Objective To observe the effect of Buyang Huanwu Decoction on hippocampal tissue structure and blood perfusion in rats with focal cerebral ischemia using multi-modal MRI;To analyze the mechanism of Buyang Huanwu Decoction on hippocampal neuroplasticity combined with the expression changes of neuroplasticity proteins and glucose metabolism related transporters.Methods Focal cerebral ischemia rat model induced by right middle cerebral artery occlusion were established.The rats were divided into sham-operation group,sham-operation+Buyang Huanwu Decoction group,model group and model+Buyang Huanwu Decoction group.The rats in the sham-operation group and model group were given normal saline for 30 days,and those in the sham-operation+Buyang Huanwu Decoction group and model+Buyang Huanwu Decoction group were given Buyang Huanwu Decoction for 30 days.T2 mapping imaging was used to detect the changes in hippocampal tissue structure,the changes of cerebral blood perfusion in hippocampus were detected by arterial spin labeling imaging,Western blot was used to detect the protein expressions of SYN,GAP-43,glucose transporters and MCT.Results Compared with the sham-operation group,the T2 relaxation time of the right and left hippocampus in the model group rats significantly increased(P<0.01,P<0.001),the blood flow in the right hippocampus was significantly reduced(P<0.05),the protein expressions of SYN,GAP-43,MCT4 and MCT2 in the right hippocampus were significantly decreased(P<0.01,P<0.001),the protein expressions of GLUT1 and GLUT3 in bilateral hippocappal tissue significantly decreased(P<0.05,P<0.01,P<0.001).Compared with the model group,the T2 relaxation time in the right hippocampus of rats in model+Buyang Huanwu Decoction group was significantly reduced(P<0.05),the blood flow in the right hippocampus significantly increased(P<0.05),the protein expressions of SYN,GAP-43,GLUT1 and GLUT3 in bilateral hippocampal tissues significantly increased(P<0.01,P<0.001),and the protein expressions of MCT4 and MCT2 in right hippocampal tissue significantly increased(P<0.01,P<0.001).Conclusion Buyang Huanwu Decoction can alleviate hippocampal injury in rats with focal cerebral ischemia,which may be related to improving blood perfusion,up-regulating neuroplasticity-related proteins,promoting hippocampal axon regeneration and synaptic remodeling,regulating energy metabolism of nerve cells.

Objective To investigate the effect of transcranial alternating current stimulation(tACS)on cerebral blood flow(CBF)in patients with Alzheimer's disease(AD).Methods A ret-rospective study was conducted on 21 mild AD patients admitted in our hospital from September 2019 to April 2022.All of them received tACS treatment for 3 weeks.Mini-mental state examina-tion(MMSE),auditory verbal learning test(AVLT)and MRI were applied to obtain the data at baseline(T0),the end of the treatment(T1)and in three months after treatment(T2).Z-trans-form CBF(zCBF)was performed to reduce individual variability.The changes in MMSE and AVLT scores,as well as brain zCBF and CBF values before and after tACS treatment were ana-lyzed.Spearman correlation analysis was used to examine the relationship of zCBF and CBF with cognitive scores.Results In the AD patients,their MMSE score was significantly increased at T1 than at T0[22.00(20.00,25.00)vs 20.00(18.00,21.50),P＜0.01].Based on voxel analysis,the AD patients exhibited significantly increased zCBF in the bilateral frontal and temporal cortex at T1,and in the right frontal and temporal cortex at T2 when compared with the levels at T0(P＜0.05).The most pronounced increase in zCBF was observed in the right insular.Based on region of inter-est analysis,increased zCBF and CBF in the right frontal and temporal cortex at T1 were observed(P＜0.05).There was a positive correlation between the change of CBF in the right frontal cortex and AVLT-recognition recall at T1(r=0.617,P=0.005)and between the change of CBF in the left frontal cortex and MMSE at T2(r=0.596,P=0.012).Conclusion MRI 3D-ASL can objec-tively evaluate the changes of CBF in AD patients after tACS treatment,and it provides a reliable imaging marker for evaluating the efficacy of tACS.

