Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

ObjectiveTo analyze the epidemiological characteristics and influencing factors of clustered influenza-like illness (ILI) outbreaks in Yangpu District, Shanghai from 2012 to 2022, and to provide a scientific basis for formulating specific prevention and control measures of influenza in this district. MethodsData on clustered ILI outbreaks from 2012 to 2022 were collected, and the epidemiological pattern of the cluster outbreaks of influenza and its influencing factors of prevalence and duration were explored using statistical methods such as descriptive epidemiology, χ² test and logistic regression analysis. ResultsA total of 60 clustered ILI outbreaks were reported in Yangpu District, Shanghai from 2012 to 2022, with a cumulative number of 543 cases and an annual average incidence rate of 16.96%. The male-to-female ratio was1.06∶1. The largest number of ILI were reported in 2019, mainly from November to January of the next year, with December being the peak of outbreaks. The Streets of Changhai Rd. in Yangpu District had the largest number of reported outbreaks, accounting for 30.00% of the total outbreaks. Influenza cluster outbreaks occurred in schools, with the majority of outbreaks and cases reported in primary schools (accounting for 65.00% and 62.06% of the total, respectively). The outbreaks were mainly caused by influenza B virus, accounting for 50% of the total number of outbreaks. The prevalence rate of influenza cluster outbreaks varied among different schools in terms of their affiliated streets, school attributes and school types, with those in Kongjiang Rd. Subdistrict, private schools, and childcare institutions being relatively high. The duration of outbreaks reported for >2 days was longer than those reported for ≤2 days (OR=8.604, 95%CI: 1.509–49.067). ConclusionThe ILI outbreaks in Yangpu District present a seasonal pattern, with primary schools and Changhai Rd. Street as the targeted places for implementing prevention and control measures. Timely detection and reporting and active disposal can prevent a further spread of the outbreaks.

The field of post-marketing benefit-risk assessment for traditional Chinese medicine（TCM） is still in its nascent stage， lacking a universally accepted and cohesive evaluation framework and standards. This study presented a strategy developed for the benefit-risk assessment of post-marketing of TCM， and explored the critical techniques and specific implementation steps involved in the assessment process. Initially， appropriate qualitative assessment frameworks and quantitative analysis models were selected for the integrated qualitative and quantitative benefit-risk assessment. Subsequently， key technologies were outlined， including the establishment of a benefit-risk indicator system， the assignment of indicator weights， and the definition of criteria attributes. Furthermore， the implementation steps were elaborated， which involved defining decision-making issues， data collection， evaluation methodologies， variability factors， and sensitivity analysis. Finally， a case study of the benefit-risk assessment of a TCM injection for hepatitis B treatment was conducted to validate the feasibility of the proposed strategy. The objective of this research was to provide theoretical support and practical references for the development of a comprehensive post-marketing benefit-risk assessment system for TCM.

OBJECTIVE To establish a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things （IoT） and blockchain technology， and evaluate its implementation effects. METHODS A closed-loop management system for the whole-process traceability of outpatient drugs covering the entire drug lifecycle was designed using drug traceability codes integrated with IoT and blockchain technology. System effectiveness was evaluated from three dimensions： work efficiency， medication management quality and data safety by comparing indicators such as the acceptance time of incoming drugs and the number of collected drug traceability codes before the system implementation （October to December 2024） and after the system implementation （January to March 2025）. RESULTS A closed-loop management system for the whole-process traceability of outpatient drugs， centered around the drug traceability code management system， was successfully established. The acceptance time for incoming drugs was shortened from （4.65±0.26） h before implementation to （0.34±0.08） h after implementation （P＜ 0.05）. The number of collected drug traceability codes increased from 419 018 to 1 236 522， and the coverage rate of traceability codes rose from 28.36% to 89.88% （P＜0.05）. The time pharmacists spent on drug expiry management per week decreased from （128.40±19.20） min to （0.56±0.13） min （P＜0.05）， and the dispensing time for a single prescription （excluding a part of injections and repackaged drugs） was reduced from （143.25±17.67） s to （15.24±10.08） s （P＜0.05）. The time for drug return was reduced from 129.90 （122.32， 137.00） s to 104.36 （89.91， 117.33） s（P＜0.05）； the number of drug dispensing errors decreased from 2 cases to 0 cases. After the system was launched， there were no data security incidents in our outpatient pharmacy. CONCLUSIONS The constructed closed-loop management system for the whole-process traceability of outpatient drugs can significantly enhance drug traceability accuracy and drug management quality， improve pharmacist work efficiency， and reduce drug management risks， thus providing a feasible solution for the digital transformation of hospital pharmaceutical services.

