Alzheimer disease is a common neurodegenerative disease among the elderly and has abnormal accumula-tion of amyloid plaques as the typical pathological feature.Because of its strict selective permeability,the blood-brain bar-rier prevents all macromolecular substances from entering the central nervous system and has thus become a"bottleneck"for delivering therapeutic drugs to the brain.Studies have shown that low-intensity focused ultrasound combined with ultra-sound microbubbles can safely and reversibly open the junction between endothelial cells of the blood-brain barrier through cavitation and reduce amyloid deposition by promoting the activation of microglial cells into an anti-inflammatory state.This article reviews the latest research advances in low-intensity focused ultrasound in the treatment of Alzheimer disease,in order to provide a theoretical basis and new strategies for the treatment of Alzheimer disease.

Objective To establish an evaluation criterion for high-quality nursing services in comprehensive hospitals of Grade Three in Guangdong Province and provide references for promoting the evaluation of high quality nursing services and standardising high quality nursing services.Methods Based on literature review,brainstorming and references of relevant domestic systems,standards and policies,a pool of evaluation index items and a preliminary questionnaire were constructed.Delphi method was used for two rounds of expert consultations on evaluation indicators.Results The positive coefficients of the two rounds of expert consultations were of 80.00%and 91.67%,respectively,with the authority coefficients both at 0.93.The Kendall coordination coefficients for hospital part were 0.128 and 0.116 respectively,for ward part were 0.193 and 0.107 with statistical differences(both P＜0.001).The evaluation criteria for high-quality nursing services in general hospitals above the third level in Guangdong Province involved in nursing services of hospitals and wards.There were 8 primary indicators,22 secondary indicators and 65 tertiary indicators in the nursing services at hospital part,and 9 primary indicators,23 secondary indicators and 50 tertiary indicators in the nursing services at ward part.Conclusions The evaluation criteria for high-quality nursing services in comprehensive hospitals above the third level in Guangdong Province,established in this study,are scientifically valid and reliable.They allow improvement of management system for the high-quality nursing services as well as guide the healthy development of high-quality nursing services.

Objective To investigate the characteristics and clinicopathology of v-raf murine sarcoma viral oncogene homolog Bl(BRAF)V600E mutations in papillary thyroid carcinoma(PTC)in Air Force flight personnel.Methods Data of cases and test results of BRAF V600E mutation were collected from Air Force aviators pathologically diagnosed with PTC.A univariate analysis of the relationship between BRAF V600E mutations and clinicopathologic features was performed.Results The overall rate of BRAF V600E mutations among 55 PTC flight crew members was 70.91％.The univariate analysis showed that the number of lymph node metastases in the BRAF V600E mutated group was larger than in the BRAF V600E unmutated group,and the proportion of BRAF V600E mutations in flight crews at intermediate risk of recurrence was higher than that in those at low risk of recurrence(P＜0.05).The presence or absence of BRAF V600E mutations did not affect the results of medical evaluation of PTC in flight personnel.Conclusion The rate of PTC BRAF V600E mutations in Air Force flight crews is similar to that of the general Chinese population.BRAF V600E mutations are associated with an increased number of lymph node metastases and risk of recurrence,and follow-up is recommended for flight personnel with PTC,especially those with BRAF V600E mutations.

