[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.

ObjectiveTo explore the possible mechanism of Yigan Fupi Prescription （抑肝扶脾方， YFP） in treating diarrhea-type irritable bowel syndrome （IBS-D） by investigating the AKT/mTOR signaling pathway. MethodsSixty SD rats were randomly divided into control group， model group， YFP low-， medium-， and high-dose group， and pinaverium bromide group， with 10 rats in each group. All groups but the control group， were subjected to 21 days of tail-clamping stimulation and 14 days of senna leaf gavage to establish a liver stagnation and spleen deficiency-type IBS-D rat model. After successful modeling， the YFP low-， medium-， and high-dose group were administered 0.96， 1.93， and 3.87 g/（kg·d） of the prescription， respectively. The pinaverium bromide group was given 13.5 mg/（kg·d）， while the control and model groups were given 10 ml/（kg·d） distilled water. All groups were administered once daily for 14 consecutive days. General conditions of the rats were recorded during the experiment， and after modeling and drug administration， body weight， Bristol stool score， abdominal withdrawal reflex （AWR） score， and histo pathology of colon tissue were observed under HE staining. ELISA was used to detect serum levels of tumor necrosis factor α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Immunofluorescence was employed to detect the levels of AKT/mTOR pathway-related proteins including phosphorylated AKT （p-AKT）/AKT and phosphorylated mTOR （p-mTOR）/mTOR in the colon tissue. Western Blotting was used to detect the levels of autophagy-related proteins， including UNC-51-like kinase 1 （ULK1）， Beclin1 and LC3， and tight junction proteins including Occludin and ZO-1 in the colon tissue. ResultsAfter modeling， compared to the control group， the body weight of rats in the other groups decreased， and Bristol stool scores， as well as AWR scores under 20， 40， 60， and 80 mmHg increased （P＜0.05 or P＜0.01）. After drug administration， compared to the control group， the model group showed reduced body weight， decreased ULK1， Beclin1， LC3Ⅱ/LC3Ⅰ， Occludin， and ZO-1 protein levels in the colon tissue （P＜0.05 or P＜0.01）， and increased Bristol stool scores， AWR scores， serum TNF-α， IL-1β， and IL-6 levels， as well as p-AKT/AKT and p-mTOR/mTOR protein relative expression levels （P＜0.05 or P＜0.01）. Pathological results showed a significant reduction in goblet cells in the upper part of the glandular layer of the colon， with mild inflammatory cell infiltration. The submucosal collagen fibers were dissolved， with unclear boundaries， pale staining， and microvascular congestion and dilation. Compared with the model group， the YFP low-， medium-， and high-dose group and the pinaverium bromide group showed increased body weight， Beclin1， Occludin， and LC3Ⅱ/LC3Ⅰ protein levels （P＜0.05 or P＜0.01）， and decreased Bristol stool scores， AWR scores under 40， 60， and 80 mmHg， serum IL-1β， IL-6， TNF-α levels， and p-AKT/AKT， p-mTOR/mTOR protein relative expression levels （P＜0.05 or P＜0.01）. The pathological morphology of the rats in the YFP groups and pinaverium bromide group showed varying degrees of improvement. Compared with the pinaverium bromide group， the YFP low- and medium-dose group showed increased AWR scores under 20， 40， and 60 mmHg （P＜0.05）. The YFP low-dose group had reduced TNF-α， IL-1β， and IL-6 levels， and increased p-mTOR/mTOR protein relative expression levels occured in all YFP groups （P＜0.05）. Compared with the YFP low-dose group， the YFP high-dose group and pinaverium bromide group showed decreased AWR scores under different pressure levels and reduced p-AKT/AKT protein relative expression levels， while the YFP medium- and high-dose group had elevated serum TNF-α， IL-1β levels and reduced p-mTOR/mTOR protein relative expression levels （P＜0.05）. ConclusionYFP can effectively improve the pathological injury of colon tissue in IBS-D model rats with liver stagnation and spleen deficiency， reduce Bristol stool and AWR scores， and its mechanism may be related to reducing level of inflammatory factors and inhibiting AKT/mTOR pathway-related proteins in colon tissue， thereby enhancing the expression of autophagy-related proteins in the colon tissue.

