Objective:To preliminarily explore the long-term improvement of low-frequency deep brain stimulation (DBS) on the nucleus basalis of Meynert (NBM) in cognitive disorders, neuropsychiatric symptoms and sleep disorders of patients with early-onset severe Alzheimer's disease (AD).Methods:A retrospective study was performed; 18 patients with early-onset severe AD admitted to Department of Neurosurgery, First Medical Center of PLA General Hospital from January 2016 to December 2022 were included. These patients were divided into NBM-DBS group and control group according to different treatments; 6 patients received low-frequency NBM-DBS on basis of conservative treatments; 12 patients accepted conservative treatments. Changes in Brief Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Hamilton Depression Rating Scale (HAMD), Becker-Lavanson Mania Scale (BRMS), Pittsburgh Sleep Quality Index (PSQI), and Zarit Caregiver Burden Interview (ZBI) were observed before treatment and 1 year after follow up.Results:MMSE and MoCA scores 1 year after follow up obviously reduced compared with those before treatment in both NBM-DBS and control patients; MMSE and MoCA scores in NBM-DBS patients showed no significant differences between 1 year after follow up and before treatment ( P>0.05), while significant differences were noted in the control group between 1 year after follow-up and before treatment ( P<0.05); and no significant differences in MMSE and MoCA scores were noted between the 2 groups 1 year after follow up ( P>0.05). NPI, HAMD, BRMS and ZBI scores in the NBM-DBS group 1 year after follow up were significantly different compared with those before treatment ( P<0.05); no significant differences were noted in NPI, HAMD and ZBI scores in the control group between 1 year after follow up and before treatment ( P>0.05), while significant difference was noted in BRMS scores ( P<0.05); significant differences in NPI, HAMD, BRMS and ZBI scores were noted between the 2 groups 1 year after follow up ( P<0.05). Conclusion:Low-frequency NBM-DBS is not only effective in improving cognitive disorders, but also effective in improving neuropsychiatric symptoms and sleep disorders, as well as reducing caregiver burden in patients with early-onset severe AD.

AIM:To investigate the effect of Tongsai granules(TSG)on epithelial barrier dysfunction in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and the underlying mechanism.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into control group,model group,TSG group,and moxifloxacin(MXF)+salbutamol(STL)group.Rat COPD model was established over 8 weeks.On day 3 of week 9,the rats with COPD were intratracheally administered Klebsiella pneumoniae to establish the AECOPD model.On days 1 to 2 and 4 to 7 in week 9,saline was administered via oral gavage to the rats in control and model groups,and the rats in TSG and MXF+ STL groups were treated daily with TSG and MXF+STL by gavage,respectively.Peak expiratory flow(PEF),histopatho-logical changes,and the expression levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),matrix me-talloproteinase 2(MMP2),MMP9,zonula occludens-1(ZO-1),E-cadherin(E-Cad)and occludin(OCC)were deter-mined.Moreover,human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract(CSE)and treated with different TSG fractions,and the protein levels of ZO-1,E-Cad,OCC,epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)were determined.RESULTS:Treatment with TSG significantly reduced bronchial wall thickness,mean linear intercept,and the levels of IL-1β,IL-6,TNF-α,MMP2 and MMP9(P＜0.05 or P＜0.01),significantly increased mean alveolar number and PEF(P＜0.01),and up-regulated the ZO-1,E-Cad and OCC protein levels(P＜0.01)in the lungs of AECOPD rats.Treatment with TSG2,the second TSG fraction,increased the protein levels of ZO-1,E-Cad and OCC in a dose-dependent manner in CSE-exposed BEAS-2B cells(P＜0.05 or P＜0.01).Network pharmacology analysis of 328 targets of the com-pounds in TSG2 and 3 864 genes related to AECOPD suggested that TSG2 relieved AECOPD likely through the regulation of ERBB2,ERK,EGFR,IL and WNT signaling pathways.Treatment with TSG2 also inhibited CSE-induced increases in p-EGFR and p-ERK levels in BEAS-2B cells(P＜0.05 or P＜0.01).CONCLUSION:Treatment with TSG could maintain airway epithelial barrier function in AECOPD rats,likely through the inhibition of EGFR/ERK signaling pathway.