Type 2 diabetes (T2D) is often accompanied with an induction of retinaldehyde dehydrogenase 1 (RALDH1 or ALDH1A1) expression and a consequent decrease in hepatic retinaldehyde (Rald) levels. However, the role of hepatic Rald deficiency in T2D progression remains unclear. In this study, we demonstrated that reversing T2D-mediated hepatic Rald deficiency by Rald or citral treatments, or liver-specific Raldh1 silencing substantially lowered fasting glycemia levels, inhibited hepatic glucogenesis, and downregulated phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) expression in diabetic db/db mice. Fasting glycemia and Pck1/G6pc mRNA expression levels were strongly negatively correlated with hepatic Rald levels, indicating the involvement of hepatic Rald depletion in T2D deterioration. A similar result that liver-specific Raldh1 silencing improved glucose metabolism was also observed in high-fat diet-fed mice. In primary human hepatocytes and oleic acid-treated HepG2 cells, Rald or Rald + RALDH1 silencing resulted in decreased glucose production and downregulated PCK1/G6PC mRNA and protein expression. Mechanistically, Rald downregulated direct repeat 1-mediated PCK1 and G6PC expression by antagonizing retinoid X receptor α, as confirmed by luciferase reporter assays and molecular docking. These results highlight the link between hepatic Rald deficiency, glucose dyshomeostasis, and the progression of T2D, whilst also suggesting RALDH1 as a potential therapeutic target for T2D.

Objective:To explore the coverage of influenza and pneumonia vaccination and factors influencing the vaccination in children.Methods:A cross-sectional questionnaire survey was conducted in children's parents in Beijing and Gansu by using two-stage cluster-sampling to investigate the influenza and pneumonia vaccination rates and influencing factors in children.Results:A total of 2 377 parents were included in the study, and the results indicated that the influenza vaccination coverage was 35.93% and the pneumonia vaccination coverage was 16.58% in children in survey areas, the vaccination rate of both vaccines was 11.65%. The top three reasons for vaccination for both vaccines were being aware of severity of the diseases (influenza vaccine: 36.02%; pneumonia vaccine: 49.61%), being required by school or organization (influenza vaccine: 28.76%; pneumonia vaccine: 25.45%) and being aware of the susceptibility of the diseases (influenza vaccine: 26.41%; pneumonia vaccine: 13.88%). The top three reasons for having no vaccinations were personal unwillingness, concern about vaccine and vaccine accessibility. Families with multi children, living in rural areas and lower family income were the negative factors for both types of vaccinations.Conclusions:The influenza and pneumonia vaccination coverage in children need further improvement, and rural families and families with multi children are the key concern groups for expanding vaccination coverage. Health education about influenza and pneumonia vaccinations, coordinating vaccine supply and decreasing vaccine prices play an important role in improving influenza and pneumonia vaccination coverage.

Human challenge trial (HCT) is a test in which human volunteers are intentionally infected with pathogens in order to evaluate the efficacy of candidate preventive or therapeutic drugs. During the COVID-19 pandemic, the HCT of vaccines has aroused people's attention due to its significant advantages over clinical trial. This paper introduces the concept, development and application of HCT, the advantages and limitations of HCT for vaccine evaluation, and the consideration of future HCT of COVID-19 vaccine in China.

Objective:To investigate the incidence and determinants of vaccine hesitancy towards national immunization program in China and understand the current status of parents' hesitancy to different vaccines used in national immunization program.Methods:A cross-sectional survey was conducted in Beijing, Sichuan and Gansu. The methods of proportional probability sampling and convenience sampling were used to select the eligible study subjects for questionnaire surveys.Results:A total of 3 592 parents were enrolled in the study, in whom 38.22% fully accepted all the vaccines, 59.35% agreed to let their children to receive all the vaccines but showed slight concern, and 2.42% had hesitancy to the vaccines. The vaccine with the most hesitancy was polio vaccine (0.89%), followed by diphtheria pertussis tetanus vaccine (0.70%) and hepatitis A vaccine (0.64%). The dominant reason for vaccine hesitancy was the risk-benefit perception of vaccination (31.03%), followed by the low awareness of the parents (21.84%) and the inconvenience caused by distance and time (21.84%).Conclusions:The incidence of vaccine hesitancy towards national immunization program was low in parents in China, but over 50% of the parents showed concern to the vaccines. It is essential to improve the service quality of national immunization program and strengthen the health education about the vaccination to reduce the incidence of vaccine hesitancy in parents.

