Objective Using female mice to investigate the reparative effects of human umbilical cord mesenchymal stem cells on radiation-induced ovarian injury. Methods Mice were randomly divided into three groups: a blank control group, a radiation model group, and a cell therapy group. Mice in the radiation model group and the cell therapy group received a single whole-body irradiation of 5 Gy X-rays. Within 2 hours post-irradiation, mice in the cell therapy group underwent ovarian transplantation of UC-MSCs. On days 1, 7, and 14 post-irradiation, body weight was measured, ovarian index was calculated, histopathological changes in ovarian tissue were examined, serum levels of reproductive hormones (follicle-stimulating hormone, anti-Müllerian hormone, and estradiol) were determined, and the colonization of implanted UC-MSCs in the mice was observed. Results On days 1, 7, and 14 post-irradiation, both the cell therapy group and the radiation model group showed decreased body weight compared to the blank control group (P < 0.05). On day 1 post-irradiation compared to day 1 pre-irradiation within the same group, the radiation model group exhibited a greater decrease in body weight than the cell therapy group (P < 0.05). On days 1, 7, and 14 post-irradiation, the ovarian index decreased in both the radiation model group and the cell therapy group compared to the blank control group (P < 0.05). On days 7 and 14 post-irradiation, the ovarian index in the cell therapy group was significantly higher than that in the radiation model group (P < 0.05). Ovarian tissue in the radiation model group exhibited atrophy and a reduction in the number of follicles at all stages. In contrast, follicles in the cell therapy group were large and abundant. On days 1, 7, and 14 post-irradiation, serum follicle-stimulating hormone levels in the cell therapy group were lower than those in the radiation model group, while anti-Müllerian hormone and estradiol levels were higher than those in the radiation model group (P < 0.01). In vivo fluorescence imaging demonstrated that UC-MSCs successfully colonized the ovarian tissue on days 1, 7, and 14 after transplantation. Conclusion UC-MSCs exert a repair effect on radiation-induced ovarian injury in mice.

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating enzyme (E2), and E3 NEDD8-ligase (E3). The most extensively studied substrates of neddylation are members of the cullin family, which act as scaffold components for cullin ring E3 ubiquitin ligases (CRLs). Since cullin neddylation activates CRLs, which are frequently overactive in tumors, inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies. This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions (PPIs) within the neddylation enzymatic cascade.

Objective To explore the role and mechanism of warm malate ringer's solution(MR)in resuscitation of the lethal triad caused by severe trauma.Methods A rat model of severe trauma was established in SPF-grade SD rats(half male and half female,weighing 200～220 g)using combined multiple injuries and hemorrhagic shock,and the rats were randomly divided into 8 groups(n=8):Sham group,only arterial and venous catheterization;Trauma(Tra)groups with different time points(10,30,60,90,120,180 min)and a Trauma group that were observed without any treatment for 180 min after model establishment.The changes of activated clotting time(ACT),reaction time(R),maximum amplitude(MA),and rate of blood clot formation(Angle)at different time points were detected by using thromboelastography,and tail bleeding,core body temperature and arterial blood gas parameters,were also observed and detected.The plasma von Willebrand Factor(vWF)level,mitochondrial respiratory control ratio in pulmonary venous endothelium,and expression levels of vascular endothelial cadherin(VE-Cadherin),peroxisome proliferator activating receptor gamma coactivator 1α(PGC1α),dynamin-related protein 1(Drp1),p-Drp1,and mitofusin 2(Mfn2)were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction.Another group of SD rats were randomly divided into severe trauma group(no treatment for 180 min after injury),and MR solution at room temperature and at 37 ℃ groups.MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma.Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.Results Compared with the Sham group,the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values(P＜0.05),shortened MA and decreased Angle values(P＜0.05),extended tail bleeding time(P＜0.05),lower partial pressure of carbon dioxide(PCO2)and HCO3-and base excess(BE)levels(P＜0.05),and continuously increasing K+(P＜0.05)and decreasing Na+(P＜0.05)and Ca2+levels(P＜0.05).Additionally,plasma vWF level(P＜0.05)and protein levels of VE-cadherin,PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced(P＜0.05),the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury(P＜0.05).MR solution resuscitation shortened tail bleeding time(P＜0.05),increased core body temperature(P＜0.05),elevated plasma vWF level(P＜0.05),increased protein levels of VE-cadherin,PGC1α and Mfn2(P＜0.05),and decreased that of p-Drp1 protein expression(P＜0.05)when compared with the rats at 180 min after severe traumatic injury.The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.Conclusion Warm MR solution significantly improves the lethal triad in rats after severe trauma,which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.

