Objective To determine the effects of hypoxia pre-treatment combined with radiation damage on the hematopoietic cells in the bone marrow of mice.Methods A total of 165 male C57BL/6 mice(10～12 weeks old,weighing 20～25 g)were randomly divided into 7 groups:normal control(Control,n=33),6 Gy irradiation(6-Gy,n=43),7 d hypoxia-6 Gy irradiation(Hy-7 d+6 Gy,n=43),7 Gy irradiation(7 Gy,n=12),7 d hypoxia-7 Gy irradiation(Hy-7 d+7 Gy,n=12),7 Gy continuous hypoxia treatment(Hy-7 d+7 Gy+Hy,n=12),and 6 Gy continuous hypoxia treatment(Hy-7 d+6 Gy+Hy,n=10).The mice of the hypoxia treatment groups were given 7-day hypoxic pretreatment(12%oxygen)in a normobaric hypoxic chamber,while those of the other groups were housed in normoxic condition.After pretreatment,the mice of the irradiation groups were exposed to a single 6 or 7 Gy of whole-body 60Co γ-irradiation in normoxia.The mice of the hypoxia and irradiation groups were kept in hypoxic condition in 24 h post-irradiation followed by being resumed to normoxia,while those of the continuous hypoxia treatment groups were remained in hypoxia.After bone marrow cell suspensions were prepared from the Control,6 Gy,and Hy-7 d+6 Gy groups,bone marrow nucleated cells(BMNCs)were counted via automated cell counter.HE staining was employed to observe pathologic changes in medullary cavity,and flow cytometry was used to assess Lin-Sca1?c-Kit?(LSK)hematopoietic stem/progenitor cells,myeloid progenitors(MPs),and mature T/B/myeloid cells.The mice of the 7 Gy,Hy-7 d+7 Gy,and Hy-7 d+7 Gy+Hy groups were monitored for 30-day survival after hypoxic pretreatment.The dynamic changes in the counts of red blood cells(RBC),white blood cells(WBC)and platelets(PLT),and hemoglobin(HGB)level were observed in the 6 Gy,Hy-7 d+6 Gy,and Hy-7 d+6 Gy+Hy groups with aid of a fully automatic blood analyzer.Single-cell RNA sequencing was performed on bone marrow cell suspension derived from the mice euthanized in 17 d after irradiation from the Control,6 Gy,and Hy-7 d+6 Gy groups.Results ①Compared to the Control group,the 6 Gy group showed significantly reduced BMNCs(P<0.01),dilated bone marrow sinusoids,and erythrocyte extravasation.The Hy-7 d+6 Gy group exhibited higher cellular density and attenuated BMNC loss than the 6 Gy group(P<0.01).②Flow cytometry revealed less LSK,MP,and mature T/B/myeloid cells in the 6 Gy group than the Control group(P<0.05),and the reduced counts of LSK and MP were mitigated in the Hy-7 d+6 Gy group(P<0.01).③The Hy-7 d+7 Gy group demonstrated improved 30-day survival than the 7 Gy group(P<0.01),while continuous hypoxia(Hy-7 d+7 Gy+Hy)failed to enhance the survival.No statistical difference was seen in the survival rate between the 2 groups(P=0.12),though the Hy-7 d+7 Gy group showing higher survival rate.④Routine blood test revealed that the Hy-7 d+6 Gy group showed faster WBC recovery(vs the 6 Gy and Hy-7 d+6 Gy+Hy groups,P<0.05),higher pre-irradiation RBC/HGB levels,and accelerated PLT restoration(P<0.05).⑤Single-cell RNA sequencing indicated that hypoxia pretreatment suppressed the numbers of long-term hematopoietic stem cells/short-term hematopoietic stem cells(LT-HSC/ST-HSC)depletion in the Hy-7 d+6 Gy group when compared with the 6 Gy group,which was consistent with the results of flow cytometry.Pseudotime trajectory aligned the Hy-7 d+6 Gy group,as the Control group,showed enriched undifferentiated LSKs.Differential gene analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that oxidative phosphorylation pathway was strongly activated in the 6 Gy group,while the Hy-7 d+6 Gy group had enriched in chromatin remodeling and mRNA surveillance pathways.Conclusion Hypoxic preconditioning alleviates radiation-induced bone marrow injury,and post-irradiation normoxia restoration promotes hematopoietic recovery in acute radiation-exposed mice.

