[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.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of dupilumab in the treatment of severe asthma with rapid health technology assessment （HTA）， and to provide evidence-based evidence for clinical treatment. METHODS Retrieved from PubMed，Cochrane Library，CNKI，Wanfang， VIP database， and other related websites of HTA. HTA reports， systematic review/meta-analysis， and economic studies of dupilumab in the treatment of severe asthma were collected. Researchers independently identified literature， extracted data， and assessed the quality of included studies. Qualitative description was performed. RESULTS A total of 15 pieces of literature were included， involving 9 systematic reviews/meta-analyses and 6 economic studies. In terms of effectiveness， dupilumab was significantly better than placebo. Compared with other biological drugs， in the patients with severe asthma aged 12 years and above， for those with eosinophil （EOS） ≥300 cells/μL， dupilumab ranked first in improving forced expiratory volume in one second （FEV1）， outperforming tezepelumab， benralizumab， and mepolizumab. It ranked second in reducing acute exacerbations， surpassed only by tezepelumab， while its effect on improving asthma control questionnaire score was relatively lower， being better only than benralizumab. For those with 150 cells/μL ≤EOS＜300 cells/μL， dupilumab was superior to mepolizumab in reducing asthma exacerbation， while the effect on FEV1 was weaker than benralizumab and mepolizumab. In terms of safety， there was no significant difference in the incidence of adverse events and serious adverse events between dupilumab and placebo or other biological drugs， while the incidence of injection site reactions of dupilumab was significantly higher than placebo. In terms of cost-effectiveness， the research results of different countries were not consistent， and there was a lack of research data from China. CONCLUSIONS Dupilumab is an effective and safe choice in the treatment of severe asthma， and its cost-effectiveness requires further research based on China’s medical environment to be determined.

Objective To investigate the impact of two different surgical methods, orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, on the surgical outcomes of pig-to-pig kidney transplantation and the short-term survival of recipient pigs after surgery. Methods Twenty-four Bama miniature pigs were divided into two groups, with 12 pigs in each group, and underwent orthotopic kidney transplantation and abdominal heterotopic kidney transplantation, respectively. The perioperative indicators of the recipient pigs, renal blood perfusion, the overall incidence rate of complications and survival rate were compared between the two surgical methods. Results The total surgical time, renal artery anastomosis time, renal vein anastomosis time, cold ischemia time and total ischemia time were all shorter in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group, with statistically significant differences (all P<0.05). The number of satisfactory renal perfusion cases was higher in the abdominal heterotopic kidney transplantation group than in the orthotopic kidney transplantation group (83% vs. 75%), but the difference was not statistically significant (P>0.05). The total incidence of postoperative complications was 33% in the heterotopic kidney transplantation group, with a survival rate of 92%, and the cause of death was rupture of the vascular anastomosis. The total incidence of postoperative complications was 50% in the orthotopic kidney transplantation group, with a survival rate of 83%, and the causes of death were renal vein thrombosis and renal artery thrombosis. There were no statistically significant differences in the total incidence of postoperative complications and survival rates between the two groups (all P>0.05). Conclusions Compared with orthotopic kidney transplantation, abdominal heterotopic kidney transplantation showes better surgical outcomes in pig-to-pig kidney transplantation and is more beneficial for the short-term survival of recipient pigs after surgery. This provides experience for improving the stability of pig-to-non-human primate kidney xenotransplantation models in the future.

Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.

