IgG4-related disease （IgG4-RD） is an idiopathic fibroinflammatory condition characterized by a predilection for tumor-forming lesions， an increase in the serum level of IgG4， excessive infiltration of IgG4-positive plasma cells， storiform fibrosis， and/or obliterative phlebitis. This article reports a rare case of IgG4-RD in which the patient developed recurrent transient ischemic attacks （TIA） after the diagnosis of IgG4-RD. This report explores the potential pathological mechanisms， clinical features， treatment， and prognosis of IgG4-RD with TIA， in order to enhance the awareness of the possible neurological complications associated with IgG4-R among clinicians.
Glucocorticoids

Acute kidney injury (AKI) is one of the most common complications in critically ill patients, and sepsis is the main cause of AKI in the intensive care unit (ICU), which can lead to a poor prognosis in severe cases. For patients with sepsis-associated acute kidney injury (SA-AKI) for whom urgent dialysis is indicated, it is now clear that renal replacement therapy (RRT) can be initiated immediately to control disease progression. However, the optimal timing to initiate RRT in patients whose disease is not severe enough to warrant urgent dialysis remains controversial. Some previous studies were small and heterogeneous, and there was a lack of effective reference indicators for guiding RRT in SA-AKI patients. Therefore, this article reviews the relevant experimental studies on the treatment of critically ill patients with AKI in recent years, and reviews the latest research progress on the optimal timing of RRT initiation, in order to provide an effective reference for clinical practice.
Humans ; Acute Kidney Injury/etiology* ; Renal Replacement Therapy/methods* ; Sepsis/therapy* ; Time Factors ; Intensive Care Units

Objective To establish a mouse model of bronchiectasis with acute infection and evaluate the immunogenicity and protective effect of a self-assembling Pseudomonas aeruginosa(PA)nanoparticle vaccine rePO-FN based on fusion of PcrV-OprI(rePO)protein with self-assembling ferritin(Ferritin).Methods ① SPF-grade female C57BL/6 mice(aged 6～8 weeks,weighing 18～20 g)were randomly allocated into normal saline group,and low-,medium-and high-dose elastase groups(n=6).A mouse model of bronchiectasis was established via intratracheal instillation of different doses of elastase(30 μL of normal saline containing 0.65,1.30 and 2.60 IU elastase)for 3 consecutive days.At 14 and 21 d after modeling,ELISA and HE staining were performed respectively to detect the concentration of IL-6 and to observe pathological changes in lung tissue in order to confirm the modeling.② A recombinant plasmid encoding the gene of fusion protein rePO-FN was constructed and expressed in E.coli.The target protein was purified via affinity chromatography and renatured to obtain the desired protein.The physicochemical properties of the rePO-FN protein were characterized using SDS-PAGE protein gel electrophoresis,dynamic light scattering,molecular sieve chromatography,and transmission electron microscopy.③ C57BL/6J mice were randomly divided into PBS group,rePO group,rePO-FN group,and Ferritin group(n=10).The mice in the above groups were immunized intramuscularly with 100 μL PBS buffer alone or containing 10 μg of corresponding proteins on days 0,7,and 14.ELISA was used to measure the specific antibodies in serum.In 7 d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the PBS,rePO,and rePO-FN groups.After establishing a bronchiectasis model by intratracheal instillation of 2.60 IU of elastase in C57BL/6J mice as described above,the mice were randomly divided into bronchiectasis PBS group,bronchiectasis rePO group,and bronchiectasis rePO-FN group(n=10).Immunization was conducted at the same dose and procedure as described above,in 21 d after bronchiectasis modeling.At the 7th d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the groups.Results ①Repeated intratracheal instillation of elastase significantly increased the concentration of IL-6 in the lung tissue when compared to the content of the normal saline group(P＜0.05).Pathological observations revealed varying degrees of bronchial wall destruction,alveolar fusion,edema,neutrophil infiltration,and hemorrhage,with the severity increasing with elastase dose,which confirming successful establishment of the mouse model of bronchiectasis.② Well-dispersed rePO-FN nanoparticles were successfully prepared,with an average particle size of 91.28 nm,a Zeta potential of approximately-6.5 mV,and a polydispersity index(PDI)of 0.306.Molecular sieve chromatography determined the elution volume of rePO-FN protein to be 8.80 mL,corresponding to a molecular weight of approximately 1 400 kDa.③ Under acute PA XN-1 strain infection,the survival rate of the rePO-FN immunization group and the bronchiectasis rePO-FN immunization group were significantly higher than that of the PBS control group(P＜0.05).Additionally,bacterial colonization in the lung tissues was significantly lower in the rePO-FN immune group and the bronchiectasis rePO-FN immune group under acute PA XN-1 strain infection than that in the rePO group and the bronchiectasis rePO group(P＜0.05).Conclusion Our vaccine rePO-FN can effectively trigger a strong humoral immune response and provide significant protection against PA infection in a mouse bronchiectasis model.

