Stroke is a global disease that seriously threatens human life. The pathological mechanisms of ischemic stroke include neuroinflammation, oxidative stress, and the destruction of blood vessels at the lesion site. Here, a biocompatible in situ hydrogel platform was designed to target multiple pathogenic mechanisms post-stroke, including anti-inflammation, anti-oxidant, and promotion of angiogenesis. Double-crosslinked responsive multifunctional hydrogels could quickly respond to the pathological microenvironment of the ischemic damage site and mediate the delivery of nitric oxide (NO) and ISO-1 (inhibitor of macrophage migration inhibitory factor, MIF). The hydrogel demonstrated good biocompatibility and could scavenge reactive oxygen species (ROS) and inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-10 (IL-10), and MIF. In a mouse stroke model, hydrogels, when situated within the microenvironment of cerebral infarction characterized by weak acidity and elevated ROS release, would release anti-inflammatory nanoparticles rapidly that exert an anti-inflammatory effect. Concurrently, NO was sustained release to facilitate angiogenesis and provide neuroprotective effects. Neurological function was significantly improved in treated mice as assessed by the modified neurological severity score, rotarod test, and open field test. These findings indicate that the designed hydrogel held promise for sustained delivery of NO and ISO-1 to alleviate cerebral ischemic injury by responding to the brain's pathological microenvironment.

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

BACKGROUND:At present,the traditional powder sintering method is easy to introduce impurities in the process of preparing porous titanium,and the manufacturing of porous titanium still faces two major problems:impurity pollution and difficult control of the material forming process. OBJECTIVE:To prepare pure porous titanium with certain porosity,and analyze the microstructure evolution and properties of the porous titanium. METHODS:Porous titanium was prepared at a low energy density by selective laser melting technology.The parameter range of porous titanium with large porosity was obtained by measuring the porosity of the formed specimen,and the evolution of the microstructure and mechanical properties of the specimen in the range were analyzed. RESULTS AND CONCLUSION:(1)With the increase in energy density,the porosity of the porous titanium specimen decreased gradually.When the energy density was between 10.61 and 27.78 J/mm3,porous titanium with a porosity of 11.23%-33.67%could be formed.When the energy density was between 27.78-37.88 J/mm3,the forming parts were relatively dense.(2)The phase composition of porous titanium formed was mainly α titanium.With the increase in energy density,the porosity gradually decreased,and the pore morphology changed from irregularly connected pores to closed nearly spherical pores.The powder particles changed from a slightly sintered neck to a continuous fuse.The CT scan results revealed that there were a large number of connected pores in the forming specimen with a large specific surface area and the pore radius was roughly distributed between 2-6 μm at the energy density of 10.61 J/mm3.Simultaneously,porous titanium with compressive strength of 188-1 000 MPa could be obtained at the energy density of 10.61-27.78 J/mm3,which could meet the requirements of biomedical applications.(3)These results have confirmed that the selective laser melting technology can overcome the problems of impurity pollution and long manufacturing cycle caused by the traditional preparation process,and provide an effective solution for the preparation of porous titanium with excellent mechanical properties.

To investigate the differences in methylation levels of cuproptosis related genes in cervical cancer and their effects on clinical prognosis.Methods:The methylation data of 310 cervical tissue specimens were acquired from public databases. The UALCAN database was used to analyze the methylation level differences of 12 cuproptosis-related genes and study their level in different stages or grades of cervical cancer. Genes with statistically significant differences were selected for prognosis analysis using the EWAS datahub. Finally, gene-enrichment analysis, pathway analysis, immune infiltration analysis, the mutation rate and tumor mutation burden (TMB) of the genes in cervical cancer were analyzed using the cBioportal database. Two independent samples rank-sum test was used for differences in methylation levels and immune cell infiltration; comparative analyses of overall survival were performed using KM survival curves and Log-rank two-sided tests. TMB analyses were performed using the Wilcoxon Test for statistical analyses; Pearson correlation analysis was used for assessment in GSEA and pathway analyses.Results:The methylationβvalue of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A gene) in the cervical cancer tissues of patients was 0.075 which was significantly higher than the methylationβvalue of 0.049 in normal human tissues ( P=0.008). Dihydrolipoamide S-Acetyltransferase (DLAT gene) methylation with a β value of 0.102 was significantly higher than normal human tissue methylation with a β value of 0.08 ( P=0.002), and the methylation level β value of Lipoyltransferase 1 (LIPT1 gene) in cervical cancer tissues was 0.06,which was significantly lower than normal human tissue methylation value of 0.092 ( P=0.009). Patients with CDKN2A gene methylation levels≥0.199 had an overall survival of 14.75 years, which was lower than that of patients with methylation levels<0.199 (17.56 years) ( P=0.034).The results of gene enrichment analysis indicated that it mainly involves biological processes such as the response to type I interferon and DNA replication. The expression of CDKN2A gene is positively correlated with the number of neutrophils and dendritic cells in the tumor microenvironment( P<0.05), and negatively correlated with the number ofmacrophages( P<0.05). TMB was higher in the group of variants of the CDKN2A gene than in the group of non-variants ( P=0.019). Conclusion:CDKN2A methylation is a potential biomarker for predicting the prognosis of cervical cancer.

