Objective:To explore the application value of P1 response threshold of cortical auditory evoked potential（CAEP） in evaluating the rehabilitation effect of cochlear implant in young children. Methods:Thirty-three young children after cochlear implantation were divided into groups according to hearing age: Group A（hearing age 1-<2 years old） 10 people; Group B（hearing age 2-<3 years old） 13 people; Group C（hearing age 3-<4 years old） 10 people. The subjective assessment was carried out using the assessment tool for hearing-impaired children- "Criteria and Methods for assessing Auditory and language ability of hearing-impaired children" and objective electrophysiological examination was carried out using CAEP to evaluate the rehabilitation effect. SPSS 25.0 software was used for statistical analysis. Results:The results of subjective assessment of auditory ability and language ability in each group showed an increasing trend with the increase of auditory age. In this study, the P1 response threshold of CAEP in CI implanted children had a significant positive correlation with the 2 kHz hearing threshold after intervention, and the P1 response threshold of CAEP was negatively correlated with many items in subjective auditory ability and language ability assessment. Conclusion:The P1 response threshold of CAEP has a stable correlation with the results of speech audiometry, which can effectively and objectively evaluate the postoperative rehabilitation effect of young children with cochlear implantation.
Humans ; Child, Preschool ; Infant ; Male ; Female ; Evoked Potentials, Auditory ; Cochlear Implantation/rehabilitation* ; Cochlear Implants ; Auditory Threshold

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

OBJECTIVE: While higher therapeutic doses of toxic cardiac glycosides derived from Cerbera odollam are frequently employed in cases of suicide or homicide, ongoing research is investigating the potential anticancer properties of low-concentration extracts obtained from the fruits of C. odollam. The present study aimed to determine the enhanced anticancer effects and minimize potential side effects of combining extracts from C. odollam fruits from Thailand with sorafenib against HCT116 and HepG2 cells. METHODS: The dried powder of fresh green fruits of C. odollam was fractionated, and its phytochemical contents, including total cardiac glycosides, phenolics, flavonoids, and triterpenoids, were quantified. The cytotoxic effects of these fractions were evaluated against HCT116 and HepG2 cells using the MTT assay. The fractions showing the most significant response in HCT116 and HepG2 cells were subsequently combined with sorafenib to examine their synergistic effects. Apoptosis induction, cell cycle progression, and mitochondrial membrane potential (MMP) were then assessed. The underlying mechanism of the apoptotic effect was further investigated by analyzing reactive oxygen species (ROS) generation and the expression levels of antioxidant proteins. RESULTS: Phytochemical analysis showed that C. odollam-ethyl acetate fraction (COEtOAc) was rich in cardiac glycosides, phenolics, and flavonoids, while the dichloromethane fraction (CODCM) contained high levels of triterpenoids and saponins. Following 24 h treatment, HCT116 showed the most significant response to COEtOAc, while HepG2 responded well to CODCM with IC₅₀ values of (42.04 ± 16.94) μg/mL and (123.75 ± 14.21) μg/mL, respectively. Consequently, COEtOAc (20 μg/mL) or CODCM (30 μg/mL), both administered at sub-IC₅₀ concentrations, were combined with sorafenib at 6 μmol/L for HCT116 cells and 2 μmol/L for HepG2 cells, incubated for 24 h. This combination resulted in a significant suppression in cell viability by approximately 50%. The combination of treatments markedly enhanced apoptosis, diminished MMP, and triggered G₀/G₁ phase cell cycle arrest compared to the effects of each treatment administered individually. Concurrently, increased formation of ROS and decreased expression of the antioxidant enzymes superoxide dismutase 2 and catalase supported the proposed mechanism of apoptosis induction by the combination treatment. Importantly, the anticancer effect demonstrated a specific targeted action with a favorable safety profile, as evidenced by HFF-1 cells displaying IC₅₀ values 2-3 times higher than those of the cancer cells. CONCLUSION Utilizing sub-IC₅₀ concentrations of COEtOAc or CODCM in combination with sorafenib can enhance targeted anticancer effects beyond those achieved with single-agent treatments, while mitigating opposing side effects. Future research will focus on extracting and characterizing active constituents, especially cardiac glycosides, to enhance the therapeutic potential of anticancer compounds derived from toxic plants.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

