OBJECTIVE To explore the potential mechanism of ketamine-induced cognitive impairment in mice based on metabolomics. METHODS Male C57BL/6 mice were randomly divided into control group and ketamine group （25 mg/kg）， with 12 mice in each group. Each group of mice was intraperitoneally injected with normal saline or corresponding drugs， 4 times a day， for 10 consecutive days. On the last 2 days of drug administration， the cognitive behavior was evaluated by Y maze and novel object recognition test， and the histopathological changes in the prefrontal cortex （PFC） were observed. Ultra-high performance liquid chromatography-tandem mass spectrometry technology was used to analyze the changes of metabolites in PFC， screen for differential metabolites， and perform pathway enrichment analysis. RESULTS Compared with the control group， the morphology of PFC neurons in the ketamine group of mice was inconsistent. There were cavities around the nucleus， and the number of deeply stained cells increased. The mean optical density value of the Nissl staining positive area was significantly reduced， and the alternation rate and discrimination index were significantly reduced （P＜0.05 or P＜0.01）. In the PFC tissue samples of mice of the two groups， there were a total of 114 differential metabolites， including 73 up-regulated and 41 down-regulated metabolites， including glutamine， succinic acid， ketoglutarate， and choline， etc. The differential metabolites mentioned above were mainly enriched in metabolism of alanine， aspartate and glutamate， metabolism of arginine and proline， γ aminobutyric acid synapses， pyrimidine metabolism， cholinergic synapses pathways， etc. CONCLUSIONS Ketamine can induce cognitive impairment in mice. Its neurotoxicity is related to abnormal synaptic transmission and energy metabolism， and neuroimmune regulation disorders.

OBJECTIVE To systematically investigate the changes of volatile components in Euphorbia wallichii after milk and wine processing， and preliminarily elucidate the material basis for reducing toxicity. METHODS Using headspace gas chromatography-mass spectrometry technology， the volatile components in raw E. wallichii， milk-processed E. wallichii， and wine- processed E. wallichii were isolated and identified， and the relative percentage content of each component was calculated by the peak area normalization method. Combining chemometric methods such as principal component analysis and orthogonal partial least- squares discriminant analysis， changes in volatile components in samples after milk and wine processing were compared. Differential components were screened. RESULTS A total of 66 volatile components were identified from the three samples， with the types of compounds primarily comprising alkanes， olefins， heterocycles and esters， among others. A total of 39， 24 and 36 volatile components were identified from raw E. wallichii， milk-processed E. wallichii， and wine-processed E. wallichii， respectively， with 10 components common to all three preparations. Compared with raw E. wallichii， the relative percentage of other components in milk-processed E. wallichii decreased， except for alkanes and esters. The relative percentage of alkanes， olefins， aldehydes and esters in wine-processed E. wallichii increased， but the contents of heterocyclic compounds， ketones， ethers and alcohols decreased. The results of chemometric analysis showed that the volatile components of raw and processed products were significantly different. A total of 5 kinds of differential components in milk-processed products and 3 kinds of differential components in wine-processed products were screened out. Among them， the relative percentage of potential toxic components such as linalool， octanal and 3-pentanone decreased significantly after processing（P＜0.05）. CONCLUSIONS Milk and wine processing may exert a toxicity-reducing effect by reducing the contents of toxic components such as linalool， octanal and 3-pentanonein E. wallichii.

This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias. We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between October 2012 and October 2022. In total, 31 patients underwent the conventional Byars procedure (conventional group), and 45 patients underwent the modified Byars staged procedure (modified group). Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage. Notably, there were no statistically significant differences in the preoperative baseline characteristics, duration of surgery, amount of blood loss, or occurrence of postoperative complications, including urethral fistula, stricture and diverticulum, or penile curvature, between the conventional and modified groups. However, there was a significantly lower incidence of coronal sulcus fistula (0 vs 16.1%, P = 0.02) and glans dehiscence (0 vs 12.9%, P = 0.02) in the surgical group than that in the conventional group. In addition, the modified group exhibited a notably greater rate of normotopic urethral opening (100.0% vs 83.9%, P = 0.01) and a higher mean score on the Hypospadias Objective Penile Evaluation (HOPE; mean ± standard error of mean: 8.6 ± 0.2 vs 7.9 ± 0.3, P = 0.02) than did the conventional group. In conclusion, the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula. Consequently, it offers a promising approach for achieving favorable penile esthetics, thereby providing a reliable therapeutic option for severe hypospadias.
Humans ; Hypospadias/surgery* ; Male ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Child, Preschool ; Child ; Postoperative Complications/etiology* ; Urethra/surgery* ; Plastic Surgery Procedures/methods* ; Surgical Flaps ; Penis/surgery* ; Treatment Outcome ; Infant

Humans ; Consanguinity ; Exome Sequencing ; Mutation/genetics* ; Sequence Analysis, DNA ; Ciliary Motility Disorders ; Axonemal Dyneins/genetics*