Objective:To explore the cardioprotective effects of icariin (ICA) against radiation-induced cardiac disease (RICD) in C57BL/6 mice.Methods:A total of 48 female C57BL/6J mice aged 6-8 weeks were randomly divided into three groups: the control group (CON), the irradiation group (IR), and the irradiation combined with icariin group (IR+ ICA), with 16 mice in each group. The IR and IR+ ICA groups received a single cardiac irradiation at a dose of 30 Gy, while the CON group received no radiation treatment. The IR+ ICA group was treated with ICA (70 mg·kg -1·d -1) two weeks before irradiation until the end of the experiment through intragastric administration. In contrast, the CON and IR groups were treated with an equal volume of vehicle solution (0.5% sodium carboxymethyl cellulose, NaCMC) via intragastric administration. The mice′s mental status, food intake, body weight, and survival rates were monitored during the experiment. At two weeks post-irradiation, the venous blood of the mice was collected and serum was separated for the enzyme-linked immunosorbent assays (ELISA) of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT/TNNT2). At 12 weeks post-irradiation, the cardiac function of the mice was assessed using echocardiography. After the mice were euthanized under anesthesia, the histopathological changes and fibrosis degree of their myocardial tissues were assessed using hematoxylin and eosin (HE) and Masson′s trichrome staining, followed by the calculation of collagen volume fraction (CVF). The differential gene expression of brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), and interleukin-6 (IL-6) in the cardiac tissues of the mice was detected using real-time reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis-related proteins and proteins associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were determined using Western blotting. The survival curves of the mice were plotted using Kaplan-Meier, and the survival differences of the mice among various groups were compared using the log-rank test. Results:After irradiation, the mice in the IR group showed lethargy, as well as decreased food intake and activity, while these symptoms in the IR+ ICA group were significantly alleviated. At two weeks post-irradiation, the CK-MB and cTnT levels of the IR group were significantly elevated compared with the CON group ( t = 5.28, 8.89, P < 0.01). At 12 weeks post-irradiation, the mice in the IR group exhibited significantly decreased body weight ( t = 2.47, P < 0.05) and decreased survival rates ( HR = 8.25, 95% CI: 1.157-58.770, P < 0.05) compared with the CON group. Echocardiography revealed that the IR group featured decreased left ventricular ejection fraction (EF), decreased fractional shortening (FS), and increased left ventricular end-diastolic diameter (LVDD) compared with the CON group ( t = 7.02, 4.45, P < 0.05). Histopathological examination revealed that the IR group suffered from cardiomyocyte edema, disordered arrangement, and increased fibrosis, with an elevated CVF. The IR group exhibited significantly upregulated gene expression of BNP, TGF-β, and IL-6 in cardiac tissues compared with the CON group ( t = 4.23, 6.39, 4.61, P < 0.05). After-irradiation, the IR group exhibited upregulated apoptosis-related proteins Cleaved Caspase-3 and Bax ( t = 6.29, 9.54, P < 0.05), decreased Bcl-2 expression ( t = 8.20, P < 0.001), and decreased phosphorylation levels of PI3K and Akt ( t = 6.47, 3.42, P < 0.001). The symptoms of the mice were partially ameliorated after treatment with ICA. Specifically, the mice in the IR+ ICA group exhibited higher body weight ( t = 5.13, P < 0.001) and significantly higher survival rates ( HR = 0.121, 95% CI: 0.017-0.864, P < 0.05) than the IR group. Compared to the IR group, the IR+ ICA group showed elevated cardiac function indicators EF and FS( t = 3.23, 3.05, P < 0.05), and reduced LVDD ( t = 3.02, P < 0.05). The histopathological analysis revealed mitigated edema and disordered arrangement of cardiomyocytes in the IR+ ICA group. Furthermore, the IR+ ICA group exhibited significantly lower BNP, TGF-β, and IL-6 expression levels than the IR group ( t = 2.83, 4.15, 2.96, P < 0.05). The expression of apoptosis-related proteins Cleaved Caspase-3 and Bax was lower ( t = 3.23, 3.24, P < 0.05), Bcl-2 expression was higher ( t = 5.92, P < 0.001), and restored phosphorylation levels of PI3K and Akt ( t = 2.89, 8.35, P < 0.001). Conclusions:Icariin has protective effects against the RICD. It alleviates cardiomyocyte apoptosis possibly by upregulating the phosphorylation levels of PI3K and Akt.

