Objective: To evaluate the suitability of the existing hemolysis rate standards for locally processed red blood cell components by retrospectively analyzing 5-year hemolysis rate data at the end of storage. Methods: A total of 720 blood samples of three types of red blood cell components from our blood station from January 2019 to December 2023 were collected. Parameters included hemoglobin concentration (Hb), hematocrit (Hct), and free hemoglobin concentration (fHb). Hemolysis rate were taken as the control standard of 0.8% in accordance with the national standard. The hemolysis rates were compared against the national standard threshold of 0.8% (GB18469-2012), and annual trends of the detection parameters were observed. Results: The hemolysis rates (x-+s,%) of leukocyte-depleted whole blood at the end of storage were (0.038±0.023 8) in 2019, (0.049±0.039 5) in 2020, (0.043±0.040 7) in 2021, (0.049±0.030 7) in 2022, and (0.058±0.054 8) in 2023, respectively; The hemolysis rates (x-+s" />,%) of leukocyte-depleted suspended red blood cells at the end of storage were (0.093±0.050 2) in 2019, (0.086±0.049 5) in 2020, (0.123±0.072 3) in 2021, (0.122±0.052 1) in 2022, and (0.106±0.058 6) in 2023, respectively; The hemolysis rates (x-+s,%) of washed red blood cells at the end of storage were (0.127±0.038 2) in 2019, (0.150±0.066 5) in 2020, (0.121±0.052 2) in 2021, (0.124±0.038 9) in 2022, and (0.128±0.044 3) in 2023, respectively. Conclusion: Hemolysis rates at the end of blood storage of three red blood cell components were significantly lower than the limits specified in Quality Requirements for Whole Blood and Components (GB18469-2012), as well as standards from the EU, AABB and the United States. The results demonstrate excellent product quality control. A regional internal control standard of <0.2% is proposed for hemolysis rates at the end of storage.

Tic disorder (TD) is a neurodevelopmental disorder characterized by sudden, rapid, repetitive, non-rhythmic motor or vocal tics at single or multiple sites.Attention deficit hyperactive disorder (ADHD) is one of the common comorbidities of TD.Early identification and intervention of inattention, hyperactivity, impulsivity, as well as comorbid ADHD in TD patients can improve its prognosis.Currently, a significant amount of research on TD accompanied by ADHD has been conducted both domestically and internationally.This article provides a systematic review and summary of the epidemiology, etiology, pathogenesis, clinical features, treatment and intervention for TD comorbid with ADHD, aiming to enrich the understanding of clinicians regarding TD comorbid with ADHD and promote its early identification and intervention.

BACKGROUND:Autoimmune regulator gene(Aire)and Wnt signaling pathway play an important role in the maintenance and differentiation of mouse embryonic stem cell pluripotency.However,whether the Wnt signal and Aire are involved in the differentiation of embryonic stem cells to thymic epithelial progenitor cells remains poorly understood. OBJECTIVE:To investigate the relationship of the Wnt signaling pathway and Aire with the differentiation of embryonic stem cells. METHODS:A two-step differentiation method was used to induce mouse embryonic stem cells to differentiate into endoderm and then into thymic epithelial progenitor cells.Mouse embryonic stem cells were infected with Aire shRNA lentivirus,and monoclonal stable strains were screened by puromycin.Mouse embryonic stem cells were collected on days 0,3 and 10 of the directed induction of differentiation after the induced differentiation by the two-step differentiation method.Cellular immunofluorescence,flow cytometry,western blot assay,and real-time qPCR were used to detect the expression changes of related genes and proteins. RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed positive expression of SSEA1 and OCT4 on day 0 of targeted induction of differentiation.(2)Immunofluorescence staining showed double-positive expression of SOX17 and FOXA2 on day 3 of targeted induction of differentiation.(3)Flow cytometry results showed positive expression of EPCAM1,K5 and K8 on day 10 of targeted induction of differentiation.(4)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,and Gsk-3β proteins were elevated,and the expression level of Aire protein was decreased in induced differentiated thymic epithelial progenitor cells.(5)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,Gsk-3β and Aire mRNA were elevated in thymic epithelial progenitor cells.(6)Compared with normal cultured mouse embryonic stem cells and their ultimately differentiated thymic epithelial progenitor cells,the expression levels of Wnt7a,β-catenin and Gsk-3β proteins were reduced in mouse embryonic stem cells with knockdown of Aire genes and their final differentiated thymic epithelial progenitor cells.In conclusion,the Wnt signaling pathway and Aire are jointly involved in the process of targeted induction of differentiation of mouse embryonic stem cells into mouse thymic epithelial progenitor cells.

