[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

ObjectiveTo investigate the effect of Dingzhi Xiaowan （DZXW） in post-stroke cognitive impairment （PSCI） model mice. MethodsThe cerebral ischemia-reperfusion injury model of mice was established by using the middle cerebral artery occlusion method. Forty C57BL/6 male mice were randomly divided into the sham operation group， model group， low-dose DZXW group （1.43 g·kg^-1）， and high-dose DZXW group （2.56 g·kg^-1）， with 10 mice in each group. Both the sham operation group and the model group were treated with equal amounts of normal saline by gavage， and the above four groups of mice were gavaged once a day for 30 consecutive days. Morris water maze test was used to evaluate the learning memory ability of mice. Serum levels of amyloid precursor protein （APP）， amyloid 42 （Aβ₄₂）， acetylcholinesterase （AChE）， and superoxide dismutase （SOD） were measured by enzyme-linked immunosorbent assay （ELISA）. Deoxyribonucleotide end transferase-mediated nick end labelling （TUNEL） assay was applied to detect the degree of apoptosis in the mouse's hippocampal neurons. Western blot was used to detect the protein expression of phosphoinositol-3 kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor 1-alpha （HIF-1α）， B-cell lymphoma 2 （Bcl-2） homologous structural domain protein （Beclin1）， sequestosome 1 （p62）， microtubule-associated protein light chain 3 （LC3）， Bcl-2， and Bcl-2-associated X protein （Bax） in hippocampal tissue. Prussian blue staining was used to detect iron deposition in hippocampal tissue. Transmission electron microscopy was taken to observe the ultrastructure of the mouse's hippocampal neurons. ResultsCompared with the sham operation group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly increased in the model group （P<0.01）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly decreased （P<0.01）. Compared with the model group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity rate， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly reduced in the DZXW groups （P<0.05）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly higher （P<0.05）. ConclusionDZXW can alleviate cognitive impairment induced by oxidative stress-aggravated hippocampal neuronal damage in PSCI model mice by modulating the PI3K/Akt/mTOR/HIF-1α autophagy signalling pathway.

ObjectiveTo provide a basis for the establishment of an ideal animal model of allergic asthma by statistically analyzing the modeling characteristics and the selection of indicators of the available models. MethodsWe retrieved the relevant articles from China National Knowledge Infrastructure（CNKI）， VIP， Wanfang Data， SinoMed， and PubMed with "allergic asthma" as the keyword and the time interval from January 2019 to January 2024. Through integrating the literature and extracting data， we used Excel 2021 to create a personal database and sorted out the animal strains， genders， allergenic substances， modeling routes， and test indicators and methods. Excel 2021， Cytoscape 3.10.2， and SPSS Modeler 18.0 were then used to analyze the relevant characteristics of the animal models. ResultsA total of 418 articles were included in the database， and the comparative analysis showed that the most frequently used animal strain for modeling was BALB/c mice， and female animals were mostly used. The main modeling method was sensitization by intraperitoneal injection of ovalbumin （OVA）， which was combined with intranasal inhalation. The test indicators mainly included appearance signs， cellular analysis， lung histopathology， lung function indicators， and protein and gene expression in the lung. The test methods mainly involved pathological staining， enzyme-linked immunosorbent assay， immunohistochemistry， immunofluorescence， Western blot， and polymerase chain reaction（PCR） assays. ConclusionThere is no recognized modeling method or evaluation standard for the animal models of allergic asthma. Based on the results of data analysis， the OVA-induced allergic asthma model in BALB/c mice is recommended. The main criteria for evaluating the success of modeling are the general behavioral changes， the morphological changes of the airway and inflammatory cell infiltration in the lung tissue， the changes of pro-inflammatory and anti-inflammatory cytokines in the serum， and the alterations of inflammatory cells in the bronchoalveolar lavage fluid.

OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

OBJECTIVE To explore the clinical characteristics of cardiotoxicity caused by lidocaine， and provide a reference for the safe use of drug in clinical practice. METHODS Chinese and English search terms， such as “lidocaine”“ cardiotoxicity”， were used to search for literature related to lidocaine-induced cardiac toxicity from CNKI， Wanfang Data， VIP， PubMed and Embase， and conduct descriptive analysis. RESULTS A total of 31 papers were included， with 40 patients. Of the 40 patients， 23 were male and 17 were female； ages ranged from 5 months to 73 years， with 4 patients≤18 years old， 17 patients 19-59 years old， and 19 patients≥60 years old. The main indications for medication were surgical anesthesia （26 cases）， and the main routes of administration were intravenous administration， nerve block anesthesia and local infiltration anesthesia （15， 6， 6 cases）； the dosage of medication for 34 patients complied with the instructions； the most of cardiotoxicity occurred 1 min-1 h after medication （19 cases）， and the main symptoms were bradycardia， atrial conduction slowing， atrioventricular block， sinus arrest， etc. Thirty- four patients improved after resuscitation and symptomatic treatment， and six patients died. CONCLUSIONS Lidocaine-induced cardiotoxicity can occur in all ages， mainly within 1 h after administration， and is manifested as arrhythmia， tachycardia or tachycardia， atrioventricular block， etc.， which is severe. When using it clinically， it is necessary to strengthen pharmaceutical monitoring of medication dosage， administration route， toxic reactions， etc.； when relevant symptoms appear， medication should be stopped promptly and symptomatic treatment should be carried out， to protect the safety of drug use.