Evaluation of cardiac structure and function in patients with non-ST-segment elevation myocardial infarction is important for diagnosis,treatment,and prognosis prediction.Echocardiography serves as the preferred imaging modality for assessing cardiovascular diseases,enabling rapid and accurate evaluation of cardiac structure and function.Due to technological advances in recent years,there are now new echocardiographic techniques with new methodologies and parameters that can be used for evaluation of cardiovascular condi-tions.This article summarizes the new echocardiographic techniques currently used for evaluation of non-ST-segment elevation myocardial infarction,which mainly include speckle tracking echocardiography,contrast echocardiography,stress echocardiography,and three-di-mensional echocardiography,and reviews the diagnostic and prognostic predictive values of these techniques for non-ST-segment elevation myocardial infarction.

Objective:To explore the cardioprotective effects of icariin (ICA) against radiation-induced cardiac disease (RICD) in C57BL/6 mice.Methods:A total of 48 female C57BL/6J mice aged 6-8 weeks were randomly divided into three groups: the control group (CON), the irradiation group (IR), and the irradiation combined with icariin group (IR+ ICA), with 16 mice in each group. The IR and IR+ ICA groups received a single cardiac irradiation at a dose of 30 Gy, while the CON group received no radiation treatment. The IR+ ICA group was treated with ICA (70 mg·kg -1·d -1) two weeks before irradiation until the end of the experiment through intragastric administration. In contrast, the CON and IR groups were treated with an equal volume of vehicle solution (0.5% sodium carboxymethyl cellulose, NaCMC) via intragastric administration. The mice′s mental status, food intake, body weight, and survival rates were monitored during the experiment. At two weeks post-irradiation, the venous blood of the mice was collected and serum was separated for the enzyme-linked immunosorbent assays (ELISA) of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT/TNNT2). At 12 weeks post-irradiation, the cardiac function of the mice was assessed using echocardiography. After the mice were euthanized under anesthesia, the histopathological changes and fibrosis degree of their myocardial tissues were assessed using hematoxylin and eosin (HE) and Masson′s trichrome staining, followed by the calculation of collagen volume fraction (CVF). The differential gene expression of brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), and interleukin-6 (IL-6) in the cardiac tissues of the mice was detected using real-time reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis-related proteins and proteins associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were determined using Western blotting. The survival curves of the mice were plotted using Kaplan-Meier, and the survival differences of the mice among various groups were compared using the log-rank test. Results:After irradiation, the mice in the IR group showed lethargy, as well as decreased food intake and activity, while these symptoms in the IR+ ICA group were significantly alleviated. At two weeks post-irradiation, the CK-MB and cTnT levels of the IR group were significantly elevated compared with the CON group ( t = 5.28, 8.89, P < 0.01). At 12 weeks post-irradiation, the mice in the IR group exhibited significantly decreased body weight ( t = 2.47, P < 0.05) and decreased survival rates ( HR = 8.25, 95% CI: 1.157-58.770, P < 0.05) compared with the CON group. Echocardiography revealed that the IR group featured decreased left ventricular ejection fraction (EF), decreased fractional shortening (FS), and increased left ventricular end-diastolic diameter (LVDD) compared with the CON group ( t = 7.02, 4.45, P < 0.05). Histopathological examination revealed that the IR group suffered from cardiomyocyte edema, disordered arrangement, and increased fibrosis, with an elevated CVF. The IR group exhibited significantly upregulated gene expression of BNP, TGF-β, and IL-6 in cardiac tissues compared with the CON group ( t = 4.23, 6.39, 4.61, P < 0.05). After-irradiation, the IR group exhibited upregulated apoptosis-related proteins Cleaved Caspase-3 and Bax ( t = 6.29, 9.54, P < 0.05), decreased Bcl-2 expression ( t = 8.20, P < 0.001), and decreased phosphorylation levels of PI3K and Akt ( t = 6.47, 3.42, P < 0.001). The symptoms of the mice were partially ameliorated after treatment with ICA. Specifically, the mice in the IR+ ICA group exhibited higher body weight ( t = 5.13, P < 0.001) and significantly higher survival rates ( HR = 0.121, 95% CI: 0.017-0.864, P < 0.05) than the IR group. Compared to the IR group, the IR+ ICA group showed elevated cardiac function indicators EF and FS( t = 3.23, 3.05, P < 0.05), and reduced LVDD ( t = 3.02, P < 0.05). The histopathological analysis revealed mitigated edema and disordered arrangement of cardiomyocytes in the IR+ ICA group. Furthermore, the IR+ ICA group exhibited significantly lower BNP, TGF-β, and IL-6 expression levels than the IR group ( t = 2.83, 4.15, 2.96, P < 0.05). The expression of apoptosis-related proteins Cleaved Caspase-3 and Bax was lower ( t = 3.23, 3.24, P < 0.05), Bcl-2 expression was higher ( t = 5.92, P < 0.001), and restored phosphorylation levels of PI3K and Akt ( t = 2.89, 8.35, P < 0.001). Conclusions:Icariin has protective effects against the RICD. It alleviates cardiomyocyte apoptosis possibly by upregulating the phosphorylation levels of PI3K and Akt.

