of serum pharmacochemistry， response profile of absorbed components in serum， network pharmacology and drug-likeness prediction was used to screen the potential active ingredients of Yanghetang against breast cancer. MethodsUPLC-Q-TOF-MS/MS was used to identify the main components in different solvent extracts of Yanghetang， and serum pharmacochemistry was applied to analyze the absorbed components from the serum of female SD rats after 0.5， 1， 2 h of administration. Combined with the response characteristic values of serum drug components obtained from UNIFI 1.8.2， the absorbed prototype components and metabolites were screened to get the absorbed components of Yanghetang with a significant patterns of elimination and growth. Network pharmacology was applied to construct a drug-component-pathway-target-disease network， and molecular docking was performed between absorbed components and key targets of breast cancer， and the drug similarity was analyzed by SwissADME. ResultsForty-two compounds were identified in Yanghetang samples extracted with different solvents， of which 16 compounds were common to the three different extraction solvents（methanol， 50% methanol and water）. The results of drug-containing serum analysis showed that there were 16 absorbed components in serum， including 5 prototypes and 11 metabolites. Network pharmacology results showed that Yanghetang against breast cancer involved 15 key targets such as proto-oncogene tyrosine-protein kinase Src（SRC）， epidermal growth factor receptor（EGFR） and phosphoinositide 3 kinase catalytic alpha polypeptide（PIK3CA）. Molecular docking results showed that 16 potential active ingredients were well combined with the predicted targets. Combined with drug likenesses， 12 compounds in the absorbed components of Yanghetang were considered to have potential for anti-breast cancer activity， mainly including α-pinene and γ-eudesmol and their metabolites， of which one was from Ephedrae Herba， one was from Rehmanniae Radix， and eight were from Cinnamomi Cortex. ConclusionThe chemical components of Yanghetang mainly include polysaccharides， monoterpene glycosides and coumarins， and its prototype components mainly undergo oxidation， hydrolysis and acetylation after entering the blood. Its anti-breast cancer mechanism may be related to the regulation of signaling pathways such as the mitogen-activated protein kinase（MAPK） and phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）. The results of this study can lay a foundation for further exploration of Yanghetang in the treatment of breast cancer.

ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）， and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group （n=3）， common psoriasis group （n=5）， spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）， and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）. The spleen deficiency and dampness obstruction syndrome （external dampness type） rat model was established through 32-week exposure to an artificially simulated high-humidity environment， while the common psoriasis model was developed via 7-day topical application of imiquimod cream， and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）. Rats in the normal group were housed under normal humidity conditions. The general state， tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations； the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes； the severity of psoriasis in rats was evaluated through skin pathological changes， psoriasis area and severity index （PASI）， proliferating cell nuclear antigen （PCNA） expression and spleen tissue changes； changes in rat CD4⁺ interferon-γ⁺ cells （CD4⁺IFN-γ⁺ cells）， CD4⁺ tumour necrosis factor-α+ cells （CD4⁺ TNF-α⁺ cells）， and forkhead framing protein P3⁺ regulatory T cells （CD3⁺CD4⁺FoxP3⁺ Treg cells） were detected by flow cytometry. ResultsMacroscopically， both the spleen deficiency and dampness obstruction syndrome （external dampness type） group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited manifestations of spleen deficiency and dampness obstruction， including lethargy， huddling behavior， dull and disheveled fur， as well as soft or loose stools and perianal soiling in some individuals； both these two groups displayed enlarged tongue， swollen， and moist tongue texture， accompanied by slippery tongue surface. Microscopically， compared to the common psoriasis group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group showed increased epididymal fat index （P＜0.05）； compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group demonstrated significantly elevated spleen mass （P＜0.05）， while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited significantly higher erythema scores， scaling scores， infiltration scores， PASI total scores， and proportions of CD3⁺CD4⁺FoxP3⁺Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）， with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis； the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group displayed significantly increased proportions of CD4⁺TNF-α⁺cells compared to the spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）； whereas no significant differences were detected in CD4⁺IFN-γ⁺cell proportions among groups （P＞0.05）. ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.

