Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

AIM:To investigate the antitumor activity and targets of baicalein(Bai)in pancreatic cancer using network pharmacology combined with in vitro and in vivo experiments.METHODS:The targets of Bai and pancreatic can-cer were analyzed via multi-data screening.A protein-protein interaction network was constructed using STRING,and core targets were identified via Cytoscape.Functional enrichment was analyzed by Gene Ontology(GO)and Kyoto Ency-clopedia of Genes and Genomes(KEGG).Antitumor effects of Bai were assessed in pancreatic cancer cells Aspc-1 and Bxpc-3 using MTT and colony formation assays for proliferation,flow cytometry for apoptosis and cell cycle analysis,and Transwell assays for migration and invasion.A xenograft tumor model was established to evaluate tumor proliferation,im-munohistochemistry was performed to detect the protein expression of AKT in tumor tissues,and Western blot was used to analyze the expression levels of AKT,β-catenin,N-cadherin and Slug.RESULTS:A total of 108 overlapping targets were identified between Bai and pancreatic cancer.Among these,7 core targets were recognized,including proto-onco-gene tyrosine-protein kinase Src,heat shock protein 90 alpha family class A member 1(HSP90AA1),estrogen receptor 1(ESR1),tumor protein p53(TP53),epidermal growth factor receptor(EGFR),AKT1,and mitogen-activated protein ki-nase 3(MAPK3).The GO analysis revealed significant enrichment in oxidative stress response,protein phosphorylation,and serine/threonine kinase activity.The KEGG analysis primarily enriched the PI3K/AKT,MAPK and Ras signaling pathways.The MTT and colony formation assays showed that Bai inhibited the viability of Aspc-1 and Bxpc-3 cells in a dose-dependent manner(72 h IC50 values were 73.6 μmol/L and 83.4 μmol/L,respectively)and reduced cell colony for-mation(P<0.05 or P<0.01).Flow cytometry confirmed that Bai induced apoptosis of Aspc-1 and Bxpc-3 cells(P<0.01)and blocked the cell cycle at the G0/G1 phase(P<0.05 or P<0.01).Transwell experiments indicated that Bai inhibited the migration and invasion of Aspc-1 and Bxpc-3 cells(P<0.05 or P<0.01).In vivo,Bai significantly inhibited the growth of Aspc-1 cell xenograft tumors(P<0.01).Immunohistochemistry revealed a significant reduction in AKT expression in tu-mor tissues(P<0.01),and Western blot showed decreased expression of AKT,β-catenin,N-cadherin and Slug in both Aspc-1 and Bxpc-3 cells(P<0.01).CONCLUSION:Baicalein inhibits pancreatic cancer cell proliferation,migration,and invasion,potentially through down-regulation of AKT,β-catenin,N-cadherin,and Slug expression.

Objective:To investigate the efficacy of neuromuscular electrical stimulation (NMES) combined with limb rehabilitation therapy in improving limb function of patients with hemiplegia due to stroke.Methods:A randomized controlled study was conducted on 110 patients with hemiplegia due to stroke admitted to the 987 Hospital of the PLA Joint Logistic Support Force from January 2021 to January 2023. These patients were divided into a control group and an observation group, with 55 cases each, using a random number table method. The control group received conventional rehabilitation therapy, while the observation group received NMES combined with limb rehabilitation therapy. All patients were treated for 3 months. The Trunk Impairment Scale, Brunnstrom Motor Function Scale, Surface Electromyography, Brunel Balance Scale, Simple Gait Test Scale, and Modified Ashworth Scale were used to evaluate trunk control function, limb control function, neuromuscular disorders, balance control function (forward-backward inclination angle, left-right inclination angle), gait temporal-spatial parameters, symmetry parameters, and muscle tone recovery in both groups before and after treatment.Results:After treatment, the Total Impairment Scale and Brunnstrom scores for upper and lower limbs in the observation group were higher than those in the control group [(18.31 ± 1.61) vs. (14.38 ± 1.42), (3.78 ± 0.41) vs. (3.01 ± 0.63), (3.75 ± 0.42) vs. (3.28 ± 0.63), t = 13.58, 7.60, 4.60, all P < 0.05]. Additionally, the scores for tibialis anterior, fibularis brevis, fibularis longus, medial gastrocnemius, lateral gastrocnemius muscle control were higher in the observation group compared with the control group. The scores for Berg Balance Scale, forward-backward inclination angle, left-right inclination angle, step frequency, step length, step speed, and step width in the observation group were also superior to those in the control group. All differences were statistically significant ( t = 17.88, 20.15, 24.62, 19.53, 22.80, 3.31, 8.66, 7.88, 6.08, 4.21, 7.43, 3.35, all P < 0.05). Furthermore, the deviations in step length, the ratio of support on the affected side to the unaffected side, and the ratio of swing on the affected side to the unaffected side in the observation group were lower than those in the control group [(3.53 ± 2.55) vs. (5.35 ± 3.21), (1.11 ± 0.04) vs. (1.14 ± 0.03), (1.10 ± 0.06) vs. (1.24 ± 0.09), t = 3.29, 4.45, 9.60, all P < 0.05]. Additionally, the level of muscle tone recovery in the observation group was higher than that in the control group ( Z = 2.53, P = 0.011). Conclusions:In the treatment of hemiplegia due to stroke, NMES combined with limb rehabilitation therapy can effectively improve patients' trunk and limb control, enhance balance function, and greatly promote muscle strength recovery.

