[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.

Artificial intelligence （AI） and population pharmacokinetics （PPK） technologies have demonstrated significant potential in the personalized medication of immunosuppressants after organ transplantation, enabling precise prediction of drug dosages. This article provides a comprehensive review of the application status of AI and PPK in the individualized administration of immunosuppressants after organ transplantation， focuses on monitoring blood drug concentration， predicting efficacy/adverse reactions， and establishing individualized dosing models for organ transplant recipients after immunosuppressant administration， and analyzes and compares the application characteristics of different methods in different organ transplant patients as well as the integration and future development of AI and PPK technologies. AI and PPK technologies can not only significantly reduce the dependence on human resources， but also greatly improve the level of individualized treatment of immunosuppressants after organ transplantation， and reduce the discomfort and burden caused by frequent blood concentration monitoring to patients.

Glucagon-like peptide-1 （GLP-1） receptor agonists are a novel class of antidiabetic drugs that also possess lipid- lowering and cardiovascular protective effects， with liraglutide and semaglutide being their representative medications. Based on a systematic literature search， this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney （regulating autophagy， key lipid metabolism pathways， reverse cholesterol transport， etc.）， direct actions on adipose tissue （affecting adipocyte proliferation and differentiation， expression of lipid metabolism proteins， and gene transcription）， activation of sympathetic pathways through the central nervous system， and modulation of the gut microbiota. Additionally， it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus， overweight individuals， and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems， providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.

Objective: To analyze the trajectories of body mass index for age z-score (BAZ) and its influencing factors among children with congenital hypothyroidism (CH) based on latent class growth modeling (LCGM), so as to provide the evidence for improving treatment measures and optimizing growth management among children with CH. Methods Children with CH aged 0 to 3 years from the Newborn Disease Screening Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) between 2017 and 2022 were selected as the research subjects. Basic information, height and weight data from 3 to 36 months of age, age at treatment initiation, thyroid-stimulating hormone (TSH) levels at diagnosis, and family information were retrospectively collected. BAZ for children with CH at each month of age was calculated based on the WHO Child Growth Standards. The trajectories of BAZ were analyzed using LCGM, and factors affecting the trajectories of BAZ among children with CH were analyzed using a multinomial logistic regression model. Methods: Children with CH aged 0 to 3 years from the Newborn Disease Screening Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) between 2017 and 2022 were selected as the research subjects. Basic information, height and weight data from 3 to 36 months of age, age at treatment initiation, thyroid-stimulating hormone (TSH) levels at diagnosis, and family information were retrospectively collected. BAZ for children with CH at each month of age was calculated based on the WHO Child Growth Standards. The trajectories of BAZ were analyzed using LCGM, and factors affecting the trajectories of BAZ among children with CH were analyzed using a multinomial logistic regression model. Results: A total of 299 children with CH were included. There were 140 boys (46.82%) and 159 girls (53.18%). The median of BAZ was 0.50 (interquartile range, 1.68). The LCGM analysis categorized the subjects into three groups: the persistent high-growth pattern group with 24 cases (8.03%), the slow-growth pattern group with 39 cases (13.04%), and the appropriate-growth pattern group with 236 cases (78.93%). Multinomial logistic regression analysis showed that compared to the children with CH in the appropriate-growth pattern group, those who started treatment at the age of 30 to 60 days (OR=0.109, 95%CI: 0.016-0.732; OR=0.166, 95%CI: 0.032-0.852) had a lower risk of persistent high-growth and slow-growth patterns; CH children with TSH levels of 50 to 150 mIU/L at diagnosis (OR=3.554, 95%CI: 1.201-10.514) and those whose paternal had a senior high school/technical secondary school education (OR=2.975, 95%CI: 1.003-8.823) exhibited a higher risk of the persistent high-growth pattern. Conversely, CH children whose paternal reproductive age was 30 to 35 years (OR=0.166, 95%CI: 0.034-0.806) had a lower risk of the persistent high-growth pattern. Conclusions The BAZ trajectory of children with CH aged 0 to 3 years exhibited three patterns: persistent high-growth, slow-growth, and appropriate-growth. The persistent high-growth and slow-growth patterns were associated with treatment timing, TSH levels at diagnosis, paternal reproductive age, and paternal education level. It is recommended to strengthen early treatment interventions and provide family follow-up guidance.

