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.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Objective To investigate the detection rate,epidemiology and resistance mechanism of methicil-lin-resistant Staphylococcus aureus(MRSA)in a hospital in recent 5 years.Methods A total of 762 strains of non repetitive Staphylococcus aureus detected from 2016 to 2020 in a hospital were collected retrospectively.Methicillin-sensitive Staphylococcus aureus(MSSA)was 392 strains(MSSA group)and 370 strains caused by MRSA(MRSA group),and 95 strains of MRSA isolated in 2020 were further used for resistance mechanism.Staphylococcus aureus was identified and tested for drug sensitivity by Vitek 2 automatic microbial system.Molecular epidemiological typing was determined by multilocus sequence typing.The biofilm formation was performed by crystal violet staining.PCR amplification was used to detect drug resistance genes,virulence genes and biofilm related genes,and logistic regression analysis was used to investigate the independent risk factors of its occurrence.Results The detection rate of MRSA in past five years was 48.56％,mainly was from pus samples and secretion samples(38.38％,33.51％respectively).MRSA was found in the general sur-gery(18.65％)and otorhinolaryngology(12.70％).ST88 was the most common multilocus sequence typing(37.89％),and followed by ST951(24.21％).Moderate biofilm formation was the most common,accounting for 74.73％.Multivariate regression analysis showed that compared with MSSA group,hypoproteinemia,en-docrine system diseases,wound infection and history of antibiotic use within six months were the independent risk factors for infection in MRSA group.Compared with the control group,hospital transfer,wound infection and tumor were independent risk factors for infection in MRSA group(P＜0.05).Conclusion The detection rate of MRSA in a hospital is high,and the carrying rate of various drug-resistant genes is high.The hospital should pay attention to the prevalence of MRSA and related risk factors,so as to prevent it early.

Objective The ICD intelligent-assisted coding system for the first pages of medical records enhances the in-telligent review and entry of ICD codes on medical records through data collection of medical records information,and improving accuracy and efficiency.Methods The coding rule library for the first page of medical records was constructed,clinical informa-tion across systems was obtained,the operation steps of manual coding review and entry was simulated through coding intelligent analysis,and an intelligent system was introduced into coding review and entry.Three coding methods,namely coding manually by coders,by the intelligent coding system,and by a man-machine collaboration,were adopted to conduct coding review and en-try.The coding results were compared between the three methods.Results Compared to manual coding method,the ICD intelli-gent-assisted coding system exhibited the same accuracy and completeness of coding but a significant increase in coding efficien-cy.The method of human-machine collaborative coding had a better improvement in coding accuracy and efficiency as well com-pared with the manual coding.Conclusion Artificial intelligence technology has superiority in coding entry on the first page,through the ICD Intelligent Assisted Coding Review and Entry System.for it can increase the accuracy of review and entry.The method of human-machine collaboration enhance both the efficiency and accuracy in coding review and entry.

Objective:To investigate the status quo of multi-level pre-job training for clinical nursing teachers and analyze their training needs, so as to provide reference for the design of pre-job training for clinical nursing teachers.Methods:A cross-sectional survey method was used to investigate 172 clinical nursing teachers in a tertiary general hospital in Harbin from April 2020 to June 2020 with multi-level pre-job training mode. The status quo of pre-job training and the training needs of teachers were analyzed. SPSS 17.0 was used to process the original data statistically.Results:Among the 172 respondents, 138 teachers (80.2%) were under 35 years old, and 133 teachers (77.3%) had a bachelor's degree or less; 89 teachers (51.7%) confirmed that hospitals or departments would carry out pre-job training in a planned and organized way, 10 teachers (5.8%) said that hospitals or departments had never organized training, 41 teachers (23.8%) had never participated in pre-job training, and 80 teachers (46.5%) had participated in pre-job training 1-3 times. There were 5 duplicates in the first 8 training contents of in-hospital training and in-department training, including knowledge of common diseases, nursing procedures, communication skills, hospital rules and regulations, and teaching methods. The total score of training demand was (154.51± 40.35) points, and the overall demand rate was 81.3%, which was at the high level. The dimensions with the highest scoring rate were legal system and humanistic literacy, with a scoring rate of 83.0%. The dimension with the lowest score was teaching management, with a score of 74.9%. The scoring rate of training needs with the highest points won nine items respectively on students' basic quality (self-supervision, willingness to learn, professional quality, etc.) (84.7%), training of legal knowledge (84.4%), incompatibility of drugs commonly used in department (84.3%), nurse etiquette (83.3%), nursing risk prevention (83.1%), evaluation methods of student education (83.1%), nurse-patient communication skills (83.0%), nurses and patients medication observation points of commonly used drugs in the department (83.0%), and effects of commonly used drugs in department (82.9%). Among the top three training forms, 84 students (48.8%) received online learning, 74 students (43.0%) received lectures from experienced teachers in hospitals, and 72 students (41.9%) received experience exchange and sharing seminars.Conclusion:The talent structure of clinical nursing teachers in this hospital is relatively young, and the first education level is low. Therefore, the pre-job training of clinical nursing teachers should be strengthened vigorously. The awareness rate and participation rate of pre-job training are average, so we should strengthen the release of training information from various channels, improve the awareness rate of training activities, clarify the encouragement or reward measures to participate in pre-job training activities, and improve the participation rate of training activities. Pre-job training content is repeated at every level, with a gap between the training needs of teachers in clinical nursing teaching. It's suggested that the teaching hospitals combine with their training objects of training needs, take the online-offline mixed mode of training, reasonably plan training contents as a whole at all levels, avoid training content repetition and waste of teachers, and organize teachers to timely exchange and share experiences.

