Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.

Objective To explore the efficacy of low-dose and short-course glucocorticoid treatment on moderate coronavirus disease 2019(COVID-19)in elderly patients.Methods Clinical data of patients aged ≥80 years,diag-nosed with COVID-19,and admitted to a hospital from December 9,2022,to February 9,2023 were investigated retrospectively.According to whether low-dose glucocorticoids was administered intravenously after admission,pa-tients were divided into non-hormone usage group and hormone usage group.General information and laboratory test results of two groups of patients were described,changes of patients'conditions within 30 days were observed,and difference in efficacy between the two groups was compared.Results A total of 62 patients were recruited,in-cluding 21 in the non-hormone usage group and 41 in the hormone usage group.The general information and labora-tory test indicators before treatment between two groups of patients showed no statistically significant differences(both P＞0.05).Except hormone usage,there was no statistically significant difference in other treatment methods(all P＞0.05).After treatment with glucocorticoids for 10 days,the clinical manifestations of cough(34.1％vs 66.7％),expectoration(19.5％vs 61.9％),palpitation(4.9％vs 23.8％)and shortness of breath(7.3％vs 28.6％)in the hormone usage group decreased compared with those in the non-hormone usage group,differences were statis-tically significant(all P＜0.05).After 10 days of treatment,compared with patients in the non-hormone usage group,the oxygenation indicator and lymphocyte count of patients in the hormone usage group increased,while the values of C-reactive protein and D-dimer decreased,with statistically significant differences(all P＜0.05).The inci-dence of disease exacerbation in the hormone usage group was lower than that in the non-hormone usage group(14.6％vs 47.6％),difference was statistically significant(x2=7.895,P=0.005).Conclusion Low-dose and short-course systemic glucocorticoid usage in elderly patients with moderate COVID-19 can effectively control the progress of the disease and improve prognosis.

Objective To analyze the outcomes of catheter ablation for persistent atrial fibrillation(AF)and the independent risk factors for its recurrence in the elderly.Methods A total of 194 patients with persistent AF who underwent catheter ablation at our department from January 2019 to December 2021 were enrolled in this study.They were divided into elderly group(≥60 years old,99 cases)and non-elderly group(＜60 years old,95 cases).Their surgical characteris-tics,postoperative complications and recurrence were compared between the two groups,and the independent risk factors for postoperative recurrence were analyzed in the elderly group.Results Advanced age,higher B-type natriuretic peptide,larger proportions of hypertension and coronary heart disease,and increased CHA2DS2-VASc and HAS-BLED scores,while lower male ratio and estimated glomerular filtration rate were observed in the elderly group than the non-elderly group(P＜0.05,P＜0.01).The elderly group had a higher proportion of left atrial fibrosis than the non-elderly group(30.3％vs 8.4％,P=0.001).Postoperative complications in the elderly group in-cluded 1 case of pericardial effusion and 2 cases of hematoma at the puncture site,and all of these were improved after treatment.There were no significant differences in the 1-year success rate(71.7％vs 69.5％,P=0.763)or recurrence rate during blanking period(21.2％vs 21.1％,P=0.981)between the elderly and non-elderly groups.AF duration(HR=1.020,95％CI:1.007-1.032,P=0.002)and recurrence during blanking period(HR=6.781,95％CI:3.078-14.935,P=0.001)were independent risk factors for postoperative recurrence in the elderly group.Conclu-sion Catheter ablation is safe and effective in the treatment of persistent AF in the elderly.The elderly patients with long duration of AF and recurrences during blanking period are more likely to experience recurrences within 1 year after ablation.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.
Humans ; Female ; Breast Neoplasms/pathology* ; Retrospective Studies ; B7-H1 Antigen/metabolism* ; Lymphocytes, Tumor-Infiltrating/pathology* ; Carcinoma ; Tumor Microenvironment ; Triple Negative Breast Neoplasms/pathology* ; Prognosis ; Biomarkers, Tumor/metabolism*

Humans ; Floods ; Paraffin ; Paraffin Embedding

Male ; Humans ; Urinary Bladder/diagnostic imaging* ; Prostate/diagnostic imaging* ; Multiparametric Magnetic Resonance Imaging ; Cystitis/diagnostic imaging* ; Hemorrhage/etiology* ; Urinary Bladder Neoplasms/complications*

Humans ; Forensic Medicine ; Poisoning/diagnosis*

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

ObjectiveTo investigate the causes of discontinuation of subcutaneous allergen immunotherapy （SCIT） in patients with allergic rhinitis （AR） and / or bronchial asthma （BA） in the Pearl River Delta region， and to improve the compliance of these patients. MethodsIt was a retrospective， multi-center real world study. Patients with AR and / or BA receiving SCIT in six hospitals in the Pearl River Delta region from January 2015 to December 2020 were recruited. The clinical data of all patients were collected， and the patients with abscission were followed up by telephone. ResultsIn this study， 1 244 patients who received SCIT were included. A total of 427 patients stopped SCIT before 3 years （34.3%）. Children， married patients and patients with positive family history of allergy and total immunoglobulin E （tIgE） > 200 U / mL showed relatively good compliance （P<0.05）， while more patients of AR alone stopped SCIT before 3 years than patients of AR complicated with BA （P<0.05）. Patients with high symptom score and drug score before treatment had better compliance （P<0.001）. A total of 279 cases （65.3%） of the non-adherence group were followed by telephone. The first three reasons for discontinuing treatment were the treatment did not achieve the expected effect （115 cases， 41.2%）， factors pertaining to learning and daily life （74 cases， 26.5%） and adverse reactions （29 cases， 10.4%）. The number of patients stopping SCIT decreased gradually with time； the proportion of patients who discontinued treatment due to adverse reactions in the first year of treatment was higher than that in the second and third years （P<0.05）. ConclusionFailure to achieve the expected effect was the primary reason for poor compliance of patients receiving SCIT and discontinuation mainly occurred on the early stage of the treatment. The supervision from family members is helpful to improve the compliance， suggesting that individualized measures need to be taken to reduce the loss of SCIT.