This article presents three detailed case reports of refractory schizophrenia with varying degrees of improvement in psychiatric symptoms,cognitive function,and insight after 16 sessions of group metacognitive training(MCT)across an 8-week period,and aims to explore the curative effect of group MCT in patients with refractory schizophrenia,thus to provide references for improving symptoms in refractory schizophrenia.

Objective To observe the effect of pre-hospital and intra-hospital collaborative ther-apeutic model in the treatment of patients with acute cerebral infarction.Methods A total of 67 pa-tients with acute cerebral infarction were selected as the research objects,and they were divided into observation group(n=37)and control group(n=30)according to the therapeutic model.The con-trol group was conducted with the traditional therapeutic model,while the observation group was con-ducted with the pre-hospital and intra-hospital collaborative therapeutic model.The time efficiency of intravenous thrombolysis,early recovery of nerve function and oxidative stress indexes were compared between the two groups.Results There was no significant difference in the time from onset to visit between the two groups(P＞0.05);the time from seeing a doctor to thrombolysis and the time from seeing a doctor to signing the informed consent for intravenous thrombolysis in the observation group were significantly shorter than those in the control group(P＜0.05).On the hospital admission,there was no significant difference in the National Institutes of Health Stroke Scale(NIHSS)score be-tween the two groups(P＞0.05);at the time points of 7 days after admission and 90 days after thrombolysis,the NIHSS scores of patients in the observation group were significantly lower than that in the control group(P＜0.05).There were no significant differences in the levels of serum glutathione peroxidase(GSH-Px)and malonaldehyde(MDA)between the two groups(P＞0.05);the level of serum superoxide dismutase(SOD)in the observation group was significantly higher than that in the control group(P＜0.05).One patient died in the control group,with a mortality rate of 3.33％;no patient died in the observation group.Conclusion Pre-hospital and intra-hospital collaborative therapeutic model can effectively improve the time efficiency of intravenous thrombolysis for patients with acute cerebral infarction,alleviate the neurological damage,and reduce degree of oxidative stress reaction and death risk.

Objective:To investigate the effect and mechanism of treadmill training on Purkinje cells in the cerebellum of the rats with spinal cord injury(SCI). Method:Total of 108 female SD rats were randomly divided into 3 groups:the sham-operated group,the SCI group,and the SCI+treadmill training(TT)group.The rats in the SCI exercise group started treadmill train-ing after surgery,and BBB scores were used to assess the hindlimb motor function of rats with spinal cord in-jury.The cerebellum tissues were collected on the 3,7 and 14 day after surgery respectively,and the number and morphological changes of Purkinje cells in the cerebellum were detected by HE staining and Nissler stain-ing.The expression of caspase-9 and mGluR1 in Purkinje cells was detected by immunohistochemistry;the ex-pression of caspase-3 and mGluR1 was detected by immunofluorescence;the expression of apoptosis-related proteins Bax,Bcl-2,Cyt-C,caspase-9 and caspase-3 in cerebellar tissue was detected by Western Blot. Result:Compared with the sham-operated group,the BBB scores in SCI and SCI+TT groups were significant-ly decreased(P＜0.05).The number of Purkinje cells in cerebellum was reduced,and the size was reduced and lost the normal morphology.The expression levels of apoptosis-related proteins Bax,Cyt-C,activated caspase-9,and activated caspase-3 proteins in cerebellum were significantly increased(P＜0.05),and Bcl-2 expression was significantly decreased;caspase-9 and caspase-3 expression was increased and mGluR1 expression was decreased in Purkinje cells(P＜0.05).Compared with the SCI group,there was no significant difference in the BBB scores of the SCI+TT group(P＞0.05);the number and normal morphology of Purkinje cells in cerebellum increased;the expression levels of apoptosis-related proteins Bax,Cyt-C,activated caspase-9 and activated caspase-3 de-creased(P＜0.05),and the expression of Bcl-2 increased;the expression levels of caspase-9 and caspase-3 in Pur-kinje cells were decreased,and the expression level of mGluR1 was significantly increased(P＜0.05). Conclusion:Treadmill training can reduce the apoptosis of Purkinje cells in the cerebellum of the rats with spi-nal cord injury through the mitochondrial apoptosis pathway.