Objective To investigate the protective effects of remimazolam(Remi),a novel benzodiazepine sedative,on intestinal barrier function in septic mice.Methods A mouse model of sepsis was established using cecal ligation and puncture(CLP).A total of 96 SPF-grade adult male C57BL/6 mice were randomized into sham operation(Sham),sepsis(Sepsis),and sepsis with Remi intervention(Sepsis+Remi)groups.Survival rate and survival time were recorded within 72 h after modeling.Intestinal pathological alterations,barrier functional indicators,ZO-1 expression,and macrophage polarization status were observed and detected to evaluate the effects of Remi.Lipopolysaccharide(LPS)was used to treat RAW264.7 cells for 24 h to simulate in vitro sepsis model.The cells were divided into control(Control),LPS,and LPS+Remi groups.Immunofluorescence staining was performed to assess macrophage phenotype,mitochondrial morphology,and mitochondrial reactive oxygen species(MtROS),and Western blotting was applied to detect the protein expression of iNOS and CD206.Results Compared with the sepsis group,Remi intervention significantly improved the survival rate of septic mice from 12.50%to 68.75%and markedly prolonged survival duration(P<0.05).Histopathological analysis demonstrated partial restoration of intestinal villus architecture,accompanied with attenuated interstitial edema and reduced inflammatory cell infiltration after Remi intervention.Furthermore,the intervention group demonstrated significant improvement in functional indicators.Both in vivo and in vitro experiments demonstrated elevated iNOS and decreased CD206 expression in the septic mice and LPS-stimulated macrophages(P<0.05),which were partially reversed after Remi intervention.Furthermore,LPS-stimulated macrophages exhibited fragmented mitochondria and elevated MtROS level,whereas Remi intervention ameliorated these conditions(P<0.05).Conclusion Remi protects intestinal barrier function in septic mice by mitigating mitochondrial dynamics imbalance-induced oxidative damage and ameliorating inflammatory macrophage activation.

Objective:To analyze the epidemiological and clinical characteristics of respiratory syncytial virus (RSV) infection in children in Jiangsu Province from 2014 to 2023.Methods:The acute respiratory infection cases in children aged 0-14 years were selected from outpatient/emergency or inpatient departments in 2 surveillance sentinel hospitals, respectively, in Nanjing, Suzhou and Taizhou of Jiangsu from 1 July 2014 to 31 December 2023, and RSV nucleic acid test was conducted and the intensity of the RSV infection was accessed by WHO influenza epidemiological threshold method, and case information and clinical data were collected. χ2 test was used to compare the differences between groups, and the Bonferroni method was used for pairwise comparisons between groups. Results:In 4 946 cases of acute respiratory infections, the RSV positive rate was 8.21% (406/4 946), and the age M( Q1, Q3) of the cases was 1 (0, 3) years. The RSV positive rate was 10.92% (258/2 362) during 2014-2019 and 6.06% (118/1 948) during 2019-2023, the difference was significant ( χ2=31.74, P<0.001). RSV infection mainly occurred from October to March during 2014-2019, with the incidence peak in December and moderate or higher intensity. The seasonality of RSV infection was not obvious during 2019-2023, with low intensity. The RSV positive rate was highest in children in age group 0- years (17.85%, 151/846), and the positive rate declined gradually with age ( χ2=184.51, P<0.001). The RSV positive rate was higher in inpatient cases (9.84%, 244/2 480) than in outpatient/emergency cases (6.57%, 162/2 466) ( χ2=17.54, P<0.001). In the 155 RSV infection cases with complete clinical data, the clinical symptoms mainly included cough (99.35%, 154/155), fever (55.48%, 86/155), and shortness of breath (45.16%, 70/155). In the cases aged <6 months, the proportion of those with fever was low, but the proportion of those with shortness of breath, transferred to intensive care units, and receiving oxygen therapy were higher (all P<0.05). Children aged <6 months and those with underlying diseases were more likely to have severe RSV infection (all P<0.05). Conclusions:RSV infection in children in Jiangsu Province showed seasonal prevalence in winter from 2014 to 2019. Since 2020, the seasonal characteristics of the epidemic have changed, the epidemic period has been dispersed and the epidemic intensity has decreased. Infants <1 year old were at high risk for RSV infection, and those <6 months old and with underlying diseases might have severe infection.

