OBJECTIVES: To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres, achieving synergistic enhance-ment of mechanical robustness and biofunctionality. METHODS: Methacrylated hyaluronic acid (HAMA) and thiolated silk fibroin (TSF) were synthesized. Monodisperse microspheres generated via microfluidics were UV-cured (420 nm) through thiol-ene click reaction. These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites. The grafting rate of TSF and HAMA was characterized by H1-NMR; particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy; gel point of composite microsphere hydrogels was determined by advanced extensional rheometer; microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy; elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy; tunability of composite microsphere hydrogels was observed by inverted confocal microscopy; mechanical properties of composite microsphere hydrogels were tested by compression testing; swelling ratio, degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method. Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay; cell migration capability was observed by scratch assay. RESULTS: The grafting rates of HAMA and TSF was 48.03% and 17.99%, respectively. Microsphere hydrogels with particle sizes of (43.3±1.2), (78.1±3.0), and (130.8±1.9) μm were prepared. The gel time of the composite microsphere hydrogels was 48-115s. The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels. The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40% strain after 20 compression cycles. The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments, and reducing microsphere particle size could significantly enhance its stability under moist conditions. The degradation rate of the composite microsphere hydrogels was (49.1±0.9)% after 200 h, and water retention rate was maintained at 40%-60% after 96 h. Biocompatibility assays confirmed >95% cell viability and unimpaired cell migration abilities. CONCLUSIONS The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication, adjustable mechanical properties, enhanced environmental stability and excellent biocom-patibility, thus providing a new material solution for tissue repair and regenerative medicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Microspheres ; Hyaluronic Acid/chemistry* ; Humans

OBJECTIVES: To investigate the effects of early life intervention with Bifidobacterium bifidum BD-1 (B. bifidum BD-1) on hyperactivity in a female mouse model of attention deficit hyperactivity disorder (ADHD) and explore the underlying mechanisms. METHODS: Eight newborn female Wistar-Kyoto (WKY) rats and 6 spontaneous hypertensive rats (SHRs) were gavaged with saline and another 6 SHRs were gavaged with B. bifidum BD-1 (10⁹ CFU) daily for 3 weeks. Open field test of the rats was conducted at 7 weeks, and fecal samples were collected at weaning (3 weeks) and at 7 weeks for 16S rRNA sequencing. Immunofluorescent staining was used to detect dopamine transporter (DAT) and tyrosine hydroxylase (Th) levels in the striatum and activated microglia in the prefrontal cortex. Treg cells in the mesenteric lymph nodes, spleen and blood were analyzed using flow cytometry. RESULTS: The SHRs traveled a significantly greater distance in open fields test than WKY rats, and this behavior was significantly attenuated by B. bifidum BD-1 intervention. The expression of DAT and Th in the striatum was significantly lower in the SHRs than in WKY rats, while B. bifidum BD-1 treatment obviously increased Th levels in the SHRs. B. bifidum BD-1 intervention significantly deceased the number of activated microglia and increased Treg cell counts in the spleen of SHRs. The treatment also enhanced α diversity in gut microbiota of the SHRs and resulted in a decreased Firmicutes/Bacteroidota ratio, more active Muribaculaceae growth, and suppression of Clostridia_UCG-014 proliferation. CONCLUSIONS Early life intervention with B. bifidum BD-1 alleviates hyperactivity in female SHRs by modulating the gut microbiota and peripheral immune response, suppressing neuroinflammation and improving dopaminergic system function. These findings provide evidence for early prevention strategies and support the development and application of psychobiotics for ADHD.
Animals ; Female ; Rats ; Rats, Inbred WKY ; Rats, Inbred SHR ; Attention Deficit Disorder with Hyperactivity/therapy* ; Bifidobacterium bifidum ; Probiotics/therapeutic use* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Tyrosine 3-Monooxygenase/metabolism* ; Gastrointestinal Microbiome ; Disease Models, Animal

