Objective To observe the effect of hippocampal DNA methyltransferases (DNMTs)on neonatal cognitive impairments induced by sevoflurance exposure.Methods Sixty-four 7-day old male Sprague-Dawley rats were randomly divided into the following four groups (n =1 6):control group (group C),sevoflurane group (group S),sevoflurane+NaCl group (group SN),and sevoflurane+5-AZA group (group SA).Sevoflurane animals received 3% sevoflurane plus 30% oxy-gen for 2 hours daily for 3 consecutive days,and rats in group C were placed into the same container, which contained 30% oxygen only.Animals in group SA were intracerebroventricularly injected with 5-AZA (1 mg/kg),while group SN same volume of NaCl one hour before sevoflurane exposure. Open field and Morris water maze were given the four weeks after anesthesia (n =8).Rats without any behavior tests from each group (n =8)were euthanized 4 weeks after the treatment and the hip-pocampus was harvested.Quantitative real-time PCR and Western blot were used to detect the mRNA and protein levels of DNMT1,DNMT3a and DNMT3b.Results In the open field test,no significant difference was observed in the distance travelled and the time spent in the center of the arena.Com-pared with the group C,group S showed an increase in the latency,decreased time spent in the target quadrant,and the mRNA and protein levels of DNMT3a and DNMT3b in the hippocampus were sig-nificantly increased (P < 0.05).Compared with the group SN,group SA showed a decrease in the la-tency,more time spent in the target quadrant,and the mRNA and protein levels of DNMT3a and DNMT3b in the hippocampus were decreased (P < 0.05).There was no significant difference in the expression of DNMT1 among the four groups.Conclusion Sevoflurane exposure induces neonatal cog-nitive impairments later in life,which was accompanied by the increased mRNA and protein levels of DNMT3a and DNMT3b in the hippocampus.By contrast,pretreatment of 5-AZA decreased hipp-ocampal DNMT3a and DNMT3b,and ameliorated cognitive impairments.These results suggest that DNMTs are involved in sevoflurane induced neonatal cognitive impairments.

Objective To investigate the role of histone lysine methyltransferase G9a in sevoflurane-induced cognitive impairment in the developing brain of neonatal rats.Methods Thirty-six 5-day-old male SD rats were randomly divided into 3 groups (n =12):control group,sevoflurane group and Bix01294 (the inhibitor of histone lysine methyltransferase G9a)group.The rats in the sevoflurane group and the Bix01294 group received 3% sevoflurane anesthesia for 2 hours once a day at postnatal 5-7 days (P5-P7 ).The rats in the Bix01294 group received Bix01294 (10 mg/kg)subcu-taneously at 1 5 min before anesthesia,and the rats in the control group and sevoflurane group received normal saline for injection (0.1 ml)at the same time.The open-field test and fear condition-ing test were performed at P3 5 and P3 9-P41 ,respectively.The tissues of hippocampus were collected at P42 to measure the levels of G9a,histone H3 lysine 9 dimethylation (H3K9me 2 )and synapsin 1. Results Compared with the control group,the percentage of freezing time of sevoflurane group was significantly decreased in the contextual fear condition test,while the levels of G9a and H3K9me 2 were significantly increased and the level of synapsin 1 was significantly decreased (P <0.01).How-ever,the percentage of freezing time of Bix01294 group was significantly increased,while the levels of G9a and H3K9me 2 were significantly decreased and the level of synapsin 1 was significantly in-creased compared with the sevoflurane group (P <0.05).There was no difference in the total distance and residence time in the central grid in the open-field test,and the percentage of freezing time in the cued fear condition test among the three groups.Conclusion Histone lysine methyltransferase G9a is involved in the sevoflurane-induced long-term cognitive impairment in developing brain of neonatal rats,which may be associated with the increase of H3K9me 2 and the down-regulation of synapsin 1 in the hippocampus.