Objective:To investigate the influence of changes in the cognitive load of anesthesia residents on the teaching effectiveness of high-fidelity scenario simulation.Methods:Eighty-seven anesthesia residents in a grade-A tertiary hospital from February to November 2022 were divided into groups A, B, and C according to the random number method. Three cases were selected from the anesthesia crisis resource teaching case library for high-fidelity simulation training for the three groups, respectively, using the crossover design to control the order of the cases. Each round of training consisted of pre-training instruction, simulation teaching, and post-training summarization and analysis. After three rounds of simulation teaching, cognitive load, anxiety status, test scores, and non-technical skills were evaluated for all the study participants. SPSS 20.0 was used to perform analysis of variance with repeated measures and Pearson's correlation analysis.Results:All the three groups showed significantly higher cognitive load and anxiety scores during the first-round simulation training than during the second-round and third-round simulation trianing. The test scores were significantly lower in the first round [(87.07±5.66), (88.38±5.41), (89.07±6.17)] than in the second round [(95.69±2.29), (96.10±2.08), (96.07±2.60)] and the third round [(96.34±1.45), (96.38±1.50), (96.17±1.73); all P<0.05]. The non-technical skill scores were also significantly lower in the first round [(37.24±7.58), (38.69±7.27), (39.24±8.74)] than in the second round [(46.17±5.55), (47.07±5.59), (47.59±6.74)] and the third round [(47.17±5.21), (48.48±5.38), (48.24±6.83); all P<0.05]. For simulations with the same cases, the trainees showed significantly higher cognitive load and anxiety scores and significantly lower test scores and non-technical skill scores in the first round than in the second and third rounds ( P<0.05). Conclusions:Anesthesia residents have higher levels of cognitive load and anxiety in the first scenario simulation training, which can reduce learning outcomes, and repeated simulation training can reduce trainees' cognitive load and anxiety.

Objective:To investigate the clinical value of ultrasound-guided thoracic paravertebral block (TPVB) combined with bronchial blocker (BB) placement in thoracoscopic surgery.Methods:A randomized controlled study was conducted involving 60 patients scheduled for thoracoscopic surgery at The First Affiliated Hospital of Xiamen University from November to December 2023. These patients were classified as American Society of Anesthesiologists (ASA) I-II. They were divided into an observation group (BB placement) and a control group (double-lumen bronchial blocker placement) using the random number table method, with 30 patients in each group. Preoperatively, TPVB was performed under ultrasound guidance. After the induction of general anesthesia, a single-lumen tracheal tube was inserted, followed by the placement of a BB in the observation group, while a corresponding type of double-lumen bronchial tube was inserted in the control group. A fiberoptic bronchoscope was used for positioning and fixation in both groups, and anesthesia was maintained with intravenous anesthesia. The following parameters were assessed in each group: positioning time for intubation; number of cases with tube displacement; number of cases of postoperative pharyngeal pain; hemodynamic parameters [mean arterial pressure (MAP) and heart rate (HR)] before and after intubation; and blood gas analysis [partial pressure of oxygen (PaO 2) and carbon dioxide (PaCO 2)]. Additionally, the surgical field exposure score and the dosages of propofol and remifentanil administered during surgery were recorded. Levels of inflammatory markers [interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF) -α, and TNF-β] and Visual Analog Scale scores for pain at rest and during cough, recorded at 2, 4, 8, 10, 12, and 24 hours postoperatively were compared between the two groups. Results:The total amounts of propofol [(569.7 ± 29.2) mg] and remifentanil [(289.3 ± 46.3) μg] in the observation group were significantly lower than those in the control group [(612.6 ± 28.7) mg, (361.7 ± 40.6) μg, t = 5.74, 6.44, both P = 0.001]. The recovery time in the observation group [(31.8 ± 11.4) minutes] was significantly shorter than that in the control group [(37.5 ± 10.1) minutes, t = 2.10, P = 0.040]. There was no significant difference in positioning time for intubation between observation and control groups [(67 ± 13) seconds vs. (80 ± 36) seconds, t = 1.86, P = 0.068). There was no significant difference in percentage of cases who underwent tube displacement after intubation between observation and control group [23.3% (7/30) vs. 16.7% (5/30), χ2 = 0.58, P = 0.445]. The incidence of postoperative pharyngeal pain in the observation group was significantly lower than that in the control group [10.0% (3/30) vs. 33.3% (10/30), χ2 = 5.02, P = 0.025). There were no statistically significant differences between the two groups in terms of number of cases with tube displacement, hemodynamic parameters, blood gas analysis, inflammatory markers, surgical field exposure, and postoperative Visual Analog Scale scores between the two groups (all P > 0.05). Conclusion:Ultrasound-guided TPVB combined with BB placement during thoracoscopic surgery can reduce airway injury compared with the use of a double-lumen bronchial tube. It provides adequate sedation and analgesia during the procedure, facilitates rapid awakening, promotes early recovery of spontaneous breathing, and has fewer adverse reactions, making it worthy of clinical promotion.