Objective To explore the relationship between triglyceride-glucose index(TyG)and acute ischemic stroke with large vessel occlusion(AIS-LVO)of anterior circulation.Methods A retrospective study was conducted on patients with anterior circulation AIS-LVO who underwent emergency endovascular thrombectomy at Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2019.According to modified Rankin scale(mRS)score 90 d after operation,the patients were assigned to favorable outcome group(mRS score 0-2)or unfavorable outcome group(mRS score 3-6),and the TyG was compared.According to the median of TyG,the patients were assigned to low-TyG group(TyG＜8.57)or high-TyG group(TyG ≥8.57),and the clinical data,laboratory indexes,and imaging characteristics were compared.Receiver operating characteristic curve was used to evaluate the predictive value of TyG for poor prognosis.Results A total of 135 patients were enrolled,with 72 in the favorable outcome group and 63 in the unfavorable outcome group.The TyG of the unfavorable outcome group was significantly higher than that of the favorable outcome group(8.82+0.63 vs 8.43+0.60,P＜0.001).There were 67 patients in the low-TyG group and 68 in the high-TyG group.Compared with the low-TyG group,the proportion of patients with hyperlipidemia history(P=0.003),systolic blood pressure at admission(P=0.018),fasting blood glucose level(P＜0.001),and triglyceride level(P＜0.001)were significantly higher in the high-TyG group,the infarct core volume was significantly larger(P=0.025),the high density lipoprotein-cholesterol level was significantly lower(P=0.013),and the mRS score 90 d after operation was significantly higher(3[1,5]vs 1[0,5],P=0.049).The TyG had certain predictive value for poor prognosis in anterior circulation AIS-LVO patients(area under curve value=0.662,95％confidence interval 0.571-0.753).Conclusion TyG is elevated in anterior circulation AIS-LVO patients with poor prognosis,and may be a potential prognostic indicator for anterior circulation AIS-LVO patients.

Objective To systematically evaluate the risk prediction models for neonatal early-onset sepsis(EOS),aiming to provide reference for the construction and optimization of models,as well as for clinical selection of appro-priate prediction models.Methods PubMed,Web of Science,Embase,Cochrane Library,China National Know-ledge Infrastructure(CNKI),Wanfang Data,China Biology Medicine disc(CBM),and VIP databases were re-trieved,and studies relevant to neonatal EOS risk prediction models were collected.The retrieval period was from the inception of the database to January 18,2025.Two researchers independently screened literatures,extracted da-ta,and evaluated the quality of the included literatures using PROBAST tool.Any disagreements were resolved through consultation with a third reviewer.Results A total of 14 literatures were included in analysis,containing 19 risk prediction models.The area under receiver operating characteristic(ROC)curve(AUC)of the included model ranged 0.71-0.999.The number of prediction factors ranged 3-21.Common prediction factors included young gestational age,low birth weight,1-minute Apgar score,abnormal neonatal temperature,prolonged prema-ture rupture of membranes,amniotic fluid turbidity,maternal Group B streptococcal infection,maternal chorioam-nionitis,as well as elevated levels of procalcitonin and C-reactive protein in neonates.The risk of model overall bias was high,mainly due to insufficient number of outcome variable events in the analysis field,improper processing of missing data,screening of prediction factors based on univariate analysis,lacking model performance evaluation,and overfitting of model.Conclusion The neonatal EOS risk prediction model is still at the development stage.Al-though the current prediction models have better overall predictive performance,the overall quality needs to be im-proved.Future modeling can follow the PROBAST and TRIPOD specifications to reduce bias risk,explore the com-bination of multiple modeling methods,and focus on strengthening external validation and localized application to enhance the clinical applicability and promotion value of the model.

This study was aimed at exploring the prevalence and drug sensitivity of Gordonia strains isolated from sputum samples in Henan Province,to provide data to aid in the prevention and treatment of Gordonia infection.A combination of 16S rDNA and sec A1 gene sequencing was used to identify the isolated strains,and susceptibility to16 drugs was determined with the broth microdilution method.A total of 21 strains were identified through 16S rDNA gene and sec A1 gene sequencing,including five strains of Gordonia broncians,eight strains of Gordonia paraphernivans,seven strains of Gordonia sputi,and one strain of Gordonia aichiensis.Drug sensi-tivity testing showed high Gordonia sensitivity to drugs such as ceftriaxone,linezolid,doxycycline,amoxicillin/clavulanic acid,mino-cycline,cefotaxime,trimethoprim/sulfamethoxazole,imipenem,tobramycin,and clarithromycin.The sensitivity rates of the isolated strains were 90.48%(19/21),100%(21/21),90.48%(19/21),90.48%(19/21),95.24%(20/21),90.48%(19/21),90.48%(19/21),90.48%(19/21),and 95.24%(20/21),respectively.Gordonia showed high resistance to rifampicin and cefepime,with rates of 28.57%(6/21)and 19.05%(4/21),respectively.Meanwhile,the resistance varied among bacterial strains.The resistance rate of G.sputi to rifampicin reached 71.43%(5/7),whereas that of G.parapffinivoras to cefepime was 37.5%(3/8).The main species of Gordo-nia isolated from sputum samples of patients in Henan Province were G.bronchialis,G.paraffinivoras,G.sputi,and G.aichiensis.Drug sensitivity tests indicated that drugs including amoxicillin/clavulanic acid,ceftriaxone,cefotaxime,tobramycin,clarithromycin,mi-nocycline,trimethoprim/sulfamethoxazole,linezolid,and doxycycline had good antibacterial effects against Gordonia.

