OBJECTIVE To provide reference for the establishment and improvement of the regulatory system of patients’ medicine instructions in China. METHODS Through searching the official website of the European Medicines Agency （EMA） and related literature， the definition， basic nature， and content of patients’ medicine instructions in the European Union were introduced， and the characteristics of the management system of patients’ medicine instructions in the European Union were analyzed in terms of the management department， approval and change procedures， readability requirements and information accessibility requirements. At the same time， the pilot situation of patients’ medicine instructions in China， as well as problems in the paths of classification and management， readability of content， and information timeliness were analyzed to put forward suggestions. RESULTS & CONCLUSIONS European Union had a dedicated department for the management of medicine instructions； the approval and change procedures for patients’ medicine instructions were clear， the readability requirements were detailed， the readability verification program with patient participation was established， and multi-channel and timely information disclosure was adopted. It is recommended that China establish a mechanism to categorize and manage professionals’ and patients’ medicine instructions， guide multiple parties to participate in the design of patients’ medicine instructions and refine the readability requirements， and improve the mechanism for disclosure of medicine instructions to enhance the timeliness of medication information.

Dysregulation of immune response is currently recognized as one of the important pathological factors in ulcerative colitis (UC). Based on the confirmation that the Sini San (SNS) can significantly improve the colon inflammation induced by dextran sulfate sodium sulfate (DSS) in mice, the present work systematically studied the xenobiotics in the colon and mesenteric lymph nodes, spleen, and thymus of UC mice after administration of SNS by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry (HPLC-IT-TOF-MS). The results showed that, in addition to the colon, some components and their metabolites in SNS could be distributed in immune tissues, and it was found that the quality of relatively low-abundance and weakly responsive components such as saikosaponin a, paeoniflorin, and glycyrrhizic acid had the characteristics of efficient transmission to the colon and lymphoid organs. These components were very likely to be the source of pharmacodynamic substances of SNS. The findings of this study lay a foundation for the study of the efficacy and molecular mechanism of the components against ulcerative colitis, and also provide a scientific basis for the rational clinical application of SNS, which is expected to promote the secondary development of its preparations.

Objective:To investigate the relationship between symptoms of vertigo and vestibular functions and short-term hearing outcomes in patients with flat descending sudden sensorineural hearing loss （SSNHL）. Methods:A retrospective review was conducted of the vestibular symptoms observed in 48 patients with unilateral flat-down sudden sensorineural hearing loss treated at the Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Symptoms of vertigo and the results of cervical vestibular-evoked myogenic potentials （cVEMP）, ocular VEMP （oVEMP）, caloric test and video head-impulse test （vHIT） were collected to determine whether these factors could predict therapeutic efficacy. Results:The symptoms of vertigo was not correlated with prognosis （P>0.05） or with abnormal vestibular functions （P>0.05）. Patients with abnormal cVEMP, oVEMP, caloric test or vHIT showed significantly lower effective rates （32.0%, 44.0%, 32.0%, and 24.0%, respectively）; the greater the number of abnormal tests, the poorer the outcome. Patients with all four tests abnormal gained only （3.13±15.97） dB HL in hearing recovery, whereas those with normal cVEMP, oVEMP, caloric test or vHIT showed better chances of hearing improvements by （29.22±20.31）, （31.18±21.59）, （26.17±21.31）, and （26.38±24.05） dB HL, respectively. Conclusion:Vestibular function effectively predicts prognosis in flat descending SSNHL. Patients with abnormal vestibular tests, regardless of symptoms of vertigo, responded poorly to treatment, whereas those with normal cVEMP, oVEMP, caloric test and vHIT results achieved better hearing recovery. Abnormal vestibular function implies more extensive and severe inner-ear lesions in patients with SSNHL.
Humans ; Male ; Female ; Retrospective Studies ; Prognosis ; Adult ; Middle Aged ; Vertigo/diagnosis* ; Hearing Loss, Sensorineural/diagnosis* ; Young Adult ; Hearing Loss, Sudden/diagnosis* ; Adolescent ; Aged ; Vestibular Evoked Myogenic Potentials