Objective To analyze the symptomatic improvement effects of vitamin D in children with autism spectrum disorder(ASD)based on the microbiota-gut-brain axis.Methods Seventy-two children with ASD were randomly divided into an observation group and a control group,with 36 cases in each group.Three cases dropped out in the control group.The observation group received 1200 IU/day of vitamin D supplementation in addition to conventional rehabilitation training,while the control group received only conventional rehabilitation training.The intervention lasted for 12 weeks.Assessments were conducted before and after the intervention using the childhood autism rating scale(CARS),autism behavior checklist(ABC),and repetitive behavior scale-revised(RBS-R).Resting-state functional connectivity of the brain was measured using near-infrared functional imaging,and serum levels of 25(OH)D3,inflammatory cytokines,and gut microbiota were analyzed.The differences in these indicators before and after the intervention were compared between the two groups to evaluate clinical efficacy.Results The between-group differences in pre-and post-intervention changes showed that the observation group had significantly greater improvements than the control group in the following measures:CARS scores(-5.92±1.40 vs.-2.55±1.43),RBS-R scores(-5.99±1.01 vs.-3.10±1.47),resting-state brain functional connectivity(0.19±0.15 vs.0.10±0.18),serum 25(OH)D3 levels[(34.89±8.18)ng/mL vs.(0.68±6.73)ng/mL],serum interleukin-6(IL-6)levels[(-6.60±6.07)pg/mL vs.(-0.74±9.45)pg/mL],IL-1β levels[(-2.56±1.33)pg/mL vs.(-0.04±2.13)pg/mL],and tumor necrosis factor-α(TNF-α)levels[(-4.09±3.85)pg/mL vs.(0.21±4.05)pg/mL](P<0.05).Post-intervention,significant differences in gut microbial β-diversity were observed between the two groups(R2=0.030,P=0.040,Adonis).LEfSe analysis revealed that the observation group exhibited enrichment in Clostridia(LDA=4.747,P=0.003),Clostridiales(LDA=4.747,P=0.003),Clostridiaceae(LDA=3.476,P=0.001),Lachnospiraceae(LDA=4.709,P=0.004),Odoribacteraceae(LDA=3.458,P=0.027),Odoribacter(LDA=3.458,P=0.027),Burkholderiales(LDA=3.339,P=0.038),Firmicutes(LDA=4.764,P=0.003),and Betaproteobacteria(LDA=3.338,P=0.037).Conclusion Vitamin D supplementation can modulate gut microbial diversity in children with ASD,significantly influence the abundance of specific gut microbiota,reduce systemic inflammatory cytokines,enhance brain functional connectivity,and alleviate clinical symptoms of ASD.

Objective To construct machine learning models to predict the incidence of linezolid-induced thrombocytopenia(LIT).Methods A total of 198 patients treated with linezolid in a hospital between January 2020 and March 2024 were retrospectively included.Firstly,the patients were divided into LIT and non-LIT groups,and the basic characteristics of the two groups were compared.Then,the variables with significant differences between the two groups were selected as potential risk factors to construct models for predicting LIT,including Logistic regression,decision tree and random forest models,and the prediction performance of the models was evaluated and compared.Results There were 52(26.3％)patients developed LIT during the treatment.The univariate analysis showed significant differences in linezolid trough concentration(Cmin),baseline platelet counts and creatinine clearance,the incidence of cerebrovascular disease,acute respiratory distress syndrome,and abdominal infection in patients with and without LIT.Among the three models built based on these variables,the random forest model has the best predictive performance.The results of variable importance analysis based on random forest model showed that Cmin,baseline platelet count and combined with acute respiratory distress syndrome had higher importance scores.Conclusions The random forest model has high accuracy in predicting the occurrence of LIT,and the risk of LIT is higher in patients with higher levels of linezolid exposure and lower baseline platelets.