Objective: To investigate the clinicopathological characteristics and surgical outcomes of adrenal hemolymphangioma,so as to enhance the understanding of this disease. Methods: Clinical and pathological data of 8 patients with adrenal hemolymphangioma admitted to the Department of Urology of our hospital during Jan.2013 and Dec.2022 were retrospectively analyzed,and relevant literature was reviewed. Results: The patients included 5 males and 3 female,median age 54(25-75) years.Adrenal hemolymphangioma was detected in all patients in physical examinations without obvious symptoms.And 4 of the patients had a history of hypertension.Adrenal function test results showed no abnormalities.A total of 9 tumors were identified by imaging examination,including 1 unilateral multiple and 7 unilateral solitary tumors,with a median diameter of 3.6(1.0-5.4) cm.Posterior laparoscopic adrenal tumor resection was performed in 7 cases and robot-assisted laparoscopic adrenal tumor resection in 1 case；all of the tumors were completely removed.The median operation time was 77(53-115) min,median intraoperative blood loss 7.5(2.0-20.0) mL,and median postoperative hospital stay 4(1-7) d.Postoperative pathology showed interwoven deformed and dilated blood vessels and lymphatic vessels in the cystic tumors,with a large amount of lymphoid fluid,lymphocytes and red blood cells.Chronic lymphocyte infiltration was visible between the tube walls.The cystic cavity was partially connected,with flat endothelial cells lining.The pathological diagnosis was adrenal hemolymphangioma.During the median follow-up of 53.5(12.0-106.8) months,all patients recovered well,with stable blood pressure and no tumor recurrence or metastasis. Conclusion: Adrenal hemolymphangioma has no specific clinical symptoms.As adrenal functional tests show no obvious abnormalities,the diagnosis depends on pathological examinations.Popsterior laparoscopic or robot-assisted laparoscopic resection has good efficacy and prognosis.

INTRODUCTION: Odour recognition is influenced by culture. Odour identification tests need to be adapted to a population to accurately assess olfactory function. This study's objectives were to validate the Singapore version of the Sniffin' Sticks (SS-Sg) and a locally-developed odour recognition test (Scentsor) for Singapore. METHOD: This prospective study was performed in 3 otolaryngology outpatient clinics in 3 phases (1 May to 15 November 2024). Phase 1 was a survey evaluation of 93 odour descriptors to identify familiar odour descriptors to be used in the tests (n=414); Phase 2 evaluated and finalised SS-Sg and Scentsor to ensure test odours were recognised by ≥75% of healthy controls (n=130); and Phase 3 validated both tests on healthy controls (n=473) to obtain normative data, to determine test-retest reliability (n=50), and to assess the ability to distinguish patients with olfactory loss (n=67). RESULTS: In Phase 1, the unmodified SS blue and purple sets had 15/32 (46.9%) unfamiliar test odours and 25 unfamiliar distractors combined. In Phase 2, after modification, all odours in SS-Sg and Scentsor were correctly identified by ≥75% of controls. In Phase 3, normative data (age 21-83 years) was obtained. Both tests had good test-retest reliability (Pearson's correlation coefficient of 0.88 with<0.001 for SS-Sg; and at 0.90 with<0.001 for Scentsor). Both tests differentiated among normosmia, hyposmia and anosmia (SS-Sg scores: 12.6 [±2.4] versus [vs] 9.8 (±3.2) vs 6.0 [±2.3] respectively,<0.001; Scentsor scores: 14.3 [±1.8] vs 11.3 [±2.8] vs 5.8 [±3.4] respectively,<0.001). CONCLUSION SS-Sg and Scentsor have been validated to assess olfaction in Singapore.
Humans ; Singapore ; Male ; Female ; Odorants/analysis* ; Middle Aged ; Prospective Studies ; Olfaction Disorders/diagnosis* ; Adult ; Reproducibility of Results ; Aged ; Smell/physiology* ; Young Adult

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD + R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods:The clinical data of 26 patients with FLT3-ITD + R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results:A total of 26 patients with FLT3-ITD + R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95% CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment ( P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion:The Gilt-based combination therapy is highly effective in treating FLT3-ITD + R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.

Sick sinus syndrome(SSS)refers to damage to the sinoatrial node and its surrounding tissues,which leads to excitation and conduction dysfunction of the sinoatrial node,Resultsing in arrhythmia diseases.A better understanding of the pathogenesis of SSS is required to provide a basis for its treatment,including establishing an animal model that can simulate human sinus node dysfunction.In this paper,we review the animal selection,the principles and method of modeling,and the evaluation method and detection indicators of the models,to provide a basis for further studies of the pathogenesis of SSS.