With the continuous progress of modern science and technology, the research of TCM inspection is gradually moving towards a new stage of objectification and intelligence. By systematically sorting out the key technologies involved in the objectification of inspection and diagnosis, and summarizing its clinical application progress in the three core areas of face diagnosis, tongue diagnosis and visual diagnosis, it is found that the inspection and diagnosis of TCM can not only significantly improve the efficiency and accuracy of clinical diagnosis with the help of modern technology, but also achieve more results in disease differentiation, constitution identification and efficacy evaluation. The key technologies include digital image processing, infrared thermal imaging, spectroscopy, photoelectric volume and artificial intelligence (AI) technology. In terms of clinical application, facial diagnosis focuses on image and infrared thermography feature analysis, tongue diagnosis involves image, spectral feature research and AI model construction, and eye diagnosis focuses on white eye collaterals extraction, fundus sign analysis and eye movement information research. However, there are still some problems, such as imperfect standardization system, bottleneck of multi-modal fusion and interpretation, insufficient clinical verification and practicability. In the future, the deep integration of TCM observation and modern science and technology should be promoted by means of technological integration and innovation and strengthening interdisciplinary cooperation, so as to help the modernization of TCM diagnosis.

The occurrence and development of type 2 diabetes mellitus(T2DM)are closely as-sociated with defects in insulin secretion.Synaptosomal-associated protein 25(SNAP25),as a core component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor(SNARE)complex,directly mediates the fusion of insulin secretion granules with the cell membrane and regu-lates the dynamic balance of insulin secretion stimulated by glucose.The expression defect of SNAP25 in patients with T2DM and model animals directly leads to vesicle fusion disorder,constituting the core pathological link of insulin secretion disorder and exacerbating the deterioration of β-cell func-tion.SNAP25 may serve as a key hub for multi-target synergistic intervention,and its genetic poly-morphism and the plasticity of its regulatory network offer novel strategies for precision therapy.This article innovatively integrated multidimensional regulatory mechanisms,including calcium channel ac-tivity,G-protein-coupled signaling and epigenetic modifications,to systematically analyze the spatio-temporal-specific regulatory network of SNAP25 in insulin secretion,providing a theoretical basis for T2DM therapeutic strategies targeting vesicle fusion.

ObjectiveTo analyze the failure of antiretroviral therapy (ART) and drug resistance characteristics among the newly reported HIV-infected patients in Taizhou City from 2020 to 2022. MethodsBlood samples, sociodemographic characteristics and ART information of the newly reported HIV-infected patients who received ART for ≥6 months in Taizhou City from 2020 to 2022 were collected for the detection of recent infections and HIV-1 genotypic drug resistance. Multivariate logistic regression analysis was used to analyze the influencing factors of treatment failure. The gene sequences of cases with failed ART were submitted to the HIV drug resistance database of Stanford University to determine the drug resistance mutation sites and drug resistance characteristics. ResultsAmong the 1 023 newly reported HIV-infected patients receiving ART, the median age （P₂₅，P₇₅） was 47 (33, 58) years, 81.4% were male, 66.4% (679/1 023) were infected through heterosexual transmission, 74.7% had a WHO clinical stage Ⅰ/Ⅱ, 62.2% had a baseline CD4 count of >200 cell·μL^-1, 94.4% (966/1 023) received an immediate ART, and 78.7% were long-term infected. Among the 66 patients with treatment failure (6.5%), the likelihood of treatment failure was lower in those with homosexual transmission (OR=0.39, 95%CI: 0.17‒0.84) and without history of sexually transmitted disease (STD) (OR=0.45, 95%CI: 0.24‒0.92), but higher in those with a baseline CD4 count of ≤200 cell·μL^-1, delayed ART (OR=3.19, 95%CI: 1.24‒7.52), and primary drug resistance (OR=4.69, 95%CI: 1.68‒11.89). Among the 36 HIV-infected patients with virological failure, 27 sequences were successfully amplified, with a successful amplification rate of 75.0% (27/36). The total drug resistance rate was 55.6% (15/27), of which the drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 37.0% (10/27), 51.9% (14/27) and 3.7% (1/27), respectively. Among the NNRTIs, the degree of resistance to efavirenz and nevirapine was consistent, with a majority (51.9%) of highly drug-resistant. K103N and M184V were the most common mutation sites, but PIs mutations occured less frequently. A total of 8 genotypes of HIV-1 were detected, in which subtype CRF01_AE accounted for 37.0% (10/27), followed by CRF07_BC [14.8% (4/27)], CRF08_BC [14.8% (4/27)] and subtype C [14.8% (4/27)]. ConclusionDuring the period from 2020 to 2022, the newly reported HIV-infected individuals in Taizhou City were predominated by long-term infections. Immediate initiation of ART can reduce the risk of treatment failure in HIV-infected individuals. Virological treatment failures are primarily associated with resistance to NRTIs and NNRTIs. It is recommended to strengthen active detection and promptly initiate ART to minimize the occurrence of ART failure. Simultaneously, there is a need to intensify drug resistance detection targeted for those with treatment failure, so as to provide a scientific guidance for drug replacement.

