Objective To investigate the mechanism of fisetin inhibiting the activation of microglia NOD-like receptor family protein 3(NLRP3)inflammasome in microglia and alleviating cognitive impairment after sepsis.Methods C57BL/6 mice were used to establish the sepsis model by cecal ligation and puncture.Mice were divided into four groups:the sham group,the sepsis group,the sepsis+caspase-1 knockout group(sepsis+Cas-1-/-group)and the sepsis+fisetin group.Evans blue was used to detect the permeability of blood-brain barrier(BBB).Morris water maze was used to evaluate the cognitive function of mice.Western blot assay and immunofluorescence double staining were used to detect the expression of NLRP3 inflammasome-related proteins including caspase-1,N-terminal fragment of the GSDMD(GSDMD-N),interleukin(IL)-1β,IL-18 and mitophagy-related proteins(Pink1,Parkin and LC3-Ⅱ)in brain tissue and microglia.Results Compared with the sham group,expression levels of caspase-1,GSDMD-N,IL-1β and IL-18 were significantly increased in the sepsis group(P＜0.05).Compared with the sepsis group,expression levels of caspase-1,GSDMD-N,IL-1β and IL-18 were significantly decreased in the sepsis+Cas-1-/-group(P＜0.05).The expression levels of Pink1,Parkin and LC3-Ⅱ were significantly higher in the sepsis+fisetin group than those of the sepsis group(P＜0.05),and expression levels of caspase-1,GSDMD-N,IL-1β and IL-18 were significantly lower(P＜0.05).After fisetin intervention,the permeability of BBB was decreased and the cognitive impairment(decreased escape latency and increased frequencies of crossing the platform)was alleviated in the sepsis+fisetin group compared with those of the sepsis group(P＜0.05).Conclusion Fisetin may alleviate central inflammation and cognitive impairment after sepsis by inhibiting the activation of microglial NLRP3 inflammasome through activating mitophagy.

Undicalcified autologous dentin particles(UADP)combined platelet rich fibrin(PRF)were used in a case after extraction of the left mandibular second molar for tooth extraction site preservation.CBCT images at 3,9 and 24 months after operation showed that the bone mass maintenance effect was obvious.Histological sections showed a large number of new bone formation around dentin particles.

Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.

Atherosclerotic plaque rupture is the main cause of many cardiovascular diseases, and biomechanical factors play an important role in the process of plaque rupture. In the study of plaque biomechanics, there are relatively few studies based on fatigue fracture failure theory, and most of them mainly focus on the whole fatigue propagation process from crack initiation to plaque rupture, while there are few studies on the influence of crack on plaque rupture at a certain time in the process of fatigue propagation. In this paper, a two-dimensional plaque model with crack was established. Based on the theory of fracture mechanics and combined with the finite element numerical simulation method, the stress intensity factor (SIF) and related influencing factors at the crack tip in the plaque were studied. The SIF was used to measure the influence of crack on plaque rupture. The results show that the existence of crack can lead to local stress concentration, which increases the risk of plaque rupture. The SIF at the crack tip in the plaque was positively correlated with blood pressure, but negatively correlated with fibrous cap thickness and lipid pool stiffness. The effect of the thickness and angle of lipid pool on the SIF at the crack tip in the plaque was less than 4%, which could be ignored. This study provides a theoretical basis for the risk assessment of plaque rupture with cracks.
Biomechanical Phenomena ; Computer Simulation ; Humans ; Plaque, Atherosclerotic ; Stress, Mechanical

Objective To observe the influence of Peiyuan Tongluo Fang(Qi-tonifying Collateral-dred-ging Decoction,PTF)on clinical efficacy and micro-inflammation state in patients with phase IV diabetic kidney disease(DKD),and investigate the mechanism of PTF in treatment of DKD.Methods Phase IV DKD patients(n=106)were randomly divided into treatment group and control group(each n=53).There were actually 98 patients had complete treatment in 2 groups(each n=49).Besides of basic therapy,the treatment group was treated with PTF,and control group was treated with Niaoduqing Gran-ule for 8 weeks.The changes of TCM patterns and levels of serum creatinine(SCr),estimated glomeru-lar filtration rate(eGFR),24 h urinary protein excretion(24 h U-pro), urinary microalbumin protein (U-Alb),high sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α)and interleu-kin-6(IL-6)were observed and analyzed statistically in two groups.Results After treatment,all TCM patterns were significantly relieved(P<0.05 or P<0.01)in treatment group compared with before, which were superior to those in control group(P<0.05 or P<0.01).After treatment,levels of SCr,24 h U-pro and U-Alb decreased significantly(P<0.01)and eGFR level increased(P<0.05)in treat-ment group compared with before treatment,which were superior to those in control group(P<0.05 or P<0.01).After treatment, levels of hs-CRP, TNF-αand IL-6 decreased significantly(P <0.01)in treatment group compared with before treatment, which were superior to those in control group(P <0.05).The total effective rate was 73.47%(36/49)in treatment group,and 44.90%(22/49)in con-trol group(P<0.05).No adverse reactions were observed in 2 groups.Conclusion PTF combined with basic therapy of Western medicine can effectively reduce urine protein,protect kidney and alleviate micro-inflammation state in patients with phase IV DKD.