The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

Objective To summarise and analyse the qualitative studies on the factors that influence patient involvement in decision-making for the initial administration of insulin for the patients with Type II diabetes,from the perspectives of patients and healthcare staff in order to provide a reference to promote patient involvement in decision-making.Methods Systematic searches were conducted across databases,such as CINAHL,Cochrane Library,EMBASE,PubMed,Web of Science,PsycINFO,China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP,and SinoMed,for qualitative studies on the factors that affect patient involvement in initial insulin decision-making for the patients with Type II diabetes.The search was limited to articles from the inception of the databases to 30th September,2023.Quality of the included studies was assessed using the Joanna Briggs Institute(JBI)evidence-based healthcare centre for qualitative research quality assessment tool.The results were integrated using a synthesising integration method.Results A total of 19 articles were included,yielding 20 study results,which were categorised into 7 themes of patient decision-making related values,patient role preferences in decision-making,condition of patient,the role of healthcare staff in patient participation in decision-making,professional quality of healthcare staff,relationship between patient and healthcare staff,and the support from a medical institution.The data were ultimately integrated into 4 overarching themes of patient personal factors,healthcare staff factors,patient-staff interaction factors and medical institution factors.Conclusion The involvement of the patients with Type II diabetes in the decision-making for the initial administration of insulin is influenced by patients themselves,healthcare staff and medical institutions.It requires efforts of multiple parties:not only with the patients actively participate in decision-making,but also with the healthcare staff and institutions who provide effective decision supports.

OBJECTIVE To analyze the practices of electronic drug instructions in the European Union （EU）， the United States （US） and Japan， so as to provide references for promoting electronic drug instructions under Chinese existing regulatory systems. METHODS By searching the official websites of FDA， European Medicines Agency （EMA） and Pharmaceuticals and Medical Devices Agency （PMDA）， as well as relevant literature， the practice and system of electronic drug instructions in different countries/regions were compared and analyzed. The problems of regulatory system， accessibility form and management system of electronic drug instructions in China were analyzed to put forward the suggestions. RESULT ＆＆ CONCLUSIONS The EU， the US and Japan had established relevant laws for the implementation of electronic drug instructions， issued guidance to specify management requirements and work processes， and set up information platforms to standardize data requirements and enrich search channels. In contrast， the practice of electronic drug instructions in China is still in its infancy， the implementation of electronic drug instructions in China still lacks legislative support， and its accessibility form and future regulatory system need to be further explored. It is suggested to take the opportunity to carry out the pilot reforms of the age-friendly and barrier-free environment for drug instructions in China， improve the regulatory system of electronic drug instructions， promote the readability of drug instructions by exploring the accessibility form of electronic drug instructions in stages， establish and improve the regulatory system of electronic drug instructions， actively build an electronic information platform for it， and promote the development and implementation of electronic drug instructions.

Objective To construct the triple pre-rehabilitation program for the patients undergoing pancreaticoduodenectomy to provide a theoretical basis for the preoperative management of this operation mode.Methods The raft plan was formed by the literature research and group discussion,then the experts were invited to conduct the two rounds of expert consultation,and the final draft of the plan was finally formed.Results The draft plan included the 3 first-level items,9 second-level items and 28 third-level items.The questionnaire recovery rate of the two rounds of expert correspondence was 100%,and the authority coef-ficients were 0.88 and 0.93,respectively.The mean importance and feasibility scores of each item in the two rounds of expert consultation were ≥3.5,and the coefficient of variation was<0.25.The first draft of the final formation plan included the 3 first-level items,9 second-level items and 31 third-level items.Conclusion This program has ne-cessity,scientificity and feasibility.Clarifying the specific contents and scope of preoperative management of this operation mode could provide a theoretical basis for medical staff to carry out pre-rehabilitation.

