Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG)instillation after transurethral resection of bladder tumor(TURBT)in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC),and to construct a prediction model for recurrence after BCG treatment.Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation.The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set,while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set.A total of 17 variables were included and analyzed.Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation,and nomograms were plotted to predict 1-year,3-year,and 5-year recurrence-free survival(RFS).Calibration curve,decision curve analysis(DCA),and receiver operating characteristic(ROC)curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model.Results In the training set,26 patients(23.64%)experienced recurrence during the follow-up period,with a median RFS of 32.00(18.00～50.50)months.Univariate Cox regression analysis suggested that platelet count,eosinophil to lymphocyte ratio(ELR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune inflammation(SII)index,and neutrophil-monocyte to lymphocyte ratio(NMLR),pathological T1 stage(pT1)tumor and hemoglobin,albumin,lymphocyte,and platelet(HALP)score were potential factors influencing recurrence after BCG instillation.Multivariate Cox regression analysis identified high HALP score(HR=0.185,95%CI:0.046～0.736,P=0.017)as an independent protective factor,while high ELR(HR=3.599,95%CI:1.505～8.608,P=0.004)and pT1 stage(HR=3.240,95%CI:1.191～8.818,P=0.021)were independent risk factors for recurrence.Based on this,a nomogram prediction model was constructed.The calibration curves demonstrated good agreement between predicted and actual 1-,3-,and 5-year recurrence risks.Decision curve analysis indicated clinical utility across a wide threshold probability range.In the training set,the model showed strong predictive performance for 1-(AUC=0.842),3-(AUC=0.847),and 5-year(AUC=0.887)recurrence risks,which was further validated in the external cohort.Conclusion Higher HALP score prior to BCG instillation therapy is a protective factor against tumor recurrence,while higher ELR and pT1 stage are risk factors.Our nomogram prediction model based on HALP score,ELR and pathological T stage,can identify individuals at high risk of recurrence after BCG instillation therapy.

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AIM: To evaluate the effects of 3% diquafosol ophthalmic solution(DQS)on the ocular surface and tear film in adolescents with mild dry eye syndrome during the early stage of wearing orthokeratology lenses.METHODS: Prospective study. Totally 60 myopic adolescents(120 eyes)with mild dry eye syndrome who were fitted with orthokeratology lenses for the first time in our hospital from January 2023 to September 2023 were enrolled in this study. They were randomly divided into control group and observation group. Both groups wore the same brand of orthokeratology lenses for 8-9 h a day and 7 d a week. In the control group(30 cases, 60 eyes), the patients were treated by routine eyelid cleaning and warm compresses from the day of fitting. In addition to the control group's treatment, patients in the observation group(30 cases, 60 eyes)were given DQS 6 times a day for 3 mo, and follow-up for 6 mo after discontinuation of DQS. According to the follow-up requirements of orthokeratology lens, uncorrected visual acuity(UCVA), corneal curvature, corneal topography, and corneal fluorescein staining were rechecked. The ocular surface disease index(OSDI)scores, tear meniscus height(TMH)of lower eyelid, non-invasive tear film break-up time [first and average, NIBUT(f)and NIBUT(av)] and corneal fluorescein staining were measured at baseline, 1, 2 and 3 mo after treatment, and 3 and 6 mo after DQS discontinuation.RESULTS: All patients completed follow-up. The NIBUT(f), NIBUT(av)and TMH of lower eyelid in the observation group were higher than those in the control group at 2 and 3 mo after treatment and at 3 and 6 mo after discontinuation of DQ3(all P<0.05). The OSDI scores for both groups decreased significantly at 2 mo after treatment(all P<0.05). At 3 mo after treatment and 3 and 6 mo after discontinuation of DQS, the OSDI scores in the observation group was significantly lower than the control group(all P<0.01). There was no significant difference of corneal fluorescein staining between the two groups(P=0.731).CONCLUSION: The combination of DQS with eyelid hygiene and warm compresses shows better efficacy in enhancing the stability of the tear film for adolescents with mild dry eye syndrome while wearing orthokeratology lenses.