Objective:To establish a method for determining the concentration of gatifloxacin in rabbit ocular tissue and compare the ocular pharmacokinetics of 0.3% gatifloxacin eye gel after a single and multiple topical instillations in rabbits.Methods:Ninety-four healthy New Zealand rabbits were selected.Ten rabbits were randomly selected without any treatment for blank tissue collection, and the remaining 84 rabbits were randomly divided into a single-dose group (36 rabbits) and a multiple-dose group (48 rabbits) equally between males and females using a random number table.The left eye was taken as the experimental eye.The single-dose group was given one drop of 0.3% gatifloxacin eye gel into the left eyes, and the rabbits were divided evenly into six subgroups.In each subgroup, tear specimens and blood specimens were collected at 0.5, 1, 3, 5, 7, 10 hours after gel application, then cardiac blood samples were taken, after which animals were sacrificed immediately to collect ocular tissue including aqueous humor, conjunctiva, cornea, sclera, iris-ciliary body, lens, vitreous body, retina, and choroid.The multiple-dose group was given 1 drop of gatifloxacin ophthalmic gel in the left eye three times a day.At 0.5 hour after the first administration days 4 and 6, and 0.5, 1, 3, 5, 7, and 10 hours after the first administration on day 7, the cardiac blood sampling and ocular tissue collection were performed.The methanol precipitation protein method was used to pretreat samples, and the concentration of gatifloxacin in rabbit plasma and eye tissue was measured and calculated by high-performance liquid chromatography-tandem mass spectrometry method to obtain pharmacokinetic-related parameters such as peak concentration (C max), peak time (T max), and area under curve (AUC).The mobile phase was a methanol-0.1% acetic acid aqueous solution (volume ratio=70∶30), and a positive ion multiple reaction detection mode was used.Ciprofloxacin was used as the internal standard, the selectivity, standard curve and lower limit of quantification, accuracy and precision, extraction recovery rate, matrix effect, and stability of the method were validated in accordance with the 9012 Guidelines for Validation of Quantitative Analysis Methods for Biological Samples in Chinese Pharmacopoeia ( 2020 edition).Combined with the minimum inhibitory concentration (MIC 90) of gatifloxacin on common ocular infectious bacteria, C max/MIC 90 and AUC/MIC 90 were calculated.The study protocol was reviewed and approved by the Animal Ethics Committee of Shenyang Xingqi Pharmaceutical Co., Ltd.(No.XQ-2016-011). Results:Gatifloxacin has a good linear relationship in various eye tissues and plasma.The between-run precision in corneal tissue is within the range of -1.5%-6.0%, and the daytime precision was not greater than 15%.The extraction recovery rate in corneal tissue ranged from 92.0% to 94.8%, and the precision of the matrix effect at low, medium, and high concentrations calculated by internal standard normalization was not greater than 3.3%.After a single topical instillation, gatifloxacin reached a high concentration in anterior and posterior segment ocular tissues and its distribution ranked in order from the highest to the lowest by AUC 0-t as follows, tears, cornea, conjunctiva, iris-ciliary body, sclera, aqueous humor, choroid, retina, lens and vitreous body, with the C max of 94.90 μg/g, 7.34 μg/g, 3.65 μg/g, 1.81 μg/g, 1.75 μg/g, 1.31 μg/ml, 0.86 μg/g, 0.53 μg/g, 0.13 μg/g and 0.07 μg/ml, respectively.T max was 1 hour in all ocular tissues except in the lens, choroid, and vitreous body fluid, where T max was 0.5 hour.There was no significant difference among the concentrations of gatifloxacin in ocular tissues at 0.5 hour on days 4, 6 and 7 after multiple dosing ( P>0.05), and the AUC 0-t in the cornea, conjunctiva, and sclera was approximately 2.04, 2.12, and 2.32 times that of the single dosing.The concentration of gatifloxacin released into the systemic circulation after single and multiple dosing was less than 25.00 ng/ml.For both Staphylococcus aureus and Staphylococcus epidermidis, pharmacokinetic/pharmacodynamics in the conjunctiva, cornea, sclera, iris-ciliary body, aqueous humor, and choroid were satisfied with C max/MIC 90≥10 and AUC/MIC 90≥30 after continuous administration of gatifloxacin ophthalmic gel. Conclusions:A rapid and sensitive method for measuring gatifloxacin concentration in ocular tissues is successfully constructed.Gatifloxacin ophthalmic gel administered three times a day for three days can achieve stable concentrations in ocular tissues, and the concentration of gatifloxacin in ocular tissues is increased compared with a single dose.Effective treatment of common bacterial infections of the conjunctiva, cornea, sclera, and iris-ciliary body can be achieved with topical application of gatifloxacin ophthalmic gel.

Objective To explore the clinical characteristics of patients with heart failure(HF)treated with lyophilized Yiqifumai injection based on real-world data,providing evidence for the rational and standardized use of Yiqifumai injection.Methods Hospitalized HF patients from 81 hospitals across China were included in this study between April and November 2023.We collected demographics information[sex,age,New York Heart Association(NYHA)functional classification],length of hospital stay,duration of medication use,and biomarkers such as N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),and left ventricular end-diastolic diameter(LVEDD).Clinical features of HF patients treated with Yiqifumai injection were analyzed,and comparisons were made among different HF subtypes.Results A total of 457 HF patients were included:96 with heart failure with reduced ejection fraction(HFrEF),70 with HF with mildly reduced ejection fraction(HFmrEF),and 291 with HF with preserved ejection fraction(HFpEF).The majority of HFpEF type and HFrEF type patients were classified as NYHA class Ⅲ[48.1％(140/291)and 54.2％(52/96),respectively],while most HFmrEF type patients were classified as class Ⅳ[41.4％(29/70)].The longest average hospital stay was recorded in HFmrEF type patients[(9.30±3.02)days],while the shortest was recorded in HFrEF type patients[(8.77±3.11)days].The shortest average medication duration was found in the HFrEF type[(8.54±2.95)days],while the longest was observed in HFpEF type patients[(8.82±2.82)days].Serum NT-proBNP levels were significantly decreased post-treatment in all three types[ng/L:HFrEF was 2 435.00(1 169.25,5 607.75)vs.5 334.00(2 077.33,9 108.88),HFmrEF type was 2 313.25(598.09,6 224.67)vs.4 559.21(1 325.75,8 922.75),HFpEF type was 824.00(169.46,2298.75)vs.1 265.00(215.00,3 458.80),all P<0.05],with the most pronounced decrease observed in the HFrEF type.LVEF was significantly improved in the HFrEF type[0.340(0.290,0.378)vs.0.336(0.280,0.360),P<0.05],while no significant changes were noted in the HFmrEF type and HFpEF type.No significant differences in LVEDD were found before and after treatment in any type(all P>0.05).Conclusion In the real-world setting,the advantages of Yiqifumai injection in treating HFrEF are more pronounced,while further evidence from evidence-based medicine is needed to support its use in other types of heart failure.

