[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.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE To explore the mechanism of Zadi-5 pill in improving myocardial ischemia-reperfusion injury （MIRI）. METHODS The targets and pathways of potential effects of Zadi-5 pill improving MIRI were screened based on the network pharmacology. Seventy-two rats were randomly divided into model group， sham operation group， Danshen group [Compound danshen dripping pills 80 mg/（kg·d）] and Zadi-5 pill high-dose， medium-dose and low-dose groups [1.6， 0.8， 0.4 g/（kg·d）]， with 12 rats in each group. The rats in each group were given corresponding drugs intragastrically， once a day， for 14 consecutive days. After the last administration， MIRI model was established by ligating the anterior descending branch of left coronary artery in rats， while rats in the sham operation group were threaded without ligation. The contents of creatine kinase （CK）， lactate dehydrogenase （LDH）， aspartate transaminase （AST）， cardiac troponin T （CTn-T）， apoptotic rate of cardiomyocyte， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax） and caspase-3 in myocardial tissue were detected in each group after modeling； the morphological changes of myocardial tissue were observed. RESULTS A total of 177 active ingredients and 220 targets of Zadi-5 pill were obtained， including 51 targets involved in improving myocardial ischemia； the core target of Zadi-5 pill improving MIRI was AKT1， including PI3K-Akt， endoplasmic reticulum and hypoxia-inducible factor-1. Compared with model group， the contents of CK， LDH， AST and CTn-T， the apoptotic rate of cardiomyocyte as well as the protein expressions of caspase-3 and Bax were significantly decreased in Danshen group and Zadi-5 pill high-dose group （P＜0.05 or P＜0.01）， while the protein expressions of PI3K， Akt and Bcl-2 in myocardial tissue were significantly increased （P＜0.05 or P＜0.01）， respectively； the myocardial histopathological changes were significantly improved. The above indicators were improved to varying degrees in Zadi-5 pill low-dose and medium-dose groups， too. CONCLUSIONS Zadi-5 pill may inhibit apoptosis by activating the PI3K-Akt signaling pathway， thus playing a role in improving MIRI.

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

Objective:To investigate the correlation between plasma total α-synuclein (α-syn), phosphorylated α-synuclein (p-α-syn), neurofilament light chain(NfL) and subtypes of Parkinson disease(PD).Methods:A total of 62 PD patients admitted to the Department of Neurology, the Affiliated Huai 'an No. 1 People 's Hospital of Nanjing Medical University from September 2021 to January 2023 were selected and scored on the Hoehn-Yahr stage(H-Y), unified Parkinson's disease rating scale Ⅲ(UPDRS-Ⅲ), levodopa equivalent daily dosage(LEDD), mini-mental state examination(MMSE), Parkinson disease quality of life questionnaire(PDQ-39) and activities of daily living(ADL). During the same period, 25 healthy individuals matched in age and sex were enrolled as the control group (HC). Clinical characteristics and blood samples were collected. The plasma levels of α-syn, p-α-syn and NfL were detected by enzyme-linked immunosorbent assay(ELISA). PD patients were divided into tremor dominant type (TD, n=27) and akinetic-rigid dominant type (AR, n=35) based on UPDRS-Ⅲ scores. Multifactorial Logistic regression analysis was performed by SPSS 25.0 software to determine the influencing factors of subtypes of Parkinson disease. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off point of plasma NfL between the AR type and the TD type. Results:Plasma α-syn, p-α-syn, NfL levels in the PD group were significantly higher than those of the HC group ( Z=-2.537, -6.580, -7.101, all P<0.05). There were statistically significant differences between the AR type and the TD type in disease duration, H-Y stage, UPDRS-Ⅲ scores, LEDD and MMSE scores ( Z=-2.503, -3.021, -2.025, -2.086, -2.409, all P<0.05). While no significant difference was found in plasma α-syn and p-α-syn levels between the AR type and TD type ( Z=-0.341, -0.085, both P>0.05), the plasma NfL levels were notably higher in the AR type(92.79(16.84, 117.53) pg/mL) compared to the TD type (12.10(6.99, 100.17) pg/mL)( Z=-2.236, P<0.05). Plasma NfL levels were correlated with rigidity scores ( r=0.438, P<0.001), UPDRS-Ⅲ scores ( r=0.337, P<0.05) and motor subtypes ( r=0.286, P<0.05) in PD patients. Multivariate Logistic regression analysis showed that NfL was risk factor for AR( B=0.002, OR=1.002, 95% CI=1.001-1.003, P=0.017). The ROC curve analysis indicated that plasma NfL levels could predict different subtypes of PD with an AUC=0.667, optimal cutoff =26.527. Conclusion:There is a correlation between elevated plasma NfL levels and the occurrence of AR type of PD, suggesting that nerve injury is probably involved in the occurrence and progression of various motor subtypes of PD.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective: Cognition impairments are considered as a fundamental characteristic of severe mental disorders (SMD). Recent studies suggest that hyperprolactinemia may exert a detrimental influence on cognitive performance in patients with SMD. The objective of this study was to investigate the correlation between serum prolactin levels and cognitive function in female individuals diagnosed with SMD. Methods: We conducted a study on 294 patients with SMD and 195 healthy controls, aged between 14 to 55 years old. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), while prolactin levels were measured in serum. Descriptive analysis and comparative analysis were performed to compare cognitive function and prolactin levels between groups, and linear regression models were used to explore the relationship between prolactin and cognitive function. Results: Compared to the healthy control, individuals with SMD exhibited significantly higher levels of prolactin, while scoring lower on RBANS total and every index scores. Furthermore, a negative association between prolactin levels and cognitive function (RBANS total index score, attention, and delayed memory) was observed in SMD patients. Importantly, this inverse correlation between prolactin and cognition function (RBANS total index score, total scale score, and attention) persisted in patients who were not taking medications that could potentially influence serum prolactin levels. Conclusion Our study reveals a significant correlation between elevated prolactin levels and cognitive impairment in female patients with SMD, underscoring the importance of monitoring prolactin levels in order to prevent cognitive deterioration among female SMD patients.

