Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Over the past 50 years,the global incidence of obesity has dramatically increased,posing a serious threat to human health.Conventional weight loss methods,such as dieting and exercise therapy,are difficult to obtain a stable and rapid weight-loss effect.Besides,most weight-loss drugs available nowadays are not specifically designed for the pure obese population,they are mainly used for diabetes.The prevalence of traditional bariatric surgery is low,and it carries high surgical costs and high risk of developing complications.Therefore,bariatric artery embolization(BAE),regarded as a new weight-loss therapy,has emerged and it has developed rapidly.BAE can not only achieve long-term weight control,but also provide glycemic benefit to patients with pre-diabetes.Compared with traditional bariatric surgery,BAE has the advantages of less trauma,quick recovery and low risk of postoperative complications.However,there is no unified standard for the selection of intraoperative embolization materials and embolization sites so far,and the postoperative changes of gastric function and the specific mechanism of body metabolism improvement need to be further explored.This paper aims to make a detailed review about BAE,focusing on the research background,the technical principles,the latest research progress,and the existing problems.

Objective To analyze the clinical outcomes of extended thymectomy for myasthenia gravis (MG) patients under different surgical approaches, and to determine the factors affecting the prognosis of MG. Methods The MG patients who underwent extended thymectomy from January 2014 to March 2021 in our hospital were retrospectively collected. According to the surgical approach, they were divided into a subxiphoid group and an intercostal group, and the perioperative results and prognosis were compared between the two groups. A “good outcome” was defined as complete stable remission (CSR), pharmacological remission (PR) or minimal manifestations state (MMS); a “poor outcome” was defined as outcomes worse than MMS. Univariate and multivariate logistic regression analyses were performed to assess the factors associated with the good outcomes. Results A total of 187 MG patients were included in the study, including 82 males and 105 females, with a median age of 50 (36, 60) years. There were 134 patients in the intercostal group and 53 patients in the subxiphoid group. Compared with the intercostal group, although the operation time of the subxiphoid group was longer [200.0 (172.0, 232.0) min vs. 141.0 (118.0, 169.0) min, P<0.001], the intraoperative blood loss was less [10.0 (10.0, 20.0) mL vs. 20.0 (10.0, 50.0) mL, P<0.001], the postoperative hospital stay was shorter [3.0 (2.5, 4.0) d vs. 5.0 (3.0, 7.0) d, P<0.001], and the incidence of complications was lower [1 (1.9%) vs. 26 (19.4%), P=0.001]. A total of 159 (85.0%) patients were followed up for a median period of 46 (13, 99) months, with a good outcome rate of 90.6% and CSR rate of 33.3%. There were no statistical differences in PR, MMS or overall good outcome rates between the two groups (P>0.05). Multivariate logistic analysis showed that age≤50 years was an independent predictor for "good outcome" of MG patients. Conclusion Extended thymectomy via subxiphoid for MG is a safe, feasible and effective surgical approach.

The traditional Chinese medicine （TCM） in pediatric care has a long history，proven efficacy，and distinctive characteristics.The China Association of Chinese Medicine has organized a series of youth salons to discuss the clinical advantages of treating diseases.Experts at this seminar proposed that the superior disease categories in pediatric TCM are significant for showcasing the unique strengths and advantages of TCM in the treatment of pediatric diseases，enhancing diagnostic and treatment levels，inheriting TCM knowledge，promoting the integration of TCM and Western medicine，and meeting patients' needs.The strengths of pediatric TCM are summed up as "having what others do not，excelling at what others have，being special in what others excel at，and ensuring safety in what others specialize in." The scope of superiority in pediatric TCM covers multiple systems，including respiratory，digestive，endocrine，psychological，and dermatological systems.This article summarized the advantages of TCM in treating 13 diseases discussed in the salon，such as upper respiratory tract infections，coughs，pneumonia，allergic rhinitis，bronchial asthma，atopic dermatitis，functional dyspepsia，functional constipation，enuresis，marginal short stature，simple obesity，attention deficit hyperactivity disorder，and tic disorders.The overall advantages were reflected in three aspects：First，the holistic concept and treatment based on syndrome differentiation in TCM highlight the advantage of treating the root causes of diseases，making the treatment methodical and precise.Second，most traditional Chinese herbs are natural and have strong safety profiles.Third，TCM treatment methods are abundant，especially the external treatment methods，which are widely used in pediatrics，highly accepted by parents，and have definite efficacy，as well as good safety and compliance.