Objective:To investigate different regulatory effects of S100A8/A9 expressed by keratinocytes in 3 common inflammatory skin injury modes: UVB-induced skin injury, allergic contact dermatitis, and psoriasis.Methods:Wild-type C57BL/6JGpt mice aged 6 to 8 weeks were selected for the following experiments: (1) mouse models of UVB-induced skin injury were established by single exposure to ultraviolet B (UVB) radiation on the shaved dorsal skin of mice (UVB group, n = 4), with the mice receiving no UVB radiation serving as a control group ( n = 4) ; (2) mouse models of allergic contact dermatitis were established by application of 2,4-dinitrochlorobenzene (DNCB) to the right ears of mice (DNCB group, n = 4), with the left ears of mice treated with a vehicle control serving as a control group ( n = 4) ; (3) mouse models of psoriasis-like skin inflammation were established by topical application of imiquimod cream to the depilated dorsal skin of mice (imiquimod group, n = 4), with the mice treated with vaseline serving as a control group ( n = 4). Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in mouse skin tissues obtained from each group, and immunohistochemical study and Western blot analysis were performed to determine the expression of S100A8 and S100A9 in the mouse dorsal epidermis or ear skin lesions. In vitro cultured HaCaT cells were subjected to the following experiments: (1) cells in the UVB group were treated with a single UVB irradiation at a dose of 50 mJ/cm 2, and cells in the control group received no irradiation; (2) some cells were treated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) (collectively referred to as TI), and named as the TI group, which simulated the inflammatory environment in allergic contact dermatitis, while cells treated with corresponding solvents served as the control group; (3) cells were treated with 5 cytokines (interleukin 17A [IL-17A], IL-22, IL-1α, oncostatin M, and TNF-α, collectively referred to as M5), and named as the M5 group, which simulated the inflammatory environment in psoriasis, while cells treated with corresponding solvents served as the control group. Real-time fluorescence-based quantitative PCR, Western blot analysis, and enzyme-linked immunosorbent assay were performed to determine the mRNA and protein expression of S100A8 and S100A9, and to detect the extracellular secretion level of S100A8/A9, respectively. Results:Immunohistochemical study and Western blot analysis revealed that S100A8 and S100A9 expression levels were significantly higher in the skin lesions of mouse models of UVB-induced skin injury, allergic contact dermatitis, and psoriasis-like skin inflammation than in their corresponding control groups; immunohistochemical study further demonstrated that the increase in the expression of the two proteins was more pronounced in the mouse models of psoriasis-like skin inflammation. In the in vitro cell experiments, the mRNA expression of S100A8 and S100A9 in HaCaT cells at 12 and 24 hours were markedly higher in the UVB group (e.g., at 24 hours, 6.14 ± 0.60 vs. 1.00 ± 0.08, 2.58 ± 0.06 vs. 1.02 ± 0.22, respectively, both P < 0.01), TI group (e.g., at 24 hours, 3.90 ± 0.75 vs. 1.00 ± 0.02, 2.42 ± 0.30 vs. 1.01 ± 0.13, respectively, both P < 0.05), and M5 group (e.g., at 24 hours, 157.59 ± 9.30 vs. 1.00 ± 0.11, 251.37 ± 6.63 vs. 1.00 ± 0.03, both P < 0.001) than in the corresponding control groups, so were the extracellular secretion levels of S100A8/A9 at 24 and 48 hours (all P < 0.001), with some differences observed in their response patterns; notably, the response was more pronounced in the mouse model of psoriasis-like skin inflammation. Additionally, the protein expression levels of S100A8 and S100A9 in HaCaT cells were significantly higher in the M5 group than in the control group ( t = 4.66, 4.63, respectively, both P < 0.01), but were significantly lower in the UVB group ( t = -3.75, -3.34, P = 0.020, 0.029, respectively) and TI group ( t = -3.30, -4.50, P = 0.030, 0.011, respectively) than in the control groups. Conclusion:Keratinocytes exhibited active responses following 3 common inflammatory skin injuries, with their effector molecules S100A8 and S100A9, as damage-associated molecular patterns, playing crucial roles in UVB-induced skin injury, allergic contact dermatitis, and psoriasis, and the response seemed to be more pronounced in psoriasis-like dermatitis.

Objective To analyze the epidemiological characteristics and risk factors of gastric cancer after eradication of ( Helicobacter pylori , Hp) in Fuzhou area, to provide a theoretical basis for reducing the incidence and mortality of gastric cancer after eradication of Hp, and to provide effective suggestions for the prevention of gastric cancer in residents in Fuzhou. Methods A total of 699 patients with Hp eradication admitted to our hospital from January 2020 to December 2020 were selected. According to whether the patients had gastric cancer after eradication, they were divided into control group (no gastric cancer) and observation group (gastric cancer). The serum levels of tumor markers including CEA, CA125 and CA199 were detected and compared between the two groups. Clinical data of the two groups, including age, sex, family history of gastric cancer, course of Hp infection, open atrophy, severe atrophy of gastric mucosa, presence of intestinal metaplasia (IM) of gastric mucosa, xanxoma of gastric mucosa, and long-term use of proton pump inhibitors (PPIs), were analyzed using the self-made survey scale in our hospital. Univariate analysis and logistic regression were used to analyze the risk factors for gastric cancer after Hp eradication. Results Among of 699 patients with Hp eradication, 48 cases (6.96%) developed gastric cancer, including 29 male cases and 19 female cases. The incidence rate of males was significantly higher than that of females (P<0.05). The incidence rate of elderly patients was significantly higher than that of non-elderly patients (P<0.05). Serum CEA, CA125 and CA199 levels in the observation group were significantly higher than those in the control group (P<0.05). There were statistically significant differences in open atrophy, severe atrophy of gastric mucosa, presence of IM, xanxoma of stomach and PPIs use time >3 years between the two groups (P<0.05). The presence of IM (OR=4.874), severe atrophy of gastric mucosa (OR=4.412) and the time using PPIs >3 years (OR=3.631) were independent risk factors for gastric cancer after Hp eradication (P<0.05). Conclusion There is a high risk of gastric cancer after HP eradication in Fuzhou, mainly in elderly male patients, especially in patients with IM, severe atrophy of gastric mucosa and long-term use of PPIs, often accompanied by elevated levels of tumor markers. Close gastroscopy follow-up examination must be conducted within 4 to 5 years after Hp eradication, which is helpful for screening high-risk groups of gastric cancer, preventing gastric cancer and treating gastric cancer as early as possible after Hp eradication.