This study was aimed at exploring the prevalence and drug sensitivity of Gordonia strains isolated from sputum samples in Henan Province,to provide data to aid in the prevention and treatment of Gordonia infection.A combination of 16S rDNA and sec A1 gene sequencing was used to identify the isolated strains,and susceptibility to16 drugs was determined with the broth microdilution method.A total of 21 strains were identified through 16S rDNA gene and sec A1 gene sequencing,including five strains of Gordonia broncians,eight strains of Gordonia paraphernivans,seven strains of Gordonia sputi,and one strain of Gordonia aichiensis.Drug sensi-tivity testing showed high Gordonia sensitivity to drugs such as ceftriaxone,linezolid,doxycycline,amoxicillin/clavulanic acid,mino-cycline,cefotaxime,trimethoprim/sulfamethoxazole,imipenem,tobramycin,and clarithromycin.The sensitivity rates of the isolated strains were 90.48%(19/21),100%(21/21),90.48%(19/21),90.48%(19/21),95.24%(20/21),90.48%(19/21),90.48%(19/21),90.48%(19/21),and 95.24%(20/21),respectively.Gordonia showed high resistance to rifampicin and cefepime,with rates of 28.57%(6/21)and 19.05%(4/21),respectively.Meanwhile,the resistance varied among bacterial strains.The resistance rate of G.sputi to rifampicin reached 71.43%(5/7),whereas that of G.parapffinivoras to cefepime was 37.5%(3/8).The main species of Gordo-nia isolated from sputum samples of patients in Henan Province were G.bronchialis,G.paraffinivoras,G.sputi,and G.aichiensis.Drug sensitivity tests indicated that drugs including amoxicillin/clavulanic acid,ceftriaxone,cefotaxime,tobramycin,clarithromycin,mi-nocycline,trimethoprim/sulfamethoxazole,linezolid,and doxycycline had good antibacterial effects against Gordonia.

[Purpose]To investigate the choice of medical institutions for the first-treatment of can-cer patients after diagnosis and the factors influencing it,so as to provide a reference basis for the rational allocation of health resources and the promotion of hierarchical diagnosis and treatment of cancer.[Methods]A total of 1 140 common cancer patients from 1 provincial,3 municipal and 6 county-level medical institutions in Shandong Province were included in the study,and a ques-tionnaire survey was conducted on their basic personal information and the selection of medical institutions.Chi-square test and Fisher exact test were used to compare different groups,and mul-ti-classification unordered Logistic regression were used to explore the factors influencing the se-lection of cancer patients.[Results]1 077 valid questionnaires were collected.The selection rates of first-treatment institutions for cancer patients were county hospitals(29.90％),city hospitals(35.28％),and provincial hospitals(34.82％),and the high level of medical care was the main reason for the selection of first-treatment institutions for cancer patients.The results of multi-clas-sification unordered Logistic regression showed that when choosing municipal and county medical institutions as the first treatment institution compared to choosing a county medical institution for the first treatment as a reference,compared to patients with stage Ⅰ tumors,patients with tumor stages at stage Ⅲ(OR=1.789,95％CI:1.014～3.158)and stage Ⅳ(OR=2.005,95％CI:1.179～3.409)were more likely to choose municipal medical institutions;and patients with annual house-hold income of 10 000～＜50 000 CNY(OR=0.625,95％CI:0.414～0.943)were less likely to choose mu-nicipal medical institutions compared to those with an annual household income of＜10 000 CNY.When choosing provincial and county medical institutions as the first treatment institution com-pared to patients in stage Ⅲ(OR=2.885,95％C1:1.549～5.372)and stage Ⅳ(OR=3.104,95％CI:1.724～5.586)compared to patients with stage Ⅰ tumors when choosing a county medical institu-tion for the first treatment was used as a reference;married(OR=2.248,95％CI:1.127～4.484)patients were more likely to choose provincial healthcare organizations than unmarried/divorced/widowed patients;patients with a family history of cancer compared to patients without a family history of cancer(OR=1.650,95％CI:1.115～2.441)were more inclined to choose provincial healthcare institutions;compared with patients＜45 years old,patients over 60 years old(OR=0.483,95％CI:0.242～0.962)were less inclined to choose provincial hospitals;and compared with patients who were not aware of knowledge related to cancer,those who were aware of knowledge related to cancer(OR=0.613,95％CI:0.441～0.852)patients were less inclined to choose provin-cial hospitals.[Conclusion]Vigorously carrying out publicity on cancer prevention and treatment knowledge,improving the cancer prevention and treatment literacy of cancer patients.strengthen-ing vertical cooperation among medical institutions at all levels,improving the provincial-munici-pal-county cancer prevention and treatment network,and promoting the sinking of high-quality medical resources are important ways to improve the cancer prevention and treatment capacity of counties and promote the work of hierarchical medical system.