OBJECTIVE：To evaluate the implementation of national drug centralized volume-based procurement （called “VBP”for short）in a public hospital，so as to provide reference for promoting VBP policy guided by value-based healthcare. METHODS：A total of 6 varieties and 12 specifications of antibiotics included in VBP in a public hospital in Chongqing were analyzed. The drug use data of the hospital one year before the implementation of VBP（i.e. April 20，2019- April 19，2020）and one year after the implementation（i.e. April 20，2020-April 19，2021）were collected and analyzed in respects of price change， generic drug substitution rate，average daily cost（DDDc），actual cost savings and other indicators. The problems and suggestions were put forward，and the effects of VBP policy implementation whether reflects the core connotation of value-based healthcare were evaluated. RESULTS：After the implementation of VBP，drug prices fell by an average of 63.44％，the average price drop of original drugs was 27.38％ ，and substitution rate of generic drugs was 25.59％ . DDDc of selected antibiotics in the hospital decreased in varying degrees，of which the decline of four drugs was 10％-40％，and that of Moxifloxacin hydrochloride tablets was 80.14％. Compared with bef VBP，6 kinds of antibiotics saved about 521 300 yuan，of which the imported Moxifloxacin hydrochloride tablets and Moxifloxacin hydrochloride sodium chloride injection saved 495 300 yuan（accounting for 94.97％ of the total cost savings of antibiotics）. CONCLUSIONS：The value of VBP based on the perspective of value-based healthcare is mainly reflected in the dual channel management mechanism of drugs，which improves the availability of drugs，effectively controls the unreasonable growth of medical expenses，reduces the expenditure of medical insurance fund，and helps to further reduce the drug burden of patients. At present，the implementation of VBP still faces difficulties，including the need for drug prices to return to a reasonable range，the need for foreign enterprises to change strategies to seek a breakthrough，and different therapeutic efficacy due to the difference in quality between the selected generic drugs and the original drugs. Therefore，the author believes that the pharmaceutical market structure should be transformed positively，value-based healthcare should help the regulation of medical insurance，and the consistency evaluation system should be optimized，so as to further improve the health level of patients.

Interventional medicine plays an important role in the diagnosis and treatment of cardiovascular and cerebrovascular diseases, hepatobiliary tumors and other diseases, which has become the third largest type of treatment technology besides internal and surgical treatment. In recent years, with technological breakthroughs in imaging technology, robotic surgical system, artificial intelligence, Internet of Things and other fields, unprecedented opportunities have been provided for interventional/minimally invasive+robotics. Interventional robotic surgical systems have mushroomed around this field. The authors discuss the current status and future of interventional robotic surgical system with high recognition worldwide, especially the three categories of specialized robotic surgical system for vascular intervention, percutaneous puncture intervention and natural non-vascular luminal intervention.