ObjectiveBased on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine（TCM） compounds， a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection（SHLI）， in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI. MethodAfter one week of adaptive feeding， 72 SPF-grade SD male rats were randomly divided into blank group， SHLI standard group， Lonicerae Japonicae Flos（LJF） group， Scutellariae Radix（SR） group， Forsythiae Fructus（FF） group， and 7 groups of SHLI matching groups（groups 1-7）， with 6 rats in each group. Rats in each group were administered the drug intravenously and blood samples were taken after steady state， high performance liquid chromatography（HPLC） characterization profiles of the testing drugs and plasma components in each group were established， and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified. Enzyme-linked immunosorbent assay（ELISA） was used to determine the changes of immunoglobulin E（IgE）， histamine（HIS）， tryptase（TPS）， total complement（CH50） and terminal complement complex（C5b-9） in animal blood samples. MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets， and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values. ResultELISA results showed that， compared with the blank group， groups 1-3 could significantly increase the IgE level， groups 1-2， groups 4-6 and SHLI standard group could significantly increase the HIS level， group 4 could significantly increase the CH50 level， groups 1， 3-4， LJF group and FF group could significantly increase the TPS level， SR group could significantly increase the C5b-9 level， and the differences were all statistically significant（P<0.05）. According to the retention time of chromatographic peaks， it was classified into 6 component groups from C1 to C6 by HPLC. The order of the network balance constants of each component group was C6>C4>C1>C5>C3>C2， indicating that C6 had the greatest effect on the allergic reaction， and was most likely to be the allergen. The sequence of eigenvalues was C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS， indicating that component group C2 had the greatest contribution to the whole network. ConclusionBased on the correlation analysis of SHLI component group and allergy-like target network， this study clarified that component group C6 may be a potential allergen in SHLI， and the component group C2 may be a key node in the mechanism of drug action， which can provide new strategies and methods for the screening of allergens in TCM injections.

Objective:To investigate the predictive value of preoperative D-dimer level for futile recanalization (FR) after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS).Methods:It was a nested case-control study. A total of 116 patients with large vessel occlusion (LVO) stroke, who underwent successful recanalization (modified Thrombolysis in Cerebral Infarction, mTICI≥2b) after MT at the Stroke Unit of Beijing Hospital from August 2018 to January 2022,were consecutively enrolled, including 72 males (62.1%) with the age of (72.8±13.1) years. According to the 3-month modified Rankin Scale (mRS) score after MT, patients were divided into the meaningful recanalization group (mRS 0-2, n=41) and the futile recanalization group (mRS 3-6, n=75). The baseline clinical data of enrolled patients was collected. Logistic regression analysis was used to identify the independent risk factors for FR after MT in patients with AIS. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of D-dimer for FR. Results:Multivariate logistic regression analysis showed that high baseline systolic blood pressure (SBP) ( OR=1.038, 95% CI: 1.012-1.065, P=0.004), baseline National Institutes of Health Stroke Scale (NIHSS) score≥12 ( OR=10.157, 95% CI: 3.624-28.470, P<0.001) and high preoperative D-dimer level ( OR=4.536, 95% CI: 1.379-14.922, P=0.013) were independent predictors of FR after MT in AIS patients with LVO. ROC curve analysis indicated a good predictive value of preoperative D-dimer for the occurrence of FR ( AUC=0.733, 95% CI: 0.638-0.829, P<0.05), the optimal cut-off value of D-dimer was 2.65 μg/L(Lg), with the Youden index, sensitivity, specificity and accuracy of 0.435, 53.3%, 90.2% and 66.4%, respectively. Conclusion:High preoperative D-dimer level is an independent predictor of futile recanalization after MT in AIS patients with LVO, which shows good predictive ability for futile recanalization.