Objective:To exploring the application effect of doctors-nurses-patients theory of goal attainment combined with StMarys cluster intervention mode in patients with tracheotomy after stroke.Methods:Using convenient sampling method, a total of 130 stroke patients with tracheostomy who were admitted to Shangqiu First People's Hospital from August 2020 to February 2022 were selected as the research objects. The patients were divided into the control group and the observation group using the random number table method, with 65 cases in each group. The control group received routine nursing care, while the observation group applied doctors-nurses-patients theory of goal attainment combined with StMarys cluster nursing intervention mode on the basis of the control group. After intervention, scores of Self Rating Anxiety Scale (SAS) and Self Rating Depression Scale (SDS) and patient nursing satisfaction were compared between the two groups.Results:After intervention, the SAS and SDS scores of the observation group were lower than those of the control group, and the nursing satisfaction was higher than that of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The doctors-nurses-patients theory of goal attainment combined with StMarys cluster intervention mode can help improve the psychological state of patients and increase nursing satisfaction.

Objective:To explore the regulatory role of the melanin-concentrating hormone (MCH) neural pathway from the lateral hypothalamus (LHA) to the nucleus accumbens (NAc) in modulating anxiety-like behavior in mice.Methods:Totally 37 male SPF-grade C57BL/6J mice, aged 6 to 8 weeks and weighed 18-22 g, were used for the following experiment: (1) Five mice received an injection of Fluoro-Gold (FG) into the NAc, followed by retrograde tracing combined with immunofluorescence staining after one week to observe the coexistence of FG and MCH immunopositive neurons in the LHA.(2)Thirty-two mice were injected with adeno-associated virus which could activate the MCH neurons into the LHA.After two weeks, they were randomly divided into four groups and received different drug injections: normal saline (NS, intraperitoneal injection)+ NS (1.5 μL, injection in the NAc) group, NS(intraperitoned injection) + SNAP94847 (SNAP, 2 mg/mL, 1.5 μL, injection in the NAc) group, chlorprothixene N-oxide (CNO, 0.15 mg/kg, intraperitoned injection) + NS(1.5 μL, injection in the NAc) group, and CNO(intraperitoned injection) + SNAP(1.5 μL injection in the NAc) group, and the SNAP94847 was an antagonist for MCH typel receptor.The open field test (OFT), elevated plus maze (EPM), and marble burial test (MBT) were employed to assess the impact of chemogenetic activation of MCH neurons on anxiety-related behavior in mice.Results:(1) The results of FG retrograde tracing combined with immunofluorescence histochemistry showed that MCH neurons in the LHA project their neural fibers to NAc neurons.(2) In the chemogenetic experiment, there was no significant interaction effect between CNO and SNAP in terms of the duration of stay ( Finteraction=2.899, P>0.05) and the distance moved ( Finteraction=1.603, P>0.05) in the central area during OFT experiments.However, the main effects of both CNO and SNAP intervention were significant in the duration of stay ( FCNO=6.767, FSNAP=7.656, both P<0.05) and the distance moved ( FCNO=12.480, FSNAP=7.999, both P<0.01) in the central area.Compared to the NS+ NS group, mice in the CNO+ NS group exhibited a shortened duration of stay ((89.00±19.16)s, (63.75±13.58)s, P<0.05) and a decrease in distance moved ((593.79±108.18)cm, (426.81±66.14)cm, P<0.05) in the central area.In contrast, mice in the CNO+ SNAP group had an extended duration of stay ((87.38±16.57)s) and an increase in distance moved ((569.27±73.20)cm) in the central area compared to the CNO+ NS group.There was no significant interaction effect between CNO and SNAP in the number of entries ( Finteraction=2.79, P>0.05) and the dwell time ( Finteraction=2.871, P>0.05) into the open arms of EPM experiments.However, the main effects of both CNO and SNAP interventions in the number of entries ( FCNO=10.43, P<0.01; FSNAP=4.96, P<0.05) and the dwell time ( FCNO=5.232, FSNAP=7.597, both P<0.05) into the open arms were significant.Compared to the NS+ NS group, mice in the CNO+ NS group showed a decrease in the number of entries ((13.13±3.36), (7.63±3.70), P<0.01) and a decrease in open arm dwell time ((37.68±11.37) s, (22.98±7.00) s, P<0.05) into the open arms.The CNO+ SNAP group had an increased number of entries (12.00±3.02) and an increased dwell time ((39.41±10.58)s) into the open arms compared to the CNO+ NS group(both P<0.05).There was no significant interaction effect between CNO and SNAP in the MBT experiment ( Finteraction=2.746, P>0.05).However, the main effects of both CNO and SNAP interventions were significant ( FCNO=8.125, P<0.01; FSNAP=5.383, P<0.05).Compared to the NS+ NS group, the number of buried beads increased in the CNO+ NS group ((16.13±2.10), (11.88±3.23), P<0.05).Conversely, the number of buried beads decreased in the CNO+ SNAP group compared to the CNO+ NS group ((12.38±2.33), (16.13±2.10), P<0.05). Conclusion:Enhanced activity in the MCHergic neural pathway from LHA to NAc can promote anxiety-like behavior in mice, providing new insights into the mechanisms underlying anxiety.

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.