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To analyze the clinical characteristics, prognosis and gene mutation in patients with dilated cardiomyopathy (DCM) in Keshan disease area of Sichuan Province, and to explore the risk factors for all-cause death in DCM patients.Methods:In June 2016, 55 DCM patients diagnosed at the local disease prevention and control center through clinical manifestations, electrocardiogram examination, and echocardiography were selected as the survey subjects in Mianning County, Liangshan Yi Autonomous Prefecture, and Renhe District, Panzhihua City, Keshan disease areas of Sichuan Province. Baseline clinical data were analyzed and long-term follow-up was conducted. The follow-up period ended June 15, 2021, with the endpoint of all-cause death. Univariate Cox regression was used to analyze the influencing factors of all-cause death in patients, and Kaplan-Meier (K-M) survival curve was used to analyze the survival time of patients. At the same time, peripheral venous blood was collected from 27 DCM patients. After separating white blood cells, DNA was extracted, and whole exome sequencing was performed to screen potential pathogenic genes.Results:Among the 55 DCM patients, 40 were males and 15 were females. The age was (54.09 ± 12.38) years old. The heart function classification of New York Heart Association (NYHA) was mainly grade Ⅱ and Ⅲ, accounting for 94.55% (52/55). The follow-up time for 55 DCM patients was (7.02 ± 2.96) years, and 17 patients experienced all-cause death, accounting for 30.91% (17/55), including 15 males and 2 females. Compared with the survival group, the death group had a lower incidence of syncope (χ 2 = 6.57, P = 0.010), but higher rates of bilateral lower limb edema (χ 2 = 6.43, P = 0.017), pulmonary congestion (χ 2 = 7.61, P = 0.006), intraventricular conduction block (χ 2 = 6.41, P = 0.011), and angiotensin-converting enzyme inhibitor (ACEI) use (χ 2 = 6.57, P = 0.010), as well as increased left ventricular diameter ( t = 2.36, P = 0.022). Univariate Cox regression analysis showed that bilateral lower limb edema [hazard ratio ( HR) = 4.61, P = 0.042] and intraventricular conduction block ( HR = 3.20, P = 0.019) were risk factors for all-cause death of DCM patients. The results of K-M survival curve analysis showed that patients with bilateral lower limb edema and intraventricular conduction block had higher all-cause death rates (log-rank χ 2 = 5.02, 6.24, P = 0.025, 0.012). Whole exome sequencing results showed that 4 patients were detected to carry pathogenic or suspected pathogenic gene mutations, with a positive rate of 14.81% (4/27), involving three genes: β-myosin heavy chain 7 (MYH7), calreticulin 3 (CALR3), and gelsolin (GSN). Conclusions:The all-cause death rate of DCM patients in the Keshan disease area of Sichuan Province is relatively high. Dead patients are prone to bilateral lower limb edema, pulmonary congestion, and intraventricular conduction block, as well as increased left ventricular diameter. Bilateral lower limb edema and intraventricular conduction block are independent predictive risk factors for all-cause death in DCM patients. MYH7, CALR3 and GSN are involved in the pathogenesis of DCM.

Purpose: Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. Materials and Methods: We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. Results: The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. Conclusions Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Objective: To investigate the species, concentration and seasonal trends of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. Methods: The Department of allergy, Beijing Shijitan Hospital Affiliated to Capital Medical University conducted a cross-sectional study about monitoring the airborne allergenic pollen from August 1, 2021 to July 31, 2022 by the gravitational method in 4 districts and 5 counties of Hohhot City, which include Yuquan District, Xincheng District, Huimin District, Saihan District, Tuoketuo County, Helingeer County, Tumotezuoqi County, Wuchuan County and Qingshuihe County. Daily pollens were counted and identified by optical microscopy, and the data were analyzed. Results: The airborne allergenic pollen was collected every month all year round in 4 districts and 5 counties of Hohhot city. Through the whole year of the total quantity of pollens ranged from 24 850 to 50 154 grains per 1 000 mm² and two peaks of pollen concentration in air were observed,which happened in spring (from March to May) and in summer and autumn (from July to September). In spring, the main pollens were tree pollens, which principally distributed in Populus pollen (18.29%), Ulmus pollen (8.36%), Pinus pollen (6.20%), Cupressaceae pollen (5.23%), Betulaceae pollen (2.73%), Salix pollen (1.80%) and Quercus pollen (1.16%). In summer and autumn, the main pollens were weed pollens, which mainly included Artemisia pollen (42.73%), Chenopodiaceae pollen or Amaranthaceae pollen (7.46%), Poaceae pollen (2.26%), Humulus pollen or Cannabis pollen (0.60%). Conclusion: There were two peaks of main airborne allergenic pollen in 4 districts and 5 counties of Hohhot City. In the spring peak of pollen, the main airborne pollens were tree pollens. In the summer and autumn peak of pollen, the main airborne pollens were weed pollens. The Artemisia pollen was the most major airborne pollen in this area.
Humans ; Cross-Sectional Studies ; Pollen ; Hospitals