Background:Understanding and minimizing existing global coronavirus disease 2019(COVID-19)vaccination disparities is critical to global population health and eliminating health inequities.The study aims to investigate the disparities of vaccination coverage and progression and the associated economic and educational determinants to inform global COVID-19 vaccination strategies.Methods:COVID-19 vaccination coverage data from 206 countries used in the study were derived from"Our World in Data"website.After obtaining the vaccination coverage indicators,we fitted the progression indicators for vaccination.Correlation and multiple linear regression analysis were used to examine the effects of gross domestic product(GDP)per capita,Gini index,education,and their interactions on the coverage and progression of the COVID-19 vaccination.Results:The coverage of COVID-19 vaccination ranged from less than 30 doses to more than 150 doses per hun-dred people,from less than 15％to more than 75％for proportion of people vaccinated,from less than 15％to more than 60％for proportion of people fully vaccinated.Similarly,the progression of vaccination ranged from less than 0.1 to more than 0.6 for progression of total number of doses,from less than 0.1 to more than 0.3 for progression of proportion of people vaccinated,and from less than 0.1 to more than 0.4 for progression of propor-tion of people fully vaccinated.GDP per capita and education were positively associated with the coverage and progression,while Gini index was negatively associated with the coverage and progression.Negative interaction between GDP per capita and education was also observed for coverage(β=-0.012 to-0.011,P＜0.05)and progression(β=-0.012 to-0.011,P＜0.05).Conclusions:Substantial geographic disparities existed for the coverage and progression of COVID-19 vaccination.Economy and education are two important factors contributing to the disparities.Different countries may adopt varied strategies to promote the national distribution and vaccination of COVID-19 vaccines.

Objective To investigate the indications of optic canal decompression in the patients with front-orbital fibrous dysplasia and the methods of intraoperative optic canal localization and decompression. Methods We collected 30 cases of fibrous dysplasia. All patients had sufficient images assessment. Patients with symptoms underwent surgery, including front-orbital cranioplasty and optic canal decompression. The frontotemporal epidural approaches were used. If there was a proptosis, the approach was extended with the removal of superior orbital ridge. Six patients undertook intraoperative CT and MRI fusion navigation, assisting in confirming the trunk, orbital and cranial orifice of optic nerve. During the operation, the optic canals were decompressed by three-bits method, to confirm the position of optic nerve. Results There were 30 cases of optic canal decompression and one case of vision loss. The visual acuity and vision field of the remaining patients improved to varying degrees. The proptosis disappeared or alleviated after the operation. Thirteen cases were reconstructed with normal internal plate, five cases with titanium plate, nine cases without reconstruction, and two cases were paved with proliferative broken bone on the orbital top; one case recurred with exophthalmos again after five years, but the visual acuity did not decline. Conclusion For the patients with front-orbital fibrous dysplasia, active surgical treatment should be taken, optic canal decompression should be chosen for diminution of vision, craniofacial anaplasty and orbital decompression should be performed in patients with facial deformity. The epidural approach is a good option to locate the optic nerve from the orbital orifice or cranial orifice. Combined with the three-bits method, we can achieve safe and meticulous optic nerve decompression.

Background: Controlling the coronavirus disease 2019 (COVID-19) epidemic requires information beyond new and cumulative cases.This study aims to conduct an in-depth analysis by geographic strata: Wuhan City (hereafter referred to as Wuhan) only,Hubei Province (hereafter referred to as Hubei) excluding Wuhan,and China excluding Hubei.Methods: Daily cumulative confirmed COVID-19 cases between December 8,2019 (the date of symptom onset based on patients' recall during the investigation),and March 1,2020,from official sources and published studies were analyzed.The second derivative model was used for information extraction.Data analysis was conducted separately for the three strata.Results: A total of 80 026 diagnosed COVID-19 cases were reported during the first 85 days of the epidemic,with 49 315 cases from Wuhan,17 788 from Hubei excluding Wuhan,and 12 923 from China excluding Hubei.Analytical results indicate that the COVID-19 epidemic consists of an Acceleration,a Deceleration,and a Stabilization Phase in all three geographic strata,plus a Silent Attack Phase for Wuhan only.Given the reported incubation period of 14 days,effects of the massive anti-epidemic actions were revealed by both the Acceleration and Deceleration Phases.The Acceleration Phase signaled the effect of the intervention to detect the infected;the Deceleration Phase signaled the declines in new infections after the infected were detected,treated and quarantined.Conclusion: Findings of the study provide new evidence to better monitor the epidemic,evaluate its response to intervention,and predict the trend long.In addition to re-evaluating the control of the COVID-19 epidemic in China,this study provided a model for monitoring outbreaks of COVID-19 in different countries across the world.