Objective:To investigate the clinical characteristics of patients with malignant tumors and immune checkpoint inhibitors (ICI) related multisystem adverse events as well as therapeutic efficacy of ICI.Methods:The general data, immune-related adverse events (irAE) type, onset time, severity and ICI efficacy of patients with malignant tumors who developed irAE after receiving ICI in China-Japan Friendship Hospital between January 2019 and November 2021 were retrospectively analyzed. All patients were divided into multisystem irAE group and single system irAE group according to whether patients with more than 1 organ or system developed irAE for once. The occurrence of irAE was summarized, and the clinical characteristics of patients were compared. Progression-free survival analysis was not performed owing to the pause of immunotherapy caused by some irAE, so the efficacy of ICI was evaluated by using ICI treatment duration (TD).Results:A total of 47 patients with malignant tumors and irAE were included in this study, with 70 times of irAE in total. The median onset time was 90 d (35 d, 196 d). Among them, 12 patients (25.53%) developed multisystem irAE (32 times of irAE in total); the other 35 patients (74.47%) developed single system irAE (38 times of irAE in total). Cutaneous toxicity for 7 times, thyroid toxicity for 7 times and pulmonary toxicity for 5 times were the most frequent among multisystem irAE group; pulmonary toxicity for 13 times, thyroid toxicity for 12 times and cutaneous toxicity for 5 times were the most frequent among single system irAE group. There were no statistically significant differences in the proportion of patients stratified by age, gender, the combination of other treatments and different body mass between the two groups (all P > 0.05). The median follow-up time was 20 months (9-40 months). The median TD of ICI was 16.00 months (95% CI 3.62-31.22 months) in multisystem irAE group and 4.60 months (95% CI 4.12-11.30 months) in single system irAE group; TD in multisystem irAE group was longer than that in single system irAE group, and the difference was statistically significant ( HR = 0.413, 95% CI 0.202-0.844, P = 0.038). Conclusions:The efficacy of ICI in patients with malignant tumors and multisystem irAE is better than that in those with single system irAE. It suggests that the better efficacy of ICI may be associated with greater risk of irAE. There is no significant difference in the clinical features between multisystem irAE and single system irAE.

OBJECTIVE To provide reference for safe use of bevacizumab in tumor patient. METHODS Retrospective analysis was performed for a case of tracheomediastinal fistula caused by bevacizumab after radiotherapy in which clinical pharmacist participated. Retrieved from PubMed ，Elsevier Science Direct ，Springer Link ，Wiley Oline Library ，CNKI and Wanfang database ，the cases of respiratory fistula caused by bevacizumab were collected ，and the causes of respiratory fistula were analyzed. RESULTS & CONCLUSIONS Referring to relevant literatures ，combined with the formation position of fistula and considering its correlation with the use time of bevacizumab ，considering that it may be bevacizumab related tracheomediastinal fistula，clinical pharmacists recommended that patients stopped bevacizumab and underwent stent implantation. The patient refused to implant stent for personal reasons ，but the tracheomediastinal fistula improved 3 months after drug withdrawal. Combined with the data of 16 patients with respiratory fistula caused by bevacizumab ，it could be inferred that the use of bevacizumab on the basis of radiotherapy may be the cause of tracheomediastinal fistula ；the mechanism may be related to bevacizumab inhibiting angiogenesis and affecting wound healing. This suggests that for patients who have received radiotherapy ，clinical pharmacists should strengthen medication monitoring and medication education when using bevacizumab ；clinical pharmacists should not only pay attention to the common adverse reactions such as hypertension and bleeding caused by the drug ，but also pay attention to rare but life-threatening adverse reactions such as respiratory fistula ，so as to ensure the safety of drug use.

Retinoids are a group of natural or synthetic compounds that have similar structures or biological activities as retinoic acid. Previous studies have demonstrated that retinoids can improve the pathophysiology and symptoms of Alzheimer's disease (AD) in a variety of ways. This article reviews the recent advance in mechanism of retinoids in the prevention and treatment of AD, in order to provide some references for selection of clinical treatment direction in AD.

Objective To retrieve and analyze the guidelines on diabetic foot offloading, and summarize the evidence of high quality guidelines, so as to provide reference for standardizing the offloading treatment of diabetic foot in China. MethodsThe clinical practice guidelines of diabetic foot in the major guideline networks, databases and professional association websites were retrieved by computer. Three researches evaluated the quality of the guidelines, and two researches extracted evidence from documents that met the quality criteria. ResultsA total of 7 guidelines were included, and 5 aspects, 30 recommendations were extracted, including comprehensive treatment, the principle of offloading, offloading of the plantar ulcer, offloading of the non-plantar ulcer, and the gap between the evidence and practice. ConclusionsThis study summarize the best evidence of the diabetic foot offloading therapy, and provides a reference for medical institution to develop appropriate procedures and standardize the practice of diabetic foot offloading therapy. Most of the interventions recommended in the guidelines come from relatively developed countries, but their application may be limited in less developed countries or regions. Therefore, it is urgent to explore offloading methods which have positive offloading effect as well as conform to our national conditions, and apply them to clinical practice gradually in order to improve the therapeutic effect of diabetic foot and improve prognosis.