Objective To analyze the symptomatic improvement effects of vitamin D in children with autism spectrum disorder(ASD)based on the microbiota-gut-brain axis.Methods Seventy-two children with ASD were randomly divided into an observation group and a control group,with 36 cases in each group.Three cases dropped out in the control group.The observation group received 1200 IU/day of vitamin D supplementation in addition to conventional rehabilitation training,while the control group received only conventional rehabilitation training.The intervention lasted for 12 weeks.Assessments were conducted before and after the intervention using the childhood autism rating scale(CARS),autism behavior checklist(ABC),and repetitive behavior scale-revised(RBS-R).Resting-state functional connectivity of the brain was measured using near-infrared functional imaging,and serum levels of 25(OH)D3,inflammatory cytokines,and gut microbiota were analyzed.The differences in these indicators before and after the intervention were compared between the two groups to evaluate clinical efficacy.Results The between-group differences in pre-and post-intervention changes showed that the observation group had significantly greater improvements than the control group in the following measures:CARS scores(-5.92±1.40 vs.-2.55±1.43),RBS-R scores(-5.99±1.01 vs.-3.10±1.47),resting-state brain functional connectivity(0.19±0.15 vs.0.10±0.18),serum 25(OH)D3 levels[(34.89±8.18)ng/mL vs.(0.68±6.73)ng/mL],serum interleukin-6(IL-6)levels[(-6.60±6.07)pg/mL vs.(-0.74±9.45)pg/mL],IL-1β levels[(-2.56±1.33)pg/mL vs.(-0.04±2.13)pg/mL],and tumor necrosis factor-α(TNF-α)levels[(-4.09±3.85)pg/mL vs.(0.21±4.05)pg/mL](P<0.05).Post-intervention,significant differences in gut microbial β-diversity were observed between the two groups(R2=0.030,P=0.040,Adonis).LEfSe analysis revealed that the observation group exhibited enrichment in Clostridia(LDA=4.747,P=0.003),Clostridiales(LDA=4.747,P=0.003),Clostridiaceae(LDA=3.476,P=0.001),Lachnospiraceae(LDA=4.709,P=0.004),Odoribacteraceae(LDA=3.458,P=0.027),Odoribacter(LDA=3.458,P=0.027),Burkholderiales(LDA=3.339,P=0.038),Firmicutes(LDA=4.764,P=0.003),and Betaproteobacteria(LDA=3.338,P=0.037).Conclusion Vitamin D supplementation can modulate gut microbial diversity in children with ASD,significantly influence the abundance of specific gut microbiota,reduce systemic inflammatory cytokines,enhance brain functional connectivity,and alleviate clinical symptoms of ASD.

Objective To construct machine learning models to predict the incidence of linezolid-induced thrombocytopenia(LIT).Methods A total of 198 patients treated with linezolid in a hospital between January 2020 and March 2024 were retrospectively included.Firstly,the patients were divided into LIT and non-LIT groups,and the basic characteristics of the two groups were compared.Then,the variables with significant differences between the two groups were selected as potential risk factors to construct models for predicting LIT,including Logistic regression,decision tree and random forest models,and the prediction performance of the models was evaluated and compared.Results There were 52(26.3％)patients developed LIT during the treatment.The univariate analysis showed significant differences in linezolid trough concentration(Cmin),baseline platelet counts and creatinine clearance,the incidence of cerebrovascular disease,acute respiratory distress syndrome,and abdominal infection in patients with and without LIT.Among the three models built based on these variables,the random forest model has the best predictive performance.The results of variable importance analysis based on random forest model showed that Cmin,baseline platelet count and combined with acute respiratory distress syndrome had higher importance scores.Conclusions The random forest model has high accuracy in predicting the occurrence of LIT,and the risk of LIT is higher in patients with higher levels of linezolid exposure and lower baseline platelets.