Objective To measure the peripheral dose distributions of the mobile head cone beam computed tomography (CBCT) and evaluate the impact of CBCT on the surrounding personnel and environment, and provide data support for clinical radiation protection management. Methods Combined with the structural characteristics of CBCT, AT1123 was used in the direction of 0° (counterclockwise), 45°, 90°, 135°, 180°, 225°, 270° and 315° in front of CBCT to measure the ambient dose equivalent rate of 30 cm, 80 cm and 130 cm away from the ground when the equipment was normally out of the beam, and the boundary of the temporary control area was drawn. At the same time, the dose level behind the lead screen 1 m away from the external surface of the equipment was measured and analyzed. Results The dose field around CBCT was symmetrically distributed with the dividing line of 0° and 180°, and the radiation dose level of 5.5 m in the direction of 0°, 3.5 m in the direction of 45°, 0.5 m in the direction of 90° and within 1.0 m in the direction of 180° (inside the "spoon" type) was higher than 2.5 μSv/h. The radiation dose levels of CT aperture 0° (straight forward), 45° and 315° behind the lead screen 1 m away from the equipment surface were 0.37 μSv/h, 0.22 μSv/h and 0.54 μSv/h, respectively. Conclusion The results show that the radiation dose around the mobile head cone beam CT is in a low dose level, the distribution of the dose field can provide necessary reference for the administrative and medical personnel to strengthen the radiation safety management. At the same time, it is suggested that lead screens should be set up in the clinical use of mobile CT to ensure the health and safety of the surrounding people and the environment.

Objective:To explore the impact of primary immune thrombocytopenia (ITP) on patient's quality of life and emotional well-being, and both the physician and the patient's perception of the treatment.Methods:This study was a Chinese Subgroup analysis of I-WISh survey, including 102 physicians and 286 ITP patients invited to complete the survey. A descriptive analysis of the results of the physician-patient survey was conducted in three parts: symptoms, impact of ITP on quality of life and emotion, and treatment perception.Results:Fatigue and anxiety about unstable platelet counts were the main symptoms after treatment. Physicians reported inadequate frequency of anxiety and fatigue. In terms of quality of life, over 90.0% of patients thought that ITP had a negative impact on their working life/studies, daily tasks, energy, capacity to exercise, and sexual life. With regard to emotion, 60.8% (174/286) patients thought that ITP had a greater impact on overall emotion, concerns about the fluctuation in platelet level (74.8%, 214/286) , disease itself (71.7%, 205/286) and disease progression (68.9%, 197/286) were the common issues, which were similar to the physicians' evaluations. Both physicians and patients agreed that reducing spontaneous bleeding, maintaining a healthy blood count and improving quality of life were the top three important treatment goals. Physicians considered reducing bleeding risk as the most important factor for decision making. Physicians believed that patients receiving glucocorticoid (54.9%, 56/102) were most likely to succeed in achieving sustained response while patients had the best response to thrombopoietin receptor agonist (TPO-RA) treatment, with about 83.9% (240/286) being satisfied with the overall effectiveness of TPO-RA.Conclusions:Physicians in the I-WISh Chinese subgroup had low awareness on patients' fatigue and anxiety. The quality of life and emotion of patients were significantly negatively affected by ITP. There are differences in the selection of treatments between physicians and patients, suggesting that physicians should raise concerns about the quality of life of ITP patients and make individualized treatment options through physician-patient shared decisions.

