Objective To report a case of urethral stricture, bladder stones and right ureteral stones in a patient with bilateral lower limb paralysis treated with innovative ureteral flexible endoscopic lithotripsy through cystostomy, so as to provide a new therapeutic approach for such complex cases.Case Report The patient, a 63-year-old male, was admitted due to fever for 45 days.He had been paraplegic in both lower limbs for 19 years and underwent cystostomy 2 years ago at another hospital. Abdominal computed tomography (CT) revealed right ureteral calculi complicated with multiple bladder stones.After adequate anti-infective therapy, cystoscopy was performed, during which complete posterior urethral atresia was identified.A flexible ureteral lithotripsy via the cystostomy site was successfully completed, with favorable therapeutic outcomes.On day 23 postoperatively, a follow-up plain radiograph of the urinary tract showed that the ureteral stent was in good position, with only a small number of residual stones in the prostatic fossa and no other stone remnants.Conclusion This provides a novel minimally invasive treatment approach for ureteral stones in patients who cannot undergo ureteroscopic intervention.

Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Objective To investigate the levels of serum adrenomedullin precursor(pro-ADM),soluble leukocyte differentiation antigen 14 subtype(presepsin),and eosinophil chemotactic factor-1(Eotaxin-1)in patients with acute stroke(AS)complicated with pulmonary infection and their relationship with prognosis.Methods A total of 146 patients with AS admitted to the hospital from January 2022 to January 2024 were selected as the research subjects.According to whether the research subjects were complicated with pulmonary infection,they were divided into the infection group with 54 cases and the non-infection group with 92 cases.In addition,100 healthy individuals who underwent physical examinations in the hospital during the same period were selected as the control group.The prognosis of patients was evaluated using the modified Rankin scale score,which was divided into good prognosis and poor prognosis.The levels of serum pro-ADM,presepsin,Eotaxin-1 and C-reactive protein(CRP)were detected by enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to analyze the influencing factors of AS complicated with pulmonary infection,and the receiver operating characteristic(ROC)curve was plotted to analyze the diagnostic value of serum CRP,pro-ADM,presepsin,and Eotaxin-1 levels for patients with AS complicated with pulmonary infection.Compare the levels of serum pro-ADM,presepsin and Eotaxin-1 in patients with different prognoses.The rela-tionship between the levels of serum pro-ADM,presepsin and Eotaxin-1 and the prognosis of patients was ana-lyzed by the Kaplan-Meier method.Results The levels of smoking history and serum CRP,pro-ADM,presep-sin,and Eotaxin-1 in the infection group were higher than those in the non-infection group and the control group,and the difference was statistically significant(P<0.05).The results of multivariate Logistic regres-sion analysis showed that the levels of serum CRP,pro-ADM,presepsin and Eotaxin-1 were the influencing factors of AS complicated with pulmonary infection(P<0.05).The results of the ROC curve analysis show that the area under the curve(AUC)of the combined diagnosis of AS complicated with pulmonary infection by serum pro-ADM,presepsin and Eotaxin-1 levels was higher than AUC of the individual diagnosis of CRP,pro-ADM,presepsin and Eotaxin-1(Z=3.921,2.445,2.825,3.076,P<0.05).The levels of serum pro-ADM,presepsin and Eotaxin-1 in patients with poor prognosis were higher than those in patients with good progno-sis,and the difference was statistically significant(P<0.05).The results of survival analysis by the Kaplan-Meier method showed that the survival rate of patients with high expression of serum pro-ADM,presepsin,and Eotaxin-1 was lower than that of patients with low expression(P<0.05).Conclusion The levels of ser-um pro-ADM,presepsin and Eotaxin-1 in patients with AS complicated with pulmonary infection are related to their prognosis.

