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.

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

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 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: Evidence that long-term exposure to ambient air pollution increases mortality among older adults, particularly those residing in low-level air pollution locations, remains scarce. This study investigated the potential links between long-term low-level air pollution exposure and mortality among Chinese older adults. METHODS: A population-based study with 317,464 individuals aged ≥ 65 years was conducted in Shenzhen, China during 2018 and 2020. Logistic regression models were used to analyze the associations between long-term exposure to air pollution and all-cause mortality, as the primary outcome, as well as non-accidental, cancer and cardiovascular mortality. RESULTS: Significant associations of PM ₁, PM _2.5, PM ₁₀, SO ₂, CO, and O ₃ exposures with a higher risk of all-cause mortality were found. Adjusted odds ratio ( OR) for each 1 µg/m ³ increment was 1.49 [95% confidence interval ( CI): 1.46, 1.53] for PM ₁, 1.30 (1.27, 1.32) for PM _2.5, 1.05 (1.04, 1.06) for PM ₁₀, 5.84 (5.39, 6.32) for SO ₂, 1.04 (1.04, 1.05) for CO, and 1.02 (1.00, 1.03) for O ₃, respectively. Long-term PM ₁, PM _2.5, PM ₁₀, SO ₂, and CO exposures also elevated the risks of non-accidental, cancer and cardiovascular mortality. CONCLUSION Long-term low-level air pollution exposure was associated with an increased mortality risk among Chinese older adults.
Humans ; Aged ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Air Pollutants/analysis* ; Aged, 80 and over ; Particulate Matter/adverse effects* ; Cardiovascular Diseases/mortality* ; Mortality ; Neoplasms/mortality* ; East Asian People

Objective:To explore the key targets and mechanism of Bielong Ruangan decoction in the treatment of liver cancer based on network pharmacology and molecular docking.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, PubChem database and PharmMapper database were used to search and screen the chemical components and related targets of Bielong Ruangan decoction and the targets of liver cancer diseases. The network diagram of " Bielong Ruangan decoction-traditional Chinese medicine-active ingredient-predicted target-disease" was constructed; Protein-protein interaction (PPI) network were analyzed through String database; gene ontology (GO) enrichment analysis was performed through WebGestalt database; Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out through KEGG Orthology Based Annotation System (KOBAS) database; Molecular docking of the active components and core target proteins of Bielong Ruangan decoction was carried out by using PyMOL, Auto DockVina and other software.Results:Bielong Ruangan decoction had 67 active components, 154 liver cancer targets and 244 pathways. According to the analysis of network pharmacology, Bielong Ruangan decoction may play an anti-cancer role through key targets such as epidermal growth factor receptor (EGFR), mitogen activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), MAPK8, serine threonine protein kinase 1 (AKT1), MAPK14, cysteine protease 3 (CASP3), cyclin-dependent kinase 2 (CDK2), bone morphogenetic protein 2 (BMP2), aldose reductase (AKR1B1) and other key targets. KEGG enrichment analysis showed that the treatment of liver cancer by Bielong Ruangan decoction involved the regulation of vascular endothelial growth factor (VEGF) signaling pathway, tumor necrosis factor (TNF) signaling pathway, thyroid hormone signaling pathway, T cell receptor signaling pathway and other pathways. The results of molecular docking showed that the binding energy of all compounds to protein was less than -5.6 kcal/mol, indicating that each compound and each protein could bind well.Conclusions:Bielong Ruangan decoction participates in the treatment of liver cancer through " multi-component, multi-target and multi-channel" ways, and plays an anti-cancer role mainly by regulating the proliferation and invasion of tumor cells and tumor inflammatory microenvironment.