BACKGROUND: Biliary tract carcinomas (BTCs) are relatively rare but lethal primary malignant tumors derived from the biliary tract system. The burden of BTCs varies according to sex, age, region, and country, but limited attention has been paid to the burden of BTCs. We sought to explore the up-to-date data from the Global Burden of Disease Study (GBD) and expand findings by accessing the demographic features of BTC disease burden. METHODS: Using the latest data from the GBD 2021, we evaluated and analyzed the distributions and patterns of BTC disease burden in various age groups, sexes, regions, and countries. RESULTS: The number of incident cases, deaths, and disability-adjusted life-years (DALYs) tended to increase and peaked at 216,770 (95% uncertainty interval [UI]: 181,890-245,240), 171,960 (95% UI: 142,350-194,240), and 3,732,100 (95% UI: 3,102,900-4,317,000) person-years, respectively, in 2021. However, the average global age-standardized rates (ASRs) of incident cases, deaths, and DALYs shrunk by -11.46% (95% UI: -21.91 to 3.35%), -24.09% (95% UI: -33.19 to 16.88%), and -26.25% (95% UI: -35.53 to 18.36%), respectively, from 1990 to 2021. Meanwhile, the male/female ratio (male per 100 female) of incidence, deaths, and DALYs changed from 76.40, 75.41, and 74.72 to 86.89, 79.11, and 82.29, respectively. In 2021, the highest number of incident cases, deaths, and DALYs occurred in East Asia. The top three highest incidences, deaths, and DALYs were observed in China, India, and Japan, and the highest ASRs were observed in Chile in 2021. Analysis of the Human Development Index along with disease burden estimates of BTCs also suggests that the burden of the disease is related to the level of comprehensive development of the society. CONCLUSION This study provided a comprehensive comparison of differences in the burden of disease across populations and over time, and further presented evidence concerning the formulation of prevention and control policies and etiologic studies for BTCs and proposed logical hypotheses to investigate.
Humans ; Global Burden of Disease ; Biliary Tract Neoplasms/epidemiology* ; Male ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Incidence ; Aged, 80 and over ; Quality-Adjusted Life Years ; Cost of Illness