Objective To analyze the relationship between clinical drug utilization and the risk of nosocomial infections among hospitalized patients,and provide evidence for the prevention and control of nosocomial infections.Methods This study adopted a retrospective case-control design.The case group included 209 patients with nosocomial infection reported from January 2023 to December 2023 in a tertiary hospital.The control group included 209 patients without nosocomial infection during the same period.The patients in the control group were selected by stratified sampling based on Charlson Comorbidity Index(CCI).Results Univariate analysis showed that proton pump inhibitors,antacids,immunosuppressants and prior antimicrobial combination therapy increased the risk of nosocomial infection(P＜0.05).Multivariate log-binomial regression analysis showed that proton pump inhibitors,immunosuppressive drugs,and prior antimicrobial combination therapy were correlated with nosocomial infection.The corresponding relative risk(RR)was 1.31(95％CI:1.07-1.60),1.40(95％CI:1.02-1.91),and 1.66(95％CI:1.01-2.74),respectively.Further analysis indicated that the patients with nosocomial infection had longer time in use of proton pump inhibitors and prior antimicrobial combination therapy than the patients in the control group(Z=-6.331,P＜0.001;Z=-2.667,P=0.008).The trend Chi-square test showed that there was a dose-response relationship for proton pump inhibitors(x2=73.869,P＜0.001),immunosuppressive drugs(x2=16.530,P＜0.001),and prior antimicrobial combination therapy(x2=35.107,P＜0.001).Conclusions The use of immunosuppressants,proton pump inhibitors and antimicrobial combination therapy increases the risk of nosocomial infections in hospitalized patients.The prolonged use of these drugs will further increase the risk of nosocomial infection.

Objective To understand the clinical characteristics of patients with Streptococcus anginosus group(SAG)pulmonary abscess and resistance of SAG.Methods 67 patients with pulmonary abscess admitted to a hos-pital from January 2018 to May 2022 were retrospectively analyzed,clinical data of patients with SAG pulmonary abscess were analyzed,and the minimum inhibitory concentration of antimicrobial agents to 18 SAG strains was de-tected by microbroth dilution method,the carriage of resistance genes and virulence genes of SAG were detected by high-throughput sequencing technology.Results Among 67 patients with pulmonary abscess,SAG accounted for 29.9％(20/67),out of which 2 were excluded due to bacterial inactivation,and 18 patients were included for fur-ther studies.18 patients with SAG pulmonary abscess were all community acquired,with an average age of(60.9±9.1)years.There were 13(72.2％)male patients,most patients(94.4％)complicated chronic pulmonary disease,with cough(94.4％)and expectoration(88.9％)as the initial symptoms,some patients(44.4％)had chest pain,and more than half(61.1％)didn't have fever.The proportion of neutrophils,erythrocyte sedimentation rate,and C-reactive protein were mostly elevated,while procalcitonin was normal.The resistance rate of 18 SAG strains to erythromycin,clindamycin,and tetracycline was＞65％,out of which 14 strains carried resistance gene ermB,13 strains carried resistance gene tetM,and 1 strain carried both resistance gene msrD and mefA.18 SAG strains were detected virulence gene psaA,out of which 3 strains were detected virulence gene nan A.Conclusion SAG is an im-portant pathogen that causes pulmonary abscess,and the patients'complications are mainly chronic pulmonary di-seases,with non-specific clinical manifestations;Most strains carry ermB and tetM genes,mediating resistance to macrolides,lincosamides,and tetracyclines.

Objective:To understand the activity concentrations of varying chemical forms of 131I in nuclear medicine workplaces and assess the internal irradiation doses of 131I to workers. Methods:A high-volume air sampler was used for air sampling of 131I. Glass fiber filters, activated carbon filters, and iodine cartridges, which were connected in series, were employed to collect aerosol iodine, gaseous inorganic iodine, and gaseous organic iodine, respectively. A method for analyzing the activity of 131I unevenly distributed in the iodine cartridge was developed, and an HPGe γ spectrometer was used to determine the activity of 131I in samples collected from the nuclear medicine workplaces of 15 hospitals. Results:The concentrations of aerosol iodine, inorganic iodine, and organic iodine in 15 hospitals were determined at 0.19-206.67, 0.27-138.45, and 2.35-3 821.11 Bq/m 3, respectively, with arithmetic means of 22.04, 12.79 and 365.08 Bq/m 3, respectively. The maximum annual committed effective doses of varied forms of 131I inhaled by workers were determined at 0.19, 0.19, and 3.81 mSv, respectively, with a maximum total committed effective dose of 4.13 mSv. Conclusions:Gaseous organic iodine is identified as the primary form of 131I in the air within nuclear medicine workplaces. Therefore, it is necessary to highlight the monitoring and protection of gaseous organic iodine.