[Purpose]To investigate the choice of medical institutions for the first-treatment of can-cer patients after diagnosis and the factors influencing it,so as to provide a reference basis for the rational allocation of health resources and the promotion of hierarchical diagnosis and treatment of cancer.[Methods]A total of 1 140 common cancer patients from 1 provincial,3 municipal and 6 county-level medical institutions in Shandong Province were included in the study,and a ques-tionnaire survey was conducted on their basic personal information and the selection of medical institutions.Chi-square test and Fisher exact test were used to compare different groups,and mul-ti-classification unordered Logistic regression were used to explore the factors influencing the se-lection of cancer patients.[Results]1 077 valid questionnaires were collected.The selection rates of first-treatment institutions for cancer patients were county hospitals(29.90％),city hospitals(35.28％),and provincial hospitals(34.82％),and the high level of medical care was the main reason for the selection of first-treatment institutions for cancer patients.The results of multi-clas-sification unordered Logistic regression showed that when choosing municipal and county medical institutions as the first treatment institution compared to choosing a county medical institution for the first treatment as a reference,compared to patients with stage Ⅰ tumors,patients with tumor stages at stage Ⅲ(OR=1.789,95％CI:1.014～3.158)and stage Ⅳ(OR=2.005,95％CI:1.179～3.409)were more likely to choose municipal medical institutions;and patients with annual house-hold income of 10 000～＜50 000 CNY(OR=0.625,95％CI:0.414～0.943)were less likely to choose mu-nicipal medical institutions compared to those with an annual household income of＜10 000 CNY.When choosing provincial and county medical institutions as the first treatment institution com-pared to patients in stage Ⅲ(OR=2.885,95％C1:1.549～5.372)and stage Ⅳ(OR=3.104,95％CI:1.724～5.586)compared to patients with stage Ⅰ tumors when choosing a county medical institu-tion for the first treatment was used as a reference;married(OR=2.248,95％CI:1.127～4.484)patients were more likely to choose provincial healthcare organizations than unmarried/divorced/widowed patients;patients with a family history of cancer compared to patients without a family history of cancer(OR=1.650,95％CI:1.115～2.441)were more inclined to choose provincial healthcare institutions;compared with patients＜45 years old,patients over 60 years old(OR=0.483,95％CI:0.242～0.962)were less inclined to choose provincial hospitals;and compared with patients who were not aware of knowledge related to cancer,those who were aware of knowledge related to cancer(OR=0.613,95％CI:0.441～0.852)patients were less inclined to choose provin-cial hospitals.[Conclusion]Vigorously carrying out publicity on cancer prevention and treatment knowledge,improving the cancer prevention and treatment literacy of cancer patients.strengthen-ing vertical cooperation among medical institutions at all levels,improving the provincial-munici-pal-county cancer prevention and treatment network,and promoting the sinking of high-quality medical resources are important ways to improve the cancer prevention and treatment capacity of counties and promote the work of hierarchical medical system.