Objective To validate the efficacy of the prediction model for difficulty of peroral endoscopic myotomy (POEM) through an independent cohort. Methods A total of 617 patients with achalasia who underwent POEM at the Endoscopy Center of Zhongshan Hospital, Fudan University from January 2021 to December 2023 were included. The general data of patients were collected, and the predictive value of the prediction model for POEM difficulty in the validation cohort was estimated. The stratified analysis was undergone according to the difficulty risk scores. Results In 617 consecutive patients, technical difficulty was observed in 90 cases (14.6%). The predictive model demonstrated moderate discriminatory capacity with an area under the receiver operating characteristic curve (AUC) of 0.711 (95%CI 0.643-0.780). Patients were stratified into three risk categories according to the difficulty risk scores: low-risk (＜0.1), medium-risk (0.1-0.25), and high-risk (≥0.25). The corresponding technical difficulty rates were 7.3%, 16.9%, and 51.6%, respectively. Conclusion The prediction model for POEM difficulty built by our center shows good stability and discrimination, and has good clinical application value.

Objective To explore the association between long working hours, anxiety symptoms, and insomnia symptoms among footwear industry workers, and to examine the mediating effect of anxiety symptoms between long working hours and insomnia symptoms. Methods A total of 710 workers from 15 footwear manufacturing enterprises in Guangdong Province were selected as study subjects using a stratified random sampling method. Long working hours, anxiety symptoms, and insomnia symptoms among the workers were assessed using the National Key Population Occupational Health Literacy Monitoring Questionnaire, the Chinese version of the Generalized Anxiety Disorder Self-Rating Scale, and the Self-Rating Sleep Questionnaire. Binary logistic regression was applied to analyze the associations of long working hours and anxiety symptoms with insomnia symptoms, and a mediation effect model was used to examine the mediating role of anxiety symptoms. Results The workers with long working hours accounted for 69.6% of participants. The detection rates of anxiety symptoms and insomnia symptoms were 17.0% and 20.7% in these workers, respectively. Binary logistic regression analysis showed that both long working hours and anxiety symptoms were influencing factors for insomnia symptoms (both P<0.01). Mediation analysis indicated that long working hours had a direct effect on insomnia symptoms, accounting for 67.9% of the total effect. Anxietysymptoms played a partial mediating role between long working hours and insomnia symptoms, with an effect value of 0.18 (95% confidence interval 0.07-0.30, P<0.01), accounting for 32.1% of the total effect. Conclusion Both long working hours and anxiety symptoms are influencing factors for insomnia symptoms among the footwear industry workers, and anxiety symptoms partially mediate the impact of long working hours on insomnia symptoms.

Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

An overview of the application of association rule mining(ARM)in real-world study(RWD)on drug safety to inform pharmacovigilance real-world data analysis.The applications of ARM in RWD of drug safety were divided into single drug/vaccine signal detection,combined medication risk mining,multidimensional risk factor analysis and adverse drug event occurrence characterization based on passive monitoring data;medication characterization pattern analysis,auxiliary epidemiological study design and risk mining of the whole dataset based on active monitoring data.In general,foreign scholars pay more attention to method rule setting,performance evaluation and application research,while domestic scholars pay more attention to multidimensional risk factor analysis,adverse drug event occurrence pattern,and clinical drug use characteristics research.With the accumulation of medical data and the continuous development of data mining technology,ARM may provide new ideas for RWD on drug safety.

