Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.
Animals ; Feasibility Studies ; Male ; Necrosis ; Radiosurgery/methods* ; Stroke Volume ; Swine ; Ventricular Function, Left ; Ventricular Septum

OBJECTIVE: To retrospectively analyze clinical effect of 3D mirror printing combining with minimally invasive percutaneous plate osteosynthesis(MIPPO) technology in the treatment of adult clavicle fracture. METHODS: The clinical data of 32 adult patients with collarbone AllmanⅠdisplacement of fracture who had undergone the combination of 3D mirror printing with MIPPO technology treatment were collected from October 2019 to October 2020. There were 19 males and 13 females, aged from 19 to 55 years old with an average of(34.12±16.42) years old. According to Allman classification, there were 14 cases of AllmanⅠb and 18 cases of AllmanⅠc. Fracture occurred on the left in 17 cases and on the right in 15 cases. Postoperative complications, operation time, incision length, intraoperative blood loss, the number of fluoroscopies, fracture healing time of all patients were retrospectively analyzed, and the curative effect was evaluated by Constant-Murley shoulder joint score before operation, 1 and 6 months after operation. RESULTS: All the 32 patients were followed up for 6 to 8 months, with an average of (6.67±2.13) months. All the patients did not have postoperative complications such as incision infection and skin numbness in the operating area. The operation time was (35.37±4.28) min. The incision length was (3.78±0.45) cm. Intraoperative blood loss was(37.23±4.76) ml. The number of fluoroscopies was(3.12±0.47) times. Fracture healing time was (8.18±2.58) weeks. Constant-Murley shoulder joint score of the affected side at 1 and 6 months after operation was 81.08±3.92 and 98.03±1.05 respectively, which had a significant difference compared with 54.62±5.25 before operation(P<0.05). According to Constant-Murley shoulder function score at 6 months after operation, 30 cases were excellent and 2 cases were good. CONCLUSION 3D mirror printing can effectively assist MIPPO technique in the treatment of adult clavicle AllmanⅠdisplaced fracture. It not only has the advantages of less trauma and fewer complications of the MIPPO technique, but also can further shorten the operation time and improve the operation maneuverability. It is a better method in the treatment of adult clavicle AllmanⅠdisplaced fracture.
Adolescent ; Adult ; Blood Loss, Surgical ; Bone Plates ; Clavicle/surgery* ; Female ; Fracture Fixation, Internal/methods* ; Fractures, Bone/surgery* ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures/methods* ; Printing, Three-Dimensional ; Retrospective Studies ; Treatment Outcome ; Young Adult

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

Abstract: Objective　To analyze the survival status of HIV/AIDS patients aged above 50 years receiving antiviral therapy (ART) in Shanxi Province from 2011 to 2019, and to provide evidence for further improvement of antiviral therapy. Methods　Basic information and follow-up information of HIV/AIDS patients aged above 50 years who first received HIV/AIDS antiviral therapy in Shanxi Province from 2011 to 2019 were collected. Excel database was established and SPSS23.0 software was used for analysis. Retrospective cohort study was conducted. Cox proportional risk regression model was used to analyze the factors influencing survival time. Results　A total of 1 183 subjects were included, of which 172 died, including 84(48.84%) from other causes, 74(43.02%) AIDS-related death and 14 (8.14%) from accidents, suicides and undetermined deaths. Setting AIDS-related deaths as an outcome event, life table analysis showed that the cumulative survival rates at 1, 3, 5, 7 and 9 years after receiving ART were 96.61%, 93.59%, 90.35%, 87.57% and 83.44%, respectively. Multivariate Cox proportional risk model analysis showed that the risk of death in patients aged 60-<70 years group and over 70 age group was 2.53 times (95%CI: 1.51-4.23) and 3.59 times (95%CI: 1.74-7.40) for patients aged the 50-<60 group , respectively. The risk of death in patients with baseline CD4+T lymphocyte (CD4) counts of ≥200/mm3, 50-<200 /mm3 was 0.22 times (95%CI: 0.12-0.41) and 0.37 times (95%CI: 0.21-0.67) for patients with CD4+T lymphocyte counts of <50/mm3. The risk of death in patients with opportunistic infections at baseline was 1.99 times (95%CI: 1.16-3.39) for patients without baseline opportunistic infections. Conclusions　The survival rate of HIV/AIDS patients aged above 50 who received antiviral therapy (ART) in Shanxi Province from 2011 to 2019 was relatively high. To further improve the quality of antiviral treatment in our province, the strategy of "early detection and early treatment" should be continued and improved in the future, and information collection of specific causes of non-AIDS-related deaths among this population should be further strengthened.