Objective To observe the curative effect of nourishing kidney,activating blood and expelling toxin method Chinese medicine on chronic kidney disease (CKD) ratsand influence on cellular apoptosis.Methods The UUO animal model was adopted.SD male rats were divided into the sham operation group,UUO model group,Chinese medicine low dose group and high dose group.The renal function was measured by the automatic biochemical analyzer,the renal histopathologic change was observed by HE staining,the renal tissue apoptosis rate was observed by TUNEL as well as the protein expression levels of Bcl-2 and Bax were detected by Western blot.Results Compared with the UUO model group,the levels of serum creatinine(Scr) and urea nitrogen(BUN) in Chinese medicine various doses groups were significantly decreased(P＜0.05).In the UUO pathologic observation,renal tubular epithelial cells apoptosis,necrosis,exfoliation,inflammatory cells infiltration were found in the model group,the renal damage in the Chinese medicine various doses groups were slighter compared with the UUO group(P＜0.05).The TUNEL method detection showed that the cellular apoptosis number in the UUO group was significantly increased compared with the sham operation group,the Chinese medicine various doses groups could significantly decrease the apoptosis number(P＜0.05).Compared with the UUO model group,the level of Bcl-2 in the Chinese medicine treatment groups was markedly up-regulated,the Bax level was down-regulated,and the ratio of Bcl-2/Bax was increased(P＜0.05).Above results all showed the dose dependent manner.Conclusion The nourishing kidney,activating blood and expelling toxin method Chinese medicine can obviously down-regulate serum Scr and BUN levels,inhibits the renal cells apoptosis in UUO rat and regulates the Bcl-2 and Bax levels.

BACKGROUND: As a blood concentrate rich in growth factors and fibrin, platelet-rich fibrin (PRF) is able to significantly promote bone regeneration. PRF mixed with bone substitutes is commonly used to repair bone defects in oral maxillofacial region. But it remains controversial whether PRF as a sole material in sinus floor elevation can produce enough new bone tissues.OBJECTIVE: To evaluate the osteogenic potential of PRF as a sole grafting material in sinus floor elevation by means of an animal model.METHODS: Twelve healthy adult mongrel dogs aged 12-18 months were selected and randomized into three groups (groups A, B and C), with four dogs in each group. Upper first molars on both side of each dog were extracted 12 weeks prior to sinus floor elevation and simultaneous implants placement. Different materials were used to fill in the space between the sinus membrane and implant. Groups A, B and C were filled with PRF, autologus bone particles and autologus blood clot respectively. After 12 weeks, specimens were harvested to analyze the new bone formation by gross observation, X-ray examination and histological evaluation.RESULTS AND CONCLUSION: New bone formation was found to embrace all the implants close to the bony sinus floor, and the tips of all implants were free from bone coverage. The new bone height of groups A, B and C were (3.135±0.288),(3.218±0.345), and (1.898±0.157) mm, respectively. The new bone density of groups A, B and C were (65.06±5.88),(75.34±8.18), and (56.92±4.95) g/cm3, respectively. There were significant differences between the new bone height in groups A and C as well as in groups B and C (P < 0.05). Also, significant differences were found between the new bone density in groups A and B, B and C, A and C (P < 0.05). Within the confine of this experiment, it is feasible to use PRF as a sole grafting material in the sinus floor elevation to generate new bone, but the new bone volume is limited.

Background and purpose:Head and neck cancer is common worldwide. This article aimed to describe the patterns of incidence of head and neck cancer and their changes in Shanghai from 2003 to 2012, in order to provide reference for prevention programs, research and control strategies on cancer.Methods:The data of lip, oral cavity and pharynx cancer cases were collected by the Shanghai Cancer Registry. The distributions of Shanghai lip, oral cavity and pharynx cancer incidences from 2003 to 2012 were described. The patterns were described according to gender, age, basis of diagnosis, histological type, diagnostic stage in detail. We compared incidences of recent 5 years (from 2008 to 2012) with those of previous 5 years (from 2003 to 2007).Results:On average from 2003 to 2012, 1105 new cases of head and neck cancer were diagnosed in Shanghai each year, with 2.08% among the total cancer cases. The crude rate was 8.01 per 100000 and the age-standardized rate was 4.45 per 100000. Nasopharyngeal cancer was the major subtype of the head and neck cancer, with 50.81% among the total head and neck cases. The crude and age-standardized rates among males were higher than those among females. The histologically verified percentage was 85.77%. The squamous carcinoma was the major histological type, with 57.58% among the total cases. The age-stan-dardized rate of nasopharyngeal cancer was in decline.Conclusion:The incidence of head and neck cancer was low in Shanghai during the past 10 years. Male cases were more than female cases. The major histological type was squamous carcinoma. Half of new cases were nasopharyngeal cancer which appeared to affect patients at a relatively young age. Patients with nasopharyngeal cancer were diagnosed at relatively advanced stages.