Objective To investigate the application value of multiple audiological testing methods in the audi-ological diagnosis of children with no response at maximum output intensity of auditory brainstem response(ABR).Methods We retrospectively studied the clinical data of 69 cases(138 ears)of children with no ABR response with maximum intensity,aged 42 days to 5 years old,with an average of 1 year and 6 months.The tympanogram showed type-A or positive single peak,and acoustic reflex was absent.Imaging examination showed no malformation of the inner ear.All 69 children underwent ABR,cochlear microphonic potential(CM),distortion product otoacoustic e-missions(DPOAE),and auditory steady-state response(ASSR)tests.Results Among 69 cases(138 ears),8 ca-ses(11.59％)recorded CM in 16 ears,of which 10 ears(7.25％)recorded DPOAE.The ASSR response thresh-olds at 0.5,1,2,and 4 kHz were 83.2±13.1,82.9±13.0,75.3±12.4,and 63.1±9.1 dB nHL,respectively.Combined with other examination results,these subjects were diagnosed with auditory neuropathy.The CM and DPOAE responses of the remaining 61 cases(122 ears)were absent,and the extraction rates of ASSR at 0.5,1,2,and 4 kHz were 82.3％,81.9％,76.9％,and 60.2％,respectively.Among them,20 ears of ASSR were absent at all frequencies,and 102 ears had responses in at least one frequency.The response thresholds of ASSR at 0.5,1,2,and 4 kHz were 93.2±6.1,99.8±7.0,105.4±5.4,108.2±9.8 dB nHL,respectively.These subjects were diagnosed with profound sensorineural hearing loss.Conclusion For children with no ABR response at maximum output intensity,while CM and/or DPOAE responses are present and ASSR frequency response thresholds are low-er than those with sensorineural hearing loss are helpful in the diagnosis of auditory neuropathy.Neither CM nor DPOAE response is helpful in the diagnosis of profound sensorineural hearing loss,and ASSR testing is helpful in e-valuating residual hearing.

White-matter tracts play a pivotal role in transmitting sensory and motor information, facilitating interhemispheric communication and integrating different brain regions. Meanwhile, sensorimotor disturbance is a common symptom in patients with major depressive disorder (MDD). However, the role of aberrant sensorimotor white-matter system in MDD remains largely unknown. Herein, we investigated the topological structure alterations of white-matter morphological brain networks in 233 MDD patients versus 257 matched healthy controls (HCs) from the DIRECT consortium. White-matter networks were derived from magnetic resonance imaging (MRI) data by combining voxel-based morphometry (VBM) and three-dimensional discrete wavelet transform (3D-DWT) approaches. Support vector machine (SVM) analysis was performed to discriminate MDD patients from HCs. The results indicated that the network topological changes in node degree, node efficiency, and node betweenness were mainly located in the sensorimotor superficial white-matter system in MDD. Using network nodal topological properties as classification features, the SVM model could effectively distinguish MDD patients from HCs. These findings provide new evidence to highlight the importance of the sensorimotor system in brain mechanisms underlying MDD from a new perspective of white-matter morphological network.
Humans ; Depressive Disorder, Major/pathology* ; White Matter/pathology* ; Male ; Female ; Support Vector Machine ; Adult ; Magnetic Resonance Imaging ; Middle Aged ; Case-Control Studies ; Sensorimotor Cortex ; Brain

Objective:Childhood traumatic experiences greatly influenced the brain network activities of patients with depression,and there is an urgent need to explore the temporal dynamics for these changes.This study aims to investigate the abnormalities of resting-state electroencephalogram(EEG)microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. Methods:Using resting-state EEG microstate analysis,we explored the temporal dynamics of brain activity in patients with adolescent depression.This study selected 66 adolescents with depression as a patient group,and 27 healthy adolescents as a healthy control group.A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates.Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. Results:In this study,significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group.Notably,there was a statistically significant difference(P＜0.05)in the occurrence of microstate A across 2 groups,exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores(Spearman's rho=-0.31,P=0.013).Furthermore,patient-specific,non-random transitions from microstate B to A(Spearman's rho=-0.30,P=0.015)and C to A(Spearman's rho=-0.31,P=0.013)were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group,showing statistically significant differences when comparing to the healthy controls(P＜0.05).Upon stratification into quartiles based on the emotional abuse factor scores,the occurrence of microstate A,as well as the transition rates from microstates B to A and C to A,retained statistical significance following adjustment for multiple comparisons(all P＜0.05). Conclusion:The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse.Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks.EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.