Objective:To investigate the effect of early pulmonary rehabilitation (PR) training on the improvement of respiratory function in patients with acute respiratory distress syndrome (ARDS) after weaning of invasive mechanical ventilation in the intensive care unit (ICU).Methods:The retrospective cohort research method was used. The clinical information of adult patients with ARDS receiving invasive mechanical ventilation admitted to the ICU of Qingdao Municipal Hospital from January 2019 to March 2023 was collected. The patients were divided into a control group and an observation group according to off-line training program. The control group received traditional training after weaning, and the observation group received the early PR training after weaning. Other treatments and nursing were implemented according to the routine of the ICU. The scores of the short physical performance battery (SPPB) on day 3-day 6 of the weaning training, respiratory muscle strength, level of interleukin-6 (IL-6), number of aspirations of sputum after weaning, length of stay after weaning, rehospitalization rate within 6 months after discharge, and pulmonary function indicators at discharge and 3 months after discharge [peak expiratory flow (PEF), forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC), and vital capacity (VC)] of the two groups of patients were compared. The Kaplan-Meier survival curve was drawn to analyze the cumulative survival rate of patients 6 months after discharge.Results:A total of 50 of which 25 cases received the traditional training after weaning, 25 cases received the early PR training after weaning. There was no significant difference in gender, age, acute physiology and chronic health evaluationⅡ (APACHEⅡ), oxygenation index upon admission, etiological diagnosis of ARDS upon admission, time of invasive ventilation, mode of invasive mechanical ventilation, pulmonary function indicators at discharge, and other baseline data of the two groups. The SPPB questionnaire scores and respiratory muscle strength in both groups were increased gradually with the extended offline training time, the serum level of IL-6 in both groups were descend gradually with the extended offline training time, especially in the observation group [SPPB questionnaire score in the observation group were 7.81±0.33, 8.72±0.53, 9.44±0.31, 10.57±0.50, while in the control group were 7.74±0.68, 8.73±0.37, 8.72±0.40, 9.33±0.26, effect of time: F = 192.532, P = 0.000, effect of intervention: F = 88.561, P = 0.000, interaction effect between intervention and time: F = 24.724, P = 0.000; respiratory muscle strength (mmHg, 1 mmHg≈0.133 kPa) in the observation group were 123.20±24.84, 137.00±26.47, 149.00±24.70, 155.40±29.37, while in the control group were 129.00±20.34, 126.00±24.01, 132.20±25.15, 138.60±36.67, effect of time: F = 5.926, P = 0.001, effect of intervention: F = 5.248, P = 0.031, interaction effect between intervention and time: F = 3.033, P = 0.043; serum level of IL-6 in the observation group were 80.05±6.81, 74.76±9.33, 63.66±10.19, 56.95±4.72, while in the control group were 80.18±7.21, 77.23±9.78, 71.79±10.40, 66.51±6.49, effect of time: F = 53.485, P = 0.000, effect of intervention: F = 22.942, P = 0.000, interaction effect between intervention and time: F = 3.266, P = 0.026]. Compared with the control group, the number of aspirations of sputum after weaning of patients in the observation group significantly decreased (number: 22.46±1.76 vs. 27.31±0.90), the length of ICU stay after weaning significantly became shorter (days: 6.93±0.95 vs. 8.52±2.21), and the rehospitalization rate within 6 months after discharge significantly decreased [20.00% (5/25) vs. 48.00% (12/25)]. There were significant differences. The pulmonary function indicators 3 months after discharge of two groups of patients significantly increased compared with those at discharge and those of the observation group were significantly higher than those of the control group [PEF (L/min): 430.20±95.18 vs. 370.00±108.44, FEV1/FVC ratio: 0.88±0.04 vs. 0.82±0.05, VC (L): 3.22±0.72 vs. 2.74±0.37, all P < 0.05]. The Kaplan-Meier survival curve showed that the cumulative survival rate of patients 6 months after discharge of patients in the observation group was significantly higher than that of patients in the control group [76.9% vs. 45.5%, hazard ratio ( HR) = 0.344, P = 0.017]. Conclusion:Early PR training can significantly improve the respiratory function of patients with ARDS after weaning of invasive mechanical ventilation. Continuous active respiratory training after discharge can improve the respiratory function of patients and effectively decrease mortality.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