AIM:To investigate the impact of recombinant human CC16 protein(rhCC16)on cigarette smoke extract(CSE)-induced senescence-associated secretory phenotype(SASP)in human bronchial epithelial cells(HBECs)and in the lung tissues of chronic obstructive pulmonary disease(COPD)mice,and to explore the underlying mechanism.METHODS:HBECs were induced into cellular senescence using 5%CSE.The senescent HBECs were treated with 250 ng/mL rhCC16,and the levels of reactive oxygen species(ROS)were assessed using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)method.The levels of trimethylated histone H3 at lysine 9(H3K9me3),a marker of senescence-associated heterochromatic foci(SAHF),were detected using a Western blot assay.RT-qPCR and ELISA were utilized to measure the mRNA expression and protein levels of SASP components including interleukin-1 beta(IL-1β),IL-6,IL-8,chemokine(C-X-C motif)ligand-1(CXCL-1),matrix metalloproteinase 1(MMP1)and MMP3.Passive smoking was con-ducted for six months to induce COPD in mice.RhCC16(2.5 μg/g body weight)or an equal volume of PBS(20 μL)was intranasally administered from the 16th week of smoking in the COPD+rhCC16 group or COPD+PBS group,respectively,with administration 2 hours before smoking.ROS levels in lung tissue cells were investigated using DCFH-DA staining.H3K9me3 levels in lung tissues were tested using Western blot assay.RT-qPCR and ELISA were performed to examine the mRNA expression and protein levels of IL-1β,IL-6,IL-8,CXCL-1,MMP1 and MMP3.RESULTS:DCFH-DA staining results showed that CSE stimulation increased ROS levels in HBECs,while rhCC16 treatment reduced them(P＜0.01).Western blot results indicated that CSE stimulation elevated H3K9me3 levels in HBECs,which were decreased with rhCC16 treatment(P＜0.01).RT-qPCR and ELISA assays demonstrated that CSE stimulation upregulated the mRNA and protein levels of IL-1β,IL-6,IL-8,CXCL-1,MMP1 and MMP3 in HBECs,which were reduced with rhCC16 admin-istration(P＜0.05).DCFH-DA staining results showed an increase in ROS levels in the lung tissues of COPD mice,which were decreased with rhCC16 administration(P＜0.01).Western blot data revealed an increase in H3K9me3 levels in the lung tissues of COPD mice,which were reduced with rhCC16 treatment(P＜0.01).RT-qPCR and ELISA assays demon-strated an upregulation of the mRNA and protein levels of IL-1β,IL-6,IL-8,CXCL-1,MMP1 and MMP3 in the lung tis-sues of COPD mice,which were reduced with rhCC16 treatment(P＜0.05).No statistically significant differences were ob-served in the above-mentioned indicators between the lung tissues of COPD and COPD+PBS mice(P＞0.05).CONCLU-SION:rhCC16 can effectively inhibit CSE-induced SASP in HBECs and in the lung tissues of COPD mice,with its under-lying mechanism potentially related to the inhibition of the ROS-H3K9me3 signaling pathway.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

OBJECTIVES: To evaluate the effect of artificial intelligence-assisted compressed sensing (ACS) acceleration on MRI radiomic feature extraction and performance of diagnostic staging models for nasopharyngeal carcinoma (NPC) in comparison with conventional parallel imaging (PI). METHODS: A total of 64 patients with newly diagnosed NPC underwent 3.0T MRI using axial T1-weighted (T1W), T2-weighted (T2W), and contrast-enhanced T1-weighted (CE-T1W) sequences. Both PI and ACS protocols were performed using identical imaging parameters. The total scan time for the 3 sequences in ACS group was 227 s, representing a 30% reduction from 312 s in the PI group. Eighteen first-order and 75 texture features were extracted using Pyradiomics. Intraclass correlation coefficients (ICCs) were calculated to assess the agreement between the two acceleration methods. After feature selection using the least absolute shrinkage and selection operator (LASSO), random forest regression models were constructed to distinguish early-stage (T1 and T2) from advanced-stage (T3 and T4) NPC. The diagnostic performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC) and compared using the DeLong test. RESULTS: ACS-accelerated images demonstrated good radiomic reproducibility, with 86.0% (240/279) of features showing good agreement (ICC>0.75), with mean ICCs for T1W, T2W and CE-T1W sequences of 0.91±0.09, 0.89±0.13 and 0.88±0.11, respectively. The staging prediction models achieved similar AUCs for ACS and PI (0.89 vs 0.90, P=0.991). CONCLUSIONS The MRI radiomic features extracted using ACS and PI techniques are highly consistent, and the ACS-based model shows comparable diagnostic performance to the PI-based model, but ACS significantly reduces the scan time and provides an efficient and reliable acceleration strategy for radiomics in NPC.
Humans ; Nasopharyngeal Neoplasms/diagnosis* ; Magnetic Resonance Imaging/methods* ; Nasopharyngeal Carcinoma ; Neoplasm Staging ; Artificial Intelligence ; Carcinoma ; Female ; Male ; Middle Aged ; Adult ; Radiomics