Objective:To explore the real experience and needs of successful aging among urban elderly people who participated in intergenerational raising.Methods:This study was a qualitative study. From February to April 2023, purposive sampling was used to select 10 elderly individuals from Fanjingjiayuan Community in Changqing District, Jinan City who participated in intergenerational raising as the research subject. Semi-structured interviews and face-to-face nonverbal behavior observation methods were used to collect data, while Colaizzi's 7-step analysis method was used to summarize, analyze the data and extract themes.Results:A total of three themes and 10 sub-themes were extracted, namely positive psychological feelings (self-realization, obtaining emotional support, health benefits), negative psychological feelings (intergenerational raising pressure, decreased life satisfaction, mental stress, physical and mental exhaustion), and the need to promote successful aging (family support, community support, policy support) .Conclusions:Urban elderly people who participate in intergenerational raising have both negative and positive psychological experiences. Families and society should pay attention to the psychological feelings of participating in intergenerational raising of elderly people in urban communities, so as to promote successful aging of the elderly people.

Objective:To establish an ultrasound radiomics model by integrating clinical, pathological, and conventional ultrasound features with radiomics characteristics, and to explore its clinical value in predicting endocrine resistance in hormone receptor(HR)-positive breast cancer.Methods:A retrospective analysis was performed on 478 patients with HR-positive breast cancer from January 2017 to December 2021 in the Second Affiliated Hospital of Harbin Medical University, of which 430 were resistant and 48 were sensitive. The clinical, pathological and immunohistochemical data and ultrasound images were collected.Firstly, the propensity score was used to process and match the data. Secondly, Logistic regression was used to screen clinical, pathological, and conventional ultrasound features associated with endocrine resistance. Then, PyRadiomics was used to extract the radiomic features of grayscale ultrasound images, and a series of methods such as Lasso regression were used to screen the radiomic features related to endocrine resistance. Seven machine learning methods such as random forest were used to build a radiomics model. Finally, clinical, pathological and ultrasound features were added to establish a clinical pathological model, a clinical pathological ultrasound model, a clinical pathological radiomics model and a combined model of the four features, and the model effectiveness was evaluated.Results:①Propensity score matching: 96 patients were matched, including 48 patients in the drug-resistant group and 48 patients in the sensitive group. ②Screening clinical pathological conventional ultrasound features related to endocrine resistance: lymph node metastasis, tumor diameter, posterior echo attenuation, and growth orientation were independent predictors of endocrine resistance (all P<0.05). ③Screening radiomics features related to endocrine resistance: 18 features such as Dependence Entropy. ④Establishing radiomics model: the machine learning model of random forest method (AUC=0.80) performed best. ⑤Radiomics model integrating clinical, pathological and conventional ultrasound features: the AUC of the clinical pathological model was 0.70, the AUC of the clinical pathological ultrasound model was 0.78, the AUC of the clinical pathological radiomics model was 0.82, and the AUC of the combined model was 0.86. Conclusions:The radiomics model established by the random forest method performs best in predicting endocrine resistance in HR-positive breast cancer. The model that integrates multiple features performs best in assessing endocrine resistance.which is expected to provide an objective basis for clinicians to predict endocrine resistance in HR-positive breast cancer.