Objective: To discuss the treatment, pathological subtypes and recurrence of sinonasal chondrosarcoma, and to identify the prognostic factors. Methods: Between January 1994 and May 2018, 47 patients with sinonasal chondrosarcoma who were treated in Eye, Ear, Nose and Throat Hospital, Shanghai Medwal College, Fudan University were retrospectively reviewed, including 19 males and 28 females, aging from 7 months to 71 years old, with a median age of 38 years old. The clinical symptoms, location of tumor, surgical method, pathological subtype, recurrence and prognosis were collected and analyzed. Kaplan-Meier method was used to calculate the disease-specific survival rate, disease-free survival rate and draw survival curve. Log Rank was used to analyze the prognostic factors. Cox regression was used for multivariate analysis. Results: Except for one patient who gave up treatment after tumor biopsy, other 46 patients underwent radical resection, including 31 cases of endoscopic resection and 15 cases of extranasal approach resection. Thirty-nine patients were diagnosed as conventional intramedullary chondrosarcoma with pathological grade Ⅰ of 24 cases and grade Ⅱ of 15 cases. Six cases were diagnosed as mesenchymal chondrosarcoma while 2 cases were diagnosed as myxoid chondrosarcoma. During an average follow-up period of 56.1 months (17-156 months), 23 patients had recurrence (54.8%, 23/42), among whom 9 patients had re-operations and 5 patients died. Thirty-seven patients survived, including 25 patients survived without tumors. In addition, 5 patients were lost to follow-up, including the patient who gave up treatment after tumor biopsy. Five-year overall survival rate and disease-free survival rate was 84.7% and 34.3%, respectively. Multivariate analysis showed that invasion of skull base was an independent risk factor affecting disease-free survival rate (95% confidence interval: 1.089-5.825, P=0.031). Conclusions Radical resection is the primary treatment for sinonasal chondrosarcoma. The most common pathological subtype is conventional intramedullary chondrosarcoma. Sinonasal chondrosarcoma has a high local recurrence rate. The long-term prognosis is well after complete excision of the lesion. The most important cause of death is uncontrollable local disease and invasion of adjacent key structures.

Objective:To explore the relationship between NOX4 and radiosensitivity of nasopharyngeal carcinoma cells.Methods:Western blot was used to test the expression of NOX4 in nasopharyngeal carcinoma cells (CNE1, CNE2 and HONE1) and normal nasopharyngeal epithelial cells (NP69). The lentiviral vectors for RNA interference and overexpression of NOX4 gene were constructed and nasopharyngeal carcinoma cells were transfected. After treatment with radiation or/and PI3K/AKT inhibitor LY294002, the expressions of related proteins in cells were tested by Western blot, and the cell proliferation was detected by CCK-8 assay and the cell apoptosis was determined by flow cytometry. GraphPad Prism 5 was used for statistical analysis, and P<0.05 was statistically significant. Results:The expressions of NOX4 in nasopharyngeal carcinoma cells were higher than those in normal nasopharyngeal epithelial cells. Compared with the siNC group, the siNOX4 group of nasopharyngeal carcinoma cell had lower proliferation capacity [72 h absorbance ( A) value:1.16 vs. 0.75] and higher apoptosis rate (2.9% vs. 10.0%). In contrast,compared with the vector group, the NOX4 group of nasopharyngeal carcinoma cell had higher proliferation capacity [72 h absorbance ( A) value: 1.01 vs. 1.32] and lower apoptotic rate (1.7% vs. 1.1%).Treatment with LY294002 for nasopharyngeal carcinoma cells of NOX4 overexpression,compared with the NOX4 group, the proliferation ability of nasopharyngeal carcinoma cells in the NOX4+LY294002 group was reduced (72 h absorbance ( A) value: 1.32 vs. 0.77), while the apoptotic rate was increased (1.1% vs. 3.1%).Treatment with radiotherapy, compared with the siNC/Vector group, the proliferation ability of nasopharyngeal carcinoma cells in the siNOX4 group was reduced (72 h absorbance ( A) value: 0.72 vs. 0.33), and the apoptotic rate was increased (7.8% vs. 17.3%). However, in the NOX4 group, the proliferation of nasopharyngeal carcinoma cells was enhanced (72 h absorbance ( A) value:0.65 vs. 0.78), and the apoptotic rate was reduced (8.1% vs. 3.8%). Compared with the NOX4+radiation group, the proliferation ability of nasopharyngeal carcinoma cells in the NOX4+radiation+LY294002 group was reduced (72 h absorbance ( A) value: 0.79 vs. 0.56), while the apoptotic rate was increased (3.8% vs. 8.1%). Conclusion:NOX4 can inhibit radiosensitivity of nasopharyngeal carcinoma cells possibly by activating PI3K/AKT pathway.

Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.

[Summary] Acute acromioclavicular joint dislocation is a common injury of the shoulder .Its surgical treatment is various .In recent years , with the promotion of arthroscopic techniques , arthroscopic treatment has gradually become a hot spot in the field of minimally invasive treatment for acute acromioclavicular joint dislocation .There are various types of internal fixation .The overall treatment effect is satisfactory .In this review we summarized minimally invasive treatment for acromioclavicular joint dislocation .