Objective: To analyze the patterns of female breast cancer and their incidence in Shanghai during 2003-2012, and to compare them with international data. Methods: The data of female breast cancer cases diagnosed between 2003 and 2012 were collected from the Shanghai Cancer Registry. The record of cancer cases included the patient's name, gender, date of birth, permanent and residential address, diagnosis site or name, histological type, date of first diagnosis, diagnostic basis and diagnostic stage, etc. Data source of cancer incidence of World, Developed Countries, Developing Countries, East Asia and China in 2012 sourced from GLOBOCAN 2012 database of the WHO International Agency for Research on Cancer (IARC); and the data of USA during 2008-2012 was collected from SEER 18 database from Surveillance, Epidemiology, and End Results Program of the National Cancer Institute (NCI). Incidence indicators of Shanghai female breast cancer were calculated, including the average cases, median age, average age, proportion, crude rate, age-specific rate and age-standardized rate. Results: During 2003-2012, 41 991 new cases of female breast cancer were diagnosed in Shanghai, with an average of 4 199 cases per year, accounting for 17.23% among total new female cancer cases, ranking first in female cancer incidence in Shanghai during 2003-2012, with a crude incidence rate of 60.90 per 100 000 and an age-standardized incidence rate of 33.90 per 100 000. During 2008-2012, an average 4 528 new cases of female breast cancer was diagnosed per year in Shanghai, with 16.97% among total female cancer cases. The median age was 56 years old and the mean age was 57.73 years old. The crude rate was 64.23 per 100 000 and the age-standardized rate was 35.00 per 100 0000, which was higher than those of China (22.1 per 100 000), Eastern Areas (27.0 per 100 000) and Developing Counties (31.3 per 100 000), and lower than that of World (43.1 per 100 000), and Yellow Race Population of USA (68.77 per 100 000). During 2003-2007, on average, 3 869 new cases of female breast cancer were diagnosed per year in Shanghai, accounting for 17.54% of total female cancer cases. The median age was 53 years old and the mean age was 56.44 years old. The crude rate was 57.42 per 100 000 and the age-standardized rate was 32.69 per 100 000. There was a continuing peak stage spanned 25 years old from 50 to 74 years old, during 2008-2012. Compared with those of 2003-2007, the beginning age group of the continuing peak stage was delayed for 5 years old and the ending age group was delayed for 10 years old. Conclusion The age-standardized incidence rate in Shanghai was higher than those of China, Eastern Areas and Developing Counties, and lower than that of World, and that of Yellow Race Population of USA; Compared with 2003-2007, the crude rate and age-standardized rate increased, the median age, mean age and the beginning and ending age group of the continuing peak stage were delayed.

OBJECTIVETo understand the incidence trend of malignant tumors in children aged <15 years in Shanghai.

METHODSThe <15 years old children diagnosed with cancer in Shanghai between 2009 and 2011 were included in this study. The types of malignant tumors were classified according to International Classification of Childhood Cancer, Version 3 (ICCC-3). The gender and age specific incidences of malignant tumors were analyzed. Software Joinpoint was used to calculate the annual percentage of childhood cancer cases.

RESULTSA total of 460 cases of childhood cancer were diagnosed in Shanghai during 2009-2011, accounting for 0.3% of total cancer cases. The crude incidence was 129.0 per million and the age standardized rate (ASR) was 129.6 per million. The ASR was higher in boys (142.1 per million) than in girls (116.4 per million). The boy to girl ratio was 1.2(95%CI: 1.0-1.5). The incidence was highest in age group <5 years (165.1 per million). The incidences in age groups 5-9 years and 10-14 years were 101.2 per million and 113.9 per million, respectively. Leukemia was the most common cancer in children (n=165, 35.9%, ASR: 47.0 per million), followed by central nervous system tumors (n=91, 19.8%, ASR: 25.6 per million) and lymphomas (n=45, 9.8%, ASR: 12.6 per million). The age and gender specific incidence of malignant tumors and the type specific incidence of malignant tumors in children in Shanghai had no significant changes during the study period.

CONCLUSIONSThe incidence of malignant tumors was higher in boys than in girls in Shanghai. Leukemia, central nervous system tumors and lymphomas were the three most common cancers in children. The overall incidence of malignant tumors in children in Shanghai had no significant changes during 2002-2011.

Adolescent ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Incidence ; Male ; Neoplasms ; epidemiology