Objective:To analyze the clinical efficacy of treatment of cement dislodgement after vertebral augmentation for osteoporotic vertebral fractures.Methods:A retrospective study was conducted to analyze the data of 13 patients who had been treated at Department of Orthopaedics, The First Affiliated Hospital of Soochow University for cement dislodgement after vertebral augmentation for osteoporotic vertebral fractures from July 2013 to July 2022. There were 4 males and 9 females, with an average age of (76.5±8.6) years and a T value of bone mineral density of -3.3±0.6. By the CT and MRI features of cement dislodgement, their conditions fell in 4 types: cement loosening in situ (4 cases), anterior cement moving (6 cases), anterior cement moving with posterior bone mass moving (2 cases), and posterior cement moving (1 case). They were treated by percutaneous vertebroplasty (3 cases), pedicle screw fixation combined with bone graft fusion and decompression (7 cases), and conservative therapy (3 cases). The curative effects for surgical patients were evaluated by comparing their visual analogue scale (VAS), Oswestry dysfunction index (ODI) and cobb angle of kyphosis at preoperation, 1 week and 1 month postoperation, and the last follow-up, and Frankel grading for nerve injury as well. The curative effects for patients undergoing conservative treatment were evaluated by observing their symptoms.Results:This cohort was followed up for 7 (5, 12) months after treatment. The VAS scores [5.0 (4.0, 5.0) points, 3.0 (2.0, 3.0) points, and 3.0 (2.0, 3.0) points] in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value [8.5 (8.0, 9.0) points] ( P<0.05); the VAS scores at 1 month postoperation and the last follow-up were also significantly improved compared with that at 1 week postoperation ( P < 0.05), but there was no significant difference between the last follow-up and 1 month postoperation ( P > 0.05). The ODIs (50.6%±4.2%, 37.8%±4.5%, and 29.3%±5.6%) in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value (93.2%±3.6%), showing significant differences in pairwise comparisons ( P<0.05). The cobb angles [10.0 (9.0, 11.0)°, 9.0 (9.0, 11.0)°, and 10.0 (9.0, 12.0)°] in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value [12.5 (11.0, 14.0)°] ( P<0.05) , but there was no statistically significant difference between the time points after operation ( P>0.05). The Frankel grading was significantly improved in the 6 patients with nerve injury after operation. Of the 3 patients undergoing conservative treatment, the symptoms were cured in one, showed no change during follow-up in one, and aggravated in one. Conclusion:Surgical treatment can significantly relieve pain, improve spinal dysfunction and repair nerve injury in patients with bone cement dislodgement after vertebral augmentation.

OBJECTIVE: To carry out preimplantation genetic testing for monogenic/single gene disorders (PGT-M) for a Chinese family affected with Molybdenum co-factor deficiency due to pathogenic variant of MOCS2 gene. METHODS: A family with molybdenum co-factor deficiency who attended to the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region in April 2020 was selected as the research subject. Trophoblast cells were biopsied from blastocysts fertilized by intracytoplasmic sperm injection. Embryos carrying the MOCS2 gene variant and chromosome copy number variation (CNV) of more than 4 Mb were detected by single-cell whole genome amplification, high-throughput sequencing and single nucleotide polymorphism typing. Embryos without or carrying the heterozygous variant and without abnormal chromosome CNV were transplanted. During mid-pregnancy, amniotic fluid sample was collected for prenatal diagnosis to verify the results of PGT-M. RESULTS: Eleven oocytes were obtained, among which three blastocysts were formed through culturing. Results of genetic testing suggested that one embryo was heterozygous for the maternally derived MOCS2 gene variant and without chromosomal CNV. Following embryo transfer, intrauterine singleton pregnancy was attained. Prenatal diagnosis by amniocentesis at 18 weeks of gestation revealed that the MOCS2 gene variant and chromosomal analysis results were both consistent with that of PGT-M, and a healthy male infant was born at 37⁺⁵ weeks of gestation. CONCLUSION PGT-M has helped the couple carrying the MOCS2 gene variant to have a healthy offspring, and may become an important method for couples carrying other pathogenic genetic variants.
Female ; Humans ; Pregnancy ; Aneuploidy ; China ; DNA Copy Number Variations ; Genetic Testing/methods* ; Preimplantation Diagnosis/methods* ; Metal Metabolism, Inborn Errors/genetics*

Objective:To analyze the causes of postoperative stricture of biliary-enteric anastomotic for congenital choledochal cysts.Methods:These 28 patients underwent salvage operation on an average 15 years (0.2-25 years) after initial surgeries at the Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital from Jan 2014 to Jun 2018.Results:In 26 patients the biliary-enteric anastomotic stenosis was benign, and in 2 the stricture was caused by cancerration. In 26 cases the Roux-en-Y hepaticojejunostomy was redone,among them 8 cases underwent concurrent hepatectomy for a better exposure of the intrahepatic bile duct. In 2 cases the anastomotic stenosis was found to be caused by canceration with extensive intraabdominal metastasis ,an external drainage was adopted. There were no inhospital deaths, and no serious complications. The postoperative follow-up time was 6-67 months. Two cancerated patients died within half a year, and the remaining patients had no long-term complications.Conclusions:Biliary-enteric anastomotic stenosis is one of the serious complications in postoperative patients for congenital choledochal cysts. Hence a wide, tension free biliary-enteric anastomosis performed by a experienced hand is necessary.