Objective To systematically evaluate the risk prediction models for neonatal early-onset sepsis(EOS),aiming to provide reference for the construction and optimization of models,as well as for clinical selection of appro-priate prediction models.Methods PubMed,Web of Science,Embase,Cochrane Library,China National Know-ledge Infrastructure(CNKI),Wanfang Data,China Biology Medicine disc(CBM),and VIP databases were re-trieved,and studies relevant to neonatal EOS risk prediction models were collected.The retrieval period was from the inception of the database to January 18,2025.Two researchers independently screened literatures,extracted da-ta,and evaluated the quality of the included literatures using PROBAST tool.Any disagreements were resolved through consultation with a third reviewer.Results A total of 14 literatures were included in analysis,containing 19 risk prediction models.The area under receiver operating characteristic(ROC)curve(AUC)of the included model ranged 0.71-0.999.The number of prediction factors ranged 3-21.Common prediction factors included young gestational age,low birth weight,1-minute Apgar score,abnormal neonatal temperature,prolonged prema-ture rupture of membranes,amniotic fluid turbidity,maternal Group B streptococcal infection,maternal chorioam-nionitis,as well as elevated levels of procalcitonin and C-reactive protein in neonates.The risk of model overall bias was high,mainly due to insufficient number of outcome variable events in the analysis field,improper processing of missing data,screening of prediction factors based on univariate analysis,lacking model performance evaluation,and overfitting of model.Conclusion The neonatal EOS risk prediction model is still at the development stage.Al-though the current prediction models have better overall predictive performance,the overall quality needs to be im-proved.Future modeling can follow the PROBAST and TRIPOD specifications to reduce bias risk,explore the com-bination of multiple modeling methods,and focus on strengthening external validation and localized application to enhance the clinical applicability and promotion value of the model.

Objective:To investigate the behavioral, electroencephalographic, and cognitive functional differences in drug-resistant epileptic rat models of cognitive impairment prepared by intraperitoneal injection of lithium chloride-pilocarpine followed by intracranial injection of pilocarpine or carbamylcholine.Methods:One hundred and sixty adult male SD rats were randomly divided into normal control group ( n=10), lithium chloride-pilocarpine group (establishing epileptic rat models by intraperitoneal injection of lithium chloride-pilocarpine, n=50), pilocarpine-pilocarpine group (intracranial injection of pilocarpine after intraperitoneal injection of lithium chloride-pilocarpine, n=50)and pilocarpine-carbamylcholine group (intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine, n=50). Frequency and duration of spontaneously recurrent seizures (SRSs) were observed by video monitoring system, and 2 weeks after that, phenobarbital and phenytoin sodium were injected intraperitoneally to screen drug-resistant models. Frequency and amplitude of the epileptic waves in EEG were recorded by BL-420 Bio-signal Acquisition and Processing System. Novel object recognition experiment was used to detect the novel exploration, Y-maze free exploration experiment and new and different arm experiment were used to detect the spatial recognition and memory ability, and Morris water maze experiment was used to detect the spatial memory ability. Results:(1) Twenty-four rats (48.00%) survived in the lithium chloride-pilocarpine group, 25 (78.00%) in the pilocarpine-pilocarpine group, and 21 (65.62%) in the pilocarpine-carbamylcholine group; and ultimately 7, 9, and 8 drug-resistant epileptic rat models were identified, respectively; frequency and duration of SRSs in the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group were significantly higher/longer than those in the lithium chloride-pilocarpine group ( P<0.05). (2) The pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly higher amplitude of the epileptic waves in EEG compared with the lithium chloride-pilocarpine group ( P<0.05); the frequency of the epileptic waves in EEG increased gradually in the lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group ( P<0.05). (3) Discrimination index, accuracy, ratio of distance traveled in novel arm to total distance, and time of novel arm entries gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). (4) Compared with the normal control group, the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly decreased frequency in crossing the original platform ( P<0.05); compared with the normal control group, lithium-pilocarpine chloride group and pilocarpine-pilocarpine group, the pilocarpine-carbamylcholine group had statistically shorter distance of target quadrant activity ( P<0.05); number of entries in the target quadrant gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). Conclusion:Drug-resistant epileptic rat models established by intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine have high survival rate, high SRSs rate, and severe cognitive impairment, which is suitable for studying drug-resistant epilepsy combined with cognitive impairment.