Objective:To investigate the clinical features and prognosis of prolonged cytopenia (PC) in patients with large B-cell lymphoma (LBCL) undergoing anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy.Methods:A retrospective case series study was conducted on LBCL patients who received CAR-T cell therapy with a survival time of over one month at the Hematology Department of Peking Union Medical College Hospital from March 2019 to December 2023. Statistical analyses were performed on hematologic changes at 1, 3, 6, and 12 months post-CAR-T infusion, as well as on the progression-free survival (PFS) and post-treatment adverse events, including infections. Patients were categorized into the PC and non-PC groups based on the occurrence of cytopenia at 90 days post-infusion. Differences between groups were compared, and univariate logistic regression analysis was used to identify risk factors.Results:The median age of 27 LBCL patients receiving CAR-T cell therapy was 58 years (range 27-69 years), with 18 males. Among the 27 LBCL patients who received CAR-T cell therapy, PC was observed in 19 patients (70.4%), with instances of neutropenia (48.1%, 13 cases), anemia (37.0%, 10 cases), and thrombocytopenia (22.2%, 6 cases). Univariate logistic regression analysis revealed that prior chemotherapy sensitivity ( OR=18.00, 95% CI 1.56-207.45, P=0.020) and bone marrow suppression ( OR=18.00, 95% CI 1.38-235.69, P=0.028) were associated with PC. The median follow-up time was 13.5 months. The PC group exhibited a higher risk of infection within 3 months (9/19 vs. 1/8) and a shorter mean PFS (19.3 months vs. 24.4 months), although the difference was not statistically significant (both P>0.05). Conclusions:PC is common following CAR-T cell therapy and is associated with an increased risk of infection and poorer prognosis. Prior treatment sensitivity and bone marrow suppression may serve as indicators of PC.

Objective:To investigate the role of p-AKT-mTOR-P70S6K signaling pathway in radiation therapy for polyploid cervical cancer cells.Methods:Human cervical cancer HeLa cell lines were selected and HeLa cells were radiated under 7 Gy of 6 MV X-ray. The morphological changes of the cells were observed with an inverted microscope on day 5 after radiation induction. All cells were divided into the 7 Gy group (7 Gy X-ray radiation but not transfected polyploidy HeLa cells) and the control group (the non-radiation-induced and not transfected HeLa cells). In addition, the plasmid carrying pcDNA3 negative control sequence and the plasmid carrying pcDNA3-TT-AKT sequence were transfected into HeLa cells, respectively, which were induced by 7 Gy X-ray radiation after 48 h of transfection, and then they were recorded as the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group. Cell proliferation ability was detected by using CCK-8 assay, cell cycle was detected by using flow cytometry, cell apoptosis was detected by using mitochondrial membrane potential assay, the relative expression levels of cell proliferation, cell cycle, apoptosis and autophagy related proteins were tested by using Western blot.Results:Most of the normal HeLa cells in the 7 Gy group died on day 5 after radiation induction, and only a few surviving cells increased in size with multiple nuclei. The results of Western blot showed that the relative expression levels of p-AKT, p-mTOR and p-P70S6K in HeLa cells of the 7 Gy group were lower than those of the control group (all P < 0.05). CCK-8 assay showed that the absorbance ( A) values were 0.45±0.06, 0.65±0.06 after 48 h of culture and 0.75±0.05, 1.05±0.02 after 72 h of culture, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant (all P < 0.05), and the A values in the pcDNA3-TT-AKT + 7 Gy group were all higher than those in the pcDNA3 +7 Gy group. Flow cytometry results showed that the proportion of cells was (29.2±3.6)%, (26.7±1.7)% in G 0/G 1 phase and (29.6±1.6)%, (30.3±0.6)% in G 2/M phase, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were not statistically significant (all P > 0.05); the proportion of cells in S phase was (10.2±0.9)% and (14.6±1.5)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the differences were statistically significant ( t = 2.86, P = 0.043). Mitochondrial membrane potential assay showed that the green fluorescence proportion was (23.1±2.5)% and (14.3±1.9)%, respectively in the pcDNA3 + 7 Gy group and the pcDNA3-TT-AKT + 7 Gy group, and the different was statistically significant ( t = 4.82, P = 0.009). Western blot results showed that the relative expression level of p-cdc25c (Ser216) in the pcDNA3-TT-AKT+7 Gy group was higher than that in the pcDNA3+7 Gy group ( P < 0.001); and the relative expression levels of Bak and LC3-Ⅱ/Ⅰ in the pcDNA3-TT-AKT+7Gy group were lower than those in the pcDNA3 +7 Gy group, respectively (all P < 0.05). Conclusions:The p-AKT-mTOR-P70S6K signaling pathway may be involved in the regulation of radiation-induced polyploidy HeLa cell proliferation, cell cycle and cell apoptosis.

Objective:Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) .Methods:Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients.Results:In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion:BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.