Objective: To investigate the value of the folate receptor (FR)-positive circulating tumor cell (CTC) detection in the diagnosis of benign and malignant subcentimeter pulmonary nodules(the maximum diameter ≤10 mm). Methods: Thirty-seven patients with subcentimeter pulmonary nodules (the chest CT showed the maximum diameter was ≤10 mm) in the Xuanwu Hospital of Capital Medical University from July to December 2018 were collected. Among them, 22 cases were diagnosed with early stage lung adenocarcinoma by postoperative pathological diagnosis and another 15 cases were benign lung lesion. Venous blood samples from these patients were collected before surgery and then utilized to detect FR⁺ CTC level (defined unit as FU/3 ml) by novel ligand-targeted polymerase chain reaction (LT-PCR), and the enzyme-linked immunosorbent assay was used to detect the levels of tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase(NSE), cytokeratin 19 fragment CYFRA21-1, carbohydrate antigen 125 (CA125), CA199, pro-gastrin releasing peptide (pro-GRP), etc. The t-test was used to compare the measurement values between the groups. The CTC value 8.70 FU/3 ml described in the detection kit instruction was used as the threshold. The binary logistic regression was used to analyze the risk factors of malignant pulmonary nodules. The kappa consistency test was used to identify the consistency of the diagnosis results obtained by the FR⁺ CTC level and the pathological results of surgically resected specimens. The receiver operating characteristic curve (ROC) was drawn to evaluate the efficiency of each index for the diagnosis of benign and malignant subcentimeter pulmonary nodules. Results: The level of FR⁺ CTC in patients with early stage lung cancer was higher than that in patients with benign lung lesion, and the difference was statistically significant [(11.0±3.0) FU/3 ml vs. (7.0±3.7) FU/3 ml, t=-3.327, P = 0.001]. The level of FR⁺ CTC was not related to the age, gender and smoking history of patients (all P>0.05). Logistic regression analysis indicated that high-level FR⁺ CTC was one of the risk factors for malignant pulmonary nodules (OR = 37.333, 95% CI 3.994-349.010, P = 0.002). The kappa consistency test indicated that the level of FR⁺ CTC used for the diagnosis of lung subcentimeter nodules presented a certain accuracy (κ = 0.627, P < 0.01). ROC illustrated that the FR⁺ CTC was better than CEA, NSE and CYFRA21-1 when it was used as an indicator for the diagnosis of malignant pulmonary nodules. The area under the curve(AUC) of FR⁺ CTC was 0.830 (95% CI 0.639-0.968), and the diagnostic sensitivity and specificity were 72.7% (95% CI 49.6%-88.4%) and 93.3% (95% CI 66.0%-99.7%), respectively. When FR⁺ CTC, CEA, NSE and CYFRA21-1 were combined for lung cancer diagnosis, the AUC, sensitivity and specificity were 0.776 (95% CI 0.614-0.938), 86.4% and 73.3%, respectively. Conclusion The detection of FR⁺ CTC has a high value in the diagnosis of benign and malignant subcentimeter pulmonary nodules.

Objective: To explore the prognosis and risk factors of pyelectasis in high-risk infants. Methods: This was a retrospective study. Totally 960 high-risk infants, who accepted type B ultrasonic examination for fetus at 28th week of gestation and for newborns in 48 hours after birth, were included in the study in departments of obstetrics and eonatology, Shunyi Maternal and Children's Hospital of Beijing Children's Hospital during May 2012 to April 2013. The degree of pyelectasis was classified using Grignon grade and the paients were followed up for 3 years. The factors of epidemiology, high risk pregnant women, fetus and high-risk newborns that relate to pyelectasis were summarized. High-risk factors were analyzed by using logistic multivariate regression analysis. Results: Of 960 high-risk infants, 103 had abnormal urinary ultrasound results, 87 (9.1% of high-risk infants) were diagnosed with pyelectasis, 16 (1.7% of high-risk infants) were diagnosed with congenital anomalies of the kidney and urinary tract. According to the degree of pyelectasis, 68 infants were Grignon grade Ⅰ, male:female ratio=5.8∶1, left side:right side ratio=1.91∶1; 19 infants were Grignon grade Ⅱ, male:female ratio=5.33∶1, left side:right side ratio=2.12∶1. Postnatal follow-up results showed that pyelectasis disappeared in 48 cases (55% of pyelectasis cae), 40 infants were Grignon grade Ⅰ (59% of all Grignon grade Ⅰ patients), 8 infants were Grignon grade Ⅱ (42% of all Grignon grade Ⅱ patients); The result of risk factors analysis showed that the risk of pyelectasis in males was 4.368 times that of females (95%CI: 2.33-8.189, P<0.05); the risk of pyelectasis in low birth weight infants was 22.434 times that of non low birth weight infants (95% CI: 5.883-85.547, P<0.05). Conclusion The incidence of pyelectasis in high-risk infants was 9.1%. The mitigation rate of pyelectasis in Grignon grade Ⅰ to Ⅱ in fetal or newborn period is high. Patients in Grignon grade Ⅲ and above in fetal or new born period had high risk of congenital anomalies of the kidney and urinary tract. The risk of pyelectasis of male was higher than that of female; the risk of pyelectasis of low birth weight infant was higher than appropriate for gestational age infants.