The antidepressant effect of Xiaoyaosan has been demonstrated. It is of value to explore the biological mechanism of Xiaoyaosan in the treatment of depression from the perspective of functional modules by using the method of functional module division of the metabolic network. The differential metabolites and related enzymes and proteins regulated by Xiaoyaosan were identified in the database. Pathway enrichment analysis and crosstalk pathway analysis of Xiaoyaosan regulated metabolites was carried out. A network of differentially regulated metabolites and their enzymes and proteins was constructed by using the STRING tool. The CNM decomposition algorithm was used to extract the functional modules of the network and enrichment analysis of functional modules was carried out. The results show that Xiaoyaosan regulates 97 differential metabolites, 234 related enzymes and 258 depression-related proteins. The pathways crosstalk analysis was divided into two sub-networks, one of which is related to the neural system and cell signal transduction, the other is related to the endocrine system and metabolic pathways. KEGG pathway enrichment analysis of the network and 9 functional modules extracted by the CNM algorithm shows that module 1 and module 3 belong to the pathways that can be enriched into more pathways with fewer proteins. The corresponding functions of these pathways include the endocrine system, amino acid metabolism, the nervous system and signal transduction. In this study, pathway crosstalk analysis and metabolic network module division strategies were used to explain the biological mechanism of Xiaoyaosan in the treatment of depression, providing ideas and methods for in-depth study of the pharmacological mechanism of this traditional Chinese medicine from the perspective of metabolic regulation.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.
Angiotensin I ; antagonists & inhibitors ; metabolism ; Animals ; Antioxidants ; pharmacology ; Blood Pressure ; drug effects ; Hypertension ; chemically induced ; drug therapy ; Male ; Oxidative Stress ; drug effects ; Paraventricular Hypothalamic Nucleus ; drug effects ; Peptide Fragments ; antagonists & inhibitors ; metabolism ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Sodium Chloride, Dietary ; pharmacology

Objective: To compare the clinical effect of diode laser enucleation of the prostate (DIOD) with that of transurethral resection of the prostate (TURP) on benign prostate hyperplasia (BPH) with different prostate volumes. METHODS: This retrospective study included 256 BPH patients treated by DIOD (n = 141) or TURP (n = 115) from March 2012 to August 2015. According to the prostate volume, we divided the patients into three groups: <60 ml (42 for DIOD and 31 for TURP), 60－80 ml (51 for DIOD and 45 for TURP), and >80 ml (48 for DIOD and 39 for TURP). We obtained the relevant data from the patients before, during and at 6 months after surgery, and compared the two surgical strategies in operation time, perioperative levels of hemoglobin and sodium ion, post-operative urethral catheterization time and bladder irrigation time, pre- and post-operative serum PSA levels, International Prostate Symptoms Score (IPSS), post-void residual urine (PVR) volume and maximum urinary flow rate (Qmax), and incidence of post-operative complications among different groups. RESULTS: In the <60 ml group, there were no remarkable differences in the peri- and post-operative parameters between the two surgical strategies. In the 60－80 ml group, DIOD exhibited a significant superiority over TURP in the perioperative levels of hemoglobin (［3.25 ± 1.53］ g/L vs ［4.77 ± 1.67］ g/L, P <0.05) and Na+ (［3.58 ± 1.27］mmol/L vs ［9.67 ± 2.67］ mmol/L, P <0.01), bladder irrigation time (［30.06 ± 6.22］h vs ［58.32 ± 10.25］ h, P <0.01), and urethral catheterization time (［47.61 ± 13.55］ h vs ［68.01 ± 9.69］ h, P <0.01), but a more significant decline than the latter in the postoperative PSA level (［2.34 ± 1.29］ ng/ml vs ［1.09 ± 0.72］ ng/ml, P <0.05), and similar decline was also seen in the >80 ml group (［3.35 ± 1.39］ ng/ml vs ［1.76 ± 0.91］ ng/ml, P <0.05). No blood transfusion was necessitated and nor postoperative transurethral resection syndrome or urethral stricture observed in DIOD. However, the incidence rate of postoperative pseudo-urinary incontinence was significantly higher in the DIOD (22.7%, 32/141) than in the TURP group (7.83%, 9/115) (P <0.05). CONCLUSIONS DIOD, with its obvious advantages of less blood loss, higher safety, faster recovery, and more definite short-term effectiveness, is better than TURP in the treatment of BPH with medium or large prostate volume and similar to the latter with small prostate volume.
Humans ; Lasers, Semiconductor ; adverse effects ; therapeutic use ; Male ; Operative Time ; Organ Size ; Postoperative Complications ; etiology ; Prostate ; pathology ; Prostatic Hyperplasia ; pathology ; surgery ; Quality of Life ; Retrospective Studies ; Therapeutic Irrigation ; Transurethral Resection of Prostate ; adverse effects ; methods ; statistics & numerical data ; Treatment Outcome ; Urethral Stricture ; etiology ; Urinary Catheterization ; Urinary Incontinence ; etiology

Background: Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection. Methods: We retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) between January 2003 and December 2014. The associations of patients' clinical characteristics with prognosis were estimated using Cox regression and Kaplan–Meier survival analyses. Results: During follow-up (median, 86 months; range, 24–160 months), the 5- and 10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%, respectively. Masaoka stage (P < 0.001), World Health Organization (WHO) histological classification (P < 0.001), and postoperative radiotherapy after initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post-recurrence survival. Patients with recurrent thymoma who underwent repeated resec-tion had increased post-recurrence survival rates compared with those who underwent therapies other than surgery (P = 0.017). Conclusions: Masaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post-recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.

Referring to the recent literatures, this review summarized the recent research progress of SR-MSNDDS which were responsive to different stimulus, including pH, reduction, temperature, light, magnetic field or biomolecules, etc. To review the recent research progress of stimuli responsive mesoporous silica nanoparticle (SR-MSNDDS) drug delivery systems and predict their application prospect. SR-MSNDDS could overcome the problem of controlling drug release from MSN and achieve tumor specific drug release, which has become a research hotspot in the field of tumor diagnosis and therapy.