Objective To explore the clinical value of the level of granzyme B and perforin mRNA in urine for the diagnosis of renal transplantation patients with delayed graft function (DGF). Methods Twenty-four cases of renal transplantation patients with DGF were included in this study. Seventy-three u-rine specimens were obtained from these patients who received graft biopsies. Among the 24 cases, ureteral obstruction occurred in 2 cases, vascular thrombosis in 1 case, acute CsA intoxication in 3 cases, acute tubu-lar necrosis (ATN) in 7 cases, ATN complicating borderline change in 2 cases, ATN complicating acute re-jection (AR) in 3 cases, AR in 6 cases. Total RNA was isolated from the urinary cells. Messenger RNA (mRNA) encoding the cytotoxic proteins perforin and granzyme B gene were measured with the quantitative polymerase-chain-reaction assay-(RT-PCR). SPSS13.0 software was used for data analysis. Levels of mRNA were log-transformed before analysis. Results The levels of perforin and granzyme B mRNA in u-rine among the ureteral obstruction group, vascular thrombosis group, acute CsA intoxication group and ATN group were very low. There was no significant difference among these groups (P>0.05). However,among the ATN complicating borderline change group 1.22, 0. 97 fg/μg, ATN complicating AR group (1.20±0.39), (1.07±0.30)fg/μg, and AR group(11.13±0. 33), (1.01±0.19)fg/μg, the levels were increased significantly(P<0.001). Conclusion Measurement of mRNA encoding the cytotoxic proteins perforin and granzyme B gene in urinary cells in renal transplantation patients with DGF could be helpful to etiological diagnosis of DGF, and might be used as an index for the appropriate management of the borderline change.

Objective To study the effects of different intervention time of percutaneous transhepatic gallbladder catheterizing drainage (PTGBD)on severe acute biliary pancreatitis Methods Totally 64 patients with severe acute biliary pancreatitis in Affiliated Hospital of Hebei University from July 2013 to July 2017were selected and divided into 3 groups according to the time from attack to PTGBD:group A (less than 72 hours,n =28),group B (from 72 hours to 120 hours,n =22),group C (from 120 hours to 148 hours,n =14).Intergroup comparison of level of WBC,CRP,TBIL,PLT and APACHE-Ⅱ Score,disappearance time of abdominal sign,incidence of pancreatic abscess,length of stay (LOS),mortality and patient satisfaction 48 hours before and after PTGBD were conducted.Results Compared with those in group B and C,all laboratory indexes,APACHE-ⅡScore,disappearance time of abdominal sign,incidence of pancreatic abscess,LOS,mortality and patient satisfaction in group A were all significantly different (P ＜ 0.05).Conclusion Early PTGBD (within 72 hours)can be effective and safe for the treatment of severe acute biliary pancreatitis,and can shorten LOS and reduce the mortality.