Objective: Investigation on the quality control method of bacterial endotoxin in betahistine hydrochloride injection.
Methods: The method of bacterial endotoxin gel test of 23 batches of betahistine hydrochloride injection from 5 manufacturers was studied.
Results: The limit value of endotoxin in this product was 3 EU·mg^-1, which was suitable for the bacterial endotoxin test of China Pharmacopoeia 2020.
Conclusion: The quality of betahistine hydrochloride injection can be controlled by bacterial endotoxin test, and the limit of bacterial endotoxin can be set as follows: the content of endotoxin in every 1mg of betahistine hydrochloride should not exceed 3 EU.

ObjectiveTo observe the clinical effectiveness and safety of Xuandi Ziyin Mixture （玄地滋阴合剂） for central precocious puberty （CPP） in girls with syndrome of yin deficiency and fire exuberance， and to analyse the effect of body mass index （BMI） on the effectiveness. MethodsA total of 236 girls with CPP of yin deficiency and fire exuberance syndrome were included， and all of them were given Xuandi Ziyin Mixture， 30 ml each time， twice a day， for a total treatment period of 6 months. Before and after treatment， children's weight， height and bone age were measured， BMI and BMI Z-score （BMI Z） and the difference between bone age and actual age were calculated； ultrasound was used to detect uterine and ovarian sizes， and to calculate uterine volume （V_uterus）， bilateral ovarian volume （V_{left ovary}， V_{right ovary}）， and bilateral maximal follicle diameters （r_{left follicle} and r_{right follicle}）； and serum sex hormones were measured， including follicle-stimulating hormone （FSH）， luteinising hormone （LH）， prolactin （PRL）， estradiol （E₂）， and testosterone （T）， and were scored for traditional Chinese medicine （TCM） syndrome. Multiple linear regression was used to analyse the influence factors of the difference between bone age and actual age， and changes in uterine volume. The children were divided into the normal weight group and the overweight/obesity group according to baseline BMI， and the bone age， the difference between bone age and actual age， V_uterus and BMI Z scores before and after treatment were compared between the two groups. ResultsFinally， 199 children entered the statistical analysis. Compared with pre-treatment， the bone age， BMI and BMI Z scores of the children increased after treatment， and the difference between bone age and actual age， TCM syndrome scores， V_uterus， V_{left ovary}， V_{right ovary}， r_{left follicle} and r_{right follicle} decreased； and the levels of serum FSH， LH， E₂， and T significantly decreased （P＜0.05 or P＜0.01）. The difference between bone age and actual age was negatively correlated with LH and V_uterus （P＜0.05）， and changes in uterine volume were positively correlated with LH （P＜0.01）. Comparing between the groups before and after treatment， the bone age， difference between bone age and actual age， and BMI Z scores of children in the normal weight group （100 cases） were significantly smaller than those in the overweight/obesity group （99 cases） （P＜0.01）. Compared with pre-treatment， the bone age of the children in both groups increased， but the difference between bone age and actual age and V_uterus were significantly smaller （P＜0.01）. Further comparison of Δ bone age and actual age difference and ΔV_uterus （Δ = post-treatment value - pre-treatment value） between the two groups showed no statistically significant difference （P＞0.05）. ConclusionsXuandi Ziyin Mixture can reduce bone age， sex hormone level， ovary and uterus size， and improve clinical symptoms in girls with yin deficiency and fire exuberance syndrome of CPP. It is also effective in overweight/obese children， and the inhibitory effect on bone age in girls with CPP is not affected by BMI， with good safety.

The medical-industrial fusion training model combines the knowledge and technology of medical and engineering disciplines in the training of oncology graduate students, which can help accurate diagnosis and treatment of tumors, promote cooperation and innovation in oncology research, as well as promote the cultivation and exchanges of composite and innovative medical talents in oncology, promote the innovation and development of oncology diagnostic and treatment technology, and improve the survival rate and quality of life of oncology patients. This paper discusses the application of medical-industrial fusion training model in the training of o ncology professionals, and explores the new teaching mode of medical-industrial fusion thinking in the cultivation of complex and innovative medical talents in oncology under the background of "new medical science".