[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

The presence of physiological barriers in the eye （both external and internal） makes conventional ophthalmic medications （eye drops， ointments， gels， etc.） less bioavailable and difficult to reach the posterior segment of the eye. Although intravitreal injection can deliver drugs to the posterior segment of the eye， it has disadvantages such as infection， injury， and poor tolerance. Ophthalmic microneedle breaks through the intra- and extra-ocular barriers， enabling the drug to reach the target site accurately and to be released continuously greatly avoiding intraocular infections and injuries， and improving the bioavailability of the drug， which has obvious advantages as an ophthalmic drug delivery tool. Ophthalmic microneedle can be classified into hollow microneedle， dissolving microneedle， and coated microneedle according to the usage methods. Each type of microneedle has its own advantages and has shown satisfactory performance in the treatment of diseases such as bacterial and fungal keratitis， glaucoma， exudative age-related macular degeneration， diabetic macular edema， non-infectious uveitis， corneal neovascularization， and even choroidal melanoma.

OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

OBJECTIVE To explore the clinical characteristics of cardiotoxicity caused by lidocaine， and provide a reference for the safe use of drug in clinical practice. METHODS Chinese and English search terms， such as “lidocaine”“ cardiotoxicity”， were used to search for literature related to lidocaine-induced cardiac toxicity from CNKI， Wanfang Data， VIP， PubMed and Embase， and conduct descriptive analysis. RESULTS A total of 31 papers were included， with 40 patients. Of the 40 patients， 23 were male and 17 were female； ages ranged from 5 months to 73 years， with 4 patients≤18 years old， 17 patients 19-59 years old， and 19 patients≥60 years old. The main indications for medication were surgical anesthesia （26 cases）， and the main routes of administration were intravenous administration， nerve block anesthesia and local infiltration anesthesia （15， 6， 6 cases）； the dosage of medication for 34 patients complied with the instructions； the most of cardiotoxicity occurred 1 min-1 h after medication （19 cases）， and the main symptoms were bradycardia， atrial conduction slowing， atrioventricular block， sinus arrest， etc. Thirty- four patients improved after resuscitation and symptomatic treatment， and six patients died. CONCLUSIONS Lidocaine-induced cardiotoxicity can occur in all ages， mainly within 1 h after administration， and is manifested as arrhythmia， tachycardia or tachycardia， atrioventricular block， etc.， which is severe. When using it clinically， it is necessary to strengthen pharmaceutical monitoring of medication dosage， administration route， toxic reactions， etc.； when relevant symptoms appear， medication should be stopped promptly and symptomatic treatment should be carried out， to protect the safety of drug use.

ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling （GDL） exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups： the normal group， the model group， the GDL low-， medium-， and high-dose groups （0.24， 0.48， 0.96 g·kg^-1）， and the penicillamine group （90 mg·kg^-1）， with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg^-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of hyaluronic acid （HA）， laminin （LN）， procollagen type-Ⅲ peptide （PC-Ⅲ）， and collagen type-Ⅳ （C-Ⅳ）. Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 （LncRNA H19）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR）. Western blot analysis was performed to assess the expression levels of PI3K， Akt， mTOR， and their phosphorylated forms， as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B （LC3-Ⅱ/LC3-Ⅰ） in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group， the model group exhibited inflammatory cell infiltration in hepatocytes， unclear nuclear boundaries with cell cleavage and necrosis， and collagen fiber deposition around confluent areas. The levels of HA， LN， PC-Ⅲ， and C-Ⅳ were significantly elevated （P<0.01）. Transmission electron microscopy revealed an increased number of autophagic vesicles， with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased （P<0.01）， and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were reduced （P<0.01）， while LncRNA H19 expression was increased （P<0.01）， and mRNA expression levels of PI3K， Akt， and mTOR were decreased （P<0.01）. After treatment with GDL， the degree of liver fibrosis was significantly improved， with decreased levels of HA， LN， PC-Ⅲ， and C-Ⅳ. The number of autophagic vesicles was significantly reduced， and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower （P<0.01）. The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were elevated （P<0.01）， while the expression level of LncRNA H19 was reduced （P<0.01）. Furthermore， the mRNA expression levels of PI3K， Akt， and mTOR increased （P<0.05， P<0.01）. ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.