Traditional Chinese medicine injections for the prevention and treatment of cardiotoxicity of antineoplastic drugs was summarized, including Shengmai injection, Shenmai injection, Shenfu injection, Shenqi Fuzheng injection, Kangai injection, Huangqi injection, Xinmailong injection, Danhong injection, Danshen injection, Honghua injection, Kushen injection, Cinobufacin injection and Yinxingdamo injection. The mechanism of effect mainly includes inhibition of lipid peroxidation, reduction of calcium overload and anti-cardiomyocyte apoptosis, which provides the basis for the prevention and treatment of cardiotoxicity of antitumor drugs by traditional Chinese medicine.

Non-surgical treatment programs play an essential position among hepatocellular carcinoma therapies. Precise evaluation of treatment efficacy has significant value in determination of non-surgical treatment programs for hepatocellular carcinoma. As the treatment methodologies and philosophy progress, the evaluation standards for the efficacy of non-surgical treatment of hepatocellular carcinoma are constantly updated and developed. This paper generalizes the development process of the evaluation criteria for the efficacy of non-surgical treatment of hepatocellular carcinoma, summarizes the evaluation criteria that have been and are currently applied in the clinical field in general, in order to provide a basis for patients to obtain timely and effective evaluation and treatment, and gives an outlook on the future development of the evaluation standards.

ObjectiveTo summarize the research progress of mammalian target of rapamycin （mTOR） pathway regulated by traditional Chinese medicine（TCM） and provide reference for visualization and quantitative analysis of related research based on multiple software linkage. MethodLiterature related to TCM regulation of mTOR pathway in Web of Science was taken as the research object. Citespace，VOSviewer，and carrort² were used for biliometric analysis and visualization of the literature. ResultA total of 245 papers that met the requirements were retrieved，and the visual analysis showed that the papers presented a fluctuating increase year by year after 2010，and numerous research results emerged in 2018. China had the most publications. Institutions with a large number of publications were mainly in Beijing and Shanghai，and most of the regional cooperation was centered in Beijing and Nanjing. According to the research direction and focus，it was found that the intervention of TCM in mTOR pathway in recent years mainly concentrated on the anti-tumor，anti-apoptotic and anti-inflammatory aspects， and TCM interfered with mTOR pathway to regulate cell apoptosis，autophagy，proliferation，and death. AMP-activated protein kinase （AMPK） and phosphatidylinositol 3-kinases（PI3K）/protein kinase B（Akt）/mTOR pathway were the current and future research hotspots. ConclusionResearch on the regulation of mTOR pathway by TCM had a good prospect，and the in-depth study might provide new ideas and guidance for the treatment of cardiovascular diseases，tumor and other major diseases.

Objective:To provide molecular evidence for clinical diagnosis and genetic counseling by analyzing the clinical characteristics and identifying the pathogenic genes in a SPONASTRIME-type spondyloepimetaphyseal dysplasia(SEMDSP)family.Methods:Clinical data of the family members was collected and analyzed. Case 2 was identified as the proband for whole-exome sequencing and variant analysis. Suspected variants were validated across family numbers using Sanger sequencing.Results:The two affected individuals in this family, a brother and a sister, both presented as short stature. The initial diagnosis for the sister(case 1)was made at the age of 4 years and 2 months(height: 88.6 cm), and for the brother(case 2)at 4 years and 4 months(height: 81.6 cm). Both individuals exhibited distinctive facial features, including frontal bossing, midface hypoplasia with depressed nasal bridge, upturned nostrils, ocular hypertelorism, and epicanthus, thick hair, short lingual frenulum, stubby fingers and palms, and absence of scoliosis. The parents displayed normal phenotypes. Laboratory tests indicated growth hormone deficiency in both affected individuals. Imaging studies revealed significant bone age delay in case 2, while case 1 showed longitudinal striations at the distal radius but with bone age matching their actual age(5 years and 11 months). Despite receiving recombinant human growth hormone treatment, both patients had inadequate responses. Genetic testing identified compound heterozygous mutations in the TONSL gene shared by the two siblings. These mutations included a paternally inherited c. 1291-14_1291-11delCCTC and a maternally inherited c. 1909_1920delACGCTGCAGCAG. Notably, SEMDSP families have not been reported in China, and the c. 1909_1920delACGCTGCAGCAG mutation is a novel variant.Conclusion:Two patients were diagnosed as spondyloepimetaphyseal dysplasia, SPONASTRIME type, and the compound heterozygous variant was the genetic cause of this family.