Objective To explore the feasibility, safety, and efficacy of transesophageal endoscopic surgery for mediastinal tumors. Methods A retrospective analysis was conducted on the clinical data of 17 patients who underwent transesophageal endoscopic resection for benign mediastinal tumors at the Endoscopy Center of Zhongshan Hospital, Fudan University, between January 1, 2016 and December 31, 2024. Epidemiological characteristics, surgical parameters, adverse events, and follow-up outcomes were analyzed. Results Among the 17 patients, there were 9 males and 8 females, with an average age of (42.4±14.5) years and an average tumor size of (2.6±1.6) cm. Pathological types included esophageal duplication cysts (6 cases, 35.3%), bronchogenic cysts (5 cases, 29.4%), gastroenteric cysts (3 cases, 17.6%), schwannomas (2 cases, 11.8%), and lymphangioma (1 case, 5.9%). Fourteen patients (82.4%) underwent submucosal tunneling endoscopic resection (STER), 3 patients (17.6%) underwent natural orifice transluminal endoscopic mediastinal surgery. All surgeries were successfully completed without conversion to open surgery. En bloc resection was achieved in 11 patients (64.7%), with an average operative time of (60.9±32.6) min. No intraoperative bleeding or mucosal injury occurred, and 4 patients (23.5%) experienced minor complications (pneumothorax, fever, recurrent laryngeal nerve injury), all of which resolved with conservative treatment. The average postoperative hospital stay was (3.2±1.5) days, and no recurrence was observed during the follow-up period. Conclusions Transesophageal endoscopic resection of benign mediastinal tumors is a safe, effective, and minimally invasive treatment method. Further validation of its efficacy and safety through large-scale prospective studies is warranted.

OBJECTIVE To evaluate the comprehensive value of novel oral anticoagulant drugs （NOACs） after major orthopedic surgery. METHODS The evaluation evidence was collected through literature research； evidence and value：impact on decision-making （EVIDEM） framework was introduced to integrate the evaluation process； the multi-criteria decision analysis （MCDA） method was used to construct a multi-dimensional evaluation system； the weights assigned to each evaluation criterion were determined by the combination of Delphi method and analytic hierarchy process， and the rivaroxaban， dabigatran and apixaban were comprehensively evaluated. RESULTS The clinical comprehensive evaluation system of NOACs after major orthopedic surgery was successfully established， and the final clinical comprehensive evaluation weights of NOACs （rivaroxaban， dabigatran， apixaban） after major orthopedic surgery were calculated， with scores of 0.399 7 for rivaroxaban， 0.244 4 for apixaban， and 0.355 9 for dabigatran， indicating that rivaroxaban demonstrated the highest overall clinical value. Among them， rivaroxaban had the highest weight score in the evaluation of pharmaceutical characteristics， cost-effectiveness and other attributes in a single dimension. In terms of efficacy and safety evaluation， apixaban had the highest weighting score. CONCLUSIONS Among NOACs， rivaroxaban is more suitable for routine anticoagulation management after major orthopedic surgery， especially in terms of pharmacological properties， cost-effectiveness and other attributes.