Objective:To analyze the correlation between blood pressure variability (BPV) and behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD).Methods:In this retrospective cohort study, sixty-nine patients with AD from Beijing Tiantan Hospital, Capital Medical University, the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease were consecutively collected from February 1 to August 31, 2023. The patients were divided into the BPSD group (50 patients) and the control group (19 patients) according to with or without BPSD. The patients′ general information were collected, such as age at enrolment, gender, duration of education, and history of hypertension, diabetes, cerebral infarction, hyperlipoidemia, smoking, alcohol consumption, and carrier status of apolipoprotein E epsilon4 allele (APOE ε4). The 24-hour ambulatory blood pressure monitoring instruments were also used to collect the patients′ mean systolic blood pressure, mean diastolic blood pressure and 12 BPV indicators, which covered standard deviation (SD) and coefficient of variation (CV) of systolic and diastolic blood pressure throughout the day, daytime and nighttime. The Montreal Cognitive Assessment (MoCA) was used to assess their cognitive function, and the Activity of Daily Living (ADL)-14 items was used to assess their daily living abilities; hypothesis tests were used to compare the general information, MoCA scores, ADL-14 items scores, mean blood pressure and BPV indicators between the two groups; the multivariate logistic regression analysis was conducted to explore the related factors of BPSD in AD patients; Spearman correlation analysis was used to test the correlation between the total score of neuropsychiatric inventory (NPI) and BPV indicators in AD patients with BPSD.Results:In the BPSD group, the incidence rate of hypertension and MoCA scores were both significantly lower than those in the control group [44.00% vs 73.70%, (9.72±5.60) vs (14.53±5.52) points], but ADL-14 items scores and nocturnal systolic blood pressure CV were both significantly higher [23.00 (17.00, 29.25) vs 14.00 (14.00, 17.00) points, 8.89%±2.26% vs 7.52%±2.30%] (all P<0.05). Elevated ADL-14 items scores ( OR=1.379, 95% CI: 1.131-1.681) and nocturnal systolic blood pressure CV ( OR=1.387, 95% CI: 1.003-1.918) were positive correlation factors for the risk of BPSD in AD patients (all P<0.05). The daytime systolic blood pressure SD ( r=0.375) and CV ( r=0.357) were both positively correlated with total NPI scores in AD patients with BPSD (all P<0.05). Conclusion:BPV is correlated with BPSD in AD patients. Nocturnal systolic blood pressure CV is a positive correlation factor for the risk of BPSD in AD patients, and the total scores of NPI in AD patients are positively correlated with daytime systolic blood pressure SD and CV. It suggests that controlling BPV is a potential therapeutic measure to improve the BPSD of AD patients.

Objective:To investigate the mechanism of benzyl isothiocyanate(BITC) in the treatment of anaplastic thyroid cancer(ATC).Methods:Using network pharmacological analysis, key targets of BITC and ATC were screened, followed by GO and KEGG enrichment analysis. In order to validate the findings, AutoDock software was used to dock BITC and ATC key targets. BITC was applied to two ATC cell lines(8505C and CAL-62). Flow cytometry was used to analyze cell apoptosis. Autophagy inhibitors hydroxychloroquine sulfate(HCQ) and 3-methyladenine(3MA) were used in combination with BITC. Real-time quantitative PCR was conducted to detect the gene level of LC3B, while Western blotting was utilized to examine the expression of NF-κB, LC3B Ⅱ, Beclin-1, and Bcl-2. In animal experiments, a mouse tumor model was constructed using CAL-62 cells, treated with intraperitoneal injections of BITC(100 mg/kg) and normal saline respectively, administered every other day for a total of 21 days. Immunoblotting of tumor tissue was performed to detect the expression of LC3B Ⅱ, Bcl-2, Beclin-1, and NF-κB.Results:A total of 10 key targets with binding energies≤-4.0 kcal/mol were identified. KEGG analysis showed that these genes are mainly involved in NF-κB signaling pathway and apoptosis. BITC inhibited ATC cells with IC50 values of 27.56 μmol/L for 8505C and 28.30 μmol/L for CAL-62. The expression levels of NF-κB, Beclin-1, and Bcl-2 decreased, while LC3B Ⅱ and LC3B gene expression increased. Combining 3MA with BITC enhanced cell inhibition LC3B Ⅱ expression. HCQ increased LC3B Ⅱ expression without enhancing cell and viability inhibition. In the mouse tumor model, compared to the control group, the treatment group had higher LC3B Ⅱ and lower Bcl-2, Beclin-1, and NF-κB levels.Conclusion:BITC could inhibit the growth of ATC cells in vitro and in vivo, disrupt the autophagy degradation, and inhibit the NF-κB pathway.