OBJECTIVES: To investigate the effect of Shenge powder (SGP) on myocardial fibrosis in rats with heart failure after myocardial infarction and its relation with lysyl oxidase like protein 2 (LOXL2)/transforming growth factor-β1 (TGF-β1)/IL-11 signaling pathway. METHODS: Seventy-two SPF male SD rats were divided into blank control group, model control group, SGP small dose group, SGP large dose group, positive control group, SGP large dose+LOXL2 activator group, with 12 rats in each group. Except for the blank control group, post-myocardial infarction heart failure was induced by coronary constriction. Corresponding treatments were given immediately after successful modeling, once a day for 4 weeks. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in rats were detected by color Doppler ultrasound imaging. Levels of IL-1β and IL-6 in serum were analyzed by ELISA method. Myocardial collagen volume fraction (CVF) was evaluated by Masson staining. Expressions of collagen Ⅰ and α-smooth muscle actin (α-SMA) in myocardial tissue were detected by immunohistochemical staining. The mRNA expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in myocardial tissue were detected by qRT-PCR. Expression of LOXL2, TGF-β1, and IL-11 proteins in myocardial tissue were detected by Western blotting. RESULTS: Compared with the blank control group, the LVFS and LVEF of the model control group decreased, the levels of serum IL-6 and IL-1β elevated, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins increased (all P<0.05). Compared with the model control group, the LVFS and LVEF of SGP small dose group, SGP large dose group and positive control group increased, the levels of serum IL-6 and IL-1β decreased, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins decreased (all P<0.05); while LOXL2 activator reversed the improvement effect of high-dose SGP on myocardial fibrosis in heart failure rats after myocardial infarction. CONCLUSIONS Shenge powder may inhibit myocardial fibrosis in heart failure rats after myocardial infarction by inhibiting the LOXL2/TGF-β1/IL-11 pathway.
Animals ; Male ; Rats, Sprague-Dawley ; Myocardial Infarction/complications* ; Transforming Growth Factor beta1/metabolism* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Heart Failure/pathology* ; Myocardium/metabolism* ; Fibrosis ; Amino Acid Oxidoreductases/metabolism* ; Interleukin-11/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Matrix Metalloproteinase 9/metabolism*

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To investigate the treatment regimens, therapeutic effects, and adverse events of immune checkpoint inhibitors (ICI) in the treatment of progressive multifocal leukoencephalopathy (PML).Methods:A retrospective analysis was performed on patients with PML who received ICI treatment at the Department of Neurology of Peking Union Medical College Hospital from October 2020 to September 2024. The patients′ demographic characteristics, baseline immune status, clinical manifestations, laboratory tests, treatment regimens, and clinical outcomes were analyzed.Results:A total of 2 male patients with PML, aged 40 and 59 years, received ICI treatment. One patient had underlying combined immunodeficiency, while the other had acute myeloid leukemia subtype M2 and had previously undergone umbilical cord blood stem cell transplantation. Both patients were treated with pembrolizumab (dosage range: 2-3 mg/kg, administered every 3-4 weeks), receiving a total of 2-4 courses of treatment. In terms of therapeutic effects, both patients showed significant improvement. Regarding adverse events, 1 patient experienced immune-related adverse event (irAE) of immune-related pneumonia combined with immune-related hypophysitis.Conclusions:ICI may be an effective treatment option for PML. However, the use of ICI may be accompanied by the occurrence of irAE, necessitating close monitoring during treatment.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To investigate the treatment regimens, therapeutic effects, and adverse events of immune checkpoint inhibitors (ICI) in the treatment of progressive multifocal leukoencephalopathy (PML).Methods:A retrospective analysis was performed on patients with PML who received ICI treatment at the Department of Neurology of Peking Union Medical College Hospital from October 2020 to September 2024. The patients′ demographic characteristics, baseline immune status, clinical manifestations, laboratory tests, treatment regimens, and clinical outcomes were analyzed.Results:A total of 2 male patients with PML, aged 40 and 59 years, received ICI treatment. One patient had underlying combined immunodeficiency, while the other had acute myeloid leukemia subtype M2 and had previously undergone umbilical cord blood stem cell transplantation. Both patients were treated with pembrolizumab (dosage range: 2-3 mg/kg, administered every 3-4 weeks), receiving a total of 2-4 courses of treatment. In terms of therapeutic effects, both patients showed significant improvement. Regarding adverse events, 1 patient experienced immune-related adverse event (irAE) of immune-related pneumonia combined with immune-related hypophysitis.Conclusions:ICI may be an effective treatment option for PML. However, the use of ICI may be accompanied by the occurrence of irAE, necessitating close monitoring during treatment.