IgA nephropathy（IgAN）is the most common primary glomerular disease，characterized by the deposition of IgA in the glomerular mesangial area. IgAN is a progressive disease with a protracted and relapsing course. Approximately 50%~75% of adult IgAN patients experience renal function deterioration and eventually progress to end-stage kidney disease（ESKD）within 20 years after diagnosis. Among patients with onset in childhood，about 30% ultimately progress to ESKD after 20 years of long-term follow-up. In recent years，numerous studies have continuously explored important signaling pathways and key molecules in its pathogenesis. This review introduces the therapeutic advances in IgAN，aiming to provide better treatment options for clinicians.

Objective To construct a classification model for surgical patients and apply it in the allocation of nursing human resources,providing a reference for nursing human resource management.Methods A convenience sampling method was used to retrospectively select 5,431 hospitalized surgical patients admitted to 6 surgical nursing units of a tertiary general hospital in Suzhou from July to November 2022 as the subjects of this study.The nursing hours were measured,and related influencing factors were analyzed.A decision tree classification method was used to establish a classification model for surgical patients.From August to October 2022,1,527 hospitalized surgical patients admitted to 3 nursing units of the same hospital were conveniently selected.The minimum number of nurses required daily was calculated using the surgical patient classification model,actual nursing hours measurement method,nurse-to-bed ratio method,and 8-hour continuous shift scheduling method.The application effect of the surgical patient classification model in nursing human resource allocation was evaluated with the actual nursing hours measurement method as the standard.Results The surgical patient classification model includes 7 classification indicators:length of hospital stay,diagnosis-related group weight,presence or absence of secondary care orders,surgical grade,anesthesia method,age,and presence or absence of critical illness orders.Patients were divided into 14 groups,and the model explained 90.5％of the total variance in nursing workload.The minimum number of nurses required in surgical nursing units calculated based on this model was closest to the result of the actual nursing hours measurement method and was superior to the results of the nurse-to-bed ratio method and the 8-hour continuous shift scheduling method.Conclusion The surgical patient classification model can accurately reflect the nursing workload of such patients.The classification indicators are simple and easy to obtain,and can guide the allocation of human resources in surgical nursing units.

Objective:To explore the efficacy and its related factors of rituximab (RTX) in the treatment of children with frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS).Methods:It was a single-center retrospective study. The clinical data of FRNS/SDNS children first treated with RTX in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2016 to September 1, 2023 were collected. The number of relapse within 1 year before and after RTX treatment, the time to first relapse after RTX treatment, and the time to B-cell reconstitution were analyzed. At the first treatment, a single dose of RTX was given at 375 mg/m 2, with a maximum dose of 500 mg, once a week, for 1 to 4 doses. The count of CD19 + lymphocytes in the peripheral blood of the children was continuously monitored. If B-cell reconstruction was performed, the decision on whether to proceed to the next course of RTX treatment was made based on clinical manifestations. Kaplan-Meier method was used to analyze relapse-free survival rate after receiving RTX. Cox proportional hazards regression model was used to analyze the related factors of relapse after RTX treatment. Results:A total of 98 FRNS/SDNS children receiving RTX treatment were enrolled, including 75 males (76.5%). The age at onset was 4.0 (1.9, 7.1) years and age of receiving RTX was 11.3 (8.5, 13.5) years. There were 90 children (91.8%) achieving complete remission, while 8 patients (8.2%) did not respond to RTX treatment, and 3 patients (3.1%) progressed to end-stage kidney disease after receiving RTX. The relapse-free survival rates at 6 months and 1 year after RTX treatment were 83.3% (75/90) and 57.9% (22/38), respectively. The frequency of relapse 1 year after RTX treatment decreased compared to 1 year before RTX treatment ( Z=-7.398, P<0.001). Compared with children without relapse during the period of B-cell depletion, relapsed children had a higher number of relapse within one year after RTX treatment ( Z=5.246, P<0.001). The time to first relapse after RTX treatment was 8.3 (4.6, 13.9) months in 51 relapse patients. Compared with children receiving 1 dose of RTX in the first course, those receiving 2 or more doses had a longer time to the first relapse ( Z=2.983, P=0.003). There was no statistically significant difference in time to the first relapse between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). The reconstruction time of B cells after the first course of RTX was 6.9 (5.3, 9.0) months. Compared to children receiving one dose of RTX in the first course, those receiving two or more doses had a longer B-cell reconstitution time ( Z=2.739, P=0.006). There was no statistically significant difference in B-cell reconstitution time between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). Univariate Cox regression analysis showed that recurrence after calcineurin inhibitor (CNI) treatment before RTX treatment and the number of recurrence in one year before RTX treatment were correlated factors of recurrence after RTX treatment (both P<0.05). Multivariate Cox regression analysis showed that recurrence after CNI treatment before RTX treatment was an independent correlated factor of relapse after RTX therapy ( HR=3.496, 95% CI 1.245-9.818, P=0.018). Infusion reactions occurred in 10 patients (10.2%) and infections were observed in 24 patients (24.5%) during B cell depletion. No serious adverse events occurred. Conclusions:RTX is well tolerated and effective in treating FRNS/SDNS. Recurrence after CNI treatment before RTX treatment may be an independent related factor of relapse after RTX treatment.