Objective:To investigate the effectiveness of surgical treatment for patients with T 4 stage prostate cancer. Methods:The clinical data and prognosis of 18 patients with T 4 stage prostate cancer treated in Shanghai Tenth People's Hospital from July 2013 to December 2019 were retrospectively analyzed. The average age of these 18 patients was 68.3 (53-81)years. 10 patients were castration resistant prostate cancer (CRPC) and 8 patients were hormone-sensitive prostate cancer (HSPC). 10 CRPC patients were treated with surgical treatment due to bladder clot packing and/or lower urinary tract obstruction. 8 HSPC patients had severe hematuria, severe dysuria and local symptoms. The KPS scores of all patients were ≥80 points with an average score of 84 (80-90). The average QOL score of 18 patients was 28 (21-32). 2 cases in 18 patients underwent total pelvic resection for rectal invasion (one CRPC and one HSPC). 7 cases underwent radical cystoprostatectomy for ureteral invasion (5 cases of CRPC, 2 cases of HSPC), 9 cases underwent bladder preservation surgery for bladder neck invasion (4 cases of CRPC, 5 cases of HSPC), of which 4 cases of enlarged lymph node dissection were all HSPC patients. Results:All cases of T 4 stage prostate cancer patients operation were successfully completed, the average operation time was 256 (219-310)min and the median intraoperative blood loss was about 300 (250-350)ml. Four of them (3 cases of CRPC and 1 case of HSPC) received blood transfusion after operation. The average postoperative hospital stay was 21(11-37) days. All 18 cases were followed up and the median follow-up time was 23.8 months. There was no perioperative death, and no bladder-preserving patients had true urinary incontinence or bladder outlet stenosis.2 CRPC cases died 8 and 15 months after surgery respectively, 7 patients were PSA relapse treated with docetaxel or abiterone therapy, and 1 HSPC patient with rectal invasion was followed up for 58 months after total pelvic resection, the PSA level was still 0.003ng/ml, no distant metastasis was found. 8 cases of hormone-sensitive patients were treated with endocrine therapy, and PSA was less than 0.2 ng/ml. The average QOL of 18 patients 3 months after operation was 37 points (25-45), which was significantly higher than that before operation. The average maximum urine flow rate of patients with bladder preservation was 23(19-25)ml/s. Conclusions:For T 4 stage prostate cancer, surgical treatment is feasible and safe for doctors with extensive surgical experience. For CRPC patients, the surgery can significantly improve short-term symptoms and quality of life, and long-term benefits need to be further evaluated with a large sample. For HSPC patients, it can not only improve clinical symptoms and QOL of patients, but also provide long-term benefits.

Objective:To evaluate the value of visual analysis and standardized uptake value ratio (SUVR) during 18F-florbetapir (AV45) PET/CT brain imaging in diagnosis of β-amyloid (Aβ) deposition in patients with mild cognitive impairment (MCI) and Alzheimer′s disease (AD), and to explore the clinical ancillary value of the two indexes. Methods:From December 2018 to July 2019, a total of 47 subjects, including 5 (3 males, 2 females, age (58±13) years) normal controls (NC), 8 (2 males, 6 females, age (66±10) years) patients with AD and 34 (16 males, 18 females, age (70±7) years) patients with MCI were enrolled. All subjects underwent 18F-AV45 PET/CT scan. All images were evaluated by visual analysis and SUVR were calculated. The diagnostic efficiencies of visual analysis and SUVR were compared by McNemar test and Kappa test. One-way analysis of variance and Welch test were used to compare data differences. The best threshold value of SUVR was obtained by receiver operating characteristic (ROC) curve analysis. Results:The positive rate of Aβ deposition for all subjects was 46.81%(22/47) by SUVR analysis, and 38.30%(18/47) by visual analysis. There was no significant difference between the two methods ( χ2=33.15, P>0.05), and the consistency was good ( Kappa=0.83). Considering the clinical diagnosis as the"gold standard", the Aβ deposition obtained by visual analysis and SUVR analysis can effectively distinguish AD from NC, and the sensitivities were 7/8 vs 8/8, respectively, both specificities were 5/5( χ2=9.48, P>0.05), with good consistency ( Kappa=0.84). SUVR quantitative analysis could distinguish AD from NC, AD from MCI ( F values: 3.99-8.79, all P<0.01), but could not distinguish NC from MCI (all P>0.05). ROC curve analysis showed that the best threshold value of precuneus′ SUVR was 1.08 for the differential diagnosis of AD and NC; for the differential diagnosis of AD and MCI, the best threshold value of lateral temporal′s SUVR was 1.06. Conclusion:Visual analysis was consistent with SUVR′s qualitative determination during 18F-AV45 PET/CT imaging for brain Aβ deposition, while SUVR quantitative analysis could assist in the differential diagnosis of AD and NC, AD and MCI.