Objective To investigate the characteristics of human papillomavirus (HPV) prevalence and genotype distribution of 18 535 cases in Yuncheng . Methods A sample of 18535 residents who underwent HPV testing in our hospital from August 2020 to September 2023 were enrolled, and HPV genotyping was done to all samples. Then the rate of HPV infection, age distribution, genotype distribution, and multiple infections were statistically analyzed. Results Of the 18,535 subjects included, a total of 4,639 tested positive for HPV, demonstrating a positive rate of 25.03%. The positive rate of HPV infection varied among different age groups (χ²=29.587, P<0.05), with higher rates found in <25 years old group (29.61%) and >60 years old group (25.89%). Overall, 23 genotypes, covering 5315 viruses, were detected. There were 5 low-risk genotypes with the highest percentage of HPV42 (9.29%), and there were 18 high-risk genotypes with HPV52, HPV58, HPV66 and HPV53, subtypes as the most frequent subtypes, accounting for 13.64%, 8.97%, 7.41% and 7.04%, respectively. The type of HPV infection was predominantly single infections, with an overall single infection rate of 21.62% (4008/18535), which accounted for 86.40% (4 008/4 639) of all positive cases, and a multiple genotype infections rate of 3.40% (631/18535). The 25-34 year old group accounted for the largest proportion of single infections (25.12%), while the <25 year old group accounted for the largest proportion of multiple genotype infections (30.74%). Conclusion The prevalence rate of HPV infection in Yuncheng is 25.03%, with a higher positive rate in the <25 years age group and the >60 years age group. A total of 23 HPV genotypes are detected, of which the main genotypes are HPV42, HPV58, HPV66 and HPV53, and the type of infection is dominated by single infections.

BACKGROUND:It has been shown that neural stem cells can differentiate into neurons,astrocytes,and oligodendrocytes.Mesenchymal stem cells-derived extracellular vesicles have also been shown to cross the blood-brain barrier to reach sites of central nervous injury and promote neural repair.However,it is not clear whether neuron-derived extracellular vesicles promote the differentiation of neural stem cells in a direction that is beneficial for neurogenesis. OBJECTIVE:To investigate whether neuron-derived extracellular vesicles facilitate neural stem cell differentiation towards neurogenesis. METHODS:Neurons and neural stem cells were extracted from neonatal SD rat cerebral cortex by trypsin digestion.Cell supernatants of neurons were collected.Neuron-derived extracellular vesicles were extracted.Neural stem cells cultured for 10 days were co-cultured with neuron-derived extracellular vesicles or PBS for 7 days.Immunoblotting,immunofluorescence,and RT-qPCR were used to detect proteins specifically expressed by neurons,neural stem cells,oligodendrocytes,and astrocytes. RESULTS AND CONCLUSION:The neural stem cells co-cultured with neuron-derived extracellular vesicles showed high expression of neuron-specific proteins and oligodendrocyte-specific proteins including β3-tubulin,neurofilament 200 and myelin basic protein,and low expression of astrocyte-specific protein glial fibrillary acidic protein.These results suggest that neuron-derived extracellular vesicles can promote the differentiation of neural stem cells into neurons and oligodendrocytes and prevent the differentiation of neural stem cells into astrocytes.