Objective:To observe the effects of shoulder-three-needle therapy plus joint mobilization and extracorporeal shock wave therapy(ESWT)in improving symptoms and pain mediators in patients with scapulohumeral periarthritis.Methods:A total of 82 patients with scapulohumeral periarthritis were randomized into a control group and an observation group by the random number table method,with 41 cases in each group.The control group was treated with ESWT.The observation group was treated with additional shoulder-three-needle therapy plus joint mobilization based on the treatment in the control group.After 4 weeks of treatment,shoulder joint function,pain mediators,inflammatory factor levels,and clinical efficacy were compared between the two groups.Results:The total effective rate and the score of shoulder joint function in the observation group were higher than those in the control group(P<0.05).After treatment,the levels of serum pain mediators substance P(SP),5-hydroxytryptamine(5-HT),and prostaglandin E2(PGE2),as well as inflammatory factors interleukin(IL)-6,tumor necrosis factor(TNF)-α,and C-reactive protein(CRP)decreased significantly in both groups(P<0.05).And,the serum pain mediators SP,5-HT,and PGE2,and the levels of inflammatory factors IL-6,TNF-α,and CRP in the observation group were all lower than those in the control group(P<0.05).Conclusion:Shoulder-three-needle therapy plus joint mobilization and ESWT has a better curative effect than ESWT alone in treating scapulohumeral periarthritis.It can effectively improve the clinical symptoms,reduce the levels of pain mediators and inflammatory factors,and increase shoulder joint function.

Objective:To construct a biosafety evaluation index system for major emergency public health events in medical institutions.Methods:Based on previous laboratory biosafety evaluation work, relevant regulations and standards on biosafety in China were collected through literature research and expert consultations. Candidate indicators for constructing the biosafety evaluation system for major emergency public health events in medical institutions were selected, and a framework was established. Two rounds of expert questionnaires were conducted to determine the content of the index system based on experts′ evaluation, and each indicator′s relevance and importance were scored. Finally, two rounds of Delphi consultations were carried out, and the Analytic Hierarchy Process (AHP) was applied to calculate the weights of indicators.Results:The response rates for the total four rounds of questionnaire surveys were all 100%. The first two rounds focused on determining the framework, while the latter two focused on determining the weights for each indicator. The authority coefficients of the expert consultations for the two rounds of weights were 0.65 and 0.70, respectively, indicating the reliability of the research results. In the final round of survey, the Kendall′s coefficients of concordance at each level were all greater than 0.1. Through statistical testing, the P-values were all less than 0.05, indicating good coordination of expert opinions. Ultimately, we established an operational biosafety evaluation system for major emergency public health events in medical institutions, consisting of 4 primary indicators, 26 secondary indicators, and 119 tertiary indicators, with additional deduction items, bonus items, unacceptable items, and monitoring indicators.Conclusions:Based on scientific theory, a biosafety evaluation system for major emergency public health events in medical institutions was constructed, achieving the integration of routine and emergency measures. This system can be used for self-assessment of laboratory biosafety during emergency public health events, addressing the lack of unified standards in biosafety evaluation. Through regular self-assessment, it can enhance the level of biosafety management in medical institution laboratories, to realize the value of application and dissemination.