Background An association between atmospheric fine particulate matter (PM_2.5) exposure and Parkinson's disease (PD) has been suggested by previous studies, but the results of current epidemiological studies are still inconclusive. Objective To systematically evaluate the relationship between exposure to ambient PM_2.5 and the risk of PD, as well as to explore potential influencing factors, aiming to provide scientific evidence for formulating early prevention strategies for PD. Methods Cochrane Library, PubMed, Web of Science, Medline, Embase, China National Know-ledge Infrastructure (CNKI), Wanfang Database, and VIP Chinese Science and Technology Journal Database were queried. The search terms included Parkinson's disease, particulate matter 2.5, and PM_2.5 in both Chinese and English. Cohort studies examining the association between atmospheric PM_2.5 exposure and the risk of PD were collected and searched from the inception of each database to June 26, 2023. The identified literature was screened, and the basic information of the included studies and their research subjects, outcome indicators, quantitative results of each study, as well as the information required by bias risk assessment were extracted. The Newcastle-Ottawa Scale was employed to assess the risk of literature bias. Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias analysis were conducted in Stata 15.0 software. Results Twelve cohort studies were identified. A total of 17443136 participants with follow-up periods ranging from 3.5 to 22 years were included in the analysis. The meta-analysis, utilizing a random-effects model, revealed that PD risk was elevated by 6% after exposure to PM_2.5 [HR=1.06 (95%CI: 1.02, 1.11), P=0.006]. The subgroup analysis demonstrated that exposure to PM_2.5 increased PD risk by 6% in North America [HR=1.06 (95%CI: 1.00, 1.12), P=0.033] and by 17% in East Asia [HR=1.17 (95%CI: 1.02, 1.33), P=0.020]. However, the effect was not statistically significant in Europe. PD risk exhibited a 7% rise [HR=1.07 (95%CI: 1.02, 1.14), P=0.011] in individuals aged 60 years and older, which was different from that in individuals younger than 60 years. Exposure to various concentrations of PM_2.5 was observed to associate with an elevated risk of PD. The inclusion of adjustments for PD-related comorbidities did not alter the conclusion that ambient PM_2.5 exposure might elevate the risk of PD. The studies with a follow-up duration exceeding 5 years and reporting more than 1000 PD cases suggested a significant increase in the risk of PD due to ambient PM_2.5 exposure [HR=1.06 (95%CI: 1.01, 1.12), P=0.012; HR=1.06 (95%CI: 1.01, 1.11), P=0.027, respectively]. Conversely, no significant association was identified between ambient PM_2.5 exposure and the risk of PD within the cohorts with a follow-up duration of less than 5 years and reporting fewer than 1000 PD cases [HR=1.09 (95%CI: 0.95, 1.26), P=0.214; HR=1.12 (95%CI: 0.98, 1.02), P=0.092, respectively]. The sensitivity analysis showed that the results were stable. The publication bias analysis and the combined trim-and-fill method showed that the results were robust. Conclusion The risk of PD could be increased by ambient PM_2.5 exposure and influenced by age and area. The research results might be affected by the duration of follow-up and the quantity of PD cases reported.

Sesquiterpenoids are natural compounds composed of 15 carbon atoms， which can be divided into sesquiterpene alcohols， ketones， lactones， aldehydes， and carboxylic acids according to oxygen groups. These compounds are widely distributed in nature， and their physiological activities are diverse. For example， many sesquiterpenes with potential anticancer effects have been found for anti-tumor effects， including cytotoxicity， antioxidant， immune regulation， cell proliferation， and so on. In addition， some sesquiterpenoids have good application prospects in antibacterial， anti-inflammatory， and anti-cardiovascular diseases. Malignant tumors， inflammation， bacterial diseases， and cardiovascular diseases are the main diseases that cause human death， and natural products have unique advantages in the treatment of these diseases. Therefore， the development of new drugs that are easy to promote has become a new research hotspot. In this paper， the sesquiterpenes extracted from the natural components of Chinese herbs and plants with anti-tumor， anti-inflammatory， antibacterial， and anti-cardiovascular activities， such as Xanthium， Atractylodes， Convolvulus， Acanthium， Ligularia， Artemisia， Ligularia， Ligularia， Labiaceae Mint， Acanthophyllum， Turmeria， Ginger， and other Chinese herbs and plants， were discussed. The biological activities and related mechanisms of this compound were reviewed， which provided a reference for further research and clinical application of sesquiterpenes.