ObjectiveTo investigate the potential mechanisms of Zingiberis Rhizoma in treating inflammatory bowel disease （IBD） by integrating network pharmacology with in vitro and in vivo experiments. MethodsTraditional Chinese Medicine Systems Pharmacology Database And Analysis Platform （TCMSP）， Traditional Chinese Medicine Integrated Database （TCMID） Database were used to obtain the active component targets of Zingiberis Rhizoma. GeneCards was used to obtain the IBD targets. DAVID was used to perform Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses on core targets. Cytoscape 3.10.2 was used to establish the "active component-disease target-signaling pathway" interaction network. Mice were randomly assigned to control， model， and Zingiberis Rhizoma （400 mg·kg^-1） groups. An IBD model was induced via dextran sulfate sodium （DSS）. The colonic tissue was collected post-treatment to assess histology， expression of Ly6C⁺ monocytes/macrophages， and mRNA levels of Toll-like receptor 4 （TLR4）， and inflammatory cytokines. The effect of Zingiberis Rhizoma aqueous extract on RAW264.7 cell viability was evaluated. Furthermore， the effects of the extract at 100， 10， and 1 mg·L^-1 on LPS-induced differentiation of RAW264.7 cells into Ly6C^hi monocytes/macrophages， mRNA levels of TLR4 and inflammatory cytokines， and protein levels of factors in the TLR4/mitogen-activated protein kinase （MAPK） signaling pathway. ResultsA total of 241 targets were identified for Zingiberis Rhizoma and 6 787 for IBD， with 122 shared targets among Zingiberis Rhizoma， ulcerative colitis （UC）， and Crohn's disease （CD）. The enrichment analyses yielded 297 GO terms and 88 KEGG pathways. Associations were noted between Zingiberis Rhizoma's active component targets and IBD targets. In vivo experiments： Compared with the control group， the model group showed decreased body weight and disease activity index （DAI）（P<0.01）， shortened colon length， damaged mucosal epithelium with inflammatory cell infiltration， raised pathological scores （P<0.05）， increased Ly6C^hi and Ly6C^lo monocytes/macrophages （P<0.05）， and up-regulated mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.05） and protein levels of TLR4， phosphorylated extracellular signal-regulated protein kinase 1/2 （p-ERK1/2）， and phosphorylated p38 MAPK （p-p38 MAPK） （P<0.05）. Zingiberis Rhizoma intervention reversed these changes and reduced Ly6C^hi monocytes/macrophages （P<0.01）. In vitro experiments： compared with the control， LPS increased the proportion and number of Ly6C^hi monocytes/macrophages and mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.01） and enhanced the expression of TLR4， p-ERK1/2， and p-p38 MAPK （P<0.05）. Zingiberis Rhizoma reduced Ly6C^hi monocytes/macrophages （P<0.05）， down-regulated the mRNA levels of inflammatory cytokines （P<0.05）， and suppressed the TLR4/MAPK pathway （P<0.05）. ConclusionZingiberis Rhizoma alleviates IBD by suppressing the TLR4/ERK/p38 MAPK signaling pathway and reducing inflammatory cytokine levels in Ly6C^hi monocytes/macrophages.

OBJECTIVE To establish the precise management model for the centralized preparation of cytotoxic drugs in pharmacy intravenous admixture services （PIVAS）， and evaluate the effects of its application. METHODS Pharmacists in PIVAS established the precise management model by soliciting clinical opinions and consulting literature on the centralized preparation of cytotoxic drugs and continuously refining every step of the preparation of cytotoxic drugs， based on data feedback from the information closed-loop management system and the limit of stability time of finished solutions. The indicators such as the preparation time， delivery time， the storage time of finished infusion solutions after preparation， and the completion rate of infusion within the stability time limit were analyzed before the implementation （January to December 2023） and after the implementation （January to December 2024） of this model， to evaluate its application effectiveness. RESULTS The overall framework for the precise management model included upgrading the functions of the prescription review system， improving the prescription review database， providing specialized training for PIVAS pharmacists， managing dynamic batch decision for drug preparation， managing special drugs， managing finished infusion distribution， and establishing a continuous improvement mechanism. Compared with before implementation， the average preparation time of the second and third batches of cytotoxic drugs with more concentrated morning preparation tasks in this model was significantly shorter than before implementation （P＜0.05）； the delivery time of finished infusion after implementation （[ 11.49±2.92） min] was significantly shorter than the delivery time before implementation （[ 22.11±5.03） min] （P＜0.001）； the storage time of some drugs with shorter stable time limit and carboplatin in combination regimens （paclitaxel or docetaxel+carboplatin） was significantly shortened compared to before implementation （P＜0.05）， and the completion rate of infusion within the stability time limit was significantly improved compared to before implementation （P＜0.05）. CONCLUSIONS Our hospital has successfully established a precise management model for the centralized preparation of cytotoxic drugs in PIVAS. This mode can significantly shorten the preparation time of each batch of PIVAS in the morning， make batch decisions more reasonable and improve the infusion completion rate within the stable time limit of the finished product.

OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of primary Sjögren syndrome （pSS）. METHODS Randomized controlled trials （RCTs） on the effects of RTX （trial group） versus placebo （control group） in the treatment of pSS were searched from the Cochran Library， PubMed， Embase， Medline， Web of Science， VIP， CNKI， Wanfang， and other databases during the inception to February 2024. After literature screening and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS Seven RCTs were finally included， involving a total of 518 patients. Results of meta-analysis showed that European League Against Rheumatism Sjögren syndrome disease activity index （ESSDAI） score [MD＝－1.17， 95%CI（－1.52， －0.82）， P＜0.000 01] and oral dryness visual analogue scale （VAS） score [MD＝－3.97， 95%CI （－5.08， －2.86）， P＜0.000 01] in the trial group were significantly lower than the control group； unstimulated salivary flow rate [SMD＝0.64， 95%CI（0.41， 0.87）， P＜0.000 01] and Schirmer score [MD＝0.19， 95%CI（0.18， 0.20）， P＜0.000 01] were significantly higher than the control group. There was no statistical significance in response rate [RD＝0.10， 95%CI（－0.04， 0.23）， P＝0.16]， fatigue VAS score [MD＝－12.50， 95%CI（－35.14， 10.15）， P＝0.28]， European League Against Rheumatism Sjögren syndrome patient reported index （ESSPRI） score [MD＝0.33， 95%CI（－0.53， 1.18）， P＝0.46]， Short-form 36 health survey physical component summary （SF36-PCS） score [MD＝0.90， 95%CI（－2.97， 4.78）， P＝0.65]， SF-36 mental component summary （SF36-MCS） score [MD＝0.11， 95%CI（－0.41， 0.63）， P＝0.68]， total salivary gland ultrasound score [SMD＝－1.91， 95%CI（－4.01， 0.19）， P＝0.07] or the incidence of adverse drug reactions [OR＝1.15，95%CI（0.62，2.13），P＝0.66] between 2 groups. CONCLUSIONS RTX has advantages in the improvement of ESSDAI score， unstimulated salivary flow rate， Schirmer score and oral dryness VAS score in pSS patients， and has a good safety profile. However， it did not exhibit significant improvement in fatigue VAS score， ESSPRI score， SF36-PCS score， SF36-MCS score or response rates.

Objective: To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures. Methods: Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination. Conclusion The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.

BACKGROUND:Fixed-point rotation manipulation of cervical spine is a mechanical operation with high technical requirements,but the biomechanics of fixed-point manipulation of cervical spine still lacks relevant quantitative data.Moreover,the research on the influencing factors of cervical fixed-point rotation manipulation includes many parameters and there are differences,so it is necessary to further analyze its influencing factors to improve its related data. OBJECTIVE:To quantify the biomechanical parameters of cervical spine fixed-point rotation manipulation,explore the correlation between different biomechanical parameters,and the influence of individual characteristics of the subjects on the biomechanical parameters of cervical spine fixed-point rotation manipulation. METHODS:Totally 35 cases of cervical spondylosis were Outpatients from Orthopedic Department of Renai Branch of the First Affiliated Hospital of Guangxi University of Chinese Medicine and selected as the subjects investigated.Wearable mechanical measuring gloves were used to collect biomechanical parameters of cervical spine fixed-point rotation manipulation,including:thumb preload,thumb maximum thrust,palm preload,palm wrench force,and palm wrench maximum force.Personal characteristic parameters were collected,including age,height,weight,and neck circumference.The key biomechanical parameters in the process of cervical spine fixed-point rotation manipulation were analyzed and different individual characteristics were quantified.The results of biomechanical parameters were analyzed using Spearman correlation analysis.The possible effects of different individual characteristic parameters on biomechanics were analyzed. RESULTS AND CONCLUSION:(1)Compared with bilateral mechanical parameters,there was no significant difference between left manipulation and right manipulation(P>0.05).(2)The average of thumb preload force was(7.21±1.19)N;the average of thumb maximum thrust was(28.40±4.48)N;the average of palm preload was(5.67±2.49)N;the average of palm wrench force was(10.90±5.11)N,and the average of palm wrench maximum force was(16.00±7.27)N.(3)There was a significant positive correlation between palm preload and palm wrench force(Rs=0.812,P<0.01).There was a significant positive correlation between palm preload and palm wrench maximum force(Rs=0.773,P<0.01).There was a significant positive correlation between palm wrench force and palm wrench maximum force(Rs=0.939,P<0.01).(4)The weight was positively correlated with thumb preload,palm preload,palm wrench force and palm wrench maximum force(P<0.05).(5)These findings confirm that there is a certain biomechanical standard value in the operation of cervical spine fixed-point rotation manipulation to treat cervical spondylosis.There is no significant difference between the left and right manipulations,which indicates that the manipulation has good consistency and repeatability.There is consistency and coordination among palm preload force,palm wrench force,and palm wrench maximum force.Their contributions to the therapeutic effect are similar.Body weight is an important factor affecting cervical spine fixed-point rotation manipulation.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.