Cathartic colon （CC） is a common and refractory digestive system disease， with the pathogenesis not fully clarified. The effective therapies other than laxatives and surgery remain to be developed for CC. Therefore， establishing the CC animal models that fit the disease characteristics of western medicine and syndrome characteristics of traditional Chinese medicine （TCM） is an important link to promote the research on this disease. The fitting degree of animal models with the latest Chinese and western medical diagnostic criteria is an indicator to assess the effectiveness of the animal models in simulating the disease characteristics of western medicine and syndrome characteristics of TCM. The literature review showed that the model animals， drugs and their dosage forms， doses， administration methods， and modeling period of CC varied in different studies， and the available CC animal models presented different fitting degrees with the disease characteristics of western medicine and syndrome characteristics of TCM. Rats were the preferred animals for the modeling of CC. Rhei Radix et Rhizoma preparations were commonly used for model inducing， which， however， may cause water electrolyte disorders， decreased immunity， and even death of animals at the late stage of modeling. The animals were modeled by gradually increasing the starting dose， while the starting dose and increasing dose varied. The maintenance dose was determined based on 50% of the animals having loose stools， and the end for a cycle was determined as the time when loose stools disappeared in 80% of animals. The modeling always lasted for 2-3 cycles， approximately 2-4 months. The CC models established with Rhei Radix et Rhizoma granules and rhein had high fitting degrees with the disease and syndrome characteristics. In addition， the CC animal models of TCM syndromes were still in the exploration stage. There were only the animal models of four TCM syndromes： liver depression and spleen deficiency， both Qi and Yin deficiency， Qi stagnation and blood stasis， and spleen and kidney deficiency. Efforts should be made to establish the animal models that meet the characteristics of disease of western medicine and syndromes of TCM， so as to facilitate the research on CC mechanism and drug development.

Liver fibrosis is the common result of various chronic liver injuries and can progress to liver cirrhosis and even liver cancer, and at present, there is still no effective means to reverse liver fibrosis. The transformation of activated hepatic stellate cells (HSC) in perisinusoidal space into myofibroblasts and the secretion of collagen are a central event in the process of liver fibrosis. NLRP3 inflammasome can be activated by various injury stimuli and mediate inflammatory response and pyroptosis. Recent studies have found that the activation of NLRP3 inflammasome is closely associated with HSC activation. This article introduces the activation of NLRP3 inflammasome in different pathways in HSC under various pathological factors and role of NLRP3 inflammasome in the formation of extracellular inflammatory microenvironment, thereby mediating HSC activation and playing an important role in promoting liver fibrosis.

Objective: To understand the longitudinal changes of refractive errors in adolescent myopia screening in the suburb of Shanghai, and to provide reference for targeted measures of myopia prevention and intervention. Methods: By using the cluster sampling method, 1 346 students were selected from two primary schools in a town in the suburb of Shanghai. Physical development indicators and refractive examination parameters of non ciliary muscle paralysis, and uncorrected visual acuity in 2017 and 2020 were collected from the Shanghai adolescent refractive development file. Longitudinal change of spherical equivalent (SE) refractive were assessed. A linear regression model was used to examine the relationship between the rate of SE change with characteristics of the students. Results: The average annual incidence of myopia was 16.36%, and the SE degrees of the left and right eyes of myopia students decreased by 225 degrees for three years. Girls (right eye Z=-4.33; left eye Z=-3.75, P<0.01), newly-onset myopia and persistent myopia (right eye Z=634.45; left eye Z=638.85, P<0.01) was a key for the rapid progress of refractive power. Conclusion The proportion of students with severe low vision is relatively high, and the apparent shifts toward more hyperopia in myopia students call for effective prevention and control programs based on changes in refractive to slow the progression of adolescent myopia.

Objective To establish the mathematical models of stature estimation for Sichuan Han female with measurement of lumbar vertebrae by X-ray to provide essential data for forensic anthropology re-search. Methods The samples, 206 Sichuan Han females, were divided into three groups including group A, B and C according to the ages. Group A(206 samples) consisted of all ages, group B(116 samples) were 20-45 years old and 90 samples over 45 years old were group C. All the samples were examined lumbar vertebrae through C Rtechnology, including the parameters of five centrums (L1-L5) as anterior border, posterior border and central heights (x1-x15), total central height of lumbar spine (x16), and the real height of every sample.The linear regression analysis was produced using the parameters to establish the mathematical models of stature estimation. Sixty-two trained subjects were tested to verify the accuracy of the mathematical models. Results The established mathematical models by hypothesis test of linear regression equation model were statistically significant (P<0.05).The standard errors of the equation were 2.982-5.004 cm, while correlation coefficients were 0.370-0.779 and multiple correlation coefficients were 0.533-0.834.The return tests of the highest correlation coefficient and multiple correlation coefficient of each group showed that the highest accuracy of the multiple regression equation, y=100.33+1.489 x3-0.548 x6+0.772 x9+0.058 x12+0.645 x15, in group Awere 80.6% (±1SE ) and 100% (±2SE ). Conclusion The established mathematical models in this study could be applied for the stature estimation for Sichuan Han females.