Evaluation of cardiac structure and function in patients with non-ST-segment elevation myocardial infarction is important for diagnosis,treatment,and prognosis prediction.Echocardiography serves as the preferred imaging modality for assessing cardiovascular diseases,enabling rapid and accurate evaluation of cardiac structure and function.Due to technological advances in recent years,there are now new echocardiographic techniques with new methodologies and parameters that can be used for evaluation of cardiovascular condi-tions.This article summarizes the new echocardiographic techniques currently used for evaluation of non-ST-segment elevation myocardial infarction,which mainly include speckle tracking echocardiography,contrast echocardiography,stress echocardiography,and three-di-mensional echocardiography,and reviews the diagnostic and prognostic predictive values of these techniques for non-ST-segment elevation myocardial infarction.

Objective:To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS). Methods:The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively. Results:Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN) 7, (GCN) 13, (GCN) 14, (GCN) 15 and (GCN) 20. The frequency of the (GCN) 20 allele was the highest (94.79%). And five genotypes were identified, which included (GCN) 7/(GCN) 20, (GCN) 13/(GCN) 20, (GCN) 14/(GCN) 20, (GCN) 15/(GCN) 20, (GCN) 20/(GCN) 20. The homozygous genotypes were all (GCN) 20/(GCN) 20, and the carrier rate was 89.58%. Four GCN sequences of the (GCN) 20 homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the, Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN) 20/(GCN) 25 and (GCN) 20/(GCN) 30, respectively. Conclusion:It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.

AIM: To analyze the causes of blindness and low vision in patients with visual disability in Yangpu District of Shanghai from 2019 to 2022.METHODS:Cross-sectional study. A total of 1 604 patients who participated in the evaluation of visual disability in Shanghai Yangpu District Kongjiang Hospital, from April 2019 to December 2022 were selected for the study. The grade of visual disability and the main causes of blindness and low vision were determined by trained doctors.RESULTS:A total of 804 patients with visual disabilities were identified, with 87.31% aged 60 and above. The causes of visual disability were high myopic retinopathy(30.47%), age-related macular degeneration(23.26%), glaucoma(17.04%), and diabetic retinopathy(11.07%). Glaucoma(36.96%)is the leading cause of blindness.CONCLUSION: The majority of patients with visual disability are aged 60 years and above. More attention should be paid to the elderly population. Comprehensive prevention, treatment and rehabilitation measures should be applied in different diseases based on classification, so as to early reduce the occurrence of visual disability.

Objective To compare the consistency between the estimated values of nine common resting energy expenditure estimation equations and the measured values among the elderly population in pension institutions. Methods A total of 181 elderly individuals from Henan Guangda Ouan Leling Nursing Center were recruited as study objects through cluster sampling. The differences between the estimated values of nine common equations and the measured values obtained by indirect calorimetry were compared, and subgroup analyses were conducted to compare their consistency across different subgroups. Results Among the nine equations, the Cunningham equation and the Owen equation showed relatively small deviations from the measured values, with no significant differences (deviation rates of -1.9% and -2.0%, root mean square errors of 222.7 kcal/d and 239.4 kcal/d, and coincidence rates of 48.4% and 47.5%, respectively). In subgroups stratified by gender and body mass index (BMI), the Cunningham equation showed no significant difference compared with the measured values. The Owen equation showed no significant difference compared with the measured values only in some subgroups [males with BMI of 20~ < 27 kg/m² and ≥27 kg/m², and females with BMI < 20 kg/m²]. Conclusion The Cunningham equation, which utilizes body composition data, can assess the resting energy expenditure of the elderly in pension institutions with relatively high accuracy and speed, demonstrating strong applicability in this population.