Objective To label neural stem cells (NSCs) with superparamagnetic iron oxides (SPIO) and to explore the tropism of NSCs after transplantation into the hippocampus of APP/PS1 AD mice by MRI.Methods NSCs from C57BL/6 mouse were cultured and identified.Feridex and Poly-L-Lysine were added into the medium to be co-cultured to make magnetic labeled NSCs and transmission electron microscopy was used to identify the iron particles in NSCs.Transgenic (tg) and wild-type (wt) mice at 12 months of age were divided into three groups: SPIOs labeled NSCs group (A and C),unlabeled NSCs group(B).Feridex-labeled NSCs were migrated into the hippocampus of APP/PS1 AD mice to monitor in vivo by MRI.After 1,2,4 and 6 weeks,the mice were sacrificed and their brain tissues were sectioned to investigate the migration of SPIO labeled NSCs and compared with MRI.Results NSCs of C57BL/6 mice were cultured successfully.Transmission electron microscope showed visible iron granules in cytoplasm.MRI detection of labeled cells: T2WI and T2* WI showed remarkable low signal intensity at the hippocampus injection points 1 week after transplantation,particularly on T2* WI.Area of low signal intensity enlarged increasingly along the injection points after 2 weeks.At 4 weeks,area of low signal intensity spread throughout the hippocampus,but intensity shadowed Six weeks later,low signal intensity almost disappeared.There was no obvious low signal change in unlabeled cell transplantation group.For wt mice,size and location of low signal did not appear obvious change at all designated time points.Prussian blue positive cells were observed in the hippocampus,indicating that NSCs labeled with SPIO could survive,migrate and differentiate in the brain of the APP/PS1 AD mice.Changes of pathology were well correlated with the area where a signal intensity loss was observed in MRI 1,2,4 and 6 weeks after transplantation Conclusions Diffuse migration of transplanted NSCs labeled with SPIO is observed in the hippocampus in APP/PS1 tg mice,and MRI technique is an ideal method for tracking labeled stem cells after grafting in vivo.

Objective To explore the effect of neural stem cell(NSCs) transplantation on proton magnetic resonance spectroscopy (1H-MRS) and the behavior in APP/PS1 double transgenic AD mice.Methods NSCs from C57BL/6 mice were cultured and amplified.APP/PS1 double transgenic AD mice (n=30) aged 12 months were used as the study group,and mild-type mice (n=15) were used as the control group(group C).Animals in the study group were randomly divided into two subgroups:one receiving NSCs (group A) and the other receiving PBS transplantation (group B) in bilateral hippocampal CA1 of the AD model mice.Animals in the group C were not treated.1 H-MRS and Morris water maze (MWM) were performed before transplantation and 4 weeks after transplantation,and compared with the histopathological results.Results 1H-MRS showed that there was no significant change in NAA/Cr(1.01±0.08 and 1.03±0.05) and mI/Cr (0.69±0.05 and 0.71±0.06) ratios between group A and group B before transplantation (P＞ 0.05),but the changes were significant compared with the group C (NAA/ Cr:1.21±0.05; mI/Cr:0.58±0.06) (P＜0.05).Four weeks after transplantation,NAA/ Cr ratio(1.18± 0.09) was increased and mI/Cr ratio (0.53±0.04) was decreased in group A.The difference was significant compared with the group B at the same time points (P＜0.05).MWM showed the escape latency in group A was significantly shorter than that in group B after transplantation (P＜0.05).In addition,group A also showed an exclusive preference for the target quadrant,and spent more time ((35.21±5.44) s) in the 3rd quadrant compared with group B (P＜0.05).For number of platform crossings,similar results were also shown (5.75± 3.23).Nissl's staining showed that the number of neurons in the hippocampal area increased more significantly in group A than those in group B(P＜0.05).Conclusion NSCs transplantation can improve spatial learning and memory via neurons regeneration in APP/PS1 double transgenic AD mice,and 1H-MRS is able to display intracranial metabolite changes after NSCs transplantation.