ObjectiveTo establish a theoretical system of pharmacokinetic and spectrokinetic dose-time characterization of traditional Chinese medicine（TCM）. By analyzing the pharmacokinetic and spectrokinetic behaviors of Lonicerae Flos， Houttuyniae Herba injection， Lonicerae Japonicae Flosand Buyang Huanwutang， this paper compared the similarities and differences of the three methods for characterizing the dose-time relationship， namely half-life， statistical moment and statistics， in order to find the most suitable method for characterizing the relationship. MethodTen mice were randomly selected from 100 Kunming mice as the blank group， and the remaining mice were coated with xylene in the auricle to establish the acute inflammation model of ear swelling. After successful modeling， the mice were gavaged with aqueous extract of Lonicerae Flos（30 g∙kg^-1）， and the blank group was gavaged with an equal volume of normal saline. The plasma of mice was collected at different time points to determine the content changes of components. At the same time， the pharmacokinetic results of Houttuyniae Herba injection， Lonicerae Japonicae Flos and Buyang Huanwutang were included， and the pharmacokinetic and spectrokinetic parameters were calculated. Then the difference in the time of calculating 95% total component content of metabolism by half-life method， statistical moment method and statistical method was compared. ResultOn the basis of the half-life method， the mathematical expressions of statistical moment method and statistical method suitable for the characterization of dose-time relationship of multi-component system of TCM were established. The results showed that the pharmacokinetic parameters of the individual components in Lonicerae Flos varied， with cryptochlorogenic acid and rutin showing a two-compartment model and the other components showing a one-compartment model. After calculation of spectrokinetic similarity， the metabolic patterns among the components contained in Houttuyniae Herba injection， Lonicerae Japonicae Flos， Lonicerae Flos and Buyang Huanwutang were different and varied greatly in vivo. The time to metabolize 95% of the total components of the four research subjects in vivo was calculated by the half-life method， statistical moment method and statistical method， and it was found that the difference between statistical moment method and half-life method was large， and the difference between statistical moment method and statistical method was small. ConclusionStatistical method not only reflects the characteristics of statistical moment method， characterizes the dispersion degree of each component， but also can be associated with fingerprint to form spectrokinetics， characterizing the dose-time relationship of 95% of drug components， which is a more desirable method to characterize the dose-time relationship of the component groups in TCM.

The incidence and mortality rate of heart failure (HF) are increasing annually, resulting in a huge medical and economic burden worldwide. B-type natriuretic peptide (BNP) is the gold standard biomarker of HF recommended by national and international guidelines for the diagnosis and prognosis evaluation of HF. Recent studies suggest that BNP can be truncated in multiple forms by different enzymes rather than complete fragments in circulation, which can be contributing to the diagnosis and classification of HF. The immunoassay mostly used in clinics are unable to distinguish different truncated BNP forms due to cross-reactivity of antibody, while mass spectrometry is more accurate because it can easily distinguish through their mass-to-charge ratios. With the maturation of ambient ionization mass spectrometry and ion mobility mass spectrometry, it can help to simplify sample pre-treatment and improve the separation efficiency, in order to explore the clinical value of the heterogeneity of BNP truncated forms.