Majority of type 2 diabetes mellitus (T2DM) patients are highly susceptible to several forms of cognitive impairments, particularly dementia. However, the underlying neural mechanism of these cognitive impairments remains unclear. We aimed to investigate the correlation between whole brain resting state functional connections (RSFCs) and the cognitive status in 95 patients with T2DM. We constructed an elastic net model to estimate the Montreal Cognitive Assessment (MoCA) scores, which served as an index of the cognitive status of the patients, and to select the RSFCs for further prediction. Subsequently, we utilized a machine learning technique to evaluate the discriminative ability of the connectivity pattern associated with the selected RSFCs. The estimated and chronological MoCA scores were significantly correlated with R= 0.81 and the mean absolute error (MAE) =1.20. Additionally, cognitive impairments of patients with T2DM can be identified using the RSFC pattern with classification accuracy of 90.54％ and the area under the receiver operating characteristic (ROC) curve (AUC) of 0.9737. This connectivity pattern not only included the connections between regions within the default mode network (DMN), but also the functional connectivity between the task-positive networks and the DMN, as well as those within the task-positive networks. The results suggest that an RSFC pattern could be regarded as a potential biomarker to identify the cognitive status of patients with T2DM.

Objective The aim of this study was to investigate the mechanism underlying pruritus by comparing the epidermal growth factor receptor inhibitor(EGFRI)-erlotinib mouse model with the substance P(SP)-induced pruritus mouse model. Methods Two randomized groups of mice were treated with erlotinib or SP to induce pruritus. Behavioral and skin manifestations were observed. Pathological images and neurokinin 1 receptor(NK-1R)expression of the skin were determined. Concentration of interleukin(IL)-31, IL-33, histamine, leukotriene B4, and SP was analyzed by enzyme-linked immunosorbent assay. Nitric oxide was analyzed by colorimetry. Results Transient pruritus induced by erlotinib appeared 2 to 5 days after treatment. In contrast, continuous pruritus was observed during the first hour, but was then gradually relieved. These two shared similar scratching behavior. Concentration of neurotransmitters showed similar trends in changes among the erlotinib group and SP group. Immunohistochemical expression was also consistent between the erlotinib group and SP group. Conclusions Erlotinib-associated pruritus is related to release of signaling factors through the SP/NK-1R signaling pathway.

OBJECTIVETo explore the effects of acupuncture on the expression of protein kinase B (PKB/AKT) in lung tissues of asthma rats.

METHODSForty SPF male SD rats were randomly divided into a blank group, a model group, an acupuncture group and a blocker group, 10 rats in each one. The rat model of asthma was established by egg albumin stimulation in the model group, acupuncture group and blocker group. Since the establishment of rat model, the rats in the acupuncture group were treated with acupuncture at "Dazhui" (GV 14), "Feishu" (BL 13) and "Fengmen" (BL 12) before atomization; the rats in the blocker group were treated with intervention of blocker LY294002, once every two days, for 7 times. There was no treatment in the blank group and model group. HE staining was applied to observe the morphologic changes of lung tissues; the immunohistochemical method was applied to test the protein expression of AKT in lung tissue.

RESULTSHE staining indicated the infiltration and aggregation of a variety of inflammatory cells around airways, as well as bronchial smooth muscle spasm and confined lumen in the model group; in the acupuncture group and blocker group the inflammatory cells were less and confined lumen was relieved. Compared with the blank group, the protein expression of AKT was higher in the model group (<0.05); compared with the model group, the protein expression of AKT in the acupuncture group and blocker group was reduced (both<0.05); the differences between the acupuncture group and blank group, blocker group were not significant (both>0.05).

CONCLUSIONSAcupuncture could reduce the protein expression of AKT in lung tissue in asthma rats, leading to relieved inflammation reaction and airway remodeling.