OBJECTIVE To investigate the effects of nasal administration of non-mitogenic acid fibroblast growth factor(NMFGF1) loaded nanoparticles(NMFGF1-NPs) on the improvement of cognitive function in vascular dementia(VD) mice and its mechanism. METHODS Nanoparticles containing NMFGF1(NMFGF1-NPs) were prepared by water-in-water emulsion technique and characterized. The mice were divided into sham group, VD model group, blank-NPs group, NMFGF1 solution group and NMFGF1-NPs group after repeated cerebral ischemia-reperfusion to establish VD test model, and then given the corresponding form of drug intervention by nasal cavity. After drug intervention, Morris water maze was used to evaluate the learning and memory function of the animals in each group from the perspective of behavior. Meanwhile, the morphology, arrangement and apoptosis index(AI) of hippocampal neurons in each group were evaluated by pathological methods such as HE staining, FJB staining and Tunel apoptosis staining. In addition, ELISA and Western blotting were used to investigate the molecular mechanism of NMFGF1-NPs improving VD by nasal administration. RESULTS The morphology of NMFGF1-NPs was round. The encapsulation rate of NMFGF1-NPs respectively was (87.76±5.89)%. Morris water maze results showed that the behavioral indexes of mice in VD model group were significantly different from those in sham operation group(P<0.01). At the same time, the pathological results showed that the neurons in the CA1 region of the hippocampus in the VD model group were disordered, the cells morphology and structure were missing, and the AI was significantly increased compared with that in the sham operation group(P<0.01). Meanwhile, compared with the VD model group, the NMFGF1-NPs treatment group showed significant improvement in various behavioral indexes, and the hippocampal neuron cells were intact and orderly, and the AI index was significantly decreased(P<0.01). ELISA and Western blotting analysis showed that compared with that of VD model group and other intervention groups, the content of MDA in the brain of NMFGF1-NPs treatment group was significantly decreased. While the content of SOD, NO and the expressions of Nrf2, SOD-1 and GSTO1/2 was significantly increased (P<0.01). CONCLUSION Nasal administration of NMFGF1-NPs can play the role of antioxidant stress damage by activating Nrf2/ARE signal pathway, and ultimately improve the learning and cognitive function of VD mice.

Objective:To evaluate the safety and feasibility of applying injectable cross-linked sodium hyaluronate isolation gel in radical hypofractionated radiation therapy for prostate cancer.Methods:In this prospective study, patients at Beijing Hospital who were pathologically diagnosed with clinical stage T 1-2N 0M 0 prostatic acinar adenocarcinoma by puncture and underwent radical radiation therapy were included. All patients received ultrasound-guided cross-linked sodium hyaluronate isolation gel injection and image-guided intensity-modulated radiation therapy (IG-IMRT). The prescription dose was moderately hypofractionated, with a prescription dose of 60 Gy in 20 fractions for 5 times a week, once daily, which was delivered to 95% of the planning target volume (PTV) of prostate and seminal vesicle. Analyze the prostate rectal spacing (PRS) at the baseline, on the day of injection, during the radiotherapy, 1 month and 3 months after radiotherapy, changes in rectal volume before and after injection, and incidence of rectum-related side effects. The changes in all indexes before and after injection were analyzed by using t-test. Results:A total of 13 patients were enrolled from March 2022 to February 2023. The isolation gel maintained morphologic stability without significant spatial changes during radiotherapy, and the mid-prostate had the best effect, with PRS up to 1 cm. At 3 months after radiotherapy, the isolation gel was seen to decreased in volume with a certain absorptive capacity. The irradiated volume of rectum was decreased significantly in all patients after gel injection, and the mean volumes of rectal V 60 Gy , V 50 Gy , V 30 Gy , and V 20 Gy before and after injection were 1.923% vs. 0.280%, 10.255% vs. 3.172%, 29.602% vs. 18.800%, and 49.452% vs. 40.259% (all P<0.005). The average values (range) of rectal V 60 Gy , V 50 Gy , V 30 Gy , V 20 Gy decreases were 84.9%( 29% - 100%), 69.6%(27%-100%), 36.3%(0%-75%), and 17.8%(0%-50%), respectively. No grade 3-4 side effects occurred in all patients, and there were no common grade 1-2 rectal side effects such as diarrhea, rectal bleeding, proctitis and anal pain, etc. Only one patient developed grade 1 constipation during radiotherapy. Conclusion:Injection of Chinese made cross-linked sodium hyaluronate isolation gel can significantly reduce the irradiated volume of rectum and the incidence of rectal toxicities in prostate cancer patients undergoing radical radiotherapy.