OBJECTIVE: To explore the clinical characteristics and molecular genetic mechanism of a fetus with recombinant chromosome 8 (Rec8) syndrome. METHODS: A fetus who was diagnosed with Rec8 syndrome at the Provincial Hospital Affiliated to Shandong First Medical University on July 20, 2021 due to high risk for sex chromosomal aneuploidy indicated by non-invasive prenatal testing (NIPT) (at 21st gestational week) was selected as the study subject. Clinical data of the fetus was collected. G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out on the amniotic fluid sample. Peripheral blood samples of the couple were also subjected to G banded karyotyping analysis. RESULTS: Prenatal ultrasonography at 23rd gestational week revealed hypertelorism, thick lips, renal pelvis separation, intrahepatic echogenic foci, and ventricular septal defect. The karyotype of amniotic fluid was 46,XX,rec(8)(qter→q22.3::p23.1→qter), and CMA was arr[GRCh37]8p23.3p23.1(158049_6793322)×1, 8q22.3q24.3(101712402_146295771)×3. The karyotype of the pregnant woman was 46,XX,inv(8)(p23.1q22.3), whilst that of her husband was normal. CONCLUSION The Rec8 syndrome in the fetus may be attributed to the pericentric inversion of chromosome 8 in its mother. Molecular testing revealed that the breakpoints of this Rec8 have differed from previously reported ones.
Humans ; Fetus/abnormalities* ; Chromosomes, Human, Pair 8 ; Female ; Pregnancy ; Karyotyping

OBJECTIVE To qualitatively analyze the chemical constituents from Tianzhi granules and their constituents absorbed into blood， and to provide reference for elucidating pharmacodynamic material basis of Tianzhi granules. METHODS UPLC-ESI-Q-TOF-MS/MS was adopted. The analysis was performed on an Agilent Eclipse Plus C18 column with mobile phase consisted of 0.5% formic acid solution-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min； the column temperature was 40 ℃ ；the injection volume was 10 μL. Mass spectrometry was applied for the qualitative analysis under positive ionization mode and ESI ion source. Data were collected with MS-DIAL4.60， and then chemical constituents of the extract from Tianzhi granule （by 0.5% methanol） were analyzed by comparing with relevant literature， SciFinder， PubChem， MassBank， TCMSP， TCM-ID and other databases. The blank serum， administered serum and Tianzhi granule extract were compared to analyze the constituents absorbed into the blood. RESULTS One hundred compounds were preliminarily identified from Tianzhi granules， including 46 flavonoids， 8 organic acids， 8 alkaloids， 6 terpenes， 6 coumarins， 2 quinones， 1 steroids， 7 glycosides and 16 others. Based on it， 10 prototype constituents absorbed into blood were identified preliminarily， including genistein， melatonin A， chrysin-7-O- β-glucuronide， apigenin-7-O-glucuronide， wogonin， 6-O-methylbaicalin are flavonoids， 2-hydroxyquinoline and isonacolline are alkaloids， 7-hydroxycoumarin is coumarins，1-indanol is others. CONCLUSIONS 2-hydroxyquinoline， 7-hydroxycoumarin， genistein， melatonin A， isonocolline， chrysin-7-O-β-glucuronide， apigenin-7-O-glucuronide， wogonin and 6-O-methylbaicalin may be the pharmacodynamic material basis of Tianzhi granules.

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.