Objective To observe the effect of pre-hospital and intra-hospital collaborative ther-apeutic model in the treatment of patients with acute cerebral infarction.Methods A total of 67 pa-tients with acute cerebral infarction were selected as the research objects,and they were divided into observation group(n=37)and control group(n=30)according to the therapeutic model.The con-trol group was conducted with the traditional therapeutic model,while the observation group was con-ducted with the pre-hospital and intra-hospital collaborative therapeutic model.The time efficiency of intravenous thrombolysis,early recovery of nerve function and oxidative stress indexes were compared between the two groups.Results There was no significant difference in the time from onset to visit between the two groups(P＞0.05);the time from seeing a doctor to thrombolysis and the time from seeing a doctor to signing the informed consent for intravenous thrombolysis in the observation group were significantly shorter than those in the control group(P＜0.05).On the hospital admission,there was no significant difference in the National Institutes of Health Stroke Scale(NIHSS)score be-tween the two groups(P＞0.05);at the time points of 7 days after admission and 90 days after thrombolysis,the NIHSS scores of patients in the observation group were significantly lower than that in the control group(P＜0.05).There were no significant differences in the levels of serum glutathione peroxidase(GSH-Px)and malonaldehyde(MDA)between the two groups(P＞0.05);the level of serum superoxide dismutase(SOD)in the observation group was significantly higher than that in the control group(P＜0.05).One patient died in the control group,with a mortality rate of 3.33％;no patient died in the observation group.Conclusion Pre-hospital and intra-hospital collaborative therapeutic model can effectively improve the time efficiency of intravenous thrombolysis for patients with acute cerebral infarction,alleviate the neurological damage,and reduce degree of oxidative stress reaction and death risk.

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

ObjectiveTo investigate the population with an advantage of clinical cure previously treated with nucleos(t)ide analogues (NAs), and to provide more methods for clinicians in pursuing the clinical cure of hepatitis B. MethodsA total of 42 chronic hepatitis B patients with low-level HBsAg who received NAs treatment in Hebi Third People’s Hospital from October 2017 to October 2019 were enrolled as subjects and divided into combination treatment group (group A) and NA monotherapy group (group B). The 22 subjects in group A were treated with NAs combined with PEG-IFN antiviral therapy for 48 weeks, and some patients withdrew from PEG-IFN after 24 weeks and continued to receive NA monotherapy, while the 20 subjects in group B received NA antiviral therapy alone. Both groups were observed till week 48, and the five makers for hepatitis B were measured to evaluate clinical outcome. The t-test was used for comparison of continuous data between two groups, and the Fisher’s exact test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to perform a multivariate analysis. ResultsCompared with group B at the 48-week treatment endpoint, group A had significantly higher HBsAg clearance rate (45.5% vs 0, P＜0.01) and HBsAg seroconversion rate (31.8% vs 0, P＜0.01). The population with HBsAg ＜1000 IU/ml, ＜500 IU/ml, ＜100 IU/ml, and ＜10 IU/ml had an HBsAg clearance rate of 52.6%, 61.5%, 66.7%, and 100%, respectively, and the population with an HBsAg level of 500-1000 IU/ml, 100-500 IU/ml, 10-100 IU/ml, and ＜10 IU/ml had an HBsAg clearance rate of 33.3%, 50%, 40%, and 100%, respectively. The 4 patients with baseline HBsAg ＜10 IU/ml (accounting for 18.2% in group A) achieved clinical cure at week 12 of combined treatment, and after observation to week 48, 2 patients had an anti-HBs level of ＞100 IU/ml and 2 had an anti-HBs level of ＞1000 IU/ml. The multivariate logistic regression analysis of HBsAg clearance showed that age at the initiation of combined treatment affected HBsAg clearance (odds ratio ［OR］=0.877, 95% confidence interval ［CI］: 0.781-0.985, P=0.026), and most of the patients with HBsAg clearance had an age of 36-49 (44.20±4.49) years; baseline HBsAg level also had an impact on HBsAg clearance (OR=0.996, 95% CI: 0.992-1.000, P=0.050). ConclusionThe addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with NAs can significantly improve the clinical cure rate. The younger the age and the lower the HBsAg level, the shorter the duration of combined treatment. Age and baseline HBsAg level are more important than the duration and type of NA medication.