Background:The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic is a typical global health concern.The impact of HIV/AIDS is global,and we cannot effectively solve the problem without a global effort.In this study,we report our research on global HIV/AIDS control with an innovative fourdimensional approach.Methods:Countries (n=148) with data available on area size,total population,and the total number of persons living with HIV (PLWH) were included.The HIV epidemic across the globe was described using 4 indicators,including the total count,population-based P rate,geographic area-based G rate,and population and geographic area-based PG rate.Results:A total of 35,426,911 PLWH were included,with a global prevalence rate of 0.51 per 1,000 population.The total PLWH count provided data on resource allocation in individual countries to improve HIV/AIDS care;and the top five countries with the highest PLWH counts were South Africa (7,000),Nigeria (3,500),India (2,100),Kenya (1,500),and Mozambique (1,500).The other three indicators provide a measure to assess the global risk profile of HIV transmission and to provide information on HIV/AIDS prevention strategies.The top five countries with the highest P rates (per 1,000 persons) were Swaziland (170.9),Botswana (154.7),Lesotho (145.2),South Africa (127.4),and Zimbabwe (89.7);the top five countries with the highest G rates (per 100 km2) were Swaziland (1,279.1),Malawi (1,039.5),Lesotho (1,021.1),Rwanda (810.7),and Uganda (748.1);and the top five countries with highest PG rates (per 1,000,000 persons per 100 km2) were Barbados (2,127.9),Swaziland (993.8),Lesotho (478.3),Malta (375.0),and Mauritius (319.7).With PG rate,we detected countries in two hotspots (south and middle Africa and the Caribbean region) and one belt across the Euro-Asian region with high risks of HIV transmission.Conclusions:This study expanded the conventional measures by adding two new indicators,thus forming a new four-dimensional framework to quantify the global HIV epidemic.In addition to gaining a better insight into the epidemic than before,study findings provide new data on country-level and global efforts to end the AIDS epidemic by 2030.

Objective: To investigate the clinical value of multimodal navigation-based virtual reality (MNVR) in the needle biopsy of intracranial eloquent lesions. Methods: From January 2016 to January 2017, 20 patients with intracranial deep-seated lesions involving eloquent brain areas underwent MNVR-aided needle biopsy at Department of Neurosurgery, People′s Liberation Army General Hospital. Preoperatively, MNVR was used to propose and revise the biopsy planning. Intraoperatively, navigation helped trajectory avoid the eloquent structures. Intraoperative MRI (iMRI) was performed to prove the biopsy accuracy and detect the intraoperative complications. Perioperative neurological status, iMRI findings, intraoprative complications, surgical outcome and pathological diagnosis were recorded. Wilcoxon rank-sum test was conducted to compare the preoperative and postoperative neurological scores. Results: MNVR helped revised 45%(9/20) initial biopsy trajectories, which would probably injury the nearby eloquent structures. Navigation helped biopsy trajectories spare the eloquent structures during the operation. No statistical difference was found between postoperative and preoperative neurological status, despite all the lesions were adjacent to eloquent areas. Additionally, 20 patients totally received 21 iMRI scanning. iMRI helped revise incorrect biopsy site in one case and detected intraoperative hemorrhage in another case, both of cases were treated immediately and effectively. No MNVR related adverse events and complications occurred. Conclusions MNVR-aided needle biopsy of intracranial eloquent lesions is a safe, novel and efficient biopsy modality. This technique is helpful to reduce the incidence of surgery related neurological deficits.

In order to clarify regions of production and to discriminate processing methods, quantitative and qualitative analyses for saccharides and terpenes in 35 batches of Alismatis Rhizoma were performed. Methodologies included HPLC-PDA, HPLC-VWD and UHPLC-MS , combined with principal component analysis (PCA) and partial least squares regression techniques (PLSR). The inhibitory effects of triterpenes and Alismatis Rhizoma extracts on lipase activity were evaluated . PLSR analysis revealed significant positive correlations ( = 0.5795) between the contents of triterpenes , , , and and the inhibitory effects of Alismatis Rhizoma. The present study establishes an effective method for simultaneous determination of multiple components, and identifies key bioactive triterpenes. These results can be used for systematic and novel analytical strategies for the quality control of Alismatis Rhizoma production.